cssi/SciSciGPT-SciSciNet huggingface dataset:
Effect of stannous 2-ethylhexanoate on the network formation and chain extension reactions of α,ω-dihydroxy terminated poly(dimethylsiloxane)

Abstract α,ω-Dihydroxy terminated poly(dimethylsiloxane) (PDMS) may undergo condensation with multifunctional crosslinking agents such as tetraethoxysilane (TEOS) to give networks having well defined structures, i.e. “model networks”. The curing reactions are typically carried out at 298 K by utilizing stannous 2-ethylhexanoate to catalyse the condensation. The present study shows that, at concentrations of 1.0 and 1.5 wt%, the stannous 2-ethylhexanoate promotes significant chain extension of the PDMS in the absence of the crosslinking agent at 293 K. For catalyst concentrations typically used for the preparation of model networks ( c wt %), however, no significant chain extension was observed of the PDMS. Furthermore, the results obtained for the curing of α,ω-dihydroxy terminated PDMS with TEOS at 293 K, as catalysed by 0.1 wt% stannous 2-ethylhexanoate, demonstrate that chain extension prior to, or concurrent with, the reaction of functionally terminated chains with the network junctions is insignificant for these conditions.
Use of the TIMI frame count in the assessment of coronary artery blood flow and microvascular function over the past 15 years

Since its introduction, the TIMI frame count method has contributed to the understanding of the pathophysiology of coronary artery disease. In this article, the evolution of the TFC method and its applicability in the assessment of various therapeutic modalities are described.
Bilateral subinternal limiting membrane hemorrhage with Terson syndrome

Purpose To report the anatomic location of bilateral dome-shaped posterior pole hemorrhages in a patient with Terson syndrome. Methods Case report. We performed bilateral vitrectomy for vitreous hemorrhage in a patient with Terson syndrome. After removal of vitreous hemorrhage, the tissue overlying a large discrete hemorrhage in the posterior pole was removed, and the tissue from one eye was examined histologically. Result The discrete dome-shaped hemorrhage in the posterior pole was confined to the retina anteriorly by the internal limiting membrane. Conclusion Large dome-shaped retinal hemorrhages with Terson syndrome can be located beneath the internal limiting membrane of the retina.
Tuning the near-IR band energy and redox potentials of magnesium tetra(ferrocenyl)tetraazaporphyrins

Magnesium 2(3),7(8),12(13),17(18)-tetraferrocenyl-5,10,15,20-tetraazaporphyrin (3), and magnesium 2(3),7(8),12(13),17(18)-tetracyano-3(2),8(7),13(12),18(17)-tetraferrocenyl-5,10,15,20-tetraazaporphyrin (4) complexes were prepared using template condensation reaction between magnesium butoxide and (Z)-dicyanovinylferrocene (1) and tricyanovinylferrocene (2), respectively. Redox and unusual optical properties of macrocyclic compounds 3 and 4 were investigated in details using UV-vis, MCD, electro-, and spectroelectrochemical methods as well as DFT and TDDFT calculations. It was shown that the HOMO in both compounds resembles Goutermans' a1u orbital (D4h symmetry), which is different from meso-ferrocenyl containing porphyrins. In both macrocycles 3 and 4 overlapping oxidation waves for ferrocene substituents were observed in electrochemical and spectroelectrochemical experiments. Electrochemically observed oxidation waves are rather broad because of the presence of positional isomers and span only ~300 mV range in DCM/0.05 M TBAF system. Based on the excellent agreement between experimental UV-vis spectra and TDDFT predicted excitation energies, it was suggested that the low-energy NIR and visible regions are predominantly composed by the MLCT transitions with a significant π–π* mixing.
Toxicity and neurophysiological effects of selected insecticides on the mole cricket, Scapteriscus vicinus (Orthoptera: Gryllotalpidae)

Abstract Mole crickets ( Scapteriscus spp.) are severe subterranean pests of turfgrasses, commonly targeted with neurotoxic insecticides. Ideally insecticides used against mole crickets should induce quick knockdown or mortality to minimize damage caused by their tunneling. However, neurophysiological effects of insecticides on mole crickets are mostly unknown. The aims of this study were to investigate neurophysiological and toxic effects of several insecticides on tawny mole cricket ( Scapteriscus vicinus Scudder) adults and nymphs, and potential synergy between pyrethroid and neonicotinoid insecticides. Bifenthrin, fipronil, and the combination of bifenthrin + imidacloprid provided the fastest median mortality when injected. The combination of bifenthrin + imidacloprid elicited faster toxicity than either active ingredient alone. Imidacloprid, bifenthrin, and bifenthrin + imidacloprid caused immediate knockdown, whereas fipronil immobilized mole crickets within 1–2 h. Acephate, bifenthrin, fipronil, imidacloprid, and bifenthrin + imidacloprid caused significant neuroexcitation. Bifenthrin + imidacloprid resulted in greater increases of spontaneous neural activity than the additive effects of imidacloprid and bifenthrin alone. Excitatory compounds acting at sodium and chloride channels (bifenthrin and fipronil) were the most toxic against S. vicinus . Combining a sodium channel toxin (bifenthrin) and a synaptic toxin (imidacloprid) led to greater than additive neurophysiological and toxic effects, which to our knowledge provides the first documented evidence of synergistic neurological “potentiation”.
Removal of Carbon Dioxide from Flue Gas by Ammonia Carbonation in the Gas Phase

The increasing anthropogenic CO2 emissions and possible global warming have challenged the United States and other countries to find new and better ways to meet the world's increasing needs for energy while, at the same time, reducing greenhouse gas emissions. This study explores the possibility of using ammonium bicarbonate (NH4HCO3) formation by ammonia carbonation in the gas phase to achieve reduction of CO2 emissions from industrial flue gas. Experimental results obtained in this study demonstrate that removal of flue-gas CO2 can be achieved via formation of solid NH4HCO3 through ammonia carbonation in the gas phase. Removal of CO2 is quantified by monitoring CO2 concentrations at the entrance and exit of the reactor column. The products of ammonia carbonation were identified by solid-state nuclear magnetic resonance analysis. For the experimental conditions employed in this study, current results show up to 50% removal of CO2 from the flue gas. Higher efficiencies are likely achievable by optimizing ...
Making Connections: Creative Writing in the 21st Century

Since the end of the 20th century, the nature of the global has changed. The 21st century global is something new, evolving from the impact of technologies that allow much of the world (though not ...
The finding and partial purification and characterization of thymone C.

Abstract A fraction, isolated from bovine thymus by sequences of ca. ten steps of extractions, gel filtrations, ion exchange chromatography, etc., stimulated the synthesis of both cAMP and cGMP at a level of 100 μg/ml. Thymone A stimulated cAMP, but is chromatographically remote from the fraction. Essentially pure thymone B, which stimulates cGMP, did not stimulate cAMP even at a high level of 100 μg/ml. The presence of thymone B in this fraction is supported by TLC data. This fraction also stimulated the mixed lymphocyte reaction. The cAMP-stimulating entity is designated thymone C until it is characterized and related to or differentiated from products of other investigators.
Influence of injectant Mach number and temperature on supersonic film cooling

The current work is an experimental investigation of the dependence of film cooling effectiveness on the injection Mach number, velocity, and mass flux. The freestream Mach number is 2.4, and the injection Mach numbers range from 1.2 to 2.2 for both air and helium injection. The adiabatic wall temperature is measured directly. The injection velocity and mass flux are varied by changing the total temperature and Mach number while maintaining matched pressure conditions between the injected flow and that of the freestream. The total temperature of the freestream is 295 K, and for the injection it ranges from 215-390 K. The results indicate an increase in film cooling effectiveness as the injection rate is increased. With the exception of heated helium runs, larger injection Mach numbers slightly increase the effective cooling length per mass injection rate. The results for helium injection indicate an increase in effectiveness as compared to that for air injection. Heated injection, with the injectant to freestream velocity ratios greater than 1, exhibit a rise in wall temperature downstream of the slot resulting in effectiveness values greater than 1. The experimental results are also compared with earlier studies in the literature.
cDNA Cloning, Heterologous Expression, and Characterization of Mouse CYP2G1, an Olfactory-Specific Steroid Hydroxylase ☆

CYP2G1 is expressed specifically in the olfactory mucosa in rabbits and rats. In the present study, a full-length cDNA for mouse CYP2G1 was obtained using a PCR approach with RNA preparations from the olfactory mucosa of C57BL/6 mice. Sequence comparisons indicated that mouse CYP2G1 is highly homologous in deduced amino acid sequence to rabbit (82.4% identity) and rat CYP2G1 (94.9% identity). RNA blot and immunoblot analyses indicated that mouse CYP2G1 is expressed only in the olfactory mucosa. The coding region of the mouse CYP2G1 cDNA was cloned into a baculoviral expression vector for heterologous production of the enzyme in cultured insect cells. Heterologously expressed mouse CYP2G1 was active in a reconstituted system toward testosterone and progesterone, producing all the major metabolites detected in olfactory microsomal reactions, including 15 alpha-, 15 beta-, and 2 beta-hydroxytestosterone from testosterone and two unidentified metabolites from progesterone. Kinetic analysis indicated that mouse CYP2G1 has relatively high affinities toward the steroid substrates, with K(m) values in the micromolar range for both testosterone and progesterone. At a substrate concentration of 10 microM, microsomes of olfactory mucosa had much higher turnover numbers toward testosterone and progesterone than hepatic microsomes, consistent with the olfactory-specific expression of a high-affinity sex steroid hydroxylase. These findings will facilitate further molecular genetics studies on the biological function of CYP2G1 in a mouse model.
Regulation of Cartilaginous ECM Gene Transcription by Chondrocytes and MSCs in 3D Culture in Response to Dynamic Loading

This study explored the biologic response of chondrocytes and mesenchymal stem cells (MSCs) to a dynamic mechanical loading regime. We developed a time-efficient methodology for monitoring regional changes in extracellular matrix gene transcription using reporter promoter constructs. Specifically, transfected cells were homogenously distributed throughout agarose hydrogel constructs, and spatial and temporal gene expression and the ability to form functional ECM were analyzed in response to dynamic mechanical stimuli. Theoretical analyses were used to predict the physical signals generated within the gel in response to these loading regimes. Using a custom compression bioreactor system, changes in aggrecan and type II collagen promoter activity in transfected chondrocyte-laden cylindrical constructs were evaluated in response to a range of loading frequencies and durations. In general, aggrecan promoter activity increased with increasing duration of loading, particularly in the outer annulus region. Interestingly, type II collagen promoter activity decreased in this annular region under identical loading conditions. In addition, we explored the role of mechanical compression in directing chondrogenic differentiation of MSCs by monitoring short-term aggrecan promoter activity. As an example of long-term utility, a specific loading protocol was applied to MSC-laden constructs for 5 days, and the resultant changes in glycosaminoglycan (GAG) production were evaluated over a 4-week period. This dynamic loading regime increased not only short-term aggrecan transcriptional activity but also GAG deposition in long-term culture. These results demonstrate the utility of a new reporter promoter system for optimizing loading protocols to improve the outcome of engineered chondrocyte- and MSC-laden cartilaginous constructs.
Black holes with quantum massive spin-2 hair

We show that black holes can posses a long range quantum-mechanical hair associated with a massive spin-2 field, which can be detected by a stringy generalization of the Aharovon-Bohm effect, in which a string loop lassoes the black hole. The long distance effect persist for arbitrarily high mass of the spin-2 field. An analogous effect is exhibited by a massive antisymmetric two-form field. We make a close parallel between the two and the ordinary Aharonov-Bohm phenomenon, and also show that in the latter case the effect can be experienced even by the electrically-neutral particles, provided some boundary terms are added to the action.
Constrained types and their expressiveness

A constrained type consists of both a standard type and a constraint set. Such types enable efficient type inference for object-oriented languages with polymorphism and subtyping, as demonstrated by Eifrig, Smith, and Trifonov. Until now, it has been unclear how expressive constrained types are. In this article we study constrained types without universal quantification. We prove that they accept the same programs as the type system of Amadio and Cardelli with subtyping and recursive types. This result gives a precise connection between constrained types and the standard notion of types.
Determination of the forces imposed by micro and nanopipettes during DOPC:DOPS liposome manipulation

Abstract Using micropipette-based probing methods and an image processing algorithm for measuring deformation, the bending energies of aspirated DOPC:DOPS liposomes were estimated both before and during manipulation with an injection pipette. We found that unlike cells, which are penetrable with pipettes as large as 2 μm in diameter and at speeds as slow as 4 μm/s, liposomes, without a cytoskeleton to resist deformation, are impenetrable with pipettes as small as 25 nm in diameter and at speeds as great as 4000 μm/s. Using energy calculations and the previously published mechanical properties of DOPC:DOPS liposomes, the forces that injection pipettes of various sizes can exert onto liposomes during probing were estimated. Forces ranged from ∼1 pN to 6 pN, and the forces exerted onto these liposomes increased as pipette size diminished. The quantification of the amount of force exerted on liposomes or cells during manipulation can assist in minimizing the damage during single-liposome, single-cell, or single-organelle injections and surgeries.
MEASUREMENT OF PRlMARY ELECTRON INTERACTION COEFFICIENTS (500 TO 1500 eV REGION)

Because electrons of incident energy in the 500-1 500 eV range interact appreciably within only a few atomic layers in solids, precisely measuring and applying their interaction coefficients becomes difficult. The statistics of the interactions and the sensitivity to the geometric arrangement of the target atoms require special attention. A method for the study of such interactions is presented here that is based upon the controlled deposition of monatomic layers of bivalent metal cations as targets within the framework of stearate double layers of the LangmuirBlodgett type. To demonstrate the method, cross sections of the barium cation have been measured at 466 eV, 706 eV and 1 349 eV, and those of zinc and lead at 706 eV. The measured values are shown to be consistent with recent atomic beam measurements on barium and with simple theoretical models. Measurements of this type are considered to be of great importance in the development of quantitative surface chemical analysis by low energy X-ray and electron spectroscopy.
Subalgebras of Orlicz spaces and related algebras of analytic functions

An Orlicz function ~0 is a real-valued function defined as [0, ~o) satisfying the condition (a) ~0 is non-decreasing (b) (p(0)=0 and ~o is continuous at 0 and (c) (o is not identically zero. In addition ~o satisfies the A2-condition at ~o provided for some C and x (1.0.1) ~0(2x) x or equivalently, for some C (1.0.2) q~(Zx) ~ C( (p (x )+ l ) 0 <_x <o~. I f ~0 satisfies the A.,-condition at ~o then if (S, ~, v) in a finite measure space we may define the Orlicz space L o = L o ( S , r,, v) to be the set of all complex-valued ~;-measurable functions f an S such that
Antiangiogenic and chemopreventive activities of celecoxib in oral carcinoma cell.

Objectives Chemoprevention is a promising strategy to inhibit carcinoma before invasive tumors develop, but a new molecular target is desirable. Celecoxib is a newly developed cyclo-oxygenase (COX)-2 inhibitor with significantly less toxicity. The study was conducted to determine whether celecoxib is effective and safe in prevention of oral cancer. The antiangiogenic activity of celecoxib was studied to explore the potential mechanism involved. Study Design Randomized animal study. Methods The study consisted of two phases. In the phase 1, 10 mice were used to determine the efficacy and safety of celecoxib with intradermal inoculation with oral carcinoma cells. The 10 mice were equally divided into two groups 5 mice (30 inoculated sites) in each group to receive 1,500 parts per million (ppm) celecoxib mixed in with the diet or to eat a normal diet, respectively, for 21 days. In phase 2, 10 more mice were inoculated to determine the effect of celecoxib on angiogenesis. Five mice received 3,000 ppm celecoxib in the diet, with the other five mice as control animals. The antiangiogenic activity was evaluated by comparing the density of newly growing microvessels after the inoculation. Results The results indicated that celecoxib significantly delayed cell growth and reduced tumor volume. There was statistical significance in the quantity of new vasculature in the tumor sites between the two groups. No toxic effect was found by means of measurement of body weight loss and microscopic dissection of organs. Conclusions The study provided the first evidence to show the chemopreventive efficacy of celecoxib on oral cancer in a nude mouse model. Clinical trials are warranted to determine the efficacy in humans.
Fluorescence monitoring of T4 polymerase holoenzyme accessory protein interactions during loading of the sliding clamp onto the template-primer junction.

Abstract Assembly of the T4 polymerase holoenzyme requires coordinated interactions among the core polymerase and the clamp loader (gp44/62) and sliding clamp (gp45) accessory proteins. Here we describe the creation of a mutant of gp45 that can be uniquely modified by fluorescent probes within each protein monomer at a site-specific cysteine residue. The fluorescently labeled gp45 was shown to have the same biological activity as the wild-type protein. These strike “labeled” gp45 adducts were then used in steady-state and fluorescence polarization studies to monitor the interaction of gp45 with the gp44/62 clamp-loading complex and template–primer DNA in the presence and absence of ATP, and of the non-hydrolyzable analog, adenosine 5′-O-(3-thiotriphosphate). We find that a complex of ATP-activated gp44/62 with appropriately labeled gp45 shows significant fluorescent enhancement (and an increase in fluores- cent anisotropy), that can be partially reversed by interaction with template–primer DNA. Fluorescence-monitored binding curves between gp45 and ATP-activated gp44/62 reveal that the two protein complexes bind with a 1:1 stoichiometry. Analysis shows that these methods can be used to follow the ATP-driven loading of gp45 onto the template–primer by the gp44/62 clamp-loading complex, and in combination with the kinetic data presented in the companion article, provide insight into the rate-limiting steps during clamp assembly on template–primer DNA. A reaction pathway for this processivity clamp-loading process is proposed.
Nature of passive films on iron-chromium alloys

Abstract Fe—Cr foils of a range of Cr content were anodically polarized in 1 N H2SO4 for passive film growth. The resulting oxide films were then studied while still in contact with the metal substrate with transmission electron diffraction at 100 kV. Comparisons were made between the diffraction results for the Fe—Cr foils and previous diffraction studies for Fe foils. The diffraction patterns obtained revealed that as Cr content increased the oxide films were generally less able to sustain an epitaxial relationship with the substrates. The lower Cr foils had oxide patterns that could be fitted to a spinel structure; the lattice parameter in these cases increased with increasing Cr content. The highest Cr-content alloy, Fe—24% Cr, did not show any oxide pattern. It is concluded that the films tend to become amorphous as the Cr content of the alloy is increased.
Relaxation spectra of the iron spin transition in methemoglobin

Abstract Temperature-jump relaxation spectra of methemoglobin have been monitored in the spin-sensitive region of the absorption spectrum at pH 6. A single relaxation process is observed, the amplitude of which correlates exactly with that expected for spin state changes. The time-constant is of the order of 1 to 10 ms at 13 °C. Quaternary structural effects perturb the spin dynamics, as evidenced by a slower relaxation in the αβ dimer as opposed to the tetramer. On the other hand, the spin dynamics of the tetramer are not greatly affected by binding saturating amounts of inositol hexaphosphate. This is partly a reflection of the fact that the relative perturbation, caused by inositol hexaphosphate binding, of the equilibrium between high and low-spin species is small, under the conditions studied. In addition, it means that under these conditions, inositol hexaphosphate does not significantly perturb the flexibility of the irons in the heme groups.
Altered expression of glutamate transporters under hypoxic conditions in vitro.

Regulation of extracellular excitotoxins by glial and neuronal glutamate transporters is critical to maintain synaptic terminal integrity. Factors interfering with the normal functioning of these transporters might be involved in neurodegeneration. Among them, recent studies have shown that hypoxia alters glutamate transporter function; however, it is unclear if hypoxia has an effect on the expression of glutamate transporters and which intracellular signaling pathways are involved. The C6 rat glial and GT1--7 mouse neuronal cell lines were exposed to hypoxic conditions (5% CO(2), 95% N(2)) and levels of glutamate transporter mRNA were determined by ribonuclease protection assay. After 21 hr, there was a 100% increase in levels of rat excitatory amino acid transporter 3 (EAAT3) mRNA in C6 cells and a 600% increase in levels of murine EAAT2 mRNA in GT1--7 cells. There was a similar increase in mRNA levels after hypoxia in C6 cells transfected with human EAAT2, whereas reoxygenation normalized the expression levels of glutamate transporters. Although the expression of EAATs was associated with increased immunoreactivity by Western blot, functioning of the transporters was decreased as evidenced by D-aspartate uptake. Finally, although the protein kinase C stimulator phorbol-12-myristate-13-acetate enhanced EAAT2 mRNA levels after hypoxia, protein kinase C inhibitor bisindolylmaleimide I had the opposite effect. Taken together, this study suggests that the hypoxia is capable of upregulating levels of EAATs via a protein kinase C-dependent compensatory mechanism. This increased expression is not sufficient to overcome the decreased functioning of the EAATs associated with decreased ATP production and mitochondrial dysfunction.
Expanding the Horizon of the Thymine Isostere Biochemistry: Unique Cyclobutane Dimers Formed by Photoreaction between a Thymine and a Toluene Residue in the Dinucleotide Framework

Substituted toluenyl groups are considered as close isosteres of the thymine residue. They can be recognized by DNA polymerases as if they were thymine. These toluene derivatives are generally inert toward radical additions, including the [2+2] photo-cycloadditions, due to the stable structure of the aromatic ring and are usually used as solvents for radical reactions. Surprisingly, after incorporating toluene into the dinucleotide framework, we found that the UV excited thymine residue readily dimerizes with the toluenyl moiety through a [2+2] photo-addition reaction. Furthermore, the reaction site on the toluenyl moiety is not the C5=C6 bond, as commonly observed in cyclobutane pyrimidine dimers, but the C4=C5 or C3=C4 instead. Such a reaction pattern suggests that in the stacked structure, it is one of these bonds, not the C5=C6, that is close to the thymine C5=C6 bond. A similar structural feature is found in DNA duplex with a thymine replaced by a 2,4-difluorotoluene. Our results argue that although the substituted toluenyl moieties closely mimic the size and shape of the thymine residue, their more hydrophobic nature determines that they stack on DNA bases differently from the natural thymine residue and likely cause local conformational changes in duplex DNA.
Biofilm formation by Cryptococcus neoformans under distinct environmental conditions.

Cryptococcus neoformans is an opportunistic fungal pathogen with a propensity to infect the central nervous system of immune compromised individuals causing life-threatening meningoencephalitis. Cryptococcal biofilms have been described as a protective niche against microbial predators in nature and shown to enhance resistance against antifungal agents and specific mediators of host immune responses. Based on the potential importance of cryptococcal biofilms to its survival in the human host and in nature, these studies were designed to investigate those factors that mediate biofilm formation by C. neoformans. We observed that C. neoformans preferentially grew as planktonic cells when cultured under specific conditions designed to mimic growth within host tissues (37°C, neutral pH, and ~5% CO2) or phagocytes (37°C, acidic pH, and ~5% CO2) and as biofilms when cultured under conditions such as those encountered in the external environment (25–37°C, neutral pH, and ambient CO2). Altogether, our studies suggest that conditions similar to those observed in its natural habitat may be conducive to biofilm formation by C. neoformans.
Size selection of Atlantic rangia clams,Rangia cuneata, by blue crabs,Callinectes sapidus

Male blue crabsCallinectes sapidus Rathbun were allowed to forage on six size classes of the Atlantic rangia clam,Rangia cuneata (Sowerby), in laboratory squaria under conditions of restricted or unrestricted prey size availability. Prey profitability (energy gained divided by handling time) decreased as prey size increased. Crabs preferred smaller clams (1–2 cm long, then 2–3 cm long), as predicted by an energy maximization model. Under conditions of restricted prey sizes (nonreplacement experiments), when the smaller clams were no longer available, crabs tended to choose progressively larger clams. Crabs did not exhibit selective feeding behavior among clams larger than 3 cm long. For the range of crab sizes tested (71–167 mm carapace width), there was no correlation between crab carapace width and the mean clam size that was eaten.
ASTRO keynote address “Progress in targeted therapies for breast cancer (BC)”

Optimal treatment of BC includes cytotoxic and endocrine therapies, in addition to surgery and radiotherapy. Combined modality strategies have improved survival, are safe with a modest rate of long-term serious adverse events. Research into the biological behavior of BC uncovered a number of molecular signaling processes involved in growth, proliferation, invasion and metastasis. Progress in our understanding of steroid hormone biology facilitated the development of novel endocrine agents. The discovery and identification of the estrogen receptor represented the watershed event in endocrine therapy. Thus, endocrine interventions became the prototype for “targeted therapy” for BC. Important lessons learned in endocrine therapy were that identification of the molecular target was critical to determine the population likely to benefit from this therapy, expanded understanding of the role of various co-factors (co-activators and co-repressors) in determining the specificity and direction of the signal, identification of structure-function interactions in the binding pocket of the receptor and the development of selective estrogen receptor modulators (SERMs) and selective estrogen receptor downregulators (SERDs). Tamoxifen, the first SERM became the endocrine treatment of choice for all stages of hormone receptor-positive breast cancer, and the first agent with demonstrated effect of chemoprevention of breast cancer. Recent research highlighted the critical role of estrogen deprivation (ovarian suppression/ablation and the use of selective aromatase inhibitors) as a form of endocrine therapy. The differential effects of genomic and non-genomic functions of the estrogen receptor led to better understanding of complex cross-talk functions between steroid hormone receptors and other growth factor receptors in proliferation, survival and apoptosis of breast cancer cells. Such expanded understanding led to increasing interest in combining highly targeted molecular therapeutics to more fully interrupt critical drivers of intracellular signaling.
Structural Studies of Hydrogenated Amorphous Carbon Infrared Coatings

Hydrogenated amorphous carbon thin films are well known for their mechanical hardness and optical properties which make them useful for applications in infrared device coatings. In this work films have been prepared by plasma. decomposition of methane using an RF diode reactor operating under conditions of high self bias potential (Vb = 1 KeV). The resulting ion bombardment during film growth leads to the formation of hard, insulating carbon coatings which have a band gap of ≃1.1 eV and are transparent in the IR. Nuclear reaction analysis has been used to quantify the atomic concentration of hydrogen incorporated in the films and extended x-ray absorption fine structure (EXAFS) has been used to determine local site geometry. Only first and second nearest neighbor bond lengths are observed with no evidence of further long range order or microcrystallinity. A model for atomic structure is proposed which includes both sp2 and sp3 bond configurations and direct comparisons are made with data obtained from sputtered carbon films, graphite and diamond.
Rapid Microvessel Rarefaction With Elevated Salt Intake and Reduced Renal Mass Hypertension in Rats

To identify the sequence of events associated with the development of reduced vessel density (rarefaction) in hypertension, microvessel density and ultrastructure were assessed in the cremaster muscle of rats subjected to a 75% surgical reduction of renal mass and normotensive sham-operated control rats. Rats with reduced renal mass (RRM rats) and sham-operated rats were then maintained on either a high salt (4.0% NaCl) or a low salt (0.4% NaCl) diet for 3 days. Acute exposure to the high salt diet significantly increased mean arterial pressure in RRM rats but did not affect sham-operated control rats. Quantitative fluorescence microscopy of cremaster muscle whole mounts using rhodamine-labeled Griffonia simplicifolia I lectin revealed substantial rarefaction of microvessels in both RRM hypertensive rats and normotensive sham-operated rats on a high salt diet relative to corresponding control rats on a low salt diet. Confocal microscopy revealed a heterogeneous distribution of microvessels in RRM rats on a high salt diet, with some areas largely devoid of vessels. RRM and sham-operated rats on a high salt diet both exhibited changes in arteriolar ultrastructure, which included a loss of basement membranes and a dissociation of the endothelial and smooth muscle components of the vascular wall, resulting in a loss of vessel integrity. These observations demonstrate that a rapid loss of microvessels can occur not only in rats with RRM hypertension but also in normotensive rats on a high salt diet. This loss of microvessels results from structural alterations, which differ from the degenerative processes associated with microvascular rarefaction in rats with chronic RRM hypertension.
Effects of Large-Scale Sediment Removal on Herpetofauna in Florida Wetlands

Removal of organic sediment from lakes and ponds is an established management technique that is intended to enhance sport fisheries, improve boater access, and increase stormwater capacity. Data on the effects of this management technique on lake ecosystems are limited. Our objective was to determine the effect of mechanical sediment removal on herpetofauna at five sites in northern Florida. We collected a total of 883 individuals of 31 species of herpetofauna excavated by machinery during sediment removal. Across the five sites, the average number of individuals collected was 177 per site (SD = 119, range = 71-310). The most abundant herpetofauna we encountered were aquatic turtles (Trachemys scripta, Chelydra serpentina) and large aquatic salamanders (Amphiuma means, Siren spp.). Mortality from sediment removal operations may have a detrimental effect on herpetofauna populations, especially species that depend on dried lake sediments for aestivation or with limited dispersal abilities.
Characterization of thiL, Encoding Thiamin-monophosphate Kinase, in Salmonella typhimurium

Thiamin pyrophosphate is an essential cofactor that is synthesized de novo by Salmonella typhimurium. In bacteria, the end product of the de novo biosynthetic pathway is thiamin monophosphate, which is then phosphorylated by thiamin-monophosphate kinase (EC 2.7.4.16) to form thiamin pyrophosphate. We have isolated and characterized the thiL gene of S. typhimurium and showed that thiL is a 978-base pair open reading frame encoding a 35-kDa protein with thiamin-monophosphate kinase activity. thiL was located in the 10-centisome region of the S. typhimurium chromosome. We demonstrated that altered thiamin-monophosphate kinase activity resulted in decreased repression of transcription of thiamin pyrophosphate-regulated thiamin biosynthetic genes. In contrast to other thi loci, thiL is not transcriptionally regulated by thiamin pyrophosphate. This result is consistent with a dual role for ThiL in de novo biosynthesis and in salvage of exogenous thiamin.
Pattern Recognition in the Context of an Asbestos Cancer Threshold Study

Five distinct stages of a pattern recognition problem are discussed in the context of a study of drinking water asbestos health effects. A series of nonparametric regression procedures is used to examine the possiblilty of a threshold in the relationship between asbestos in drinking water and cancer. Evidence is presented which suggests that rather than there being a threshold, the dose response curve E (Y\X) is linear. It is also shown that by choosing a large value (in comparison to earlier studies) for the 125 location parameter of the log observed-to-expected response variable, the overall significance level of the asbestos in drinking water-cancer association is greatly increased and the resolution of the threshold pattern recognition procedure is greatly enhanced.
Solid dispersions of the penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA): Formulation design and optimization studies

The penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA), which exists as an oily liquid, was incorporated into a solid dispersion for oral administration by the solvent evaporation method using blends of polyvinylpyrrolidone (PVP), Eudragit® RL PO and α-tocopherol. D-optimal mixture design was used to optimize the formulation. Formulations that had a high concentration of both Eudragit® RL PO and α-tocopherol exhibited low water absorption and enhanced stability of the DTPA prodrug. Physicochemical properties of the optimal formulation were evaluated using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). In vitro release of the prodrug was evaluated using the USP Type II apparatus dissolution method. DSC studies indicated that the matrix had an amorphous structure, while FTIR spectrometry showed that DTPA penta-ethyl ester and excipients did not react with each other during formation of the solid dispersion. Dissolution testing showed that the optimized solid dispersion exhibited a prolonged release profile, which could potentially result in a sustained delivery of DTPA penta-ethyl to enhance bioavailability. In conclusion, DTPA penta-ethyl ester was successfully incorporated into a solid matrix with high drug loading and improved stability compared to prodrug alone.
The strategic nature of changing your mind

In two experiments, we studied how people's strategy choices emerge through an initial and then a more considered evaluation of available strategies. The experiments employed a computer-based paradigm where participants solved multiplication problems using mental and calculator solutions. In addition to recording responses and solution times, we gathered data on mouse cursor movements. Participants' motor behavior was revealing; although people rapidly initiated movement to the calculator box or the answer input box, they frequently changed their minds and went to the other box. Movement initiation direction depended on problem difficulty and calculator responsiveness. Ultimate strategy selection also depended on these factors, but was further influenced by movement initiation direction. We conclude that strategy selection is iterative, as revealed by these differences between early cursor movement and eventual strategy implementation. After rapidly initiating movement favoring one strategy, people carefully evaluate the applicability of that strategy in the current context.
Identification of thresholds for dichotomizing DNA methylation data.

DNA methylation plays an important role in many biological processes by regulating gene expression. It is commonly accepted that turning on the DNA methylation leads to silencing of the expression of the corresponding genes. While methylation is often described as a binary on-off signal, it is typically measured using beta values derived from either microarray or sequencing technologies, which takes continuous values between 0 and 1. If we would like to interpret methylation in a binary fashion, appropriate thresholds are needed to dichotomize the continuous measurements. In this paper, we use data from The Cancer Genome Atlas project. For a total of 992 samples across five cancer types, both methylation and gene expression data are available. A bivariate extension of the StepMiner algorithm is used to identify thresholds for dichotomizing both methylation and expression data. Hypergeometric test is applied to identify CpG sites whose methylation status is significantly associated to silencing of the expression of their corresponding genes. The test is performed on either all five cancer types together or individual cancer types separately. We notice that the appropriate thresholds vary across different CpG sites. In addition, the negative association between methylation and expression is highly tissue specific.
Adenylyl Cyclase 6 Mediates Primary Cilia-Dependent Changes in Cyclic Adenosine Monophosphate in Response to Dynamic Fluid Flow

It is well accepted that fluid flow is an important mechanical signal in regulating bone structure and function. Primary cilia, which are solitary, microtubule-based organelles that extend from the centrosome into extracellular space in many cell types, have been shown to mediate fluid flow-induced osteogenic responses in MLO-Y4 osteocyte-like cells [1], however, primary cilia did not mediate increases in intracellular Ca2+ concentration [1]. Recently, we identified cAMP as a novel early signaling molecule in primary cilia-dependent mechanotransduction of fluid flow in osteocytes. Specifically, we show that MLO-Y4 osteocyte-like cells respond to oscillatory flow with a rapid decrease in intracellular levels of cAMP that is dependent on the primary cilium [2]. Adenylyl cyclase 6 (AC6) is an enzyme responsible for the synthesis of cAMP from ATP. We found that AC 6 localizes to the primary cilium of bone cells (Fig. 1). In this study, our goal was to determine whether AC6 mediates the primary cilia-dependent, flow-induced decrease in cAMP.Copyright © 2009 by ASME
Single injection of naked plasmid encoding hepatocyte growth factor prevents cell death and ameliorates acute renal failure in mice

Hepatocyte growth factor (HGF) is a pleiotrophic factor that plays an important role in tissue repair and regeneration after injury. The expression of both HGF and its c-met receptor genes is rapidly upregulated after acute renal injury induced by folic acid. In this study, the role of exogenous HGF in preventing acute renal failure by systemic administration of naked plasmid containing human HGF cDNA driven under the cytomegalovirus promoter (pCMV-HGF) was examined in mice. Intravenous injection of pCMV-HGF plasmid produced substantial levels of human HGF protein in mouse kidneys. Simultaneous injection of HGF plasmid DNA significantly ameliorated renal dysfunctions and accelerated recovery from the acute injury induced by folic acid. Of interest, preadministration of HGF plasmid 24 h before folic acid injection dramatically protected renal epithelial cells from both apoptotic and necrotic death and preserved the structural and functional integrity of renal tubules. Expression of HGF transgene activated protein kinase B/Akt kinase and preserved prosurvival Bcl-xL protein expression in vivo. These results indicate that a single, intravenous injection of naked plasmid containing HGF gene not only promotes renal regeneration after injury but also protects tubular epithelial cells from the initial injury and cell death in the first place. These data suggest that HGF gene therapy may provide a new avenue for exploring a novel therapeutic strategy for clinical acute renal failure.
The effect of positive peer reinforcement on psychological measures and guitar songleading performance in university students

The purpose of this study is to determine the effects of positive peer reinforcement on self-reported psychological measures and songleading performance in beginning guitar students. No differences...
From geek to sleek: integrating task learning tools to support end users in real-world applications

Numerous techniques exist to help users automate repetitive tasks; however, none of these methods fully support end-user creation, use, and modification of the learned tasks. We present an integrated task learning system (ITL) that learns executable procedures based on user demonstration and instruction, constituting a first step toward a broader solution for procedure management. We discuss our deployment of ITL into a collaborative command-and-control system. In this complex domain, ITL's performance with end users doing real tasks indicates that providing multiple, integrated learning techniques both extends functionality and improves user experience. Our experience in integrat-ing this system also provides key insights for future designs of domain-independent task learning systems, specifically in supporting users' ability to understand and edit lengthy procedures.
Family Education to Enhance the Moral Atmosphere of the Family and the Moral Development of Adolescents.

This study examined the effects of a course for families in democratic conflict resolution on the family's collective decision-making abilities and on the moral reasoning of adolescent participants. Sixteen couples and their adolescent children were divided into three groups: parents and their adolescents, parents only, and a control group. Both experimental groups met for 10 weekly 2V2hour sessions and received training in conflict resolution and the use of family meetings. Assessment was based on two self-report inventories, a behavioral role-play test, the Kohlberg Moral Judgment Interview, and an analysis of tape recordings of the family meetings. A 1-year follow-up assessment of the Kohlberg measure was also used. Parents in both experimental groups significantly increased their equalitarian attitudes toward family decision making. Furthermore, families in both groups significantly improved their effectiveness in collective decision making, the parent-adolescent group showing greater improvement than the parent group on most of the variables measured. Finally, the results suggested that adolescents who participated in the training significantly improved their scores in moral reasoning. This gain was maintained at followup.
Determinants of parental care in Mountain White-crowned Sparrows (Zonotrichia leucophrys oriantha)

ABSTRACT Extent of parental care, such as food provisioning to offspring, can vary widely between sexes in socially monogamous birds. The determinants of the sex-specific provisioning behaviors remain unclear as they could be associated with individual condition, as well as mate contribution and quality. In a population of Mountain White-crowned Sparrows (Zonotrichia leucophrys oriantha), we tested the good parent hypothesis, the reproductive compensation hypothesis, and the differential allocation hypothesis among 29 nesting pairs during the breeding season. Using multivariable linear regression, we examined the relationship of offspring food provisioning rate, a measure of parental care, with each parent's own demographic (sex, age), morphological (tail length, wing chord, tarsus, mass, body fat, and cloacal protuberance), and physiological (hematocrit and infection status) characteristics, as well as crown-white, a reliable status signal in this species. In male birds, feeding rate was positively corre...
Political Cycles, Partisan Orientation, Gridlock, and REIT Returns

Executive Summary. This study examines several aspects of the relationship between the presidential election cycle in the United States, political party in power, government gridlock, and real esta...
PP15.3 – 2545: Everolimus for patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC): Results from an expanded access study

Objective Everolimus For Fast Expanded aCcess in TSC SEGA (EFFECTS) study was designed to provide early access to everolimus for patients with SEGA associated with TSC and to further assess the safety and efficacy of everolimus in a real-world setting. Methods In this phase 3b, multicenter, expanded access study, patients ≥3 years of age with a definite diagnosis of TSC, with at least 1 SEGA lesion identified by MRI or CT scan received once daily everolimus, the dose of which was adjusted to attain a trough level of 5–15 ng/mL. Safety assessments included the collection of adverse events (AEs) and serious AEs (SAEs), with their severity and relationship to everolimus. Efficacy evaluation (secondary objective) was based on the best overall response at the end of the study. Results Overall, 100 of 120 (83.3%) patients completed the study. Median age of patients was 11 years (range 1–47); median daily dose of everolimus was 5.82 mg (range 2.0–11.8); median duration of exposure was 56.5 weeks (range 0.3–130). Overall, AEs were reported in 89 (74.2%) patients. The most common AEs were aphthous stomatitis (18, 15.0%), pyrexia (18, 15.0%), bronchitis (11, 9.2%), and stomatitis (10, 8.3%). Grade 3 and 4 AEs were reported in 25 (20.8%) and 3 (2.5%) patients, respectively. The most frequent grade 3 AE was stomatitis (4, 3.3%). A total of 62 (51.7%) patients had suspected drug-related AEs, of which 15 (12.5%) had grade 3 or 4 AEs. In 8 (6.7%) patients, AEs caused drug discontinuation. A total of 81 (67.5%) patients had a partial response, 35 (29.2%) had a stable disease, and 1 (0.8%) had progressive disease. Response was unknown in 3 (2.5%) patients. Conclusion Results confirm the acceptable safety profile and further support the efficacy of everolimus in patients with SEGA associated with TSC, in a real-world setting.