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Spin-Labeled Peptide Antibiotics Feix R01GM068829
Hemolysis, Lipid Oxidation and Vascular Dysfunction in Sickle Cell Disease Flewelen F31HL092773
Mechanisms of Metabolism of S-Nitrosothiols Hogg R01GM55792
Development of Biomedical EPR Instrumentation Hyde R01EB002052
HFSS Modeling in Aqueous Biological Samples for EPR Hyde R01EB001417
National Biomedical EPR Center Hyde P41EB001980
Advanced Instrumental Development Core: MCW. (Dartmouth College) Hyde U19AI091173
Advanced Research and Development of Chemical, Biological, Radiological, and Nuclear Medical Countermeasures Hyde HHSO100201100024C
Mitochondria-targeted Agents in Breast Cancer Kalyanaraman R01CA152810
Neuro-protection by Mitochondria-Targeted Antioxidants Kalyanaraman R01NS039958
Nitric Oxide Mediated Oxidation/Nitration in Membranes Kalyanaraman R01HL63119
Role of iNOS, Nitric Oxide & Arginase in Statin-Mediated Toxicity in Cancer Cells Kalyanaraman R01CA125112
Site-Directed Spin Labeling of ArnT Klug R01AI058024
Spin Labeling of MsbA Klug R01GM070642
Acquisition of Q-Band Pulsed EPR Capability Klug 1S10OD011937
Is Cholesterol Crystalline Domain a Barrier to Oxygen Transport in the Eye Lens? Subczynski R03TW008052
Infectious disease remains the leading cause of mortality worldwide. A significant aspect of this problem is the continuing rise of infections that are resistant to most, if not all, conventional antibiotics. To meet this challenge it is essential that new drug targets be identified, and new classes of antibiotics developed. Over the past two decades a large number of naturally-occurring antimicrobial peptides have been found in both vertebrate and invertebrate species that are capable of providing a rapid and broad-spectrum response against a wide variety of pathogens. Because the specificity of these peptides is based on recognition of general properties of the cell membrane the emergence of resistance is exceedingly rare, making them ideal starting points for the development of new antibiotics. A limiting factor in our ability to further enhance the efficacy of these peptides is the lack of detailed knowledge about their mechanism of action, and in particular the manner in which they interact with and disrupt the cell membrane. The goal of this proposal is to develop a clear understanding of peptide-membrane interactions and mechanism of action for a promising and well-defined class of antimicrobial peptides that are synthetic hybrids of the insect peptide cecropin A and the bee-venom peptide, melittin. Site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy provides a powerful and well-established approach for the analysis of peptide-membrane interactions that is uniquely suited to providing such a detailed understanding. Specifically, we will use both conventional and pulsed SDSL EPR to measure membrane binding affinities, determine structure, topology, degree of membrane insertion, and peptide-peptide interactions for cecropin-melittin hybrid peptides in model membranes that mimic both eukaryotic and bacterial membranes and in intact cells. These properties will be related to antibiotic efficacy against a panel of drug-sensitive and drug-resistant bacteria. We will systematically modify peptide composition to define relationships between sequence, membrane interactions, and antibacterial efficacy. Finally, we will synthesize and evaluate the antibiotic efficacy and membrane interactions of peptidomimetic analogs composed of non-natural beta-amino acids. These studies will significantly advance our understanding of the mechanism of action of antimicrobial peptides, and contribute to the further development of peptide and peptidomimetic antibiotics.
Sickle cell disease is one of the most commonly inherited blood disorders among Americans of Hispanic and African descent. Sickle red cells are more prone to hemolysis than normal red cells, resulting in increased levels of plasma hemoglobin, a known pro-oxidant. The vascular complications are likely due to this increase in oxidative stress. The long-term objective of this project is to understand the relationship between hemolysis, lipid oxidation and vascular dysfunction in sickle cell disease. This objective will be tested using the following Specific Aims: 1) Measure the level and oxidation state of plasma hemoglobin using novel techniques, a) Plasma hemoglobin levels and oxidation state will be determined using electron paramagnetic resonance spectroscopy. b) Hydroethidine will serve as a probe to detect plasma hemoglobin through a one-electron oxidation of HE in normal and sickle plasma and products resolving using HPLC techniques. 2) Measure oxidative products and the potential to support lipid oxidation in normal and sickle plasma, a) F2-isoprostanes, a vasoconstrictive lipid oxidation product, will be compared in both sickle cell and normal control plasma using liquid chromatography and mass spectrometry. b) The oxidation potential of sickle cell and normal plasma will be measured using an oxygen electrode-based method, c) The degree of correlation between these measurements and plasma hemoglobin levels will be examined. 3) Examine the relationship between hemolysis and vascular dysfunction using histological and vascular response assays in transgenic mouse models, a) Mouse plasma hemoglobin levels will be measured using EPR spectroscopy and an HE oxidation assay, b) Plasma F2-isoprostane levels and other oxidation potential will be measured using methods developed above; c) Measure vessel responsiveness using a facialis artery preparation; d) Analyze nitrotyrosine levels by western blot and immunohistochemistry; e) Examine histological changes using hematoxylin and eosin (H&E). The RELEVANCE to health in the proposed research project is gaining a more complete understanding of the role of hemoglobin and oxidative damage in the pathophysiology of sickle cell disease. Current treatments for an acute sickle cell crisis are mainly palliative, as patients seek medical care when complications present themselves. When completed, this research should lead to the discovery and exploitation of a new therapeutic target to aid in the treatment of sickle cell disease.
It has become apparent that S-nitrosothiols (RSNO), biological metabolites of nitric oxide and thiols, play divers roles in potentiating and modulating the effects of nitric oxide. Very little is known concerning the metabolism of RSNO. It is often assumed that these compounds spontaneously liberate nitric oxide and RSNO are commercially available as nitric oxide donors. However, this assumption is in error and RSNO are stable compounds that require an addition agent to promote decomposition. This project will investigate the molecular interactions of S-nitrosothiols with biological targets to understand more fully their role in biological systems. This will be done by addressing three hypotheses with associated specific aims: 1) The observations that protein thiols are the major intracellular targets of RSNO has led us to propose that the modification of protein thiol residues by RSNO is controlled by the local environment of the protein thiol. This specific aim will ask the crucial question of what makes a particular thiol susceptible to control by RSNO. II) Our observations that heme proteins can directly reduce S-nitrosothiols has led us to propose that ferrous heme groups are a major site of RSNO metabolism. In this specific aim we will explore the role played by heme moieties in the control of nitric oxide release from RSNO. III) Our observations concerning the metabolism of RSNO by endothelial cells has led us to propose that cells contain an active metabolic pathway for the metabolism of RSNO. These studies will investigate the mechanism of RSNO metabolism by various cell types. The biochemistry of RSNO has been linked to asthma, inflammation, hypertension, apoptosis and atherosclerosis. It is envisioned that this study will yield new insights into the roles played by these important compounds and aid pharmacological development of new and more selectively potent S-nitrosothiols.
The proposal contains five projects that are concerned with pulse (or time-domain) saturation-recovery electron-spin resonance instrumentation and methodology. 1) Digital signal processors and improved time response. 2) 2D saturation recovery. 3) Multifrequency saturation recovery and FIDs. 4) Loop-gap resonators for saturation recovery. 5) Multiquantum readout of saturation recover.
The goal of the proposed work is to improve sensitivity in EPR spectroscopy of aqueous fluid phase samples. There are two themes: (1) multifrequency enhancement from 1 to 35 GHz, and (2) optimization for samples of limited availability (ca., 1 microliter), intermediate availability (ca., 10-20 microliters) and unlimited availability (>100 microliters). This goal will be achieved by optimization of microwave resonator design and by optimization of aqueous sample cell design. The proposal is timely because of recent advances in software for finite element modeling of electromagnetic fields, coupled with greatly improved computing speeds. Computer aided design will be used for resonators, sample cells and field modulation coils, followed by experimental evaluation.
The broad aim of the National Biomedical EPR Center is to create and maintain a comprehensive center with balance in all five categories of a Research Resource:
(1) Resonator development
(2) W-band enhancement
(3) Broadband digital detection, signal analysis, and archiving in EPR spectroscopy
(4) Microwave oscillator development
(5) H1||H0 (parallel mode) EPR at Q- and W-band
(6) X-band/Q-band spin trapping methodology development: Structure/function aspects of NOS-generated radicals
(1) Graduate and post-graduate training
(2) Training established investigators
(3) Training of young investigators
The functions of a Research Resource will be accomplished with expertise in the three main application areas of EPR spectroscopy: free radicals, transition metals, and spin labels and with competence in EPR instrumental development.
Awardee Organization: DARTMOUTH COLLEGE
Project Number: 5U19AI091173-03 Sub-Project ID: 6786
Contact PI / Project Leader: HYDE, JAMES S
Abstract Text:
This core provides input from what is generally agreed to be the leading EPR instrumental development site in the world, the National Biomedical EPR Center at the Medical College of Wisconsin (MCW). The role of this core will be to provide leadership in the development of specific aspects of the technology needed to accomplish the goals of the CMCR. These developments will be carried out in collaboration with the projects and with the instrumental Core at Dartmouth, to facilitate the development of the best possible o prototype instruments for EPR dosimetry. The contributions of the core at MCW are described in four specific aims. Specific Aim 1 (50% of effort) is the Development of resonators for measurements at X-Band in vivo for nails and teeth; this will be the most extensive project and will focus on exploiting the breakthrough achieved in initial collaborative studies where for the first time, resonators that operate at the very sensitive X-Band frequency were successfully used to make measurements in vivo. This development is at the heart of project 3. During the course of the grant this core will attempt to make analogous resonators that can be used for in vivo tooth dosimetry, which could dramatically improve the already impressive sensitivity of this approach (Project 1). Specific Aim 2 (25% of effort) - Development of instrumentation to support measurements at X-Band, will especially focus on development of specifically designed microwave bridges that will facilitate both Projects 2 &3. These developments will be carried out in collaboration with a longstanding collaborative partner of both Dr. Hyde and Dr. Swartz, Dr. Froncisz of the Jagiellonian University in Krakow (Dr. Froncisz's support will come via a purchase agreement. Specific Aim 3 (20% of effort) - Improvements in resonators and bridges for measurements at L-Band. This core will similarly work with Dartmouth and Krakow in the development of improved L-Band bridges, in support of Project 1. It also will facilitate resonator development in project 1 by use of the very sophisticated modeling techniques that are highly developed at MCW, which enable different configurations of resonators to e=be rigorously evaluated so that construction can be focused on designs that are likely to be successful Specific Aim 4 -(5 % of effort) support of multifrequency studies will available an exceptional set of EPR spectrometers that can be of value to all three projects in helping to elucidate the characteristics of potentially overlapping components of EPR spectra.
5R01CA152810-03 Contact PI / Project Leader: KALYANARAMAN, BALARAMAN MEDICAL COLLEGE OF WISCONSIN
ABSTRACT We will develop mitochondria-targeted antioxidants (MTAs) and imaging probes that will mitigate cardiotoxicity and enhance antitumor efficacies of chemotherapeutic drugs. We will use doxorubicin (DOX), a front-line antitumor agent in breast cancer treatment. DOX causes delayed dose-dependent cardiotoxicity. Clinically, this side effect is managed with conventional antioxidants and iron chelators. This proposal provides a new adjuvant approach in breast cancer chemotherapy. Its genesis is based upon the following discoveries: 1) MTAs (e.g., Mito-Q, a synthetic drug analog of an endogenous antioxidant, Co-enzyme-Q, present in the mitochondrial respiratory chain) inhibit DOX-mediated cardiotoxicity in a preclinical animal model and in cardiomyocytes, and 2) MTAs (Mito-Q and Mito-CP, a nitroxide targeted to mitochondria) cause antiproliferative and cytotoxic effects in breast cancer cells (MCF-7 and MDA-MB-231) but not in non- transformed breast epithelial cells (MCF-10A) and significantly enhance DOX-induced breast cancer cell toxicity. We hypothesize that mitochondria-targeted antioxidants enhance DOX-mediated antitumor effects but attenuate DOX cardiotoxicity. Response to chemotherapy will be monitored by using the mitochondria-targeted technetium-labeled imaging agents (99mTc-Mito10-MAG3) in a chemically-induced breast carcinoma animal model. Specifically, we will: (i) Investigate the cytotoxic effects of MTAs alone and with DOX in breast cancer cells, (ii) Assess the cytotoxic effects of MTAs and DOX in breast cancer cells overexpressing multi-drug resistant protein, (iii) Evaluate the adjuvant chemotherapeutic effects of MTAs and DOX in an in vivo breast cancer model, and (iv) Assess the cardioprotective and oxy-radical scavenging effects of MTAs in DOX- treated cardiomyocytes and in DOX-treated rat cardiomyopathy model. These aims will be accomplished using HPLC-fluorescence and HPLC-electrochemical detection techniques, scintimammography and echocardiography. Abnormal generation of reactive oxygen species will be detected using novel species- and target-specific probes. We will develop innovative MTA-based adjuvant therapy that can be used to inhibit DOX-induced cardiotoxicity. This research may potentially lead to novel ways for improving the therapeutic efficacy of DOX and other antitumor agents used in breast cancer treatment.
The long-term goal of this multiple PI proposal is to develop neuroprotective strategies that involve synthesis and testing of mitochondria-targeted antioxidants in a preclinical mouse model of Parkinson's Disease (PD) that can be subsequently translated to patients with PD. In this proposal, we have combined the expertise and experience of individuals in synthetic organic chemistry, free radical biology, neuropharmacology, and neurotoxicology from two institutions, the Medical College of Wisconsin and Iowa State University. This proposal is based on the discovery that mitochondria- targeted antioxidants (MTAs) inhibit oxidative stress and neuronal damage in 1-methyl-4- phenylpyridinium (MPP+) treated neuronal cell culture models of PD as well as in 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) animal models of PD. We hypothesize that MTAs provide an effective neuroprotective strategy for treatment of PD. As a corollary, we propose that MTAs attenuate mitochondria-derived reactive oxygen and nitrogen species (ROS/RNS), thereby protecting against inactivation of key redox sensors in response to mitochondrial neurotoxin exposure. Specifically, we will: (i) Design and synthesize MTAs and assess their cytoprotection in neuronal cell culture models of PD, (ii) Determine the molecular mechanisms of cytoprotection of MTAs in neuronal cell culture models of PD, (iii) Assess the neuroprotective effects of MTAs in a well-established preclinical MPTP mouse model of PD, (iv) Determine the activation/inactivation of key redox targets in mitochondria in response to MTA treatment in the preclinical MPTP mouse model, and (iv) Investigate the long-term tolerability of MTAs during chronic treatment in the mouse model. We will use several analytical techniques (low-temperature EPR, HPLC-fluorescence and electrochemical detection, HPLC/MS, proteomics) to detect and quantitate ROS/RNS, molecular biological approaches (apoptosis measurements, transcription factor translocation) to define the molecular mechanisms, and neurobehavioral and histopathological analyses to evaluate the neuroprotective effects. Abnormal generation of mitochondrial ROS/RNS in response to environmental toxins has been implicated in the pathogenesis of PD. Numerous antioxidants and iron chelators have been used with partial success in experimental animal models of PD. Emerging literature suggests that antioxidants specifically targeted to mitochondria might serve as promising neuroprotectants for treatment of PD. In this proposal, we will assess the neuroprotective efficacy of several novel MTAs in a cell culture and preclinical mouse model of PD. Systematic characterization of neuroprotective properties and long-term tolerability of novel MTAs in both cell culture and animal models will yield comprehensive preclinical data for the clinical development of efficacious mitochondria-targeted antioxidant therapies for PD. PUBLIC HEALTH RELEVANCE: Parkinson's Disease (PD) is a debilitating neurodegenerative disease. Effective treatment to intervene the progression of neurodegenerative processes in PD remains unavailable. Using a cell culture and a mouse model of PD, we propose to develop a "mitochondria-targeted" antioxidant - based neuroprotective strategy for treating PD. Proposed studies which bring together chemical and neuropharmacological expertise from two institutions (Medical College of Wisconsin and Iowa State University), will help us develop efficacious mitochondria-targeted antioxidants for treatment of PD as well as understand the possible neuroprotective mechanisms of these novel class of agents.
Parkinson's Disease (PD) is a debilitating neurodegenerative disease. Effective treatment to intervene the progression of neurodegenerative processes in PD remains unavailable. Using a cell culture and a mouse model of PD, we propose to develop a "mitochondria-targeted" antioxidant - based neuroprotective strategy for treating PD. Proposed studies which bring together chemical and neuropharmacological expertise from two institutions (Medical College of Wisconsin and Iowa State University), will help us develop efficacious mitochondria-targeted antioxidants for treatment of PD as well as understand the possible neuroprotective mechanisms of these novel class of agents.
Increased levels of nitrotyrosine and nitrated proteins have been detected in a variety of pulmonary and cardiovascular diseases, and in neurodegenerative and chronic inflammatory disorders. The overall objective of this R01 application is to obtain new mechanistic insight into how the hydrophobic interior of biological membranes facilitates oxidation and nitration reactions of reactive nitrogen species (RNS), such as peroxynitrite (ONOO or ONOOH) or nitrogen dioxide radical (NO2). This proposal is based on the following recent discoveries: 1) peroxynitrite can cross lipid membranes through anion transport channels or passive diffusion at rates significantly faster than their reaction with any other target molecule in the aqueous phase. 2) The reaction between NO and O2 is significantly faster in the membrane interior. 3) Peroxynitrite and NO2 cause extensive nitration of alpha-tocopherol in membranes under conditions where tyrosine nitration in the aqueous phase was negligible. The investigators hypothesize that nitration of phenols and nitrosation of thiols by RNS in biological systems is increased in a hydrophobic environment. To investigate the nitration and nitrosation reactions in membranes, they will synthesize tyrosylated lipid and tyrosine- or cysteine-containing peptides that are anchored at defined locations in the lipid bilayer. The investigators will use HPLC, stop-flow spectrophotometry, mass spectrometry, and spin trapping to investigate nitration and nitrosation reactions in membranes. Specifically, the PI will: 1) compare the yields of formation of nitro-gama-tocopherol in membranes and nitrotyrosine in the aqueous phase; 2) detect and characterize nitration products of tyrosylated lipid; 3) determine the mechanism of nitration and nitrosation of tyrosine- and cysteine-containing peptides in membranes; and 4) use nitro-gama-tocopherol or nitrated transmembrane peptide as a marker product to detect peroxynitrite formation from nitric oxide synthase enzymes. This comprehensive study of RNS reactions in simple well-defined model membrane system may provide new mechanistic insight for understanding oxidative and nitrosative stress in pulmonary cardiovascular, neurodegenerative, and inflammatory diseases.
Long-term goal: Statins selectively inhibit the enzyme hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase leading to decreased cholesterol biosynthesis. Several natural and synthetic statins enhanced apoptosis in human lymphoblastoid, myeloma and breast cancer cells. This effect was directly related to their ability to inhibit HMG CoA reductase, which blocks the synthesis of isoprenylated small GTPases, and not by squalene, an immediate precursor of cholesterol. This proposal is based on the discovery that statins cause increased cytotoxicity to breast cancer cells through either increased expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) and/or decreased arginase expression. Statin-mediated cell death was partially reversed by 1400W, a more specific inhibitor of iNOS (NOS II), and by mevalonate, an immediate metabolic product of acetyl CoA/HMG-CoA reductase reaction. Mevalonate supplementation inhibited statin- induced iNOS and NO and restored arginase expression. Fluvastatin dose-dependently inhibited mammary tumor development in an in vivo animal model. Hypotheses to be tested are: (i) statins stimulate NO in breast cancer cells that is responsible for their proapoptotic, tumoricidal and antiproliferative effects, (ii) statins inhibit arginase expression and activity through inhibition of RhoA signaling in breast cancer cells, and (iii) supplementation with sepiapterin (iNOS co-factor) and tocotrienols potentiates statin-induced tumoricidal effects in breast cancer cells and in a rat model. Specific aims: (i) Assess the effects of various statins (lipophilic and hydrophilic) and tocotrienols on breast cancer cell proliferation, and apoptosis, (ii) Determine the induction of iNOS and NO formation in cells treated with statins alone and with sepiapterin and arginase inhibitors, (iii) Define the role of RhoA in statin-mediated NO generation, arginase expression, Nf:B inhibition and antiproliferative effects in breast cancer cells, (iv) Establish a chemopreventive rat model, and evaluate the effectiveness of statins alone and in combination with 3-tocotrienol or sepiapterin. Methods: We will use MCF- 7 and MDA-MB-231 cells and a chemically-induced breast cancer rat model. HPLC techniques will be used to detect and quantitate NO formation in cells treated with statins. Magnetic resonance imaging (MRI) will be used to assess the response to breast cancer therapy in a rat model. Significance: Recent research suggests that statins may prevent various types of cancers including breast cancer. However, the molecular mechanisms by which statins induce breast cancer cell death remain unknown. This proposal will advance our understanding of the chemopreventive and chemotherapeutic ability of statins, alone and in combination with naturally-occurring tocotrienols. Novelty: The overall goal is to elucidate the molecular mechanism by which statins exert antiproliferative/proapoptotic effects in breast cancer cells. The use of tocotrienols to synergistically enhance chemopreventive efficacy of statin in breast cancer cells and breast cancer animal model is innovative. MRI will be used to monitor chemopreventive effects of breast cancer in a rat model. PUBLIC HEARLTH RELEVANCE: Statins are one of the most widely prescribed group of drugs. Recent studies suggest that lipophilic statins may be beneficial for postmenopausal women. Studies also suggest that statins, when combined with other nutrients, become more potent as anticancer drugs. Breast cancer is the leading cause of death in women. Thus, it is both timely and important to understand the mechanism(s) by which statins kill breast cancer cells and to explore the possibility for clinical implementation of statins as chemopreventive drugs.
The ability of bacteria to resist host defense mechanisms is a major contributor to the virulence of bacterial infections. Bacterial resistance to antimicrobial peptides that play a key role in early stages of infection is especially significant. The proteins and substrates involved in the ability of bacteria such as Salmonella typhimurium and Escherichia coil to develop resistance to antimicrobial peptides have recently begun to be identified based on genetic analysis. The most recently identified protein involved in polymyxin resistance is the gene product for an inner membrane protein, termed ArnT, which is responsible for transferring an aminoarabinose moiety onto lipid A, conferring upon the bacteria resistance to the cationic antimicrobial peptide polymyxin. Obtaining a more thorough understanding of structure-function relationships in ArnT will be key to developing strategies to overcome resistance to polymyxin and other cationic peptides. Previous studies of ArnT have all involved in vivo enzymatic activity and genetic analyses to determine its role in polymyxin resistance; the ArnT protein has not previously been purified and studied by any methodology. The goal of this proposal is to study the structure of the purified inner membrane protein ArnT by site-directed spin labeling (SDSL) EPR spectroscopy in order to provide the first structural information on this newly identified transferase. A model is proposed in which the Salmonella typhimurium ArnT transferase is comprised of twelve transmembrane (-helices; this model will become the basis for the structural evaluation of the novel protein ArnT by SDSL EPR spectroscopy followed by the examination of structural changes in ArnT due to substrate recognition. In order to begin providing the first structural information on ArnT, a unique and new membrane protein, the following points will be addressed using SDSL EPR spectroscopy: 1) create and characterize a reactive-cysteine-free construct of ArnT; 2) evaluate the model predicting that ArnT is comprised of twelve transmembrane alpha-helices by nitroxide scanning through a putative transmembrane helical region; 3) explore the overall structural arrangement of ArnT by analyzing small sets of mutations placed within putative transmembrane, surface loop, and substrate binding regions; and 4) monitor local and global structural changes induced by substrate binding. It is anticipated that these studies will provide insights into the local and global structure of ArnT, a previously uncharacterized integral membrane protein, which is of fundamental importance in furthering our understanding of the structure and functional dynamics of membrane proteins.
The class of proteins termed ATP-binding cassette (ABC) transporters is one of the largest found in nature. Their ability, or lack thereof, to move a variety of ligands across a membrane bilayer using energy from ATP is fundamentally important to bacterial physiology and an array of human pathologies. ABC transporters mediate both the import and export of a wide variety of solutes including antibiotics, lipids, chemotherapy agents, sugars, amino acids, salts and metals. MsbA is the ABC transporter for lipid A that is found in the inner membranes of Gram-negative bacteria such as Escherichia coli. Without MsbA present, bacterial cells accumulate a toxic amount of lipid A, which is an essential component of the outer surface of the cell, within their inner membranes. A crystal structure of MsbA was recently obtained that provides an excellent starting point for structural and functional dynamics studies. Although a structure of MsbA is now available, many questions remain concerning its mechanism of transport. The goal of this proposal is to elucidate the conformational dynamics that occur in MsbA, a bacterial ABC transporter, upon binding ATP in its nucleotide binding domain and upon recognition and transport of lipid substrates in its helical core, utilizing site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy techniques. In order to address the proposal that the MsbA homodimer undergoes significant conformational rearrangements upon ATP and lipid binding that are essential to its function as a lipid exporter, the following points will be addressed: 1) evaluate the quaternary structure of MsbA reconstituted into lipid membranes; 2) investigate the conformational dynamics of the MsbA dimer upon ATP binding; and 3) investigate the conformational dynamics of the MsbA dimer upon lipid binding. It is anticipated that these studies will produce valuable insights into the local and global structural dynamics of MsbA as it functions in its role as a lipid transporter.
This application is for an upgrade to Q-band for our current Bruker X-band E580 pulse spectrometer capable of running DEER (double electron-electron resonance), DQC (double quantum coherence), and ENDOR (electron nuclear double resonance) experiments at cryogenic temperatures. The primary use of both the current and upgraded instrument will be to quantitate distance measurements between paramagnetic probes on or within biomedically relevant proteins. The major advantages of upgrading to Q-band (35 GHz) DEER from X-band (9 GHz) DEER are a >10-fold increase in sensitivity and overall higher quality distance data. The improvement in resolution, accuracy, identification, signal intensity and the collection of longer distances will be of considerable benefit to an array of biological projects. Additional advantages of pulsed Q- band over X-band include smaller sample volumes, lower overall sample concentration requirements, and significantly decreased data collection times. Pulsed Q-band ENDOR also provides technological and fundamental benefits over X-band ENDOR. The Q-band resonator allows for significantly higher radio frequency (RF) fields for a given supplied power, which is often the limiting factor in ENDOR sensitivity, and the microwave field is increased at Q-band; these allow for the study of fast-relaxing systems that are not amenable to pulsed X-band or continuous-wave ENDOR. In addition, 14N and 1H ENDOR resonances typically overlap at X-band, yet are readily assigned at Q-band. Each one of these is a remarkable advantage to biological research projects and coupled with the considerable improvement in data accuracy will have a substantial impact on current and future structural biology studies of soluble and membrane proteins and protein complexes. Frequencies higher than Q-band provide little additional benefit to the proposed experiments, thus this upgrade request is for the optimum instrument for long-term pulse EPR spectroscopy use. This type of state-of-the-art Q-band pulsed EPR instrumentation is lacking not only at the Medical College of Wisconsin but in entire the state of Wisconsin. Five major users are identified who will measure long-range distances within proteins and protein complexes. In addition, numerous minor users are identified, each with a need for advanced pulse instrumentation not available in the region. Specifically, the research benefiting from the requested upgrade will contribute to a better understanding of the physiology of disease processes such as epilepsy, arrhythmia, neurological disorders, and cancer, and to the development of novel antibiotics and cancer therapeutic agents. Additional opportunities are expected to be uncovered once the success of the initially proposed projects is evident, opening up further avenues of interdisciplinary science. This upgraded instrumentation capability will immediately and significantly advance the productivity of the projects outlined in this proposal as well as enhance the research environment for the surrounding community.
This research will be done primarily in Krakow, Poland, at the Jagiellonian University in collaboration with Dr. Marta Pasenkiewicz-Gierula as an extension of NIH Grant No. R01-EY015526. Cholesterol, the most prominent sterol of mammalian cells, is located predominantly in the plasma membrane, where it comprises 40-45 mol% of the total lipids. However, in membranes of fiber cells, the cholesterol level is extremely high, showing cholesterol-to-phospholipids mole ratios from 1 to 2 in the cortex of the lens to as high as 3 to 4 in the lens nucleus, which leads to the formation of immiscible cholesterol crystalline domains within this membrane. The long-term objective of this proposal is to achieve a greater understanding of the function of cholesterol in membranes of the eye lens, including the effect on the transport of metabolites, particularly oxygen, within the lens. It is proposed to (1) build computer models of selected domains of the fiber cell membrane, with special attention paid to its cholesterol crystalline domain, which can occupy as much as 50% of the cell surface in the lens nucleus, and (2) calculate the oxygen permeability coefficient across membrane domains arising from an oxygen concentration gradient across the membrane. This will allow testing of the hypothesis that the rigid cholesterol crystalline domain can be a barrier to oxygen transport, which, if true, should help to maintain low oxygen concentration in the eye-lens interior. Finally, it is proposed to (3) calculate profiles of both oxygen concentration and the oxygen translational diffusion coefficient across membrane domains and, based on these profiles, determine their oxygen permeability coefficients. Two methods of evaluation of the oxygen permeability coefficient will be compared, namely one that is based on oxygen flux in an oxygen concentration gradient, and one that depends on the details of oxygen self-diffusion in a membrane at equilibrium. Computer experiments will be performed using molecular dynamics (MD) membrane simulations to provide information that is not available from experimental studies about oxygen permeability, structure, and the dynamics of the cholesterol crystalline domain. When possible, the results of MD simulations will be compared with experimental data acquired by the PI under support of the Parent Grant. PUBLIC HEALTH RELEVANCE: Age-related cataracts are a major cause of blindness in developing countries. The reason for the onset of cataracts is unknown, but a great deal of evidence suggests that an increase in oxygen concentration in the lens interior can lead to the development of cataracts. The proposed studies will generate important fundamental information about the contribution of cholesterol to the process of oxygen transport within the eye lens, which should increase our understanding of the role cholesterol plays and, in turn, help contribute to the prevention of age-related nuclear cataracts.
Cholesterol Crystalline Domain Function in Eye Lens: EPR Spin-Labeling Studies (Subczynski, PI, R01 EY015526)
The cell membrane has a 2-dimensional liquid-like structure containing domains that form and disperse continuously on various time and space scales. Rafts are membrane domains that require lipid interactions for their formation. The long-term objective of this proposal is to better understand the molecular mechanisms by which rafts form, are maintained and disintegrate in biological membranes, in particular in the plasma membrane of fiber cells of the eye lens. Detergent insolubility, which has been used to define rafts biochemically, does not reflect pre-existing structures and organization of the membrane. Furthermore, such an approach is not useful for understanding the size, lifetime and dynamics of the raft-constituent molecules and the raft itself. To address these issues, it is proposed to apply the pulse EPR spin labeling technique "discrimination by oxygen transport (DOT)" for in situ studies of rafts in both model and cell membranes. Since the spin-lattice relaxation time of spin labels is sufficiently long, membrane dynamics can be observed on the time scale 0.1 - 100 mu s. The DOT method permits discrimination of different membrane domains because the collision rate between O2 and the nitroxide moiety of spin labels (oxygen diffusion-concentration product) can be quite different in these domains. Additionally, membrane domains can be characterized by profiles of the oxygen diffusion concentration product in situ without the need for separation. This method is especially suitable for obtaining time-space characteristics of small/transient domains. It is hypothesized that rafts form liquid-ordered domains in the plasma membrane liquid-disordered environment. Membrane lipid composition as well as protein content is expected to modulate raft size and dynamics. The DOT method will be used to test the hypothesis on well-defined model systems in which domain size and the lipid exchange rate will be controlled by membrane lipid composition, selected protein and peptide content, and temperature. Furthermore, it will be used to study domain structure in cell membranes. These studies will include mature and aged fiber cell membranes in which the increased cholesterol/lipid ratio and elevated level of sphingomyelin create conditions favoring the formation of rafts. It is proposed: 1) to detect coexisting liquid-ordered and liquid-disordered domains in membranes containing cholesterol; 2) to evaluate the size and stability of the raft domains in model membranes made from raft-forming mixtures; 3) to examine how membrane anchored proteins and transmembrane alpha-helical peptides affect the organization and dynamics of these lipid raft domains; and 4) to apply the DOT method to look for raft domains in fiber cell plasma membranes of the eye lens during maturation and aging, as well as membrane models of mature, aged and cataractous lenses. Age-related nuclear cataract is a primary cause of blindness in the elderly in third world countries.
Endothelial dysfunction (ED) is a critical event in the pathophysiology of atherosclerosis and other cardiovascular diseases (CVD). The underlying causes of ED have not been fully established, although unbalanced production of nitric oxide (NO) and reactive oxygen production (ROS) are causally involved. Enzymatic production of NO is dependent on optimal basal tetrahydrobiopterin (BH4) levels in the endothelium. Increased availability of the cofactor by genetic manipulation or pharmacological supplementation has been shown to be beneficial, although the mechanisms controlling BH4 in the endothelium are poorly understood. The broad objectives of this renewal is designed to bridge the gap in knowledge and is based upon the hypothesis that altering BH4 metabolism by lipid peroxidation products and ROS has important consequences in normal NO/ROS fluxes and endothelial physiology favoring phenotypical changes associated with atherogenesis. The present proposal is built on three findings: (i) BH4-free endothelial nitric oxide synthase (eNOS) generates ~100 nmoles superoxide/min/mg protein which is inhibited by BH4 (micromolar range); (ii) BH4 depletion in endothelial cells increases superoxide production by calcium-dependent mechanisms; (iii) 4-hydroxy-2-nonenal (HNE) is a potent inhibitor of BH4 synthesis, depletes BH4 and NO, and increases superoxide production in endothelial cells. The evaluation of the consequences of increased superoxide production from eNOS is critical to the implications of NO and ROS oxidant signaling in disease. Specifically we will: 1) establish the mechanisms increasing uncoupled eNOS-dependent superoxide by HNE and peroxides; 2) investigate the influence of BH4 depletion by HNE and peroxides on increased mitochondrial-superoxide release and dysfunction; 3) elucidate the role of BH4 in limiting oxidative damage, mitochondrial dysfunction and changes in cell phenotype. In the execution of this proposal we will use established endothelial cell cultures and also cells isolated from GTPCH-transgenic mice to examine the influence of endogenous variation in BH4 in the endothelial responses which have been linked to protection, "re-coupling" of eNOS and/or additional antioxidant activity. Generally this proposal is aimed at understanding these fundamental mechanisms that should provide the basis for developing new and improved strategies in the prevention and treatment of atherosclerosis and CVD.


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cloud services
Cloud services means services made available to users on demand via the Internet from a cloud computing provider's servers as opposed to being provided from a company's own on-premises servers. Cloud services are designed to provide easy, scalable access to applications, resources and services, and are fully managed by a cloud services provider.
A cloud service can dynamically scale to meet the needs of its users, and because the service provider supplies the hardware and software necessary for the service, there's no need for a company to provision or deploy its own resources or allocate IT staff to manage the service. Examples of cloud services include online data storage and backup solutions, Web-based e-mail services, hosted office suites and document collaboration services, database processing, managed technical support services and more.
Recommended Reading: Webopedia's Cloud Computing Dictionary Resource and Cloud Computing Security Challenges.
The future remains, well, cloudy. But either way: Amazon, look out. Microsoft is gaining fast. Read More »Hype Versus Action in the Developer's World
Often times technologies start as hype but with time become adopted. As a developer or technologist, it is worth reading the hype and knowing the... Read More »Microsoft Hyper-V Network Virtualization Q&A
The top 5 Hyper-V questions with answers provided by Nirmal Sharma, a MCSEx3, MCITP and Microsoft MVP in Directory Services. Read More »
This Webopedia guide will show you how to create a desktop shortcut to a website using Firefox, Chrome or Internet Explorer (IE). Read More »Flash Data Storage Vendor Trends
Although it is almost impossible to keep up with the pace of ongoing product releases, here are three recent highlights in the flash data storage... Read More »15 Important Big Data Facts for IT Professionals
Keeping track of big data trends, research and statistics gives IT professionals a solid foundation to plan big data projects. Here are 15... Read More »
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subset: commoncrawl


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Model Number: T5K65-
The Timex Ironman Sleek Women's All-Day 50-Lap watch is a stylish digital time piece that functions equally well for everyday life and when it's time to slip on your running shoes. This 'Bold' version features bright, vibrant colors and the 'mid-size' feels at home on smaller wrists.
Important Shipping Note: U.S. sales only.
Please include any relevant information such as weekly mileage, training or race pace, or foot type.
Copyright © 2014 Running Warehouse. All Rights Reserved. Contact Us
Site Map | US: 1.800.606.9598 | email@example.com | Careers


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Calamos Asset Management, Inc.
Investment Advice IL, United States
| Nasdaq: CLMS
Similar to: Aberdeen Asset Management Plc, T. Rowe Price Group, Inc., Becker Value Equity Fund
Calamos Asset Management, Inc. is an investment management firm offering equity, fixed-income, convertible and alternative investment strategies. The company serves institutions and individuals via separately managed accounts and open-end and closed-end funds, offering a risk-managed approach to capital appreciation and income-producing strategies. It offers global investment solutions: equity, fixed-income, convertible and alternatives to work with clients multi-asset allocation frameworks. It is the sole manager of Calamos Investments LLC, which owns and manages its operating companies. Calamos Asset Management was founded by John P. Calamos, Sr. on July 23, 2004 and is headquartered in Naperville, IL.


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Home » User account » User account
Latest content
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August 1, 2014 : : alex luyckx
Film Photography Podcast - Episode 108 – August 1, 2014 The internet radio show for people who love to shoot film! Special guest Mark O'Brien. The Argus Camera Company, Yunon DX-3, Wirgin Edinex...
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On the site
©2012 Film Photography Project, LLC. All rights reserved.
All images on this site and their copyrights owned by the photographers.
Images are not to be reprinted or reused without the express permission of the photographer who took them.
Design: Calleia.com


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Fertility Boosters
All you need to know about boosting your fertility... and (hopefully) getting you pregnant fast!
Well, we know you know how to get pregnant, but do you know all the tricks and tips to actually becoming pregnant? From timing to the best positions—we've got some answers for you.
Babble blogger Lauren Hartman shows you what she likes to keep in her diaper bag, and the secret to keeping it all organized.


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Add to My ListAdd to FavoritesEdit Anime InformationBuy @ RightStuf Buy from Amazon Buy from Japan-Best
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Synonyms: Mahoutsukai Sally, Sally the Witch
Japanese: 魔法使いサリー2
Type: TV
Episodes: 88
Status: Finished Airing
Aired: Oct 9, 1989 to Dec 22, 1990
Producers: None found, add some.
Duration: 20 min. per episode
Rating: G - All AgesL represents licensing company
Score: 6.461 (scored by 248 users)
Ranked: #49752
Popularity: #6070
Members: 542
Favorites: 1
1 indicates a weighted score
2 based on the top anime page.
My Info
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Site Map | Contact | Directory
Course & Scheduling Information
Key SU Academic Policies
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Professional Conduct Expectations for COE Programs
Consumer Information for Teacher Education at SU
Job Information
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College of Education View Book
Donor Options
Congratulations to College of Education alumnus David M. Johnson, EdD, '87, the winner of Seattle University's 2014 Alumni Award for Professional Achievement. Dr. Johnson, a graduate of the College's Educational Leadership doctoral program, is CEO of Navos. One of the state's largest community health centers, Navos offers a full spectrum of mental health services to low-income children and adults with serious and persistent mental illness. Dr. Johnson recently won the 2013 "Visionary Service Award" by the National Council for Community Behavioral Healthcare and the "Evergreen Award" from Washington Nonprofits for his outstanding innovation and agility in the service of his community.
Dr. Johnson is both a visionary and a pragmatist whose expertise is often used to help develop public and private policy in health care at the local and state level. He firmly believes in the importance of respecting and working with people to recognize and then build upon their strengths.
"My work is my life's mission," he said.
Learn more about Dr. David M. Johnson, or read his feature in the latest edition of the College of Education's Banner Magazine.
Dr. Johnson considers the EdD he received in Educational Leadership at the College of Education as "the most transformative experience in my life. Without hesitation, I can say that every day I use what I learned in my doctoral program. It made the difference between a good career and a remarkable career."
COE Dean Emeritus John Morford, who was EDLR's senior professor and first chair from 1977 through 1991, remembers David Johnson as a student: "It was always clear that David intended to make major improvements in mental health services in our area," Dr. Morford said. "Congratulations to him on having done so."
Learn more about the Doctoral Program in Educational Leadership at the College of Education.
National Blog Examines Assessment from Theory to Practice
College Receives NCATE Accreditation
Copyright 2008 - College of Education, Seattle University.


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Gibside - National Trust
Gibside - National Trust
nr Rowlands Gill
Newcastle Upon Tyne
Tyne and Wear
01207 541820
01207 541213
An 18th century landscape 'forest' garden once home to the Bowes-Lyons family. Now, owned and managed by the National Trust, Gibside is a magnificent 600 acre estate for you to venture, exploring our woodlands, riverside and parkland to discover some of our rare and beautiful wildlife. Learn our history as you wander around the estate visiting our historic Palladian chapel, Column to Liberty, productive Walled Garden and majestic ruins of the Hall and Green House.
Venue Type:
Garden, parklands or rural site, Heritage site, Environmental or ecological centre
Please check the National Trust website before visiting.
Admission prices:
adult £6.50, child £4 plus family and membership options
By Road: Approx. 2 miles south of MetroCentre (A1) along the A694, on the outskirts of Gateshead. Sign posted along the route.
By Train & public transport: Nearest train station at MetroCentre plus public transport links from MetroCentre and Newcastle city centre.
By cycle: within 500m of the C2C (coast 2 coast) route, as it passes through Rowlands Gill, near Gateshead
Additional info
Come and stay in our Stables, recently refurbished as our Learning & Discovery Centre. Ideal for groups to take part in our education activities, or as a base to explore the area or region.
Beginners Running Club
- 25 September 2014 6-7pm
- 2 October 2014 6-7pm
- 9 October 2014 6-7pm
- 16 October 2014 6-7pm
Meet in Market Square for a friendly, sociable run up the Avenue and around the estate. Suitable for all abilities.
Suitable for
- 18+
- 16-17
- 11-13
- 14-15
£1.00 per person, payable on the evening.
- 27 September 2014 9-10:30am
Gibside is delighted to host parkrun who organise free weekly 5km timed runs that are open to everyone and are safe and easy to take part in.
The runs will take place each Saturday throughout the Spring and Summer.
Suitable for
- Any age
Get Active! Health Walk
- 27 September 2014 11am-12:30pm
Relax in the company of our Health Walk leaders and get inspired for gentle exercise on short sociable walks around Gibside with our healthy walking group.
Each walk is tailored to suit the abilities of participants so whether you're new to walking, recovering from an injury, going back to an old hobby or just looking to spend time outdoors in good company a health walk could be right up your street!
Suitable for
- Any age
Fungi Foray and Feast
- 21 September 2014 11am-2pm *on now
Delve into some of Gibside's fungi hotspots with a local expert and learn what's edible and what's not. Discover the range of fungi you can find on your door step and how you can use it at home. Finish off with a sizzling BBQ using some of your fungi findings.
Suitable for
- Any age
Adults £15.00, children £9.00.
5K Dog Jog
- 21 September 2014 9-10am *on now
Jog around Gibside with your pooch at your own pace. Doggy bag for every competitor!
Suitable for
- Any age
£5.00. Normal admission charges apply (adult: £7.20, child: £3.70).
Fruit and Nuts Ramble with a Ranger
- 25 September 2014 2:30-3:30pm
- 28 September 2014 2:30-3:30pm
Join a Gibside Ranger as we approach Autumn and discover the edible berries and nuts that can be found growing wild in the North East - from blackberries in the hedgerows to hazelnuts and elderberries.
Pick up tips on what's tasty, where to find it and how you can use it.
Suitable for
- Any age
Free event, normal admission charges apply (adult: £7.20, child: £3.70).
Visiting the Chapel
This cross-curricular visit aimed at Key Stage 1 and 2 students involves recognising Christian symbols and their meanings, and exploring shapes and materials in the building.
How to obtain
Call 01207 541820 or email email@example.com for more information.
Getting there
By Road: Approx. 2 miles south of MetroCentre (A1) along the A694, on the outskirts of Gateshead. Sign posted along the route.
By Train & public transport: Nearest train station at MetroCentre plus public transport links from MetroCentre and Newcastle city centre.
By cycle: within 500m of the C2C (coast 2 coast) route, as it passes through Rowlands Gill, near Gateshead


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No one hesitated to grab a slab of scallion pancake.
I'm trying to remember why my family and I ended up at Golden Duck (1840 Maple Rd., Amherst).
Chang's Garden hadn't burned down yet, so that wasn't it. Maybe it was the memory I had of a waiter expertly cutting a Peking duck in the restaurant's side room on an earlier visit.
We ordered scallion pancakes, which were crunchy but weirdly lacking in scallions, and a scallop dish whose name I can't remember, which was loaded with tender seafood. That disappeared quickly, as did the vegetable lo mein.
The sauteed string beans had lots of added flavor, with oyster sauce, scallions and was it shallots? It was actually one of the better versions we've had.
The shrimp in garlic sauce was decent as well, with crispy vegetables and shrimp cooked to firmness but not rubbery.
Our last dish ended the meal on a sour note, though – squid cooked "Evil Style," which was a cousin of "salt and pepper" style. That is, the squid was deep-fried in a coating, then wok-fried with chile peppers.
The squid arrived in a relatively scanty portion, and tasted faintly fishy, which raised my antennae. But I didn't really feel queasy until I got the bill. It wasn't food poisoning, it was the price – $14.95 for the squid. Evil indeed.


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Saucing Of The Sacred McNuggets Ceremony Proposed To Commemorate End Of Chief Ex-Spence Diet
Upperdate: Spence's band was gonna kick her out: "Spence, however, was facing pressure from her own band council to end the fast and a delegation from Attawapiskat left for Ottawa to hand-deliver a letter urging her to quit the protest or face removal as chief."
Update: Attawapiskat Chief Spence agrees to end hunger strike
"And they want to define a process that will allow Spence a recovery." Read shield her from further damaging scrutiny.


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by Timo Seppa
Earlier this week, I appeared on NHL Network Radio's The War Room for a full hour with Mick Kern and Peter Berce to preview the NHL season from an analytics point of view.
The appearance can be heard in three parts. Thanks to Michael Lippa for sending it along.
Part I: Hockey Prospectus 2013-14 and using its analytics to preview the NHL season. Listen to Part I.
Part II: Team projections. Listen to Part II.
Part III: Player projections. Listen to Part III.
If you are interested in purchasing Hockey Prospectus 2013-14, either paperback or digital download, check out the product page.


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Sassy Soundbites and Audio Highlights from the Marketing with a Book and a Speech SummitFebruary 4, 2013 Book Publishing, New Audio File to Support Your DIY Publicity Success, Public Speaking No Comments
It was a full house at the Marketing with a Book and a Speech Summit in Seattle in Saturday. We laughed and learned from the likes of Henry DeVries, Bill Stainton,Mark LeBlanc … and yours truly. Wish you all could have been in room, and reading this blog post is the next best thing to being there.
They Laughed and Cried and Couldn't Put it Down:
- Dorthoy Wilhelm: "Dear Nancy and Bill, I just want to thank you two for doing the Northwest proud with your presentations yesterday at the Book and A Speech Summit. There was so much valuable, usable information, and I think the fact that you could offer material so valuable to experienced speakers and writers, and beginners, leaving out no one in between was nothing short of incredible. It was as if I heard the last pieces I needed to put my new plan together. Of course, Mark and Henry are wonderful – but you're our very own! Thanks again."
- Jennifer Malocha: " TREMENDOUS!!!!"
- Anna Goldworthy: "Once again, Nancy has knocked it out of the park by hosting the Marketing with a Book and a Speech Summit at Verity Credit Union in Seattle. The presenters were top notch, inspiring, and held nothing back. The Summit wildly exceeded our expectations. Thanks to Mark LeBlanc, Henry DeVries, Bill Stainton, and the incomparable Nancy Juetten! The overriding philosophy of 'write the darn book!' has put Nina and I on track to publish our book in 90 days!"
- Tammy Lyon Westergaard: "My head is full of incredible info from the Marketing with a Book and Speech Summit today organized by the fabulous Nancy Juetten. I think I'll just go ahead and outline my book now…
Sassy Soundbites from the Speakers to Propel Serious Authors and Speakers Forward:
- On writing a 'warm up' book for seniors: "You can write a small book with big type." — Mark LeBlanc
- Give your audience everything, trust that the rest will work itself out." — Mark LeBlanc
- "Don't fall in love with your potential. Take action." — Mark LeBlanc
- "Stay in the game and hurry up." Mark LeBlanc
- "Ask yourself this question. What is my primary speaking topic for a defined period of time?" — Mark LeBlanc
- "When setting fees for keynotes and speaking, consider your fee range based on a variety of variables — length of program, geography, type of organization, number of people in the audience, the number of programs to be offered for the event (keynote, breakout session, etc.), and factors such as whether the organization will purchase books in quantity and how the organization prefers expenses to be handled." — Mark LeBlanc
- "Would you be open to a conversation?" is a great way to open the doors to new business." — Henry DeVries
- On project scope creep: "Yes, we can do that. And there is a cost associated with that." — Henry DeVries
- Before inviting questions and answers from the audience, say this: "I've got one more story, but before I share it, what questions do you have for me?" — Bill Stainton, on making sure every talk ends on a high note.
- "Practice the art of the pause when delivering humor. And when you start to bomb, slow down!" — Bill Stainton
From me, Nancy Juetten:
- "People don't want to by your program, they want to buy your results."
- "To attract clients, focus on the who, how and wow."
- "What can you offer that eases a pain for your audience that they need, want and will pay to get?"
- Of course there was a very sassy soundbite having something to do with what happens when you sleep with a publicist, but you would have had to be there to get the joke. And it just about brought the house down. (I wrote a press release for my husband Steve Juetten about Smart Money Rules from a Bellevue Fee Only Financial Planner, inspired by Downton Abbey that earned some very compelling results …)
- If you want to LISTEN TO my 30 minute talk, you can. Here is the MP3 audio file.
- Here are more tips from yours truly around building your platform now so when your book, speech, either or both are ready, there is a ready audience of fans, followers and advocates standing by to invest wisely in what you have to offer.
A good time was had by all, and I can't wait to see what happens when everyone takes action on what LeBlanc calls the "will do" list in the next 30, 60 and 90 days. What is on YOUR list? Share, and let's keep you accountable for your results!


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Mexican Art
These fine art prints are inspired by the images that were displayed in the Museum's exhibition Revolution on Paper: Mexican Prints 1910-1960.
Free UK p&p on books & orders over £75
The British Museum online shop is able to offer a worldwide delivery service, and free UK delivery on BMP books.
View our delivery information page
Having trouble with your order? You can email us or call:
Helpline: 0800 218 2222 or +44 (0)20 7079 0970
Ticket booking: +44 (0)20 7323 8181
Membership: +44 (0)20 7323 8195
Become a fan of the British Museum Shop on Facebook and Twitter to share all the latest offers and exclusive access to new gifts.
Every purchase supports the Museum


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Central Indiana healthcare workers will have a unique opportunity involving more than 20 employers.
WorkOne Indianapolis will connect qualified healthcare workers to local hospital and medical facility hiring managers during the Healthcare Hire Fair at Bankers Life Fieldhouse on August 27.
The Hire Fair, which differs from a traditional job fair, will provide specific paths for prescreened candidates with healthcare education and experience and assist those interested in obtaining healthcare training.
The event will be held from 9 a.m. to 4 p.m. and will include access to WorkOne services, networking with healthcare professionals, onsite resources for resume development and interview skills as well as opportunities for interviews.
"The Healthcare Hire Fair is designed to help employers find the job-ready, skilled workers they need in one place, in one day," said Brooke Huntington, President and CEO of EmployIndy. "We've partnered with healthcare providers to identify the skills they are seeking in job candidates, and have worked closely with jobseekers to make sure they have those sought-after skills and can present them to the hiring managers during the Hire Fair and as they acquire new jobs."
Hire fair attendees can plan to connect with over 20 employers from local hospitals, medical offices and long term care/assisted living facilities. They include:
- IU Health
- St. Vincent
- Community Health Network
- Wishard
- Richard L. Roudebush VAMC
Ivy Tech Community College, University of Indianapolis, IU Health Science Education, Walker Career Center, J. Everett Light Community and Continuing Education, and other education providers will be on-site to provide information on training programs to attendees who are interested in advancing their career in healthcare.
While walk-ins are welcome, organizers highly recommend that anyone who attends visit an Indianapolis WorkOne office to be prescreened. Prescreening activities are taking place at the three Indianapolis WorkOne centers now though August.
"Prescreened jobseekers will have a heightened advantage over walk-in attendees," said Gina Mityas-Stanley, Healthcare Program Manager at EmployIndy. "An employer who meets a prescreened candidate at the Healthcare Hire Fair knows that the candidate's credentials have been verified, that background check requirements have been met, and that time has been spent with a Healthcare Careers Advisor to address any challenges related to communication skills, customer service skills and other soft skills."
Healthcare Career Advisors will meet one-on-one with jobseekers to verify their licensure or credentials, review their resume, perform their background check, examine and discuss customer service, communication and other skills. The advisor will provide guidance on soft skills, dress, professional development opportunities, marketability and professionalism.
Jobseekers planning to attend the Healthcare Hire Fair who would like to be prescreened should schedule an appointment by contacting Leeza Fazioli at (317) 228-0682 Ext 120, email@example.com or Sally Black at (317) 228-0682 Ext 102, email@example.com.
All jobseekers should bring a copy of their licensure, credential or unofficial transcript to prove healthcare education. They should also bring their resume, a state-issued ID and social security card.
Click here to warn more about the hire fair.


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Deer Beds by Katherine Wolkoff
Maxwell's Daily Find 01.29.14
Deer Beds by Katherine Wolkoff
• call for pricing
Another lovely find from Emily Henderson's redo of Joanna Goddard's NYC home, this series of photographs is suggestive, romantic and notable for what is not there as opposed to what is. I particularly like how big the framed print is and how and empty space becomes statement art. Genius.
9 Comments
Maxwell - this looks like a merkin!
Should it be above the landing strip instead, then?
^ this is the hardest I've ever laughed on Apartment Therapy. Thanks.
Minus 1 for art not being hung at 57" though.
I have been in love with this deer bed prints and wish I could afford one! SO beautiful. I love Emily's work and Joanna's blog. I also really love how the tv blends in so well with the gallery wall.
I don't think the strict centered tv on console serve the art wall above and perhaps the other parts of the room. You may leave the TV were it is, take the small, lowest white framed photo and the smallest (postcard size?) off, move the console right, into that space, and place the 2 removed pieces in the free up wall space near the chair.
Well the TV would not be above the dvd player. But if I had room to a large tv on a console I would try to so what ever to keep it on one side or the other of the cabinet instead of the center. It sucks energy from the room.
To clarify. TV stays in the ROOM where it is but console shifts. The small pic can stay where it is though the larger low white-framed photo moves. Thanks.


text: I have a 1990 Subaru Legacy. A few weeks ago it overheated (it wasn't a major overheat, I caught it in time) and we found the radiator had a minor leak, we replaced it and put a new cap and it didn't fix the problem. Our next step was to check the thermostat, we took it out and I drove it to school, which is over 30 miles away for a few days and it ran fine and cool without it. We put a new thermostat in a few days later (installed with the spring towards the engine). Within in 10 minutes it overheated. It doesn't seem to be using water and there is no water in the oil. It works great without a thermostat and I'm not sure if it is a head gasket problem, it doesn't seem like the symptoms point to that. It doesn't over pressurize, it seems to hold proper pressure and there are no visible leaks. Is it possible that it could be my water pump? If not, what are your suggestions....


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The trio of actors represent vastly different age groups, although the 26-year-old Michael B. Jordan and 41-year-old Marlon Wayans are considered the front runners. The project is said to center on the comedian's life in his 30s, though it isn't known if Michael B. Jordan can be aged-up through makeup to take on the role. Both Marlon Wayans and the 51-year-old Eddie Murphy had previously been attached to the gestating biopic at different points in development, which once had Bill Condon set to direct.
The project fell apart when he left to direct The Twilight Saga: Breaking Dawn - Part 1 and The Twilight Saga: Breaking Dawn - Part 2. While both actors are still in the mix, insiders claim that Marlon Wayans' screen test particularly impressed Harvey Weinstein, who is fully financing the project through The Weinstein Company.
Richard Pryor is still considered to be one of the most influential comedians of all time, although he had drug problems which lead to the actor/comedian setting himself on fire after freebasing cocaine. Producer Jennifer Pryor also brings more than 50 pages of her late husband's journal that offer a unique glimpse into his dark but brilliant mind. The comedian passed away in 2005 at the age of 65.
No screenwriter is attached to the project, although our story from March indicated that producer Forest Whitaker is developing a new screenplay. No production schedule was given.
Richard Pryor: Is It Something I Said? is in development and stars Mike Epps. The film is directed by Lee Daniels.


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The Gift of a Holiday
Want to give someone the special gift of a Farm Holiday? A very good idea, and an original, beautiful surprise! You can choose between holiday gift certificates with a specific cash value, and those issued for complete week-long or weekend getaways.
Further information is available from Mrs. Alexandra Neubauer at:
Tel.: ++43 / 662 / 88 02 02


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Fired For Breastfeeding at Work
Dr.Wendy Walsh: Marina Chavez had been a cashier for three years at Acosta Tacos in Los Angeles when she learned she was pregnant. She continued to work during her pregnancy, but her baby was born premature -- so she was able to take disability leave and nurse her baby at home for four weeks. When she returned a month after the birth, she was told she had been replaced, which is against the law. Despite this incident, she was called into work for the next two shifts to cover for an absent employee. When her boss learned that during those two night shifts that her infant had been brought to the taco restaurant at the time of her breaks and she nursed her baby the car, he fired her. She was told she couldn't work if as long as she was still breastfeeding her baby. But Marina needed the minimum wage job to support her family, and begged to get her job back. Instead, she was told her that with that "attitude" she could look for employment elsewhere, and he outright fired her on the spot.
In this recent landmark case, the court clearly stated that breastfeeding is intrinsic to the female sex (duh!) and thus, the judge determined that Marina suffered sex discrimination. After a two-day hearing, the California Fair Employment and Housing Commission found that Acosta Tacos' termination of Marina Chavez -- due to her insisting on her right to return to work and nurse her baby -- violated the Fair Employment and Housing Act's (FEHA) prohibition against sex discrimination.
Finding the employer liable for sex discrimination, retaliation, and failure to prevent discrimination, the Commission ordered Jesus Acosta, owner of Acosta Tacos, to pay Marina Chavez $21,645.00 in lost wages plus $20,000.00 to compensate for her emotional suffering. The Commission also ordered Acosta to pay the state's General Fund a $5,000.00 administrative fine, develop a written policy (printed in English and Spanish) prohibiting sex and pregnancy discrimination in the workplace; train all employees and supervisors on the policy, and post a notice stating that the Commission determined the company violated the FEHA and ordered it to pay damages.
So in the end, this small chain of Mexican restaurants has to shell out $46,645.00. Wouldn't it have been cheaper to just let the women nurse her tiny bundle on her legal breaks? Note to Acosta Tacos: We'll be looking for those pregnancy and breastfeeding policies --- printed in English and Spanish -- right beside the sign that reminds employees to wash their hands. Way to go, State of California!
|Dr. Wendy Walsh holds a Ph.D. in Clinical Psychology and her area of interest is Attachment Theory, a psychological, evolutionary and ethological theory that provides a descriptive and explanatory framework for understanding interpersonal relationships between human beings. As a psychological assistant registered with the California Board of Psychology, Dr. Walsh has treated individuals, couples and families for a variety of mental health concerns including personality disorders, anger management, eating and substance disorders, and depression.
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vincentvangonads said: I've decided to make that amazing bacon caramel marshmallow bark for Christmas. Is it very time consuming? I don't even need to ask if its worth it because I'm sure it is.
Not very. I would say it took me about 2 hours, and that was while I was also making chocolate cake and vegetable stock. The tricky part is sorting out the order of operations, because there are many moving parts. I made the caramel first but then had to reheat it. Might have been better to make it when it was needed, which would mean:
- Make the bacon topping
- While it's in the oven, melt the chocolate
- Spread the chocolate, freeze for 5 minutes, melt the marshmallows, add whiskey, spread the marshmallows, let it cool in fridge or countertop
- Make the caramel, spread the caramel
- Freeze for 5 minutes, spread second layer of chocolate, sprinkle with bacon
Finally: I used half the bacon and everything turned out dandy. There's plenty of it on the finished bark. I didn't reduce the egg white and spices in the bacon crumble recipe, though I did make less of the sugar wash (3 tbsp. sugar, 3 tbsp. water).
And yes, it's definitely worth it. Happy Holidays!
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Software Map
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|0. pgScript - pgScript is a scripting language for pgAdmin and is based on the T-SQL syntax. It provides control-of-flow capabilities, local variables and powerful random data generators in addition to the SQL (PostgreSQL) language. pgScript is included into pgAdmin.
|Activity Percentile: 3.97
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|1. Graph data type for PostgreSQL. - Adds notion of graphs to PostgreSQL extending SQL with graph type.
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|2. pgQueryManager - The idea is to create a software to manage tables, views, stored procedures, etc. Execute also Querys. Sintax highliting, modular to be extensible. Developed in C/C++.
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I have no rational explanation why but I flat out could not stop laughing about this story when I watched it this morning. Like I realize if you look at this story on the surface it's pretty sad probably but that didn't change the fact that I was laughing like George McFly watching Jackie Gleason. This story is sort of like the pyramids for me. If you don't consider the vast human suffering used to create them and just focus on the surface it's pretty incredible. And Bill Flowers can play on my team any day of the week. 93 years old and his dog drags a human leg back to his property?! No biggie. Just put that bad boy in a plastic bag and bury it in the back yard! No reason to bother the cops with something I can take care of myself. That plus there's no reason to potentially set yourself up to be thrown in the clink at age 93. Best way around that is to hide evidence from a crime you didn't commit. You do you Bill Flowers.
PS: I'm 17% certain Bill Flowers is Bill Cosby's biological father. Sounds exactly like him. If he would have just said 'Jello puddin' pops' at the end I'd be up to 85% certainty.


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"Customer service is priority #1 at Rocky Mountain ATV/MC. We value our customers and strive to be the best shopping experience- when you buy from us, you are buying lifetime service."
-Dan Thomas, CEO and Founder
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We will stand behind all products we sell with regards to manufacturing defects in workmanship and material. Most products are limited to the manufacturer's warranty. However, we will do everything in our power to take care of the problem.
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Each review submitted enters you into a $100 gift card monthly drawing, and a $500 gift card quarterly drawing!
Comments On Jul 25, 2014:Octane boost and stabilizer that does what it says it will do. Be careful not to put in too much or it will cause your bike to run rich and you will have to readjust your tuning.
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Comments On Jul 03, 2014:This product works really well,.. Yes , it raises your octane,,Yes,, it smells good. Beware of using to much though, it will make your machine run overly rich , which will throw off your jetting
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Comments On May 20, 2014:Not real happy with this and would not buy again. I used this once, it works, but it turned my white IMS tank brown. Not happy and feel people should know.
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Comments On Feb 07, 2014:Best go juice
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Comments On Apr 09, 2013:It works great with my 2 stroke!
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Comments On Feb 13, 2013:Don't mix fuels to get your octane level up. It will go heavy in a few days and will alter performance and tuning.
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Comments On Aug 28, 2012:Makes me feel like I'm using race gas, and not spending as much.
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Comments On Jul 23, 2012:Realy could feel the difference much more snappy throttle response
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Comments On Jul 06, 2012:great product and you notice the difference in throttle response
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Comments On Jul 05, 2012:Do NOT use this product if you have a light colored tank! It has some sort of dye in it that turns yor tank, and any other plastics it come in contact with, a chocolate brown color!!!
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Institutional Advancement & Giving
You are here
Happy Holidays from the Office of Institutional Advancement!
Thank you for considering a tax-year-end gift to Kansas Wesleyan University! The university is closed for the holidays from December 23-January 1. Gifts postmarked by December 31 will be credited toward 2013 giving. Gift receipts will be processed on January 2.
The Office of Institutional Advancement at Kansas Wesleyan University consists of Public Relations, Alumni Relations, Development, and Marketing. The office is charged with keeping alumni, friends, and the community connected to Kansas Wesleyan University. Fund Development is an opportunity to invest in current students and faculty as well as our future. If you are interested in reconnecting with classmates, giving to KWU, or wish to help us spread the great news about Kansas Wesleyan, please let us know!


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text: Trevecca finishes in top four in local 3K race Friday, September 19 at 9:38 AM Trevecca runners won the top five places at the annual Together We Can 3K College Challenge held on September 13, 2003, on the campus of Belmont University. This event, a charity race to benefit Second Harvest Food Bank, brings together students from four universities in the city --Vanderbilt, Belmont, David Lipscomb, and Trevecca. Students from Trevecca performed well. Nathan Barefield, a junior transfer student from Havelock, North Carolina, took first place with a time of 9:53 in the 1.86 mile race. Nicholas Landry (10:47) and James Storie (10:58), both seniors at Trevecca, took second and third places, respectively. Loni Osegueda, a member of the Lady Trojan soccer team, secured a first-place finish for the women with a time of 12:10. Overall, Trevecca entered more than fifty students in the charity race, more than Belmont University, David Lipscomb University, and Vanderbilt University combined. Trevecca also had eight staff/faculty members run in the race. ìThe race was fun, but more importantly it was for a good cause,î says participant Nicholas Landry. Trevecca raised more than $600 for the charity. Participants were also encouraged to bring canned goods to the all-day event. (9/19/03)


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Beyond good and evil
Analysis: The battle for BitTorrent's soul
We've just passed the 11th anniversary of the introduction of
BitTorrent, a file-sharing protocol which has become the scourge of
the media industries. Bram Cohen's creation made it easier than
ever to share huge files across the internet, making piracy of
films and TV shows as common as music piracy.
In 2004, Cohen founded BitTorrent, Inc., which has remained the respectable face of the technology for the past eight years by promoting legal sources of torrent content. However, it has faced a constant uphill battle, and recent developments have highlighted the technology's split personality - and the ideological battle between the company and the community for BitTorrent's soul.
Building the ultimate piracy tool: the "bad" BitTorrent
Boxopus made headlines at the end of last month with a service
described as a "pirate's dream come true" - able to download the
content torrent files on its own servers and send them directly to
your Dropbox. By handling the download process 'in the cloud',
Boxopus promised to make it simpler and safer.
Just two days later, Dropbox blocked Boxopus - presumably fearing that their service would become known as a harbour for pirates if Boxopus took off. The project is now looking into other services to connect to instead, likely Google Drive if a recent user survey is anything to go by.
While free in beta, Boxopus plans to charge for bandwidth use in the future. Customers are essentially paying for the ability to download a torrent from anywhere, with the promise of absolute anonymity.
Although Boxopus describes the process as "grab[bing] the file you need and put[ting] it in your Dropbox", there's another name that's equally appropriate: smuggling.
There are plenty of ways to stay anonymous while using BitTorrent, but leaving a third-party service to do your dirty work for you is probably the riskiest. In theory, it's foolproof; in practice, your entire downloading history may be exposed to the authorities if your partner in crime squeals. And it's written into Boxtopus' own privacy terms (emphasis added):
Boxopus may disclose Personally Identifiable Information if required to do so by law or in the belief that such action is necessary to: (a) comply with law or legal process, court order or a subpoena served on Boxopus or the Site to cooperate with law enforcement authorities; (b) investigate, prevent or take action regarding suspected or actual illegal activity or fraud on the Site; (c) protect and defend the rights, property or safety of us or Service Providers (defined below), licensees, business partners, agents, customers, users, or others; or (d) act in situations involving actual or potential threats to the physical safety of any person, violations of our agreements, abuse of this Site, security breaches of this Site, or as necessary to protect our systems, business, users or others.
So, far from being a "pirate's dream come true", using a third-party like Boxopus to download torrents for you is an expensive liability. If you're using BitTorrent legally, then why pay someone else to download a file for you?
But as the authorities becomes increasingly savvy in identifying
and prosecuting serial file-sharers we may see more "torrent
smugglers", promising anonymous downloads for a small fee.
Regardless of whether it's effective, Boxopus is yet another example of time and money being sunk into making BitTorrent more resilient to shutdown by the authorities. This version of the technology's future is of the ultimate piracy tool: safe to use and forever active.
Corporate, user-friendly file-swapping: The "good" BitTorrent
BitTorrent's other future, and the one promoted by BitTorrent,
Inc., is expanding the technology beyond just the illegal
downloading of copyrighted materials.
After all, there are plenty of legal uses already. BitTorrent as a protocol has been adopted by other companies needing to distribute large files: Facebook uses it to push updates out to its servers, while Blizzard (developer of World of Warcraft and Diablo III) uses a proprietary BitTorrent client to patch their games.
Yet despite these high-profile uses, 'BitTorrent' is still a dirty word, synonymous with piracy. No wonder the company that shares its name with the protocol is looking to clean up its reputation. If you want to see their vision of BitTorrent's future, just take a look through a couple of pages of their blog: legally-distributed movies and albums, BitTorrent-based backup services, and the recently-announced Torque (which we'll get to in a bit).
Most indicative of their future direction is a new desktop app for sending large files between individuals using BitTorrent technology, released in January with the working title 'Share'. As the pitch reads:
Have you ever been stuck trying to send an HD home movie to a friend over the Internet? Or a batch of high-resolution photos? How about longer smartphone videos?
It's not easy. You can try a complicated FTP service. Or pay big fees for a file sharing or cloud service. Or dramatically reduce the size, quality or length of your creation to send via email or social networks.
Sending large files to a friend via BitTorrent makes perfect sense, and it's a great use of the technology. BitTorrent, Inc. see this is such an important use of their protocol that they intend to incorporate it into uTorrent and other clients. There's potential for piracy, sure, but it's no greater than with standard emails.
It seems like a no-brainer - so why, after 11 years, has it only come to the official app? Perhaps because BitTorrent's primary users have no interest. A comment by 'mynameishare' on TorrentFreak's coverage states: "Vuze had sharing with friends, no one wanted it".
BitTorrent in the browser
So what can we make of BitTorrent, Inc.'s latest development?
Torque is a
browser plugin which uses the open-source btapp.js to provide
a backend for web-based BitTorrent apps. It's a smart move,
considering the increasing trend towards users performing
everything in the browser. (The other recent software trend is of
course towards Android and iOS, but BitTorrent clients are already
available on the former and aren't allowed on the latter.)
Using a browser plugin seems a bit archaic in the world of HTML5 and jQuery, but once installed it works beautifully. One initial example of the technology at work is OneClick, a Chrome
extension that promises to integrate torrents identically to regular downloads and tidy away its P2P aspect. Unfortunately we were unable to install the current version of the plugin, but essentially it promises to make downloading of public torrent files easier than ever.
On the opposite side of spectrum is the second Torque experiment, PaddleOver, which works similarly to the desktop app Share in that it allows private sharing of files between individuals. Once the Torque plugin is installed, PaddleOver works brilliantly, delivering files straight to the download folder with a simple drag-and-drop interface.
Both were developed by Patrick Williams, Engineering Lead at BitTorrent, Inc. - suggesting that even BitTorrent, Inc. themselves are unsure which way they are taking the company.
The battle for BitTorrent may already be won
Screenshot courtesy of TorrentFreak.
What is BitTorrent? Is it a way for independent creatives to
distribute their work for free? Is it a flag for pirates to rally
beneath? Is it a company working to innovate the world of
file-sharing? Or is it just a neutral protocol for distributing
large files?
Perhaps the pirates have already won this battle. It's rumoured that BitTorrent, Inc. is planning to rebrand itself as 'Gyre' - which, if true, is likely an admission that the brand they have spent eight years building is toxic when it comes to anything outside of illegal file-sharing.
In that case, BitTorrent will truly be a technology of two halves: Gyre, the legal, corporate side, promoting free private file-sharing; and on the other side BitTorrent, a tool for illegal sharing of copyrighted media - and the occasional Linux distribution.
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Tahoe Keys Condos or Lodges(120)
120 Results
103 more choices from the HomeAway Network
Recent Tahoe Keys Reviews
Our Stay Was Fantastic!!!!
Well, my friend and I stayed once again at this condo in Tahoe Keys and it was even better than last time!!!We worked ETBT which is a Bike Trek so we were never there in the day time... It was sooo relaxing to come home and grab a glass of wine and just kick back out on the patio...The location is just fantastic also. It is close to stores, so if you needed anything at all, it was at our fingertips. At night we slept like babies as the beds are so very comfortable. This place has everything you could want or need... And even a brand new 2nd bathroom for us women!! !:-) It is awesome!!! What a view... Thank you ...
Great unit for family vacation!
Rating Details: I was more than satisfied with the condition of the vacation rental. I was very happy with the location. The vacation rental was clean. The property manager was very helpful. Overall, I recommend this vacation rental. Reviewer Comments: The unit was perfect for our three-person family. Access to biking swimming how you doing water sports etc. was excellent. Several days of construction did affect our stay. I recommend better communication between the H OA and property management company. I would wait all day as excellent.
Quiet and Beautiful neighborhood
Barry's place is beautiful. It had everything we needed and more! It is very spacious for a group of 5 adults and we had so much fun! A couple of things I wish Barry would have is an outdoor grill- although it is winter at Tahoe but it gets pretty warm during the day and BBQ is certainly an option! Also, I would love to have Wifi in the house since the mobile phone service is spotty there. Overall, a great stay and I highly recommended.


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Inquiry Labs
Teaching and Learning Services is proud to announce the opening of the Inquiry Labs (aka InqLabs), new teaching and learning spaces on the second floor of the historic Powell Library. Fostering inquiry, creativity, and community, InqLabs are designed to promote the development of twenty-first-century research skills, especially through active engagement with cultural heritage materials and digital technologies. From books to bytes, feed your curiosity in the InqLabs!
InqDesk (Second Floor, West Rotunda, Powell Library)
Start your research journey at the InqDesk, where you can ask a question, check out a book, get a map of the libraries, make an appointment for a research consultation, find your way to InqSpace, and much more!
InqSpace (Room 220, Powell Library)
The hub of the InqLabs: a bright, open, flexible space, in which students consult with librarians and trained graduate and undergraduate students ("Inquiry Specialists" or "InqSpecs") on research assignments, capstone projects, theses, and other analytical and creative endeavors.
InqSpace also offers opportunities for librarians and technologists to work with faculty on assignment and course design. Equipped with configurable tables, comfortable seating, and three library consultation stations, InqSpace allows for small group and project-based work, as well as workshops and presentations. In addition, it includes a maker-space for exhibits and other creative projects.
Got a Research Question?
Working on a research assignment, capstone, or thesis project? Need inspiration or ideas? Trying to figure out how to collect, organize, and cite your sources?
Schedule a free research consultation or drop by the InqSpace during our research consultation hours to learn about resources, strategies, and tools you can use!
Powell Research Consultation Hours for Summer 2014
|Saturday - Sunday
|Monday - Thursday
|11 a.m. - 5 p.m.
|11 a.m. - 5 p.m.
Inquiry Labs
InqDrop (room 236A)
InqSpace (room 220)
InqLab 1 (room 238)
InqLab 2 (room 228)
InqLab 1
(Room 238, Powell Library)
InqLab 2
(Room 228, Powell Library)
Two innovative multi-use classroom spaces, designed to support faculty and student engagement with library collections through the use of cultural heritage materials and digital technologies. Ideal for 20-person seminars, such as those taught in Spring Quarter as part of the Freshman (GE) Cluster program. The lab space complements the Research Commons in Young Research Library by focusing especially on helping students develop research skills in preparation for capstone projects and theses.
(Room 236A, Powell Library)
Located conveniently off the Main Reading Room, this cozy space offers configurable tables, comfortable seating, and two library consultation stations. Ideal for students working on collaborative research or creative projects.
Click here to reserve the InqDrop.


text: Enjoy Dark Brewed Yuengling Porter in this 16oz Porter Worthy glass. One side features the Porter Worthy logo in full color. The opposite side has the Yuengling script printed above a brief history of Porter beer. The history text reads: "Porter beer was originally brewery for men who carried baggage through the cobblestone streets of London. Like the job, the beer wasn't for everyone. For you, the few, Yuengling brews this specialty beer to honor any Porter Worthy effort." Also appearing on the back side of this glass is an image of an 18th century London porter.