cssi/SciSciGPT-SciSciNet huggingface dataset:
Enhancing photodynamic therapy of a metastatic mouse breast cancer by immune stimulation

One in 8 women in the United States will develop breast cancer during her lifetime and 40,000 die each year. Deaths are due to tumors that have metastasized despite local control. Photodynamic therapy (PDT) is a promising cancer treatment in which a photosensitizer (PS) accumulates in tumors and is subsequently activated by visible light of an appropriate wavelength. The energy of the light is transferred to molecular oxygen to produce reactive oxygen species that produce cell death and tumor ablation. Mechanisms include cytotoxicity to tumor cells, shutting down of the tumor vasculature, and the induction of a host immune response. The precise mechanisms involved in the PDT-mediated induction of anti-tumor immunity are not yet understood. Potential contributing factors are alterations in the tumor microenvironment via stimulation of proinflammatory cytokines and direct effects of PDT on the tumor that increase immunogenicity. We have studied PDT of 410.4 variant 4T1 tumors growing in the mammary fat pad (orthotopic) in Balb/c mice and which produce metastasis. We have shown that a PDT regimen that produces vascular shutdown and tumor necrosis leads to initial tumor ablation but the tumors recur at the periphery. We studied the combination of PDT with immunostimulating therapies. Low dose cyclophosphamide (CY) is a specific mechanism to deplete the regulatory T cells (CD4+CD25+), these cells play an important role in the immunosuppression activity of tumors. In combination with PDT that produces release of tumor specific antigens, this immunostimulation may lead to generation of cytotoxic CD8 T-lymphocytes that recognize and destroy the tumor. The second alternative therapy is the use of a novel combination of the immunostimulant CpG oligodeoxynucleotides (CpG-ODN) and PDT. CpG-ODN is recognized by Toll-like receptor 9 and directly or indirectly triggers B cells, NK cells, monocyte-macrophages and dendritic cells to proliferate, mature and secrete cytokines, chemokines and immunoglobulins. Both these novel combinations gave significantly enhanced therapeutic benefit not seen with single treatments alone. Tumors grew more slowly and mice lived significantly longer, although cures were rare. We propose that a rational choice of immune stimulant is an ideal addition to PDT regimens.
Empirical Evidence of Recurring International Compensation Problems

The expansion of international business necessitates an increased number of employees based in foreign markets. These expatriates, nationals and third-country nationals represent unique and complex compensation problems. This article addresses five of the recurring compensation problems reported by members of the Society for Human Resource Management International (SHRMI) in a recent survey.
Forecasting the economic benefit of reducing non-operative time

To the Editor, With reference to Head et al.’s ‘‘swing room’’ model based on regional anesthesia, they showed that patients undergoing hand and wrist surgery with regional anesthesia can have a briefer non-operative time period and more cases can be scheduled within an eight-hour workday. They state: ‘‘These findings contrast with those of Dexter et al. who found that anesthesia-controlled time (or the time from surgical closure on one patient until anesthesia is ready on the following patient) for most types of surgeries would have to be decreased by more than 100% in order to be able to book one additional 30-min case each day.’’ First, in response to their statement, I defined anesthesia-controlled time as ‘‘the sum of 1) the time starting when the patient enters an OR to when positioning or skin preparation can begin plus 2) the time starting when the surgical dressing is completed to when the patient leaves the OR.’’ Head et al. misstate my definition. Second, the mean surgical time for hand cases was 40 min in Table 1 of both Head et al.’s and my articles. Also, the mean non-operative time in Table 1 of my article was 35 min, 12 min being anesthesia-controlled time. According to Table 3 in my article, the ‘‘decrease in anesthesia time needed to predictably finish earlier’’ was 110%, or 13 min. Since Table 3 of Head et al.’s article shows a 39-min reduction, my calculations also predict additional case(s) in the eight-hour period. Third, the cases studied by Head et al. were considered completed within an eight-hour period not rationally scheduled into an eight-hour period. Cases have predictive variability (e.g., a case scheduled for 45 min could take one hour). A rational manager whose goal is an eight-hour workday schedules fewer than eight hours’ worth of cases (e.g., 7.3 hr). The header in my Table 3 reads ‘‘predictably finish earlier’’, since my analysis takes this into account. Head et al.’s formula is economically irrational. The issue is simply their analysis, not their conclusions, as their approach to use anesthesia assistants to monitor patients after regional anesthesia has excellent potential to increase productivity. The benefit of their approach will simply be slightly less than they predict because of the issues of ‘‘reliably’’ scheduling another case and the likelihood that an entire room of appropriate cases can be scheduled daily.
Sequence-characterized amplified regions that differentiate New World screwworms from other potential wound-inhabiting flies:

New World screwworms, Cochliomyia hominivorax (Coquerel, 1858), were once devastating pests of warm-blooded animals in the United States before they were successfully eradicated using the sterile insect technique. Guarding against the introduction of screwworms to North America or any other screwworm-free area relies on rapid, reliable identification of suspected cases. In the current study, the DNA from excised markers generated by randomly amplified polymorphic DNA polymerase chain reaction was used as the basis to generate 2 species-specific sequence-characterized amplified region molecular markers. Resulting primer pairs, named CR92A1 and J1A2 (each with forward and reverse components), produced amplicons of 852 and 848 base pairs, respectively. The 2 primer pairs successfully discriminated between C. hominivorax, Cochliomyia macellaria (Fabricius, 1775), 8 other species of blowflies, 3 noncalliphorid dipterans, and 1 nondipteran outlier. These primers may become important tools for veterinary laborat...
Reflectivity changes of optically-thin nickel films exposed to oxygen

Abstract Optically-thin nickel films evaporated on the end of optical fibers show a reflectivity change when exposed to oxygen. This effect has been measured as a function of metal thickness and wavelength. Growth of NiO on the nickel surface reduces the thickness of the metal and thus the phase shift of the light passing through it. This phase change causes a change in the reflectivity. A simple classical model using Fresnel reflection coefficients fits all the data. The 4.2 A reduction in nickel thickness deduced from the optical measurements agrees well with measurements made using modern surface analytical techniques. This new optical method for monitoring chemical interactions between adsorbates and metals may prove useful for gas sensing and corrosion monitoring. In addition, it may provide information on how chemisorption modifies the local electron density of states in metals.
Adsorption of carbon monoxide on Ir(110) investigated by infrared reflection-absorption spectroscopy

Abstract The adsorption of carbon monoxide on the Ir(110) surface at 300 K has been investigated with Fourier transform infrared reflection-absorption spectroscopy. A single band was observed that shifted up from a low-coverage value of 2001 cm −1 to a saturation-coverage limit of 2086 cm −1 . This band is attributed to the carbon-oxygen stretching mode of a molecule adsorbed on top of a surface iridium atom. This frequency shift was separated into a contribution due to dipole-dipole interactions and a smaller contribution from chemical effects (d-electron competition) by using isotopic substitution. Employing knowledge of the structure of the reconstructed Ir(110) surface and temperature-programmed desorption spectra measured at various coverages, an adlayer model is proposed to reconcile a single adsorption site with the temperature-programmed desorption data.
Nonclassical equations of state for critical and tricritical points

We develop a method by which certain classical equations of state may be modified to produce nonclassical critical scaling behavior. We then apply this method to the classical free energy describing a tricritical point that was originally introduced by Griffiths. The phase behavior of the resulting nonclassical free energy is characterized by the competition between critical scaling and tricritical scaling already envisioned by previous authors.
The metabolism of 3H-cortisone and 3H-cortisol by the isolated perfused rat and guinea pig lungs

Abstract Isolated perfused rat lungs removed more than 35% of 3H-cortisone (1 × 10-9M) from the perfusate during one passage through the pulmonary circulation. The cortisone in the lung was then rapidly converted to cortisol, which was returned to the perfusate. The tritiated steroid taken up was so rapidly washed from the lung, that only 10% remained after a 12 minute perfusion with steroid-free medium. In recirculating experiments, nearly 60% conversion to cortisol occurred over 32 cycles; in addition, there was a slow increase in the percentage of polar compounds in the medium. Similarly, the perfused hindlimbs preparation from the rat converted cortisone to cortisol and returned the cortisol to the perfusate. In contrast, guinea pig isolated perfused lungs had negligible effect on cortisone. Rat lungs demonstrated only a limited ability to convert 3H-cortisol to cortisone. The results suggest that the lungs may play an important role in maintaining cortisone/cortisol levels in the plasma.
Structure-activity relationships of 1,4-dihydro-(1H,4H)-quinoxaline-2,3-diones as N-methyl-D-aspartate (glycine site) receptor antagonists. 1. Heterocyclic substituted 5-alkyl derivatives.

A series of 6,7-dichloro-1,4-dihydro-(1H, 4H)-quinoxaline-2,3-diones (1−17) were prepared in which the 5-position substituent was a heterocyclylmethyl or 1-(heterocyclyl)-1-propyl group. Structure−...
Applications of Environmental Cell - Transmission Electron Microscopy for the Microcharacterization of Bio-alteration Products and the Study of Bio-processes

Abstract : Environmental Cell (EC)- Transmission Electron Microscopy (TEM) is a powerful technique in which hydrated specimens (at tens of torr pressure) can be examined at high spatial resolution in more or less their natural state. Two methods have been used in environmental TEM instruments: closed-cell specimen holders (e.g., see Fig. 1) and open-cell differential column pumping. Several applications of closed-cell EC-TEM are discussed in which chemical and high-resolution structural information were obtained on hydrated, microbial alteration products. Also discussed is the profound application of closed-cell EC-TEM for the in-situ study of functioning biomolecules.
Overexpression of EPH Receptor B2 in Malignant Mesothelioma Correlates with Oncogenic Behavior

Introduction: Malignant pleural mesothelioma (MM) is an aggressive asbestos-associated malignancy with limited therapeutic options. This study describes the overexpression of Ephrin B2 receptor (EPHB2) in MM cell lines and tumors, and the effect of its manipulation on proliferative and invasive qualities of the disease. Methods: Using expression arrays, we investigated EPHB2 in MM tumors compared with normal mesothelium. EPHB2 and downstream target expression were evaluated using reverse-transcriptase polymerase chain reaction and immunoblotting methods. The biological significance of EPHB2 in MM was evaluated using in vitro functional assays with and without targeting by EPHB2-short hairpin RNA or blocking peptide in two mesothelioma cell lines, HP-1 and H2595. Results: EPHB2 is overexpressed in all MM cell lines, but not in benign mesothelial cells, and is significantly elevated in MM tumor tissue compared with matched normal peritoneum. Targeted knockdown of EPHB2 in HP-1 and H2595 cell lines reduced its expression and that of EPHB2 downstream targets such as matrix metalloproteinase (MMP-2) and vascular endothelial growth factor, whereas caspase 2 and caspase 8 had increased expression. Inhibition of EPHB2 resulted in a significant decrease in scratch closure (1.25-fold–1.8-fold), proliferation (1.5-fold), and invasion (1.7-fold–1.8-fold) compared with the controls. Most notably, however, EPHB2 silencing resulted in a significant increase in apoptotic proteins and activity. Conclusion: EPHB2 seems to play an important role in MM pathogenesis and these findings indicate that EPHB2 could serve as a potential novel therapeutic target for treatment of the disease.
Physiological response of Crocosphaera watsonii to enhanced and fluctuating carbon dioxide conditions.

We investigated the effects of elevated pCO2 on cultures of the unicellular N2-fixing cyanobacterium Crocosphaera watsonii WH8501. Using CO2-enriched air, cultures grown in batch mode under high light intensity were exposed to initial conditions approximating current atmospheric CO2 concentrations (,400 ppm) as well as CO2 levels corresponding to low- and highend predictions for the year 2100 (,750 and 1000 ppm). Following acclimation to CO2 levels, the concentrations of particulate carbon (PC), particulate nitrogen (PN), and cells were measured over the diurnal cycle for a six-day period spanning exponential and early stationary growth phases. High rates of photosynthesis and respiration resulted in biologically induced pCO2 fluctuations in all treatments. Despite this observed pCO2 variability, and consistent with previous experiments conducted under stable pCO2 conditions, we observed that elevated mean pCO2 enhanced rates of PC production, PN production, and growth. During exponential growth phase, rates of PC and PN production increased by ,1.2- and ,1.5-fold in the mid- and high-CO2 treatments, respectively, when compared to the low-CO2 treatment. Elevated pCO2 also enhanced PC and PN production rates during early stationary growth phase. In all treatments, PC and PN cellular content displayed a strong diurnal rhythm, with particulate C:N molar ratios reaching a high of 22:1 in the light and a low of 5.5:1 in the dark. The pCO2 enhancement of metabolic rates persisted despite pCO2 variability, suggesting a consistent positive response of Crocosphaera to elevated and fluctuating pCO2 conditions.
Mechanistic insights into glaucoma provided by experimental genetics the cogan lecture.

The objective of this lecture-based review is to summarize some of the mechanistic insights into glaucoma that have been derived from research in mice in my laboratory over the past 10 years. The mouse system provides powerful genetic tools for studying complex, asynchronous diseases such as glaucoma (see Refs. 1, 2). Because of the high degree of conservation of physiological and homeostatic mechanisms between mammals, mice often have the same diseases as do humans, and these diseases develop in a relatively short span of time. Mouse and human diseases often are caused by the same mutant gene or pathway. Although mouse and human diseases are not always identical, mouse studies are providing an important complement to those in humans and other species. This article illustrates several ways in which we have used mice to study different aspects of glaucoma, but it does not attempt to provide a comprehensive literature review. I first focus the discussion on our studies of risk factors for high intraocular pressure (IOP) and then turn to mechanisms that kill retinal ganglion cells (RGCs).
Sites of topoisomerase I action on X. laevis ribosomal chromatin: Transcriptionally active rDNA has an ∼200 bp repeating structure

Abstract The sites at which topoisomerase I interacts with the transcriptionally active ribosomal chromatin of Xenopus oocytes were mapped by treating oocyte nuclei first with camptothecin to stabilize topoisomerase I-rDNA reaction intermediates, and then with SDS to resolve these adducts as protein-linked nicks in the DNA. Strikingly, the topoisomerase I sites are concentrated in the region encoding the 18S, 5.8S, and 28S rRNAs, where they are spaced with a periodicity of ∼200 nucleotides. Plasmid rDNA that has assembled into a nucleoprotein structure in an oocyte nuclear extract yields this same restricted pattern of sites, while rDNA that is not in a chromatin structure exhibits a continuum of topoisomerase I cleavages. Thus, the ∼200 bp spacing of sites of topoisomerase I interaction evidently reflects rDNA chromatin structure. These results indicate that the active rRNA genes are organized into nucleosome-like arrays, with topoisomerase I located in the linker regions.
Transport of DNA-adducting metabolites in mouse serum following benzo [a]pyrene administration

Metabolic activation of benzo[a]pyrene (BaP) by cellular enzymes is required for DNA adduct formation. In vivo DNA adducts might also arise from BaP metabolites supplied via the systemic circulation, rather than from in situ activation. We determined whether electrophilic metabolites could be detected in mouse serum 4 h after BaP dosing (i.p.) by trapping metabolites with salmon sperm DNA (ssDNA), followed by 32P-postlabeling analysis for DNA adducts. In vitro studies demonstrated that mouse serum sequesters BaP-7,8-diol-9,10-epoxide (BPDE) and protects it from hydrolysis. BPDE was rapidly transferred from serum to ssDNA or splenocytes, with adduct levels in ssDNA 4- to 7-fold greater than in splenocytes. After BaP administration, mouse serum produced two adduct spots when incubated with ssDNA. The major adduct (spot 3) co-chromatographed with a BPDE adduct standard, while the minor adduct (spot 2) was unrelated to BPDE. A BPDE standard curve in control serum was developed to quantitate BPDE levels in dosed serum. These levels ranged from 13.1 to 19.1 nM. Tissue DNA contained three adduct spots: spots 2 and 3 appeared identical to the respective adducts arising from dosed serum. BPDE-DNA adducts in tissues were highest in liver, lung and spleen, with kidney and stomach levels significantly lower. Levels of adduct 2 did not correlate with levels of adduct 3, especially in spleen where the adduct 2/adduct 3 ratio was very low. In vitro studies in which splenocytes were presented with both adducting metabolites suggested that splenocytes preferentially form adduct 3. These results indicate that two of the three BaP electrophilic metabolites responsible for cellular DNA damage are present in mouse serum. The levels of BPDE in serum may be sufficient to account for a substantial portion of the tissue load of BPDE-DNA adducts.
Studies on the resistance of haemoglobin to alkali.

Summary Using SINGER'S test of haemoglobin alkali denaturation we have examined: 1. 61 non anaemic infants aged between 5 days and 2 years and found a foetal type of haemoglobin up to the 19th month of age. 2. 12 patients with Cooley's anaemia. The values of resistant haemoglobin were above 50 % in cases that had not received a transfusion previously. These values are much higher than those found by SINGER in similar eases. 3. 13 patients with sickle cell anaemia. The values of resistant haemoglobin fell between 5–19.5 % coinciding with those found in negro patients. 4. 2 cases of Kala-Azar. The haemoglobin was found to be of the normal type.
Transgenic introduction of androgen receptor into estrogen-receptor–, progesterone-receptor–, and androgen-receptor–negative breast cancer cells renders them responsive to hormonal manipulation

Abstract Background Estrogen-receptor (ER)–, progesterone-receptor (PR)–, and androgen-receptor (AR)–negative breast cancer cells are unaffected by treatment with dehydroepiandrosterone-sulfate (DHEAS) and an aromatase inhibitor (AI). We hypothesized that cell growth would be inhibited with DHEAS/AI treatment after successful transfection of an AR expression vector. Methods ER/PR/AR–negative breast cancer cells were transfected with an AR expression vector and treated with DHEAS/AI for 2 days. Growth inhibition of these cells was compared with that of transfected cells treated with only AI or with nontransfected cells treated with DHEAS/AI. Mann-Whitney U test was used to determine statistical significance. Results Cell death rates of 53.5% ( P = .001) and 40.1% ( P = .006) were seen in transfected cells treated with DHEAS/AI compared with controls for days 1 and 2, respectively. Nontransfected cells were unaffected by treatment. Comments ER/PR/AR–negative cells transfected with AR were killed by DHEAS/AI treatment, providing evidence that AR is responsible for this effect. This provides the first AR-targeted hormonal therapy for ER breast cancer.
Stem cells: Down's syndrome link to ageing

Triplication of the enzyme USP16 in models of Down's syndrome creates defects in the stem cells resident in adult tissues. This finding provides insight into stem-cell homeostasis during ageing. See Article p.380 People with Down's syndrome have abnormalities in multiple tissues including mental retardation and early ageing. The disease is often the result of full or partial trisomy of chromosome 21, but the molecular mechanisms underlying the observed cellular defects remain largely unknown. An analysis of haematopoietic stem cells in the Down's syndrome mouse model Ts65Dn has revealed a reduced self-renewal associated with the proliferation of cells expressing three copies of the Usp16 gene, which encodes a deubiquitination enzyme involved in chromatin remodelling and cell cycle progression. In a second Down's syndrome mouse model, Ts1Cje, haematopoietic stem cells were not defective. Downregulation of USP16 rescued the functional defects of affected Ts65Dn cells. Overexpression of USP16 in normal human fibroblasts reduced their proliferative capacity and USP16 downregulation partially rescued human Down's syndrome fibroblast proliferation defects. The authors propose that USP16 is a potential target for therapeutics designed to ameliorate the pathologies associated with this syndrome.
Oblique effects, vertical effects and meridional amblyopia in monkeys

Orientation anisotropies were investigated for monkeys with normal visual acuity and for monkeys with experimentally induced amblyopia. It was found that the majority of control monkeys showed a normal oblique effect if any existing refractive errors were carefully corrected, but a few of the control monkeys had a meridional amblyopia, i.e., an orientation anisotropy in which the grating orientation for the greatest and lowest contrast sensitivities were correlated with the principal meridians of an astigmatic refractive error even when the refractive error was corrected. For monkeys with strabismic amblyopia caused by a surgically induced divergent strabismus, the orientation anisotropies showed a vertical effect in which contrast sensitivity was lower for vertically oriented gratings than for horizontally oriented gratings. However, monkeys with the same degree of amblyopia resulting from experimental procedures that did not involve a misalignment of the visual axes showed orientation anisotropies that corresponded to the usual oblique effect.
Noradrenergic stimulation of supraoptic neuronal activity and vasopressin release in vitro: mediation by an α1-receptor

Using the isolated rat hypothalamoneurohypophysial system, the effects of noradrenaline (NA) and some adrenoceptor agonists on vasopressin (VP) release and supraoptic neuronal activity were assessed in vitro. Extracellular action potentials driven antidromically by neural stalk stimulation were recorded while fractions of the perifusate were collected every minute for radioimmunoassay of VP. NA and the alpha 1-agonist phenylephrine stimulated VP release and elicited bursts in tuberal supraoptic neurons, whereas isoprenaline (a beta-agonist) and clonidine (an alpha 2-agonist) did not. The peak rate of VP release was reached shortly after the onset of burst discharge. when intraburst firing rate was highest, and both effects were dose-dependent when tested to different concentrations of phenylephrine. Thus VP secreting neurons are excited to release VP by alpha 1-adrenoceptor activation.
An experimentally verified theoretical study of the falling cylinder viscometer

A theoretical analysis was made for laminar fluid flow in the annulus of a falling cylinder viscometer. A viscometer calibration constant was defined from the results of this analysis. This constant was expressed in terms of only the physical dimensions of the viscometer. The volues lidity of the theory was demonstrated by the agreement between predicted and experimental values of the viscometer constant. Methods of representing calibration data were compared. Temperature and pressure effects on the viscometer constants were related to the mechanical properties of the viscometer materials. The results of this investigation showed that the practical design of falling cyclinder viscometers is possible.
Graft versus host reaction in Wiskott-Aldrich syndrome: antemortem diagnosis of human GVH in an immunologic deficiency disease.

Summary. A patient with Wiskott-Aldrich syndrome developed a syndrome resembling a Graft versus Host reaction following therapy with paternal plasma containing leukocytes.
Aqueous CO2 gradients for air–sea flux estimates

The concentration of gaseous carbon dioxide (CO2) in surface seawater is a fundamental control on the CO2 flux between the ocean and atmosphere. However, the concentration gradient in the aqueous mass boundary layer determines the magnitude and direction of the flux. The gradients of CO2 in the aqueous mass boundary layer cannot be measured directly and are usually inferred from partial pressures or fugacities of CO2 (fCO2) in the air and water. In addition to the fCO2, the temperatures at the top and bottom of the aqueous mass boundary layer must be known to determine the thermodynamic driving force of CO2 gas transfer. Expressing the gradient in terms of the aqueous CO2 concentration, [CO2aq], also avoids some conceptual ambiguities. In particular, expressing the CO2 as a fugacity, which is defined relative to the gas phase, when the gas exchange rate is controlled in the aqueous mass boundary layer often leads to errors in interpretation with respect to changes in boundary layer temperature. As a result the enhanced CO2 flux caused by the cool skin effect appears to be overestimated. Apart from the difficulties estimating the temperature at the top and bottom of the aqueous mass boundary layer, the temperature dependence of solubility and fugacity of CO2 is uncertain to the degree that it can bias air–sea CO2 flux estimates. The CO2aq at the surface, [CO2aq0], is at equilibrium with the atmospheric CO2 level. As [CO2aq0] is strongly temperature dependent, it will be significantly higher at high latitude compared to low latitude, while atmospheric CO2 levels show much less of a gradient.
The effects of role perceptions on employee satisfaction and performance moderated by employee ability

Abstract Role ambiguity and role conflict were hypothesized to be negatively related to employee satisfaction and performance. Previous research, however, had revealed that these two types of role perceptions were not always negatively related to satisfaction and performance. Furthermore, when the predicted negative relationships were found, the magnitudes of the relationships varied widely. In this study employee ability was hypothesized to reduce the negative relationships between role perceptions and satisfaction and performance. In addition, the effect of ability was hypothesized to be moderated by organization level. The results generally failed to support the hypothesized relationships. There were, however, two significant interactions that partially supported one hypothesis. Employees with high ability were less affected by role ambiguity than employees with low ability.
A comparison of whole body vibration and moist heat on lower extremity skin temperature and skin blood flow in healthy older individuals

Background Tissue healing is an intricate process that is regulated by circulation. Heat modalities have been shown to improve skin circulation. Recent research supports that passive vibration increases circulation without risk of burns. Study purpose is to compare and determine effects of short duration vibration, moist heat, and a combination of the two on skin blood flow (SBF) and skin temperature (ST) in elderly, non-diabetic individuals following short-term exposure.
Astrocyte calcium elevations: Properties, propagation, and effects on brain signaling

The possibility that astrocytes are involved in brain signaling began to emerge in the late 1970s, when it was first shown that astroglia in vitro possess numerous receptors for neurotransmitters. It was later demonstrated that cultured astroglia and astrocytes in situ respond to neurotransmitters with increases in intracellular second messengers, including cyclic AMP and calcium. Astrocyte calcium responses have since been extensively studied both in culture and in intact tissue. We continue to gather information regarding the various compounds able to trigger astrocyte calcium increases, as well as the mechanisms involved in their initiation, propagation as a calcium wave within and between astrocytes, and effects on signaling within the brain. This review will focus on each of these aspects of astrocyte calcium regulation, and attempt to sort out which effects are more likely to occur in developmental, pathological, and physiological conditions. While we have come far in our understanding of the properties or potential of astrocytes' ability to signal to neurons using our array of pharmacological tools, we still understand very little regarding the level of involvement of astrocyte signaling in normal brain physiology.
In vivo detection of clonally derived methicillin-resistant/methicillin-susceptible Staphylococcus aureus strains is not a rare event.

Daskalaki and colleagues ([3][1]) recently reported the identification of mixed clonally derived Staphylococcus aureus isolates that were responsible for recurrent bacteremia and showed important genetic rearrangements during the time frame of an infection. At our institution, in addition to
Generation of Nanoparticles of Controlled Size Using Ultrasonic Piezoelectric Oscillators in Solution

We demonstrate the operation of a device that can produce chitosan nanoparticles in a tunable size range from 50-300 nm with small size dispersion. A piezoelectric oscillator operated at megahertz frequencies is used to aerosolize a solution containing dissolved chitosan. The solvent is then evaporated from the aerosolized droplets in a heat pipe, leaving monodisperse nanoparticles to be collected. The nanoparticle size is controlled both by the concentration of the dissolved polymer and by the size of the aerosol droplets that are created. Our device can be used with any polymer or polymer/therapeutic combination that can be prepared in a homogeneous solution and vaporized.
Highly Congested Nondistorted Diheteroarylnaphthalenes: Model Compounds for the Investigation of Intramolecular π-Stacking Interactions

The rigid, highly congested structure of 1,8-diacridylnaphthalenes has been studied in solution and in the solid state. The unique geometry of these compounds forces the acridyl rings to undergo face-to-face interactions while rendering T-shaped orientations and face-to-edge interactions impossible. Crystallographic analysis shows that splaying between the heteroaryl rings decreases while twisting between the cofacial rings increases as the acridyl nitrogens of the 1,8-diacridylnaphthalene framework are subsequently oxidized. The peri-acridyl rings are slightly splayed but remain perfectly planar in all cases. The significant decrease in splaying indicates enhanced π−π-attraction between the electron-rich acridyl N-oxide moieties, which is in agreement with recently reported symmetry-adapted perturbation theory calculations. The π-stacking and the molecular geometry between the acridyl rings observed in the solid state have been confirmed through in-solution studies showing characteristic proton NMR upfie...
The role of adaptations in two-strain competition for sylvatic Trypanosoma cruzi transmission.

This work was partially supported by a 2008 Norman Hackerman Advanced Research Program grant, and by the National Science Foundation under Grant DMS-1020880l; European Union Seventh Framework Programme [FP7/2007–2011] under grant agreement no. 219266. Through MTBI, this research has been partially supported by grants from the National Security Agency, the National Science Foundation, the T Division of Los Alamos National Lab (LANL), the Sloan Foundation, and the Office of the Provost of Arizona State University
Whole farm case studies and focus groups: Participatory strategies for agricultural research and education programs

Research and extension personnel are beginning to look for new strategies to involve more farmers and the non-farm public in their programs. Two approaches we have used are wholefarm case studies (WFCS) and focus groups. WFCS in Oregon and Washington led to several research and educational programming ideas that are currently being pursued in both states. A focus group to study water quality, nitrate leaching and farming practices in Skagit County, Washington is one outcome of the WFCS process. It is made up of 16 people, including farmers, university personnel, members of environmental groups, and government representatives.We review these two complementary participatory strategies for systems-oriented sustainable agriculture research and education programs. Both have been very useful for building problem-solving partnerships between the land-grant universities and agricultural and environmental constituents in our area. Noteworthy outcomes include: complementary applied on-farm and experiment station research; farming systems analysis; public education; new linkages with environmental and agricultural interest groups; additional grant funds to address identified priority issues; and interdisciplinary teams that cut across the biological and social sciences and include diverse citizen representation.
Developing qualitative LC-MS methods for characterization of Vaccinium berry Standard Reference Materials

Standard Reference Materials (SRMs) offer the scientific community a stable and homogenous source of material that holds countless application possibilities. Traditionally, the National Institute of Standards and Technology (NIST) has provided SRMs with associated quantitative information (certified values) for a select group of targeted analytes as measured in a solution or complex matrix. While the current needs of the SRM community are expanding to include non-quantitative data, NIST is attempting to broaden the scope of how and what information is offered to the SRM community by providing qualitative information about biomaterials, such as chromatographic fingerprints and profiles of untargeted identifications. In this work, metabolomic and proteomic profiling efforts were employed to characterize a suite of six Vaccinium berry SRMs. In the discovery phase, liquid chromatography-tandem mass spectrometry (LC-MS/MS) data was matched to mass spectral libraries; a subsequent validation phase based on multiple-reaction monitoring LC-MS/MS relied on both retention time matching of authentic standards along with fragmentation data for a qualitative overview of the most prominent organic compounds present. Definitive and putative identifications were determined for over 70 metabolites based on reporting guidelines set forth by the Metabolomics Standards Initiative (Metabolomics 3(3):211-221, 2007), and the capability of electrospray ionization mass spectrometry (ESI-MS) to profile untargeted metabolites within a complex matrix using mass spectral matching is demonstrated. Bottom-up proteomic analyses were possible using peptide databases translated from expressed sequence tags (ESTs). Homology searches provided identification of novel Vaccinium proteins based on homology to related genera. Chromatographic fingerprints of these berry materials were acquired for supplemental qualitative information to be provided to users of these SRMs. An unbounded set of qualitative data about a biomaterial is a valuable complement to quantitative information traditionally provided in NIST Certificates of Analysis.
Paleolithic art demystified

This huge, lavishly-illustrated volume constitutes, in my opinion, a ‘genre of one.’ There is nothing on Paleolithic art, to my knowledge, remotely like it. Guthrie, a Professor Emeritus at the University of Alaska, is a paleontologist, natural historian, artist and big-game bowhunter. All of these have a role in this intensely personal voyage through the convoluted passages of ancient cave art – he even includes some of his own poetry. But do not be misled by his flights of fancy. This is a dead-serious book, one of the most comprehensive catalogs of prehistoric art ever assembled, with over 3000 images.
Effects of postprandial state and mesenteric blood flow on the repeatability of MR elastography in asymptomatic subjects

Purpose To determine the repeatability of stiffness measurements in the liver using MR elastography (MRE) during the fasted and fed states. MRE has gained increased recognition as a noninvasive method to quantify fibrotic changes in the liver. It is well known that eating increases splanchnic blood flow, and fasting status of patients has been recognized as a factor that may affect hepatic stiffness measured with MRE. Materials and Methods Hepatic MRE stiffness and flow through the superior mesenteric vein (SMV) were measured in 12 healthy subjects in fasted and fed states, and measurements were repeated 5 weeks later. A linear mixed effects model was used to estimate the sources of variability in the data, which included day (exams on different days) and subject. Sources were combined to calculate the overall standard deviation of a single MRE measurement. Results The total within-subject standard deviation of an MRE exam is 8.5% (standard error [SE] = 1.7%) or 9.0% (SE = 1.8%) for fasted and fed states, respectively. No significant differences between fasted/fed state stiffness and no correlation between hepatic stiffness and SMV flow were observed. Conclusion As seen in this smaller population, healthy subjects scanned in a known fasted or fed state provide repeatable stiffness estimates with no relationship to SMV flow. J. Magn. Reson. Imaging 2011;33:239–244. © 2010 Wiley-Liss, Inc.
4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2, 4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine: a potent, orally bioavailable CRF(1) receptor antagonist.

Structure−activity studies in the pyrazolo[1,5-a]-1,3,5-triazine series led to the discovery that compound 11i (DMP696) is a potent hCRF1 receptor antagonist (Ki = 1.7 nM vs 7.5 nM for α-hel-CRF(9−41), hCRF1 adenylate cyclase IC50 = 82 nM vs 286 nM for α-hel-CRF(9−41)). Compound 11i has excellent oral pharmacokinetic profiles in rats and dogs (37% and 50% oral bioavailabilities, respectively). This compound displays good activity in the rat situational anxiety model (MED = 3 mg/kg (po)), whereas a literature standard 1 (CP154526-1) was inactive (MED > 30 mg/kg (po)). Analogue 11i reduced stereotypical mouth movements in rhesus monkeys by 50% at 21 mg/kg (po) using the human intruder paradigm. Overall, the profile of pyrazolotriazine 11i indicates that hCRF1 receptor antagonists may be anxiolytic agents, which have reduced motor side effect profiles.
Aerosol Deposition Study of Subject-Specific Upper Respiratory Model

An accurate model of the human respiratory system allows health professionals to gain insight into the interactions between particulate matter (PM) and the exposed surfaces of the lung airways. Respiratory dose simulations and modeling are frequently used for evaluating health effects of inhaled toxic substances [1–4] and for analyzing the risk potentials of inhaled toxic or harmful PM such as vehicle emissions [4,5].Copyright © 2012 by ASME
Interplay between Rolling and Firm Adhesion Elucidated with a Cell-Free System Engineered with Two Distinct Receptor-Ligand Pairs

The firm arrest of leukocytes to the endothelium during inflammation is known to be mediated by endothelial intercellular adhesion molecules (ICAMs) binding to activated integrins displayed on leukocyte surface. Selectin-ligand interactions, which mediate rolling, are believed to be important for facilitating firm adhesion, either by activating integrins or by facilitating the transition to firm adhesion by making it easier for integrins to bind. Although leukocytes employ two distinct adhesion molecules that mediate different states of adhesion, the fundamental biophysical mechanisms by which two pairs of adhesion molecules facilitate cell adhesion is not well understood. In this work, we attempt to understand the interaction between two molecular systems using a cell-free system in which polystyrene microspheres functionalized with the selectin ligand, sialyl LewisX (sLeX), and an antibody against ICAM-1, aICAM-1, are perfused over P-selectin/ICAM-1 coated surfaces in a parallel plate flow chamber. Separately, sLeX/P-selectin interactions support rolling and aICAM-1/ICAM-1 interactions mediate firm adhesion. Our results show that sLeX/aICAM-1 microspheres will firmly adhere to P-selectin/ICAM-1 coated surfaces, and that the extent of firm adhesion of microspheres is dependent on wall shear stress within the flow chamber, sLeX/aICAM-1 microsphere site density, and P-selectin/ICAM-1 surface density ratio. We show that P-selectin's interaction with sLeX mechanistically facilitates firm adhesion mediated by antibody binding to ICAM-1: the extent of firm adhesion for the same concentration of aICAM-1/ICAM-1 interaction is greater when sLeX/P-selectin interactions are present. aICAM-1/ICAM-1 interactions also stabilize rolling by increasing pause times and decreasing average rolling velocities. Although aICAM-1 is a surrogate for β2-integrin, the kinetics of association between aICAM-1 and ICAM-1 is within a factor of 1.5 of activated integrin binding ICAM-1, suggesting the findings from this model system may be insightful to the mechanism of leukocyte firm adhesion. In particular, these experimental results show how two molecule systems can interact to produce an effect not achievable by either system alone, a fundamental mechanism that may pervade leukocyte adhesion biology.
The Empirical Study of the Persuasive Effects of Evidence The Status After Fifty Years of Research

This article presents a review of the development of research on the persuasive effects of evidence. Focusing on research dealing with the impact of evidence on persuasive communication, this review makes three related arguments. First, past claims about the inconsistency in evidence research are largely mistaken when testimonial assertion evidence is involved; second, the conditions under which evidence should produce maximal effects can be understood by reference to Petty and Cacioppo's Elaboration Likelihood Model; finally, persuasive effects are surprisingly consistent across evidence types when careful comparison of operational definitions, rather than conclusions, is undertaken.
On correlation treatments of the nickel atom

Abstract Moller-Plesset perturbation theory to finite order in all terms (MP4(SDTQ)) and to infinite order in selected terms (CCD) is used to examine the importance of higher-order excitations in correlation treatments of the nickel atom. Allowing for relativistic effects, good agreement with experiment is achieved for the 3 F- 3 D splitting but not for the 3 F- 1 S separation. The MP perturbation expansion exhibits slow convergence for the nickel atom, and suggests that the coupled cluster (CC) technique will be necessary to obtain a balanced description of the atomic states.
Germ line differentiation factor Bag of Marbles is a regulator of hematopoietic progenitor maintenance during Drosophila hematopoiesis

Bag of Marbles (Bam) is a stem cell differentiation factor in the Drosophila germ line. Here, we demonstrate that Bam has a crucial function in the lymph gland, the tissue that orchestrates the second phase of Drosophila hematopoiesis. In bam mutant larvae, depletion of hematopoietic progenitors is observed, coupled with prodigious production of differentiated hemocytes. Conversely, forced expression of Bam in the lymph gland results in expansion of prohemocytes and substantial reduction of differentiated blood cells. These findings identify Bam as a regulatory protein that promotes blood cell precursor maintenance and prevents hemocyte differentiation during larval hematopoiesis. Cell-specific knockdown of bam function via RNAi expression revealed that Bam activity is required cell-autonomously in hematopoietic progenitors for their maintenance. microRNA-7 (mir-7) mutant lymph glands present with phenotypes identical to those seen in bam-null animals and mutants double-heterozygous for bam and mir-7 reveal that the two cooperate to maintain the hematopoietic progenitor population. By contrast, analysis of yan mutant lymph glands revealed that this transcriptional regulator promotes blood cell differentiation and the loss of prohemocyte maintenance. Expression of Bam or mir-7 in hematopoietic progenitors leads to a reduction of Yan protein. Together, these results demonstrate that Bam and mir-7 antagonize the differentiation-promoting function of Yan to maintain the stem-like hematopoietic progenitor state during hematopoiesis.
Increased toxicity of benzo(a)pyrene-7,8-dihydrodiol in the presence of polychlorobiphenylols.

Abstract Benzo( a )pyrene (BaP) and polychlorinated biphenyls (PCBs) often co-exist in contaminated environments. Polychlorobiphenylols (OH-PCBs), formed by CYP-dependent monooxygenation of PCBs, are potent inhibitors of the glucuronidation of hydroxylated BaP metabolites. We hypothesized that OH-PCBs could drive the biotransformation of (−)BaP-7,8-dihydrodiol (BaP-7, 8-D) away from detoxication and towards formation of the reactive metabolite. A mixture of five OH-PCBs with 4–6 Cl atoms was infused into isolated, perfused, biliary intact livers ( n =3 fish) removed from 3-methylcholanthrene-induced channel catfish. Controls ( n =3) were infused with vehicle. Subsequently, [ 3 H]-BaP-7, 8-D was infused into each liver and bile was collected for 1 h. The livers were taken for analysis of metabolites and DNA adducts. Induction status was confirmed by EROD assay. Bile was analyzed for metabolites. It was found that preinfusion of the mixture of OH-PCBs reduced the extent of glucuronidation of BaP-7, 8-D and increased the formation of DNA adducts 5-fold over controls. GSH conjugates, tetrols and triols were increased in the OH-PCB-infused fish, providing further support for our hypothesis that if the glucuronidation were inhibited, CYP-dependent activation would increase. These studies suggest a mechanism for synergy of toxicity of PAH and PCBs.
The Political Voice of Clergy

Whether clergy are influencing opinions, setting agendas, mobilizing, or empowering parishioners, the primary mechanism is public speech. Using a national sample of 2,400 ELCA (Lutheran) and Episcopal Church clergy, surveyed in the late summer and fall of 1998, we explore the nature, frequency, and determinants of clergy public speech. We find that clergy public speech is relatively pervasive and conveys a significant amount of normative judgments about the workings of the policy process. In assessing its determinants, we find that clergy public speech is a product of personal motivation situated in an environment conducive to action, which includes the pressures exerted by the congregation, national political cues, and community. Specifically, we find that clergy speak out publicly on political issues when mobilized, but also as a way to represent their congregations in the public sphere and to motivate members to add their distinctive voices to public debate.
Multiple forms of estrogen receptor-α in cerebral blood vessels: regulation by estrogen

The cerebral vasculature is an important target tissue for estrogen, as evidenced by significant effects of estrogen on vascular reactivity and protein levels of endothelial nitric oxide synthase a...