cssi/SciSciGPT-SciSciNet huggingface dataset:
Glycogen Synthase Kinase 3β Activation Is a Prerequisite Signal for Cytokine Production and Chemotaxis in Human Mast Cells

In addition to regulating mast cell homeostasis, the activation of KIT following ligation by stem cell factor promotes a diversity of mast cell responses, including cytokine production and chemotaxis. Although we have previously defined a role for the mammalian target of rapamycin complex 1 in these responses, it is clear that other signals are also required for maximal KIT-dependent cytokine production and chemotaxis. In this study, we provide evidence to support a role for glycogen synthase kinase 3β (GSK3β) in such regulation in human mast cells (HuMCs). GSK3β was observed to be constitutively activated in HuMCs. This activity was inhibited by knockdown of GSK3β protein following transduction of these cells with GSK3β-targeted shRNA. This resulted in a marked attenuation in the ability of KIT to promote chemotaxis and, in synergy with FceRI-mediated signaling, cytokine production. GSK3β regulated KIT-dependent mast cell responses independently of mammalian target of rapamycin. However, evidence from the knockdown studies suggested that GSK3β was required for activation of the MAPKs, p38, and JNK and downstream phosphorylation of the transcription factors, Jun and activating transcription factor 2, in addition to activation of the transcription factor NF-κB. These studies provide evidence for a novel prerequisite priming mechanism for KIT-dependent responses regulated by GSK3β in HuMCs.
Nonpharmacologic Treatment of Pediatric Hypertension

During childhood, elevated systolic and/or diastolic blood pressure (BP) is commonly secondary to diseases of the kidneys, endocrine system, and/or cardiovascular system. When diagnostic evaluation does not reveal a cause for the elevation in BP, we call that condition essential, or idiopathic, hypertension (HTN). Over 90% of HTN in adults is essential HTN; there are well over 60 million Americans with essential HTN. Much has been written about research to control essential HTN in adults; relatively less work has been done concerning children. Many pharmacologic approaches, such as β-blockade, angiotensin-converting enzyme (ACE) inhibition, afterload reduction, α-blockade, etc., have been successful in lowering BP. When essential HTN occurs in childhood, a nonpharmacologic approach to lowering BP is preferable so that the patient may not require life-long medication. Long-term use of medications may be associated with significant side-effects and produce associated morbidity and/or mortality.
Sub-100 ps silicon bipolar ECL circuit operation at liquid nitrogen temperatures

A two-dimensional device simulator is used to examine the various low-temperature profile design strategies for silicon bipolar transistors. It is found that a relaxed scaling approach offers the best overall results for high speed circuit operation at liquid nitrogen (LN/sub 2/) temperatures. To support these calculations, experimental results which demonstrate that sub-100-ps emitter-coupled-logic circuit (ECL) operation at LN/sub 2/ temperature is achievable are reported. Design tradeoffs are discussed on the basis of the experimental results. >
Market Research in the US-Part 1: industry, market, and advertising sources

Describes industry, market and advertising sources for US market research, in both print and electronic forms.
Monitoring of Vegetation Impact Due to Trampling on Cadillac Mountain Summit Using High Spatial Resolution Remote Sensing Data Sets

Cadillac Mountain—the highest peak along the eastern seaboard of the United States—is a major tourist destination in Acadia National Park, Maine. Managing vegetation impact due to trampling on the Cadillac Mountain summit is extremely challenging because of the large number of visitors and the general open nature of landscape in this fragile subalpine environmental setting. Since 2000, more intensive management strategies—based on placing physical barriers and educational messages for visitors—have been employed to protect threatened vegetation, decrease vegetation impact, and enhance vegetation recovery in the vicinity of the summit loop trail. The primary purpose of this study was to evaluate the effect of the management strategies employed. For this purpose, vegetation cover changes between 2001 and 2007 were detected using multispectral high spatial resolution remote sensing data sets. A normalized difference vegetation index was employed to identify the rates of increase and decrease in the vegetation areas. Three buffering distances (30, 60, and 90 m) from the edges of the trail were used to define multiple spatial extents of the site, and the same spatial extents were employed at a nearby control site that had no visitors. No significant differences were detected between the mean rates of vegetation increase and decrease at the experimental site compared with a nearby control site in the case of a small spatial scale (≤30 m) comparison (in all cases P > 0.05). However, in the medium (≤60 m) and large (≤90 m) spatial scales, the rates of increased vegetation were significantly greater and rates of decreased vegetation significantly lower at the experimental site compared with the control site (in all cases P < 0.001). Research implications are explored that relate to the spatial extent of the radial patterns of impact of trampling on vegetation at the site level. Management implications are explored in terms of the spatial strategies used to decrease the impact of trampling on vegetation.
A Pillar of Hope for New Multiple Sclerosis Therapeutics

Multiple sclerosis (MS) is the most common chronic neurological disease among young adults. MS is thought to result from an autoimmune-mediated attack of myelin-producing cells called oligodendrocytes in the central nervous system (CNS). Current therapies for MS include at least 10 anti-inflammatory drugs that have been approved by the U.S. Food and Drug Administration. Many of these drugs show substantial disease-modifying activity for patients by modulating the inflammatory components of the disease. However, none of these current drugs promote regeneration of lost myelin in the CNS, and therefore they are largely ineffective at preventing disease progression and ultimately disability. Now, using an innovative high-throughput screening assay, Mei et al. offer a new approach to discover drugs that may directly enhance remyelination in diseases such as MS. In this new study, the authors describe the design, fabrication, and implementation of a screening platform called BIMA (binary indicant for myelination using micropillar assays). During the process of myelination in the CNS, oligodendrocyte progenitor cells (OPCs) mature into oligodendrocytes, which physically wrap around neurons to create the myelin sheath. The authors had previously shown that oligodendrocytes will even wrap around pseudo-neuronal substrates in vitro. They leveraged this key finding to engineer arrays of compressed silica micropillars that could be incorporated into cell culture microplates. Upon addition of rodent OPCs, ~10% of the cells would wrap around the micropillars, and this could be quantified in an automated fashion by staining for “rings” of myelin markers such as myelin basic protein (MBP). The authors’ major advance was their ability to test a 1000-drug library in their assay in order to evaluate whether the extent of micropillar wrapping could be enhanced. They identified a cluster of eight antimuscarinic drugs, which have previously been approved for use in other diseases. The authors functionally validate one of these drugs, clemastine, in an in vivo rodent remyelination assay. The ability to enhance remyelination is a major unmet clinical need. New screening platforms such as the one in this paper provide a mechanism to identify promising candidates for clinical testing in MS and other myelin disorders. Given its oral bioavailability and known safety profile, clemastine is currently being tested in a phase II clinical trial for MS. However, the ability to accurately measure remyelination is not currently feasible in the context of a clinical trial, and major advances must be made in order to accurately test the plethora of remyelinating therapeutics that are likely to emerge in the near future. F. Mei et al. , Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis. Nat. Med . 10.1038/nm.3618 (2014). [[Full Text]][1] [1]: http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3618.html
Weak convergence with random indices

Abstract Suppose { X n n ⩾-0} are random variables such that for normalizing constants a n >0, b n , n ⩾0 we have Y n (·)=( X [ n, · ]- b n / a n ⇒ Y (·) in D (0.∞) . Then a n and b n must in specific ways and the process Y possesses a scaling property. If { N n } are positive integer valued random variables we discuss when Y N n → Y and Y ' n =( X [ N n ]- b n )/ a n ⇒ Y '. Results given subsume random index limit theorems for convergence to Brownian motion, stable processes and extremal processes.
Probing Rapid Ion Transfer Across a Nanoscopic Liquid−Liquid Interface

Rapid kinetics of tetraalkylammonium ion transfers (ITs) across the interface between water and 1,2-dichloroethane was measured by steady-state voltammetry at nanometer-sized pipet electrodes (with an orifice radius of 10−300 nm). Methodologies previously used for preparation and characterization of micrometer-sized pipets are shown to be suitable for experiments with nanopipets. The silanization of the outer pipet wall results in quantitative agreement between the experimentally measured and theoretically predicted values of the diffusion-limiting current to the pipet. An independent estimate of the orifice radius and the thickness of the glass wall were obtained by using a nanopipet as a scanning electrochemical microscopy (SECM) tip. The voltammograms of IT from the outer solution into the pipet and from the filling solution out of the pipet were analyzed to measure rates of both forward and reverse IT reactions (i.e., from water to organic and from organic to water). The measured standard rate constan...
Competition between Rotamerization and Proton Transfer in o-Hydroxybenzaldehyde

The proton transfer from one oxygen atom to the other within the intramolecular H-bond in a molecule like o-hydroxybenzaldehyde (oHBA) would be precluded by a prior rotational isomerism that breaks this H-bond. The likelihood of such rotamerization in the ground and several excited electronic states is investigated by ab initio calculations at the CIS and MP2 levels with a 6-31+G** basis set. In the ground state, the energetics of proton transfer and rotamerization are competitive with one another; both processes are endothermic and must surmount an energy barrier. Excitation to the singlet or triplet ππ* states presents a situation where tautomerization to the keto is exothermic, with a small barrier. In contrast, rotamerization is endothermic with high intervening barriers, so excited-state proton transfer is favored. The opposite situation is encountered in the nπ* states, where rotations of the hydroxyl and carbonyl groups are facile and lead energetically downhill, in contrast to the high barriers op...
Triad Instability of Planetary Rossby Waves

Abstract The triad instability of the large-scale, first-mode, baroclinic Rossby waves is studied in the context of the planetary scale when the Coriolis parameter is to its lowest order varying with latitude. Accordingly, rather than remain constant as in quasigeostrophic theory, the deformation radius also changes with latitude, yielding new and interesting features to the propagation and triad instability processes. On the planetary scale, baroclinic waves vary their meridional wavenumbers along group velocity rays while they conserve both frequencies and zonal wavenumbers. The amplitudes of both barotropic and baroclinic waves would change with latitude along a ray path in the same way that the Coriolis parameter does if effects of the nonlinear interaction are ignored. The triad interaction for a specific triad is localized within a small latitudinal band where the resonance conditions are satisfied and quasigeostrophic theory is applicable locally. Using the growth rate from that theory as a measure...
Biochemical status of renal epithelial Na+ channels determines apparent channel conductance, ion selectivity, and amiloride sensitivity

Purified bovine renal papillary Na+ channels, when reconstituted into planar lipid bilayers, reside in three conductance states: a 40-pS main state, and two subconductive states (12–13 pS and 24–26 pS). The activity of these channels is regulated by phosphorylation and by G-proteins. Protein kinase A (PKA)-induced phosphorylation increased channel activity by increasing the open state time constants from 160 +/- 30 (main conductance), and 15 +/- 5 ms (both lower conductances), respectively, to 365 +/- 30 ms for all of them. PKA phosphorylation also altered the closed time of the channel from 250 +/- 30 ms to 200 +/- 35 ms, thus shifting the channel into a lower-conductance, long open time mode. PKA phosphorylation increased the PNa:PK of the channel from 7:1 to 20:1, and shifted the amiloride inhibition curve to the right (apparent K(i)amil from 0.7 to 20 microM). Pertussis toxin-induced ADP-ribosylation of either phosphorylated of either phosphorylated or nonphosphorylated channels decreased the PNa:PK to 2:1 and 4:1, respectively, and altered K(i)amil to 8 and 2 microM for phosphorylated and nonphosphorylated channels, respectively. GTP-gamma-S treatment of either phosphorylated or nonphosphorylated channels resulted in an increase of PNa:PK to 30:1 and 10:1, respectively, and produced a leftward shift in the amiloride dose-response curve, altering K(i)amil to 0.5 and 0.1 microM, respectively. These results suggest that amiloride-sensitive renal Na+ channel biophysical characteristics are not static, but depend upon the biochemical state of the channel protein and/or its associated G-protein.
Yeast Importin-α (Srp1) Performs Distinct Roles in the Import of Nuclear Proteins and in Targeting Proteasomes to the Nucleus

Srp1 (importin-α) can translocate proteins that contain a nuclear localization signal (NLS) into the nucleus. The loss of Srp1 is lethal, although several temperature-sensitive mutants have been described. Among these mutants, srp1-31 displays the characteristic nuclear import defect of importin-α mutants, whereas srp1-49 shows a defect in protein degradation. We characterized these and additional srp1 mutants to determine whether distinct mechanisms were required for intracellular proteolysis and the import of NLS-containing proteins. We determined that srp1 mutants that failed to import NLS-containing proteins (srp1-31 and srp1-55) successfully localized proteasomes to the nucleus. In contrast, srp1 mutants that did not target proteasomes to the nucleus (srp1-49 and srp1-E402Q) were able to import NLS-containing proteins. The proteasome targeting defect of specific srp1 mutants caused stabilization of nuclear substrates and overall accumulation of multiubiquitylated proteins. Co-expression of a member of each class of srp1 mutants corrected both the proteasome localization defect and the import of NLS-containing proteins. These findings indicate that the targeting of proteasomes to the nucleus occurs by a mechanism distinct from the Srp1-mediated import of nuclear proteins.
A Comparison of Learning Outcomes in Culinary Education: Recorded Video vs. Live Demonstration

This study examined learning outcomes for students who were enrolled in an introductory cooking course that used online taped videos. The study sample was composed of 206 students enrolled in online taped video classes and 184 enrolled in traditional live classes. The students in both groups received the same teaching instructions except for the demonstration delivery methods. A 2-way mixed design was used to test for significant differences in student performance between 2 instructional delivery methods (i.e., online taped video and live class demonstration) for both individual and team tasks. The results indicated that both delivery methods produced similar student performance levels when individual and team tasks were considered together. However, students taught by the online delivery method had better group performance than students taught by the traditional method. The findings suggest that the online delivery method should be utilized in culinary arts education; however, efforts to enhance group sy...
Cloning and Subcellular Localization of Hamster and Rat Isopentenyl Diphosphate Dimethylallyl Diphosphate Isomerase A PTS1 MOTIF TARGETS THE ENZYME TO PEROXISOMES

To date, isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IPP isomerase; EC 5.3.3.2) is presumed to have a cytosolic localization. However, we have recently shown that in permeabilized cells lacking cytosolic components, mevalonate can be converted to cholesterol, implying that all of the enzymes required for the conversion of mevalonate to farnesyl diphosphate are found in the peroxisome. To provide unequivocal evidence for the subcellular localization of IPP isomerase, in this study, we have cloned the rat and hamster homologues of IPP isomerase and identified the signal that targets this enzyme to peroxisomes. In addition, we also demonstrate that IPP isomerase is regulated at the mRNA level.
Effect of deoxycorticosterone on soluble beef heart mitochondrial ATPase.

SummaryThe activity of solubilized, beef heart mitochondrial ATPase, as assayed both spectrophotometrically and by release of Pi from ATP, was decreased by over 35% in the presence of deoxycorticosterone.
Maximum entropy and learning theory

We derive the learning theory recently reported by Tishby, Levin, and Solla (TLS) directly from the principle of maximum entropy instead of statistical mechanics. The theory generally applies to any problem of modeling data. We analyze an elementary example for which we find the predictions consistent with intuition and conventional statistical results and we numerically examine the more realistic problem of training a competitive net to learn a one-dimensional probability density from samples. The TLS theory is useful for predicting average training behavior.
Electroantennogram-Active Components in Buffalo Gourd Root Powder for Western Corn Rootworm Adults (Coleoptera: Chrysomelidae)

Buffalo gourd, Cucurbita foetidissima Kunth, root powder contains potent, non-volatile arrestant and feeding stimulants for adults of Diabrotica virgifera virgifera LeConte, the western corn rootworm, and baits containing this powder mixed with insecticide have become a viable alternative to granular insecticide. Anecdotal evidence has indicated that these baits may also contain volatile attractants. Solvent extracts of buffalo gourd root powder were evaluated for electroantennogram activity to western corn rootworm adults, and a sequential fractionation scheme was conducted to isolate and identify the primary EAG-active components in the extract. A probability-based computer mass spectral library search indicated that the best matches for compounds in the most EAG-active fractions to be ( E,E )-3,5-octadien-2-one, ( E,Z )-2,6-nonadienal, ( E )-2-nonenal, 2-phenylethanol, benzyl alcohol, ( E,E )-2,4-decadienal, and 6,10-dimethyl-5,9-undecadien-2-one. Retention time, mass spectrum, and EAG activity of the synthetic compounds were consistent with those of compounds in the purified EAG-active fractions (synthetic material was unavailable for 6,10-dimethyl-5,9-undecadien-2-one). Previous work indicated that several of these same compounds were in the most EAG-active fractions from corn, Zea mays L., silk. EAG data are discussed in terms of possible evolutionary considerations.
Lessons from and assessment of Boussinesq aquifer modeling of a large fluvial island in a dam-regulated river

Abstract The suitability of a numerical Boussinesq aquifer model for representing groundwater dynamics in a fluvial island surrounded by a regulated river is assessed and the model is used to compare exchange fluxes for varying configurations of island hydraulic conductivity ( K ) and diffusivity. The model results are qualitatively similar to field observations of the water table although there is obvious dissimilarity between modeled and observed heads suggesting that a Boussinesq aquifer model may not be the best option for representing the island. Nonetheless, the simulations show that pronounced ridges and valleys form in the water table and that their spatial configuration may change drastically with small variations in diffusivity. Stage fluctuations significantly increase exchange flux across the island relative to the case where stage is constant. The flux increases non-linearly when island K is low but then becomes quasi-linearly dependent on K with further increases in K . Regulated river stage fluctuations due to dams significantly affect surface water–groundwater interactions between a fluvial island and a river. This deserves further inquiry for both scientific and management reasons.
Abstract 1952: Targeting the CCL2/CCR2 chemokine pathway in breast tumors through intratumoral delivery of calcium cross linked TAT peptide: siRNA complexes

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Breast tumors exhibit inflammatory responses through recruitment of stromal cells in the primary tumor microenvironment, including fibroblasts and macrophages. Accumulation of these stromal cells correlates with development of invasive breast cancer and poor patient prognosis. These stromal cells express high levels of the inflammatory chemokine CCL2, corresponding to overexpression of its receptor CCR2 in the tumor epithelium. Our laboratory and others have shown that CCL2/CCR2 signaling mediates stromal: tumor interactions to regulate breast cancer cell survival, invasion and metastasis. While the CCL2/CCR2 signaling represents a novel and potentially effective therapeutic target in invasive breast cancer, it is necessary to develop new tools to specifically inhibit CCL2/CCR2 signaling in vivo. siRNA knockdown could specifically target CCL2 or CCR2, but is unstable and toxic when delivered in vivo. The HIV-1 derived TAT peptide penetrates cell plasma membranes at high efficiency and contains nuclear translocation signals to enhance siRNA delivery to the nucleus. Recent studies from our research team have shown that CaCl2 condenses TAT/nucleic acids to nanoparticles facilitating cellular uptake. The goals of these studies are to design TAT nanoparticle formulas to target CCL2 and CCR2 protein expression in breast tumors. Using an in vitro luciferase reporter system, we identified specific N/P ratios and CaCl2 concentrations that would transfect stromal cells and PyVmT mammary tumor cells. TAT/CaCl2 nanocomplexes carrying GFP plasmid or Cy3 labeled siRNAs were then injected into PyVmT mammary tumors. We observed visible GFP expression and Cy3 labeled siRNA uptake in over 50% of the PyVmT mammary tumor at low and high N/P ratios. Normal mammary tissues did not show significant uptake of TAT nanoparticles. Flow cytometry analysis showed that high N/P ratios resulted in efficient TAT/CaCl2/siRNA uptake in breast cancer associated fibroblasts and macrophages. TAT/CaCl2/siRNA nanocomplexes formed at low N/P ratios resulted in efficient siRNA uptake in tumor epithelial cells. Preliminary studies of PyVmT mammary tumors showed a reduction in CCL2 and CCR2 expression upon delivery of TAT/CaCl2 nanoparticles carrying CCL2 or CCR2 siRNAs. These data indicate this nanoparticle strategy represents a novel, feasible approach to target the CCL2/CCR2 signaling in breast cancer, with important implications on therapeutic targeting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1952. doi:1538-7445.AM2012-1952
Beam hardening correction and quantitative micro-CT

The main use of micro-CT is to analyze bone structure, and values of the linear attenuation coefficients μ at every voxel position in the scanned volume are only used for the analysis of bone structure by establishing a threshold that separates bone from non-bone material. To additionally quantify the degree of mineralization of bone (DMB) from μ in multi-component samples, we corrected for beam hardening and its associated errors in DMB quantification caused by the polychromatic spectra of X-ray tubes used in bench-top micro-CT devices. The correction was implemented by simulating the difference of mono-chromatic and poly-chromatic X-ray sources and adding these differences to the original image in an iterative fashion. When applied to simple cylinders containing a single material, improvement on the constancy of the reconstructed voxel values could be observed to over 90% accuracy.
Studies on extracellular proteases of Streptococcus sanguis. Purification and characterization of a human IgA1 specific protease.

Abstract Extracellular caseinolytic activity was found in the culture fluid of Streptococcus sanguis ATCC 10556 grown in a dialyzed culture medium. This activity was due to multiple proteases that differed in their elution from hydroxyapatite, sensitivity to enzyme inhibitors, specificity and optimum pH. IgA protease, which splits human immunoglobulin A1 into intact Fc and Fab could be effectively separated from these relatively non-specific proteases and purified to apparent homogeneity in 20% yield by a five-step procedure. Although the bulk of the dextran sucrase activity was separated from the IgA protease, a small amount of sucrase activity remained with the final IgA protease preparation. In polyacrylamide gel electrophoresis at pH 9.5 both activities were located in the single protein band detected in this preparation. A quantitative method for the assay of IgA protease was developed, based on radial immunodiffusion to quantitate the Fab produced. This was used to follow the specific activity and yield during purification, and to characterize some of the catalytic properties of the enzyme. At an enzyme/substrate ratio of 1 : 400 (w/w) the protease could effect 50% proteolysis of IgA in overnight incubation at 37°C. The optimum activity was at pH 8.0, and 50% inhibition was achieved at 4 · 10−4 M o- phenanthroline or 8 · 10−4 M ethylene diamine tetraacetate. Concentrations of diisopropyl phosphofluoridate, phenylmethyl-sulfonyl fluoride, iodoacetate and p- chloromercuribenzoate up to 10−2 M were without effect on the IgA protease activity. Full reactivation of the chelator inhibited enzyme could be achieved by the addition of Mg2+, Mn2+ or Ca2+.
Algorithm for loading shot noise microbunching in multidimensional, free-electron laser simulation codes

We discuss the underlying reasoning behind and the details of the numerical algorithm used in the GINGER free-electron laser(FEL) simulation code to load the initial shot noise microbunching on the electron beam. In particular, we point out that there are some additional subtleties which must be followed for multi-dimensional codes which are not necessary for one-dimensional formulations. Moreover, requiring that the higher harmonics of the microbunching also be properly initialized with the correct statistics leads to additional complexities. We present some numerical results including the predicted incoherent, spontaneous emission as tests of the shot noise algorithm's correctness.
Biotic elicitors of defense reactions in lodgepole pine

Abstract Elevated levels of defensive chemicals (monoterpenes) were detected in lodgepole pine ( Pinus contorta var. latifolia ) phloem surrounding sites inoculated with living mountain pine beetles ( Dendroctonus ponderosae ) a blue-staining fungus ( Ceratocystis clavigerum ), a pectic fragment from tomato leaves (PIIF) and a fungal cell wall fragment (chitosan). Chitosan elicited the greatest production of monoterpenes at the lowest concentrations, and also elicited greater responses in large, fast-growing trees. Chitosan may prove to be a useful material for assaying the resistance of conifers to lethal bark beetle attacks. The results suggest a common recognition-defense mechanism in higher plants.
A suicide note from Alzheimer disease neurons

New findings implicate apoptosis in the death of neurons in Alzheimer disease but the evidence is still insufficient to formally indict apoptosis in the neurodegeneration associated with this disease (pages 957–962).
Stable multi-line CW vibration laser near 5 μm based on FH(CN−) centers in CsBr

Abstract Stable cw laser operation has been obtained from F center/CN - defect pairs, “F H (CH - ) centers”, in CsBr crystals. Pumped with the 676 nm krypton laser line in one of their electronic absorption transitions in the visible, the F H (CN - ) centers perform (e-v) energy transfer into higher vibrational (v) levels of the CN - molecule and lase on their v =3→2 CN - vibrational transition near 5 μm up to a crystal temperature limit of ≈30 K. Using F H (CN - ) defects with 12 C 14 N, 12 C 15 N, 13 C 14 N and 13 C 15 N isotopes in the same crystal, we could obtain simultaneous four-line laser operation at 2010, 1980, 1970 and 1940 cm −1 .
Ionization Energies and Dyson Orbitals of Cytosine and 1-Methylcytosine

Electron propagator methods are applied to the vertical ionization energies of the five most stable tautomers of cytosine and to two oxo forms of 1-methylcytosine. For both molecules, there are sev...
Utilization of Genomic Signatures to Identify Phenotype-Specific Drugs

Genetic and genomic studies highlight the substantial complexity and heterogeneity of human cancers and emphasize the general lack of therapeutics that can match this complexity. With the goal of expanding opportunities for drug discovery, we describe an approach that makes use of a phenotype-based screen combined with the use of multiple cancer cell lines. In particular, we have used the NCI-60 cancer cell line panel that includes drug sensitivity measures for over 40,000 compounds assayed on 59 independent cells lines. Targets are cancer-relevant phenotypes represented as gene expression signatures that are used to identify cells within the NCI-60 panel reflecting the signature phenotype and then connect to compounds that are selectively active against those cells. As a proof-of-concept, we show that this strategy effectively identifies compounds with selectivity to the RAS or PI3K pathways. We have then extended this strategy to identify compounds that have activity towards cells exhibiting the basal phenotype of breast cancer, a clinically-important breast cancer characterized as ER-, PR-, and Her2- that lacks viable therapeutic options. One of these compounds, Simvastatin, has previously been shown to inhibit breast cancer cell growth in vitro and importantly, has been associated with a reduction in ER-, PR- breast cancer in a clinical study. We suggest that this approach provides a novel strategy towards identification of therapeutic agents based on clinically relevant phenotypes that can augment the conventional strategies of target-based screens.
Physiologic estrogen receptor alpha signaling in non-tumorigenic human mammary epithelial cells

Currently, a number of breast cancer cell lines exist that serve as models for both estrogen receptor alpha (ERα) positive and ERα negative disease. Models are also available for pre-neoplastic breast epithelial cells that do not express ERα; however, there are no ideal systems for studying pre-neoplastic cells that are ERα positive. This has been largely due to the inability to establish an estrogen growth stimulated, non-tumorigenic breast epithelial cell line, as most human breast epithelial cells engineered to overexpress ERα have been found to be growth inhibited by estrogens. We have developed independently derived clones from the non-cancerous MCF-10A human breast cell line that express ERα and are growth stimulated by 17-beta-estradiol (E2) in the absence of epidermal growth factor (EGF), a cytokine normally required for MCF-10A cell proliferation. This effect is blocked by the selective estrogen receptor modulator (SERM), Tamoxifen and the selective estrogen receptor downregulator, ICI 182,780 (Faslodex, Fulvestrant). Exposure of these cells to EGF and E2 results in a growth inhibitory phenotype similar to previous reports. These data present a reconciling explanation for the previously described paradoxical effects of ERα overexpression, and provide a model for examining the carcinogenic effects of estrogens in non-tumorigenic human breast epithelial cells.
Regulation of crab Y-organ steroidogenesis in vitro: evidence that ecdysteroid production increases through activation of cAMP-phosphodiesterase by calcium-calmodulin.

Abstract In decapod crustaceans steroidogenic glands (Y-organs) produce the molting hormone, ecdysone. A putative neuropeptide, molt-inhibiting hormone (MIH), released from eyestalk neurosecretory cells, directly regulates Y-organs by suppressing steroidogenesis; the effect is mediated by an increase in cAMP. We explored calcium-cAMP interactions in the regulation of Y-organs in vitro of the crab, Cancer antennarius . Basal ecdysteroid production was enhanced by extracellular calcium (EC). MIH suppression did not require EC but its action was blocked by high EC. The inhibitors of Ca 2+ flux, lanthanum and ruthenium red, mimicked and enhanced MIH action. Calcium ionophore A23187 raised basal steroidogenesis dose-dependently (10 −6 to 10 −4 M) and with time course (effect evident after 2 h) similar to that of suppression by MIH. Low EC enhanced the suppressive effects on steroidogenesis of forskolin and dibutyryl cyclic AMP ((Bu) 2 cAMP) but not of MIH, lysine vasopressin (LVP), or 3-isobutyl-1-methylxanthine (IBMX); basal Y-organ cAMP levels were elevated by low EC and reduced by A23187. A23187 reduced the steroidogenic-suppressive effects of MIH, LVP, forskolin and (Bu) 2 cAMP but not of IBMX; rises in cAMP induced by MIH, LVP, and forskolin but not by IBMX were blunted by A23187. These findings suggested a stimulatory action of calcium on phosphodiesterase (PDE). The calmodulin (CM) inhibitor trifluoperazine (TFP; 10 −5 to 10 −4 M) reduced basal and A23187-stimulated steroidogenesis, enhanced the inhibitory effects of MIH and (Bu) 21 cAMP on ecdysteroid production, enhanced the stimulatory effects of MIH and forskolin on cAMP, and blocked the inhibition of cAMP by A23187. Y-organ PDE activity was enhanced by increasing free Ca 2+ (10 −7 to 10 −5 M) and inhibited by TFP (10 −5 to 10 −4 M). Adenylate cyclase activity of Y-organ cell particulate fraction was unaffected by Ca 2+ or TFP. Calcium stimulates steroidogenesis, apparently by activating a calcium-CM-dependent cAMP-PDE; the action is counter to the cAMP-mediated MIH-inhibitory system. Ca 2+ fluxes were measured with dispersed Y-organ cells, in the presence and absence of agents that alter cAMP levels. The ionophore A23187, but not MIH or forskolin, increased 45 Ca 2+ entry by 45% over untreated control cells. Efflux from 45 Ca 2+ -preloaded cells was increased 30% by MIH and forskolin, but not A23187. These data, together with those further above, suggest that MIH suppresses steroidogenesis in part by fostering Ca 2+ depletion, and that the effect is mediated by cAMP.
Complications of electrohydraulic lithotresis

The urologic literature reports excellent success with minimal complications utilizing electrohydraulic lithotresis for bladder calculi. Our recent experience with 10 patients suggests that small stones of struvite/carbonate apatite composition can be fragmented easily, but larger stones, particularly of uric acid or oxalate composition, may be better handled by open cystolithotomy. Failure to disrupt stones occurred in 6 patients. Significant complications developed in 3 of these patients, including breakage of the electrode tip in 2 and sepsis in another related to prolonged operative time.
A high precision dual feedback pump for unsteady perfusion of small organs

A dynamic pump system is described for perfusion of small organs with whole blood. The pump system was designed with the following aims: Very low flowrates to perfuse single organs in small rodents; high dynamic response for pressure or flow to permit experimenting with a harmonic signal at frequencies up to 20 Hz or by way of sharp step transients in less than 10 msec; high precision to allow detection of fine physiological details, and minimum blood cell trauma or cell activation by use of a piston principle. Representative pressure-flow curves are shown for the rat gracilis muscle after vasodilation. The curves are highly reproducible and serve as a complimentary dataset for microvascular observations in the same organ.
Marginal accuracy of temporary composite crowns

An in vitro study was conducted to quantitatively compare the marginal adaptation of temporary crowns made from Protemp material with those made from Scutan, Provisional, and Trim materials. A direct technique was used to make temporary restorations on prepared teeth with an impression as a matrix. Protem, Trim, and Provisional materials produced temporary crowns of comparable accuracy. Crowns made from Scutan material had open margins.
Hydration effects of Al2(MoO4)3 and AlPO4 phases in hydrotreating catalysts studied by solid state nuclear magnetic resonance spectroscopy

Solid state nuclear magnetic resonance spectroscopy of27Al,31P, and95Mo nuclei was used to investigate species on a NiPMo/Al2O3 hydrotreating catalyst calcined at 750 °C before and after rehydration. The Al2(MoO4)3 phase disappeared after rehydration in 100% relative humidity at room temperature. However, almost none of the observed crystalline AlPO4 reacted with adsorbed water. The results show that the Al2(MoO4)3 phase on an alumina surface reacts easily with moisture unlike Al2(MoO4)3 in the bulk phase. It also suggests that the crystalline AlPO4 phase is formed under the Al2(MoO4)3 phase or that both species are formed as neighboring islands on the surface of the alumina but have different reactivities toward moisture.
Comparison of demographic characteristics, surgical resection patterns, and survival outcomes for veterans and nonveterans with non-small cell lung cancer in the Pacific Northwest.

Introduction Lung cancer is a leading cause of death in the United States and among veterans. This study compares patterns of diagnosis, treatment, and survival for veterans diagnosed with non-small cell lung cancer (NSCLC) using a recently established cancer registry for the Veterans Affairs Pacific Northwest Network with the Puget Sound Surveillance, Epidemiology, and End Results cancer registry. Methods A cohort of 1715 veterans with NSCLC were diagnosed between 2000 and 2006, and 7864 men were diagnosed in Washington State during the same period. Demographics, tumor characteristics, initial surgical patterns, and survival across the two registries were evaluated. Results Veterans were more likely to be diagnosed with stage I or II disease (32.8%) compared with the surrounding community (21.5%, p = 0.001). Surgical resection rates were similar for veterans (70.2%) and nonveterans (71.2%) older than 65 years with early-stage disease ( p = 0.298). However, veterans younger than 65 years with early-stage disease were less likely to undergo surgical resection (83.3% versus 91.5%, p = 0.003). Because there were fewer late-stage patients among veterans, overall survival was better, although within each stage group veterans experienced worse survival compared with community patients. The largest differences were among early-stage patients with 44.6% 5-year survival for veterans compared with 57.4% for nonveterans ( p = 0.004). Conclusions The use of surgical resection among younger veterans with NSCLC may be lower compared with the surrounding community and may be contributing to poorer survival. Cancer quality of care studies have primarily focused on patients older than 65 years using Medicare claims; however, efforts to examine care for younger patients within and outside the Department of Veterans Affairs are needed.
Wavelength and temperature dependence of the Faraday effect in Cd(1 − x)Mn(x)Te

Abstract The wavelength dependence of the Faraday effect at fixed temperature and the temperature dependence at fixed wavelength have been measured in Cd(0.55)Mn(0.45)Te. These results can be explained quite well using a simple exciton model and the known temperature dependence of the magnetic susceptibility and exciton energy.
Kepler's area law in the Principia: filling in some details in Newton's proof of Proposition 1

Abstract During the past 30 years there has been controversy regarding the adequacy of Newton's proof of Prop. 1 in Book 1 of the Principia. This proposition is of central importance because its proof of Kepler's area law allowed Newton to introduce a geometric measure for time to solve problems in orbital dynamics in the Principia. It is shown here that the critics of Prop. 1 have misunderstood Newton's continuum limit argument by neglecting to consider the justification for this limit which he gave in Lemma 3. We clarify the proof of Prop. 1 by filling in some details left out by Newton which show that his proof of this proposition was adequate and well-grounded.
D region disturbances caused by electromagnetic pulses from lightning

Electromagnetic pulses from weak lightning discharges (E[sub 100] = 1 V/m, where E[sub 100] is the field strength in the radiation pattern maximum at 100 km) may substantionally heat D region electrons, while only pulses with E[sub 100] [>=] 20 V/m may create electron density enhancements [>=]10% of ambient. A E[sub 100] = 20 V/m pulse from a horizontal radiator at 5 km altitude (e.g., the cloud discharge at the stepped-leader onset) increases the electron temperature by a factor of [approximately]400 maximum and the electron density (in one ionization cycle) by [approximately]230 cm[sup [minus]3] maximum; the widths at half-maximum of the heated and ionized regions are 200 km and 90 km. A E[sub 100] = 40 V/m pulse from a vertical radiator at 0 km altitude (e.g., the vertical return stroke channel) increases the electron temperature by a factor of [approximately]350 maximum and the electron density (in one ionization cycle) by [approximately]80 cm[sup [minus]3] maximum; the widths at half-maximum of the heated and ionized regions are 440 km and 260 km. Several ionization cycles should occur during a typical lightning pulse. 4 regs., 4 figs.
On higher order computations in strong coupling

An algorithm which simplifies manipulation of higher order graphs in strong coupling is presented.
Output Feedback RHC for Constrained Linear Systems

In this paper, we address the problem of synthesizing output feedback control law for constrained linear systems. For lack of state information, the plant states will be estimated by an observer. Using the Lyapunov function of estimated plant and controller states, the constrained output feedback control problem will be formulated and solved in terms of linear matrix inequalities (LMIs). The quadratic cost function is minimized over control policies to yield an output feedback control strategy subject to input/output constraints. Both infinite-horizon and finitehorizon receding horizon control (RHC) are considered in the paper. Closed-loop stability and feasibility of RHC are guaranteed by off-line constrained control designs. The simulation results show that finite-horizon RHC provides better performance upper bound than infinite-horizon RHC.Copyright © 2007 by ASME
Interatrial block during exercise tolerance tests as an additional parameter for the diagnosis of ischemic heart disease

Abstract Introduction Interatrial block (IAB; P-wave duration, ≥120 milliseconds) is associated with increases of left atrial pressure. We studied the use of IAB during exercise tolerance test (ETT) in diagnosis of ischemic heart disease. Method Exercise tolerance tests were performed in 149 patients (mean age, 50 years; male, 60.4%). P-wave duration was measured at rest, at each stage of exercise using the Bruce protocol, and in recovery. As clinically indicated, 71 patients subsequently underwent nuclear stress test and/or catheterization. The evidence of ischemia (EOI) was considered present according to the more definite test, that is, catheterization over nuclear stress test over ETT. Results Among patients who did not have IAB at rest (n = 115), 63 patients (54.7%) developed IAB during the ETT. The incidence of IAB during the ETT was higher in patients with EOI than patients without EOI (88.9% vs 51.9%, P = .03). When IAB during the ETT and positive ETT were used together to detect EOI, they were more accurate (86.1% vs 81.7%) than the ETT alone. Among patients with IAB at rest (n = 34), patients with EOI had a higher incidence of P-wave duration increase of more than 20 milliseconds during the recovery period than patients without EOI (100% vs 21.8%, P = .015). When using P-wave duration increase of more than 20 milliseconds during the recovery period in conjunction with positive ETT, the sensitivity in detecting EOI was higher than using the ETT alone (100% vs 0%), but the specificity was worsened (68.8% vs 84.4%). Conclusion New IAB and worsening of IAB during ETT appeared in patients with ischemic heart disease and may be used as additional parameters for the ETT interpretation.
Successful repair of a gunshot wound to the head with retained bullet in the torcular herophili.

Background Nonlethal missile injuries to the dural venous sinus system are rare. To date successful repair of isolated penetrating injury to the torcular herophili has not been reported without significant associated morbidity. We report the case of a gunshot wound injury to the occipital region with retained bullet fragment in the confluence of the sinuses causing traumatic sinus venous thrombosis. Methods Occipital and suboccipital craniotomy for removal of bullet in the torcula, repair of sinus defect, and repair of depressed skull bone fragments was performed. Results The procedure resulted in restoration of proximal and distal flow across the dural sinus system and preservation of torcular sinus patency with excellent neurological outcome. Technical considerations in the repair of penetrating torcular injuries are discussed. Conclusions Gunshot wounds with retained bullet fragments in the torcula can be successfully repaired with preservation of neurological function after retrieval of metallic foreign body and restoration of venous sinus patency.
Characterization of Notch receptor expression in the developing mammalian heart and liver

Alagille syndrome (AGS) is an autosomal dominant disorder characterized by bile duct paucity along with cardiovascular, skeletal, and ophthalmologic defects. The identification of JAG1 as the AGS disease gene revealed the crucial role of the Notch signaling pathway in the development of multiple organ systems in humans. Patients with identical mutations in JAG1 demonstrate extreme clinical variability, suggesting that other factors may influence the severity of the developmental defects in this disorder. We have defined the temporal and spatial expression patterns of the Notch receptor genes in the developing mammalian heart and liver in order to identify potential ligand/receptor interactions during embryogenesis. In the developing heart, both Notch1 and Notch2 are expressed in the outflow tracts and the epicardium, in specific cell populations previously shown to express JAG1. These cells are destined to undergo epithelial-to-mesenchymal transformation. In the newborn mouse liver, Notch2 and Notch3 are expressed in opposing cell populations, suggesting they play different roles in cell fate determination during bile duct development. JAG1 is also expressed in cells adjacent to those expressing Notch2, suggesting a possible ligand receptor relationship. The Notch receptors have distinct roles in cell fate determination in different organ systems.