cssi/SciSciGPT-SciSciNet huggingface dataset:
Inhibition of Angiogenesis by Thrombospondin-1 Is Mediated by 2 Independent Regions Within the Type 1 Repeats

Background—Suppression of tumor growth by thrombospondin-1 (TSP-1) has been associated with its ability to inhibit neovascularization. The antiangiogenic activity of TSP-1, as defined by cornea pocket assays, was previously mapped to the amino-terminal portion of the protein within the procollagen region and the type 1 repeats. Methods and Results—We evaluated the specificity and efficacy of different regions of TSP-1 using recombinant fragments of the protein on chorioallantoic membrane (CAM) angiogenesis and endothelial cell proliferation assays. In both assays, fragments containing the second and third type 1 repeats but not the procollagen region inhibited angiogenesis and endothelial cell proliferation. To further define the sequences responsible for the angiostatic effect of TSP-1, we used synthetic peptides. The CAM assay defined 2 sequences that independently suppressed angiogenesis. The amino-terminal end of the type 1 repeats showed higher potency for inhibiting angiogenesis driven by basic fibr...
Presidents and Front-page News: How America's Newspapers Cover the Bush Administration

Presidency and political communication scholars have given scant attention to how local news media cover the presidency. The author offers a comparative study of coverage of the Bush presidency on the front pages of 100 American newspapers during a five-month period in 2006. Sociological and economic theories predict slanted coverage of national politics by America's newspapers, despite journalistic professional norms to the contrary.The analyses suggest there is a slant to the coverage of President Bush that is partly explained by the political leanings of the newspaper and its audience. Newspapers that endorsed Bush's reelection in 2004 tended to write more favorable headlines, and newspapers in states where Democrats are strong politically tended to write less favorable headlines.
Phthalate esters as environmental contaminants.

WE have found traces of phthalate esters in fish caught in various parts of North America. In a routine monitoring programme, gas-liquid chromatographic (GLC) analyses revealed two unidentified peaks in many fish extracts and in procedural blanks examined for insecticide residues. The two compounds have now been identified with gas chromatograph-mass spectrometer techniques1 as di-n-butyl and di-2-ethylhexyl phthalates. These compounds, widely used as plasticizers, proved to be of low toxicity, but our data suggest that they could be detrimental to some aquatic organisms.
phylogeo: an R package for geographic analysis and visualization of microbiome data

Motivation We have created an R package named phylogeo that provides a set of geographic utilities for sequencing-based microbial ecology studies. Although the geographic location of samples is an important aspect of environmental microbiology, none of the major software packages used in processing microbiome data include utilities that allow users to map and explore the spatial dimension of their data. phylogeo solves this problem by providing a set of plotting and mapping functions that can be used to visualize the geographic distribution of samples, to look at the relatedness of microbiomes using ecological distance, and to map the geographic distribution of particular sequences. By extending the popular phyloseq package and using the same data structures and command formats, phylogeo allows users to easily map and explore the geographic dimensions of their data from the R programming language. Availability and implementation phylogeo is documented and freely available http://zachcp.github.io/phylogeo Contact : zcharlop@rockefeller.edu.
Antagonism of the behavioral effects of ethanol by naltrexone in BALB/c, C57BL/6, and DBA/2 mice

The effects of naltrexone on the increase in locomotor activity induced by a low dose (1.35 g/kg IP) of ethanol and on the duration of loss of righting reflex after a high dose (3.5 g/kg) of ethanol were studied in BALB/c, DBA/2, and C57BL/6 mice. Ethanol increased locomotor activity in DBA and BALB mice, but not in C57BL mice. Naltrexone, at a dose of 0.1 mg/kg, antagonized the ethanol-induced increase in locomotion similarly in DBA and BALB mice. The duration of loss of ringting reflex was, however, differentially affected in all three strains by naltrexone. The BALB mice were the most sensitive strain (1 mg/kg naltrexone significantly counteracted ethanol hypnosis), the C57BL mice were intermediate (8 mg/kg naltrexone required to antagonize this effect of ethanol), and the DBA mice were least sensitive (no effect evident even at the highest dose of 8 mg/kg) to naltrexone. Thus, naltrexone could antagonize the behavioral effects of a low and high dose of ethanol, but the three strains, which differ in their behavioral response to ethanol, also were differentially sensitive to the effect of naltrexone in reversing ethanol-induced hypnosis and ethanol-induced changes in locomotor activity.
Nickel sulfide hollow whisker formation

Hollow, high-aspect-ratio nickel sulfide whiskers were formed during aqueous corrosion experiments at 250°C by the U. S. Department of Energy. The whiskers grew radially from Teflon thread at the waterline in acidic sodium sulfate solutions containing chloride additions. The hollow morphology is consistent with that reported for the mineral millerite found in nature in hematite cavities. The data suggest that iron and chloride impurities are necessary for the observed whisker structure.
Preparation of a new visual pigment analogue of cattle opsin using 5,6-dihydroretinal

ONLY two compounds, 11-cis-retinal I and 11-cis-3-dehydroretinal II, have been found to act as chromophores in naturally occurring visual pigments1. These compounds contain one and two double bonds respectively in the cyclic portion of the structure. The analogous compound, 5,6-dihydroretinal III which is similar in all other respects to retinal except that the ring is saturated, has not been isolated from the retina. Recombination experiments, in which visual pigments are formed from the corresponding visual protein and one of the naturally occurring retinals, show further selectivity on the part of the protein2. This selectivity is manifested by the protein's ability to discriminate between the geometrical isomers of naturally occurring retinals. Consequently, the 11-cis and 9-cis isomers combine with visual proteins to produce visual pigments, whereas the all-trans and 13-cis isomers do not. Only the 11-cis isomer combines with a visual protein to form a pigment identical to those which occur naturally. In this article, we report the formation of a new synthetic pigment from 5,6-dihydroretinal III and cattle opsin; we also describe some of its spectral properties and photochemical behaviour. Apparently, this is the first report of a direct recombination of a retinal other than the naturally occurring compounds.
Response of Early Lactation Cows to Fat Supplementation in Diets with Different Nonstructural Carbohydrate Concentrations

Abstract Twenty-four high producing (36.7 kg/d, initially) Holstein cows in early lactation were used in a 63-d lactation trial to study the effects of low (28%), medium (31%). and high (37%) nonstructural carbohydrate concentrations in diets with added fat. Diets with isonitrogenous (17% CP) and fed as TMR with 41% sorghum silage. Nonstructural carbohydrate concentrations were altered by substitution of corn gluten feed and soybean hulls (50:50) for wheat and corn in the concentrate portion of the diet. Fat was added at 3% of DM in the form of yellow grease. Production of milk (38.5, 38.9, and 40.4 kg/d) and 3.5% FCM (38.2, 37.0, and 37.6 kg/d) was not significantly different for the cows fed low, medium, and high nonstructural carbohydrate diets, respectively. Milk fat percentages (3.47, 3.22, and 3.10%) decreased, and milk output per unit of DMI (1.5, 1.6, and 1.7) increased, as nonstructural carbohydrate concentration increased. Increasing nonstructural carbohydrate concentrations of the diet increased digestibilities of DM (58.4, 60.6, and 61.5%) and nonstructural carbohydrates (76.5, 79.6, and 80.4%) and decreased digestibilities of NDF (44.3, 43.7, and 40.6%) and ADF (46.3, 45.2, and 38.8%). Altering nonstructural carbohydrate content of the diet had no effect on AA supply to or uptake by the mammary gland or efficiency of utilization of AA for milk protein synthesis.
Influence of Adsorbent Characteristics on the Performance of an Adsorption Heat Storage Cycle

The increasing importance of heat transformation applications of adsorption (refrigeration, heat pumping, and heat storage) creates a demand for adsorbents optimized in new ways. The figures of merit in these applications are different from those that guide most adsorbent design processes today. A quantity to be optimized is the total sorptive heat stored over a cycle period rather than selectivity or total adsorption capacity. This optimization requires a detailed understanding of the link between cycle thermodynamics and microscopic adsorbent characteristics. We show that a simple statistical Langmuir model of adsorption is sufficient to analyze some of the key relationships. The influence of energetic heterogeneity on cycle performance is analyzed in a model system in relation to the energy and entropy change upon adsorption. For a homogeneous system of monoenergetic adsorption sites, it is shown that for each value of the adsorbed state entropy there is an optimal adsorbent−adsorbate interaction energ...
Electroweak Symmetry Breaking from Gauge/Gravity Duality

Abstract We use the gauge/gravity duality to study a model of walking technicolor. The latter is a phenomenologically promising framework for dynamical electroweak symmetry breaking. A traditional problem for technicolor models has been the need to address gauge theories at strong coupling. Recent developments in gauge/gravity duality provide a powerful tool for handling this problem. First, we revisit previously considered holographic models of QCD-like technicolor from D-branes. In particular, we develop analytical understanding of earlier numerical computations of the Peskin–Takeuchi S-parameter. Then we apply this method to the investigation of a model of walking technicolor, obtained by embedding D 7 – D 7 ¯ probe branes in a recently discovered type IIB background dual to walking behaviour. As a necessary step, we also show that there is an embedding of the techniflavor branes, that realizes chiral symmetry breaking. Finally, we show that the divergences that appear in the S-parameter can be removed by using holographic renormalization.
Multiplex coherent anti-Stokes Raman scattering flow cytometry for real-time classification of particles in a microfluidic channel

Flow cytometry is an ever-advancing, multivariate analysis tool obtaining morphological and phenotype information from sample populations. In traditional flow cytometers, obtaining molecular information requires the use of endogenous fluorophores, which are limited by spectral overlap, nonspecific binding, available conjugation chemistries, and cellular toxicity. In this work, however, we apply multiplex coherent anti-Stokes Raman scattering (MCARS), a nonlinear optical method that probes the Raman energies within a molecule, to flow cytometry in order to demonstrate label-free, molecularly sensitive particle differentiation. To demonstrate this, we correctly differentiate 5 μm polystyrene (PS) and poly(methyl methacrylate) (PMMA), which (linearly) optically appear similar, but vary significantly in their MCARS spectrum.
Protein interactions with subcutaneously implanted biosensors.

Abstract Biofouling of in vivo glucose sensors has been indicated as the primary reason for sensitivity losses observed during the first 24 h after implant [Wisniewski N, Moussy F, Reichert WM. Characterization of implantable biosensor membrane biofouling. Fresen J Anal Chem 2000; 366(6–7): 611–621]. Identification of the biomolecules that contribute to these sensitivity perturbations is the primary objective of the research presented. Active needle-type glucose sensors were implanted in Sprague–Dawley rats for 24 h, and then a proteomics approach was used to identify the substances absorbed to the sensors. MALDI–TOF mass spectrometry was the primary tool utilized to identify the biomolecules in sensor leachate samples and species absorbed directly on sensor membranes excised from explanted in vivo sensors. Not surprisingly serum albumin was identified as the primary biomolecule present, however, predominantly as endogenous fragments of the protein. In addition, several other biomolecule fragments, mainly less than 15 kD, were identified. Based on these findings, it is concluded that fragments of larger biomolecules infiltrate the sensor membranes causing diminished glucose diffusivity, thus decreasing in vivo sensitivity.
Texture processing of bulk YBa2Cu3O6+x by zone melting

Abstract Zone melting has been used to produce texture in bulk YBa 2 Cu 3 O 6+ x . By controlling the directional solidification of the molten zone, oriented structures are produced that consist of domains of aligned grains, with some misalignment between domains. Scanning electron microscopy and optical microscopy show a high degree of texture produced by this technique. Magnetization measurements show a large increase in hysteresis at 77 K compared to unaligned polycrystalline YBa 2 Cu 3 O 6+ x . The use of BaCuO 2 as a solvent to aid the texturing process is discussed.
Heterologous expression and stability of the Escherichia coli β-galactosidase gene in Streptococcus lactis by translation fusion

Abstract An Escherichia coli/Streptococcus lactis shuttle vector for creating translation fusions to the E. coli galactosidase (lacZ) has been constructed. Random S. lactis chromosomal DNA fragments inserted upstream of the lacZ gene and in frame promote the expression of active galactosidase in both E. coli and S. lactis. One fusion pSK216 has been characterized by Western blotting to reveal a fusion protein of 116 kd. S. lactis LM0230, a plasmidless lac− derivative of S. lactis C2 when carrying pSK216, exhibits a Lac+ phenotype suggesting the presence of a chromosomally encoded lactose permease. Further evidence for this lactose permease system is provided by assay of lactose uptake by S. lactis LM0230. In the absence of selection pSK216 was less stable in S. lactis LM0230 than its derivative pSK41. The growth rate of S. lactis LM0230 carrying pSK216 is slower in comparison to the plasmid-free strain. Two genetic events were observed, the deletion of the lacZ gene and the loss of the entire plasmid. These results indicate that recombinant plasmids are unstable in S. lactis and imply that there is an obstacle in the genetic engineering of lactic acid bacteria.
Strong Receives 2008 James R. Holton Junior Scientist Award

Courtenay Strong received the James R. Holton Junior Scientist Award at the 2008 AGU Fall Meeting Honors Ceremony, held 17 December in San Francisco, Calif. The award recognizes outstanding research contributions by a junior atmospheric scientist within 3 years of his or her Ph.D.
Efficient Approach to Compute Generalized Interdependent Effects between Infrastructure Systems

Most studies on infrastructure interdependencies only explore a subset of the possible damage states in which they operate. Typically, interdependence effects (IE) are measured in terms of common failure fractions (f) of components across systems. In this paper, an expanded damage space is explored where infrastructure systems can simultaneously experience different failure fractions f. This augmented space is then mapped onto a functionality space where IEs are evaluated as a function of the efficiencies of constitutive systems: a desirable feature because efficiency is typically measured and recorded in practice whereas f is not. These new IEs conditioned on efficiency levels are termed generalized interdependent effects (GIE), which can be predicted or detected in a computationally efficient fashion. Prediction is a function of initial efficiencies before damage propagation and can be used in prefailure analyses, whereas detection is a function of final joint efficiencies for postfailure analyses. To i...
Ecosystem risk analysis: A new methodology

A method is presented for extrapolating laboratory toxicity data to aquatic ecosystem effects such as decreased productivity or reduction in game fish biomass. The extrapolation requires translating laboratory data into changes in the parameters of an ecosystem model, the Standard WAter COlumn Model (SWACOM). The translation is effected through knowledge of toxicological modes of action. The uncertainties associated with both laboratory measurements and extrapolations are explicitly retained, and risk estimates are given in the form of probabilities that an effect could occur. The approach is illustrated by scenarios in which effects of toxic substances are distributed across different trophic levels. Each scenario affects population interactions in different ways and alters both the level and the nature of the risks to ecosystem processes. Particular attention is paid to analyzing the interaction between toxicity and the uncertainties associated with extrapolation.
Noncoherent Doppler tracking: first flight results

Abstract Noncoherent Doppler tracking has been devised as a means to achieve highly accurate, two-way Doppler measurements with a simple, transceiver-based communications system. This technique has been flown as an experiment on the Thermosphere, Ionosphere, Mesosphere, Energetics and Dynamics (TIMED) spacecraft, (launched 7 December 2001), as the operational technique for Doppler tracking on CONTOUR, and is baselined on several future deep space missions at JHU/APL. This paper reports on initial results from a series of successful tests of this technique between the TIMED spacecraft and NASA ground stations in the Deep Space Network. It also examines the advantages that noncoherent Doppler tracking and a transceiver-based system may offer to small satellite systems, including reduced cost, mass, and power.
The daily timing of lamprey attacks

Laboratory and field data suggest that several species of parasitic lampreys forage primarily at night, but data forPetromyzon marinus are equivocal. Nocturnal foraging may minimize predation risk. This may be particularly important to those species of lampreys that inhabit shallow streams. Nocturnal foraging also may enhance foraging efficiency if potential hosts at night are quiescent and more easily approached. Future experiments should be designed to avoid several potential sources of bias.
Temperature dependence of the spin S=1/2 fluctuation rate and the low-spin versus high-spin transition in native chloroperoxidase

We analyzed two preparations of native, low-spin ferric chloroperoxides as a function of temperature with the following results. (i) The spin lattice transition rateW(T) is relative slow, following a power lawW=0.035 (T/K)4.98 (rad/s) for one of the samples. (ii) The quadrupole splitting is strongly temperature dependent, dropping from ¦δEQ¦ ∼ 2.94 mm/s at 100 K to ∼2 mm/s at 250 K. (iii) Starting at 190 K, the low-spin heme iron in frozen adqueous solution converts reversibly to a high-spin form, reaching ∼40% high-spin at 250 K. The two forms appear to be in thermal equilibrium, (iv) Optical data indicate that in a 70% glycerol glass, the conversion starts at lower temperature and reaches ∼50% highspin at 190 K.
A trainable cermet gas microsensor technology using cyclic voltammetry and neural networks

Abstract Argonne National Laboratory (ANL) has been developing an economical, new type of gas microsensor to evaluate and demonstrate a new gas sensing technology. The device employs neural data processing to decipher the complex information made available by applying cyclic voltammetry to a rugged, miniature cermet (ceramic metallic) sensing device. The device has demonstrated the potential to address many industrial, safety, and environmental applications. The ANL system employs stepped cyclic voltammetry to produce electrical ‘signatures’ from a cermet sensor sandwich. The sensors are composed of four overlapping screen-printed thick-films built on a ceramic substrate with an incorporated platinum heating element built on the reverse side from the sensor. The first film is a nickel metal oxide layer that provides a reference source of ions for the sensing device. This is followed by a sandwich of two platinum catalytic electrode layers separated by a tungsten-stabilized bismuth oxide solid electrolyte layer. As a cyclic voltage is ramped across the upper and lower catalytic electrodes (through the solid electrolyte), gases react at the three phase gas/solid electrolyte/electrode boundary and cause a change in the measured ionic current flowing through the sensor. This associates a unique current-voltage profile with each gas species exposed to the sensor. This profile is then digitally sampled into a signature and computational neural networks are used to process the signature and train the sensor support electronics to identify and quantify the gas or mixture. The electrocatalytic (EC) multigas microsensor technology is still under development, but exhibits significant potential advantages over many other commercial gas-sensor technologies. The advantages of the EC microsensor approach are: (a) small size — current prototype microsensor is 2 × 3 × 0.1 mm; Supported by palm-sized micro-electronics package; (b) rugged cermet materials, suitable for high-temperature operation (100–500°C); © demonstrated ‘flash’ forced overheating (>500°C) to vaporize organic contaminants; (d) demonstrated multigas monitoring potential; (e) demonstrated proof-of-concept in detecting low ppm to high percent levels of O2, N2, CO2, CO, CH4 (and other HCs), and NO; (f) flexible identification and quantification with neural data processing techniques; (g) flexible interfacing with programmable output. The ANL technology produces a ‘smart’ sensor through the use of a dedicated programmable microcontroller. It demonstrates a viable mechanism for a variety of gas monitoring and process control applications. The trainability of the device in specific environments, coupled with rugged construction materials and a powerful measurement technique, give the device the potential to overcome many of the limitations which have plagued other technologies.
A phase I clinical trial of tiopronin, a putative neuroprotective agent, in aneurysmal subarachnoid hemorrhage.

Background The neurotoxic aldehyde 3-aminopropanal (3-AP) contributes to brain injury following cerebral ischemia. Tiopronin (N-2-mercaptopropionyl-glycine[N-2-MPG]) is a US Food and Drug Administration (FDA)-approved drug for the treatment of cystinuria and a putative neuroprotective agent that has been shown to bind and neutralize 3-AP and reduce infarct volumes. Objective The objective of this trial was to establish the safety of tiopronin administration in patients with aneurysmal subarachnoid hemorrhage (aSAH) in preparation for further trials of its efficacy as a neuroprotective agent in this disease process. Methods This Phase I dose-escalation trial enrolled three-patient cohorts using a conventional "3+3" study design. Tiopronin dose began at 1 g/d until aSAH Day 14. Each subsequent cohort received a dose of tiopronin based on predetermined guidelines. A maximum dose of 3 g/d was selected, because this is the maximum FDA-approved dose for long-term cystinuria treatment. Subjects were monitored for known side effects of tiopronin. Results Nine patients were enrolled, the minimum number required based on the study design. None of these patients experienced serious side effects attributable to tiopronin, and no adverse events were noted that could not be attributed to the pathophysiology of aSAH. Conclusion The administration of 3 g/d of tiopronin following aSAH for up to 14 days appears to be safe and without the side effects associated with long-term use. Plans for a randomized, placebo-controlled Phase II trial of tiopronin for neuroprotection following aSAH are underway.
Diallyl sulfide inhibition of CYP2E1 does not rescue diabetic rats from thioacetamide-induced mortality.

Previously we have shown that hepatotoxicity of thioacetamide (TA) was increased in streptozotocin (STZ)-induced diabetic (DB) rats due to combined effects of enhanced bioactivation-based liver injury of TA and compromised liver tissue repair response. We have also shown that TA is primarily bioactivated by hepatic CYP2E1. The present study was done to further investigate the importance of liver tissue repair in determining the final outcome of hepatotoxicity. STZ-induced DB rats were pretreated with a CYP2E1 inhibitor, diallyl sulfide (DAS), to decrease the bioactivation-based liver injury of TA. The treatments were as follows: DB/DAS/TA, DB/corn oil/TA, and DB/DAS/saline. Nondiabetic (non-DB) rats received the same treatments as controls. A dose of TA (300 mg/kg ip), which was nonlethal in non-DB rats, caused 92 and 90% mortality in DB/DAS/TA and DB/corn oil/TA groups, respectively. At various times (0--60 h) after treatment, liver injury was assessed by plasma alanine aminotransferase and histopathology. Cell proliferation was evaluated by [(3)H]thymidine incorporation and immunohistochemical staining of proliferating cell nuclear antigen (PCNA). In the DB/DAS/TA rats, DAS pretreatment markedly reduced the CYP2E1-dependent liver injury of TA compared to that in DB/corn oil/TA rats. However, subsequent hepatic DNA synthesis in both DB groups was inhibited approximately 50%. PCNA analysis showed a corresponding decrease in cell-cycle progression. This compromised tissue repair response in DB rats was insufficient to compensate for cell loss, resulting in progression of liver injury and culminating in high mortality in both DB groups. Furthermore, non-DB rats were pretreated with a CYP2E1 inducer, isoniazid, to increase the bioactivation-based TA liver injury equal to the liver injury observed in DB/DAS/TA rats. Despite equal injury up to 36 h following TA treatment, the tissue repair response in the non-DB rats was highly stimulated to compensate for liver injury and led to 70% survival in this group. These studies underscore the importance of adequate and timely tissue repair in compensating for liver injury and protecting from lethality.
Induction of mutations at the hypoxanthine phosphoribosyl transferase (HPRT) locus in AHH-1 human lymphoblastoid cells.

Abstract Cells from the human lymphoblastoid cell line, AHH-1, were exposed to two dierct-acting mutagens, ethyl methanesulfonate (EMS) and ethyl nitrosourea (ENU), and to three carcinogens that require metabolic activation to an electrophile, benzo[ a ]pyrne (B(a)P), 6-aminochrysene (6-AC), and 6-nitrochrysene (6-NC); mutation induction at the HPRT locus was quantified by resistance to 6-thioguanine (6-TG r ). Exposure of AHH-1 cells to either EMS or ENU resulted in a concentration-dependent increase in mutant frequency at the HPRT locus. When AHH-1 cells were exposed to B(a)P, the increase in mutant frequency at the HPRT locus was marginally significant linearly and significant quadratically. The 32 P-postlabeling assay revealed the formation of DNA adducts derived from ((±) anti -benzo[ a ]pyrene- trans -7,8-dihydrodiol-9,10-epoxide which may account for the increase in 6-TG r clones. Although DNA adducts could be detected by the 32 P-postlabeling assay in both 6-NC- and 6-AC-treated AHH-1 cells, exposure to 6-AC or 6-NC did not result in a concentration-dependent increaese in mutant frequency at the HPRT locus. Our results are consistent with the results of previous which indicate that EMS and ENU are effective inducers of 6-TG r clones as is B(a)P when activated to an electrophile. In 6-NC- and 6-AC-exposed cells, low levels of N -hydroxy-6-aminochrysene-derived adducts were detected in only 6-NC-exposed cells. No 6-aminochrysene-1,2-dihydrodiol-derived adducts were detected following 6-NC or 6-AC exposure. Minimal metabolic activation of 6-NC or 6-AC by AHH-1 cells may account for the lack of a positive mutagenic response for either 6-AC or 6-NC.
Structure of an ETHE1‐like protein from Arabidopsis thaliana

The protein product of gene At1g53580 from Arabidopsis thaliana possesses 54% sequence identity to a human enzyme that has been implicated in the rare disorder ethylmalonic encephalopathy. The structure of the At1g53580 protein has been solved to a nominal resolution of 1.48 A. This structure reveals tertiary structure differences between the ETHE1-like enzyme and glyoxalase II enzymes that are likely to account for differences in reaction chemistry and multimeric state between the two types of enzymes. In addition, the Arabidopsis ETHE1 protein is used as a model to explain the significance of several mutations in the human enzyme that have been observed in patients with ethylmalonic encephalopathy.
Identification and functional assessment of endothelial P1H12

Monoclonal antibody P1H12 recognizes circulating endothelial cells and endothelia of all sizes of blood vessels. To identify the protein recognized by P1H12, we expressed a cDNA library in CHO cells and sequenced the cDNA from positive cells. The P1H12 sequence was identical, except at several bases, to that reported for melanoma cell surface antigen MUC18/CD146. Aggregation assays demonstrated that CD146 mediates Ca(++)-independent homotypic endothelial cell adhesion. P1H12 mAb abrogated interactions between human microvascular endothelial cells (HMVECs) but not between human umbilical vein endothelial cells (HUVECs). P1H12 mAb abrogated P1H12-positive (CHO(P1H12))-association with HMVECs or HUVECs. CD146 distribution is sparser on HUVECs than on HMVECs. These data imply that HMVECs and HUVECs express the CD146 binding partner but that CD146 is functional (or at sufficient density) only on HMVECs. HMVEC monolayers treated with soluble P1H12 mAb showed increased permeability to albumin, with accompanying changes in actin, paxillin, FAK, and caveolin distribution and changes in tyrosine phosphorylation of FAK. Stimulation with P1H12 mAb led to redistribution of NF-kappa B to the nucleus. P1H12 mAb bound to beads inhibited closure of wounded endothelial monolayers. CD146 thus joins VE-cadherin and PECAM-1 as a molecule that mediates homotypic endothelial cell adhesion. CD146 has both structural functions and signaling functions important for endothelial monolayer integrity.
Biomechanics of single chondrocytes and osteoarthritis.

Osteoarthritis is a significant, debilitating disease that afflicts millions of Americans, yet its etiology is poorly understood. However, there is substantial evidence that biomechanical factors play a role in the development and progression of osteoarthritis. Previous work has demonstrated that biomechanical factors such as an acute insult or the cumulative effects of repetitive loads can induce degenerative changes in joints, cartilage explants, and isolated chondrocytes. Nevertheless, all of these studies suffer from the limitation that the precise nature of the mechanical loads experienced by individual cells is not well defined. Implementation of a single-cell approach, employing existing cell mechanics methodologies and molecular techniques such as single-cell reverse transcriptase-polymerase chain reaction (RT-PCR), offers an exciting new means to identify which biomechanical factors precipitate pathological changes in chondrocytes indicative of osteoarthritis. This article reviews the particular methods used in mechanical studies of single cells with emphasis on techniques that have been used to investigate chondrocytes and similar anchorage-dependent cell types.The fundamentals of RT-PCR and its application at the single-cell level are also discussed.
Dielectric Properties Measurements and Data

This paper reviews measurement techniques and sources of data for the dielectric constant and loss factor of solid materials. Accurate values of such properties are basic to intelligent design of materials processing schemes utilizing electromagnetic energy. Emphasis is on techniques and data for these properties in the "microwave" range of frequencies of roughly 108 to 1011 Hz and at elevated temperatures.
Residence time distribution analysis of magnetic nanoparticle-enhanced mixing using time-dependent magnetic actuation in microfluidic system

The dynamics of an innovative time-dependent magnetic nanoparticle (MNP)-based mixing strategy is demonstrated in this study using a multiphysics finite element model. Residence time distribution (RTD) analysis, for the first time, is successfully applied to predict the performance as well as investigate and optimize a wide range of design parameters used in the magnetically actuated mixing process. Orientation of electrodes as well as the direction of current to produce desirable magnetic field are found to play a major role on mixing performance. It is also found that a two-electrode system with an optimized current can be as effective as a four-electrode system. For effective mixing, an optimum switching frequency of current supplied to electrodes is predicted. Effect of MNP size, flow condition on mixing performance is also studied using RTD analysis and optimized values are predicted. Overall, the developed “numerical prototype” in conjunction with RTD analysis demonstrates that time-dependent magnetic actuation can be effectively used to mix or tag MNPs with biomolecules in situ for further processing and the numerical model can be used as a predictive tool in the design and optimization of mixing strategy for developing efficient lab-on-a-chip systems.
Activation of the alternative complement pathway and generation of chemotactic factors by asbestos.

Abstract Five types of asbestos plus silica and glass wool fibers were tested for their ability to activate the alternative complement pathway and to generate chemotactic factor activity from fresh normal human serum (NHS). Two assays were used to detect alternative pathway activation by the fibers. The first method was a hemolytic assay that utilized glutathione-sensitized human erythrocytes (GSHE) to detect the C5b-C9 complexes generated by activation of fresh NHS with the various fibers. The second method was an immunoelectrophoretic assay to detect split products of activation of factor B after the fibers were incubated with NHS. Both assays were performed under conditions that have been shown to block the initial steps of classical pathway activation but permit activation of the alternative complement pathway. All five asbestos fibers tested, amosite, anthophyllite, crocidolite, and chrysotiles A and B activated the alternative pathway when tested by both methods. In addition, it was demonstrated that chemotactic factor activity was generated when asbestos fibers were incubated with fresh NHS. In contrast, silica and glass wool fibers did not activate the alternative complement pathway and did not generate chemotactic factor activity. These observations suggest that the complement system may mediate the initial inflammatory response observed upon exposure to certain types of asbestos fibers.
Leadership in child psychiatry: A perspective from a department chair

A departmental chairman's expectations for the leader of a division of child and adolescent psychiatry vary widely. The author shares his personal experiences in this role as he describes clinical practice goals, clinical service delivery, research productivity, teaching excellence, and faculty development, as well as other administrative issues. The current shortage in senior academic leadership is discussed, as is the question of when a division of child and adolescent psychiatry should become an autonomous department.
Metabolic abnormalities associated with weight loss during chemoirradiation of head-and-neck cancer

Purpose: Weight loss caused by acute mucositis and dysphagia is common during concurrent chemoirradiation (chemo-RT) of head-and-neck (HN) cancer. The metabolic consequences of weight loss during chemo-RT were investigated. Patients and Methods: Ninety-six patients with locally advanced HN cancer were treated from 1995 to 2001 on protocols that consisted of 1 to 2 cycles of induction cisplatin/5-fluorouracil followed by irradiation (70 Gy over 7 weeks) concurrent with cisplatin (100 mg/m2 every 3 weeks). Body weights and metabolic evaluations were obtained before and during induction chemotherapy and chemo-RT. Greatest percent changes in weight and in the laboratory values were calculated for each phase of therapy. Results: During induction chemotherapy, significant changes were found in BUN, BUN:creatinine ratio, HCO3, Mg, and albumin, but not in creatinine, Na, K, or weight. During chemo-RT, significant additional changes were observed in all parameters measured, including increases in BUN, creatinine, BUN: creatinine ratio, and HCO3 and decreases in Mg, albumin, Na, K, and weight. The magnitude of most of these changes was significantly greater during chemo-RT than during induction chemotherapy. During chemo-RT, 35% of the patients had more than 10% body weight loss and 6 patients had an increase in creatinine of more than 100%, including 5 patients with Grade 2 nephrotoxicity, all of whom had weight loss 10% or more. Significant correlations were found between weight loss and creatinine (p Conclusions: Weight loss during cisplatin-containing chemo-RT was found to be associated with reduced kidney function. These findings do not establish cause-effect relationships; however, they highlight the importance of intensive supportive measures of nutrition and hydration beyond standard hydration during cisplatin administration. These intensive measures should be enacted before a 10% weight loss is reached.
Evaluating the performance of likelihood methods for detecting population structure and migration

A plethora of statistical models have recently been developed to estimate components of population genetic history. Very few of these methods, however, have been adequately evaluated for their performance in accurately estimating population genetic parameters of interest. In this paper, we continue a research program of evaluation of population genetic methods through computer simulation. Specifically, we examine the software MIGRATEE - N 1.6.8 and test the accuracy of this software to estimate genetic diversity (Θ ), migration rates, and confidence intervals. We simulated nucleotide sequence data under a neutral coalescent model with lengths of 500 bp and 1000 bp, and with three different per site Θ Θ Θ values of (0.00025, 0.0025, 0.025) crossed with four different migration rates (0.0000025, 0.025, 0.25, 2.5) to construct 1000 evolutionary trees per-combination per-sequence-length. We found that while MIGRATEE - N 1.6.8 performs reasonably well in estimating genetic diversity (Θ Θ Θ ), it does poorly at estimating migration rates and the confidence intervals associated with them. We recommend researchers use this software with caution under conditions similar to those used in this evaluation.
Functionally Novel Tumor Necrosis Factor-α–Modulated CHR-Binding Protein Mediates Cyclin A Transcriptional Repression in Vascular Endothelial Cells

Local expression of tumor necrosis factor-alpha (TNF-alpha) at the sites of arterial injury after balloon angioplasty, suppresses endothelial cell (EC) proliferation and negatively affects reendothelialization of the injured vessel. We have previously reported that in vitro exposure of ECs to TNF-alpha induced EC growth arrest and apoptosis. These effects were mediated, at least in part, by downregulation of cell cycle regulatory proteins. In the present study, we report potential mechanism(s) for TNF-alpha-mediated suppression of cyclin A in ECs. TNF-alpha exposure to ECs completely abrogated cyclin A mRNA expression via mechanisms involving both transcriptional and posttranscriptional modifications. TNF-alpha inhibited de novo cyclin A mRNA synthesis and suppressed cyclin A promoter activity. Utilizing deletion mutants of human cyclin A promoter, we have identified CDE-CHR (Cell cycle-Dependent Elements-Cell cycle genes Homology Region) region of cyclin A promoter as a target for TNF-alpha suppressive action. Experiments to investigate CDE-CHR binding proteins/factors revealed a TNF-alpha-mediated increase in specific DNA binding activity to the CHR elements. This increase in binding activity by TNF-alpha was mediated via the induction of a functionally novel 84-kDa protein that binds specifically to CHR in Southwestern assays. UV cross-linking and SDS-PAGE analysis of proteins eluted from specific complex confirmed the presence of this 84-kDa protein. Moreover, induction of this protein by TNF-alpha was protein synthesis dependent. Additionally, exposure of ECs to TNF-alpha markedly reduced cyclin A mRNA stability. Targeted disruption of this protein could potentially be a therapeutic strategy to rescue EC proliferation in vivo.
Dynamic and static voltage stability enhancement of power systems

The static voltage stability and the dynamic voltage stability are integrated. To consider a shunt compensator and/or a more general load which is dependent on voltage, a modified criterion for the static voltage stability is developed and the system is controlled to satisfy this static stability criterion. For an accurate analysis of the dynamic voltage stability, the system model includes excitation systems, tap-changers, capacitors and power system stabilizers in addition to network equations. A parameter optimization technique with a modal performance measure is developed to determine optimal control parameters for dynamic voltage stability enhancement. >
Control of adaptive locomotion: effect of visual obstruction and visual cues in the environment

Visual information regarding obstacle position and size is used for planning and controlling adaptive gait. However, the manner in which visual cues in the environment are used in the control of gait is not fully known. This research examined the effect of obstacle position cues on the lead and trail limb trajectories during obstacle avoidance with and without visual information of the lower limbs and obstacle (termed visual exproprioception). Eight subjects stepped over obstacles under four visual conditions: full vision without obstacle position cues, full vision with position cues, goggles without position cues and goggles with position cues. Goggles obstructed visual exproprioception of the lower limbs and the obstacle. Position cues (2 m tall) were placed beside the obstacle to provide visual cues regarding obstacle position. Obstacle heights were 2, 10, 20 and 30 cm. When wearing goggles and without position cues, a majority of the dependent measures (horizontal distance, toe clearance and lead stride length) increased for the 10, 20 and 30 cm obstacles. Therefore lower limb–obstacle visual exproprioception was important for the control of both limbs, even though with normal vision the trail limb was not visible during obstacle clearance. When wearing goggles, the presence of position cues, which provided on-line visual exproprioception of the self relative to the obstacle position in the anterior–posterior direction, returned lead and trail foot placements to full vision values. Lead toe clearance was not affected by the position cues, trail clearance decreased but was greater than values observed during full vision. Therefore, visual exproprioception of obstacle location, provided by visual cues in the environment, was more relevant than visual exproprioception of the lower limbs for controlling lead and trail foot placement.
Homologous recombination and its regulation

Homologous recombination (HR) is critical both for repairing DNA lesions in mitosis and for chromosomal pairing and exchange during meiosis. However, some forms of HR can also lead to undesirable DNA rearrangements. Multiple regulatory mechanisms have evolved to ensure that HR takes place at the right time, place and manner. Several of these impinge on the control of Rad51 nucleofilaments that play a central role in HR. Some factors promote the formation of these structures while others lead to their disassembly or the use of alternative repair pathways. In this article, we review these mechanisms in both mitotic and meiotic environments and in different eukaryotic taxa, with an emphasis on yeast and mammal systems. Since mutations in several proteins that regulate Rad51 nucleofilaments are associated with cancer and cancer-prone syndromes, we discuss how understanding their functions can lead to the development of better tools for cancer diagnosis and therapy.
The role of thrombospondin 1 on intestinal inflammation and carcinogenesis.

Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD) quite common in the United States and other Western countries. Patients suffering IBD are at greater risk of developing colorectal adenocarcinoma than the general population. Both, the adenoma-carcinoma and the inflammation-carcinogenesis processes are characterized by active angiogenesis. Recent studies also have shown that anti-angiogenesis might be a novel therapeutic approach for IBD. Thrombospondin 1 (TSP1) is an extracellular protein well known for its anti-angiogenic properties. TSP1 also has key functions in inflammation, which is assumed to be the primary cause for carcinogenesis in IBD. This review is focused on the role of TSP1 in colorectal carcinogenesis. The therapeutic effects of TSP derived-peptides on inhibiting the inflammation-carcinogenesis progression are also discussed.
Design of a multi-object, high throughput, low resolution fiber spectrograph for WFMOS

We present the preliminary optical and optomechanical design of a high throughput, fiber spectrograph for the Gemini/Subaru Wide-Field, Fiber-Fed, Multi-Object Spectrograph (WFMOS) designed with the principle goal of studying the nature of dark energy via enormous high-redshift spectroscopic surveys. Developed from an original Sloan Digital Sky Survey design this multi-object spectrograph utilizes all-refractive cameras, volume phase holographic gratings, and state-of-the-art CCD detectors to produce a peak instrument throughput of ~ 70%. The instrument produces 292 spectra simultaneously in two channels covering the bandpass 390 < λ < 1000 nm with a mean spectral resolution, λ/FWHM, of R ~ 1700. WFMOS will employ approximately ten of these fiber spectrographs on an 8 m class telescope to capture nearly 3000 spectra simultaneously. When used in a nod & shuffle mode of operation these spectrographs will facilitate spectroscopy of faint 0.5 < z < 3.5 galaxies with unprecedented efficiency.
Exacerbation of Acanthamoeba Keratitis in Animals Treated with Anti-Macrophage Inflammatory Protein 2 or Antineutrophil Antibodies

Neutrophils are thought to be involved in many infectious diseases and have been found in high numbers in the corneas of patients with Acanthamoeba keratitis. Using a Chinese hamster model of keratitis, conjunctival neutrophil migration was manipulated to determine the importance of neutrophils in this disease. Inhibition of neutrophil recruitment was achieved by subconjunctival injection with an antibody against macrophage inflammatory protein 2 (MIP-2), a powerful chemotactic factor for neutrophils which is secreted by the cornea. In other experiments, neutrophils were depleted by intraperitoneal injection of anti-Chinese hamster neutrophil antibody. The inhibition of neutrophils to the cornea resulted in an earlier onset and more severe infection compared to controls. Anti-MIP-2 antibody treatment produced an almost 35% reduction of myeloperoxidase activity in the cornea 6 days postinfection, while levels of endogenous MIP-2 secretion increased significantly. Recruitment of neutrophils into the cornea via intrastromal injections of recombinant MIP-2 generated an initially intense inflammation that resulted in the rapid resolution of the corneal infection. The profound exacerbation of Acanthamoeba keratitis seen when neutrophil migration was inhibited, combined with the rapid clearing of the disease in the presence of increased neutrophils, strongly suggests that neutrophils play an important role in combating Acanthamoeba infections in the cornea.