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Monday, March 7, 2011
Best SFF Novels of the Decade!
With 10,000 votes and 1,600 nominated titles over the course of a week, the winners are...
1. Old Man's War by John Scalzi - 295 votes
2. American Gods by Neil Gaiman - 270 votes
3. The Name of the Wind by Patrick Rothfuss - 231 votes *
4. Blindsight by Peter Watts - 221 votes
5. Kushiel's Dart by Jacqueline Carey - 194 votes
6. A Storm of Swords by George R.R. Martin - 179 votes
7. Jonathan Strange & Mr Norrell by Susanna Clarke - 167 votes *
8. Anathem by Neal Stephenson - 141 votes
9. Mistborn: The Final Empire by Brandon Sanderson - 125 votes
10. Perdido Street Station by China Mieville - 124 votes
* = Debut novel
And here's a fabulously entertaining follow-up article where #1 "stews" over #3
Well, I have to hardily endorse the winner. Not just because it's the only one of the list I've read, mind you, but because OLD MAN'S WAR (the whole series for that matter) is one enthralling, thought-provoking, knock your socks off piece of SF (with a tiny touch of romance, even).
I think the SFR Brigade should hold a Readers Poll of the Best SFR of the Decade. Don't you?
6 comments:
How about best book of the year? (decade?) Some of our authors published works are not novels, lol.ReplyDelete
We could do that. Or even two categories?ReplyDelete
I haven't read all of these, so I can add to my TBR list.ReplyDelete
I did read Jonathan Strange, I cannot conceive any reason why this book should have been published. It's rambling and twice as long as it would have been if somebody actually edited it.
I am a HUGE Neal Stephenson fan. Read everything twice. But I simply couldn't get into Anathem. I give him a #FAIL on it. If your biggest fan ever (think Kathy Bates in Misery) can't finish the book, then something is definitely wrong.
John Scalzi's Old Man's War was brilliant. He should have stopped right there. Well, Ghost Brigades was okay. Lost Colony weak, but that retelling of OMW in the POV of the girl (Zoe's Tale)? Sucked every which way from Sunday.
Let the arguments begin!
As for the Best Books thing, it's impossible to read absolutely everything so any votes are inherently uninformed.ReplyDelete
Do it like the Oscars and require everybody to read all the entries first.
I agree Old Man's War was the best of the three, though I did enjoy the entire series and the wrap in The Last Colony (though the "fix" at the climax was just a little logistically-challenged, I thought.)ReplyDelete
I purchased Zoe's Tale "just because", but haven't read it. I'm not sure it could add anything more to the series even from a new perspective. Maybe someday I'll find out. I'd LOVE to read a novel told from the POV of Lt. Stross(?) Not sure I have that name right, but he was a Space Turtle.
I've heard tons of positive things about The Name of the Wind, but being that it's Fantasy, I'll probably never get around to reading it.
At my niece's wedding this weekend, my sister-in-law was raving about Brandon Sanderson, so I got some samples to check out.ReplyDelete
Not sure my TBR can handle any more books, even my digital TBR! I'm so behind.
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subset: commoncrawl


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A Summer to Remember (Unabridged)
by Victoria Connelly
Open iTunes to Buy
Escape deep into the English countryside in this perfect summer's day listen. Fans of Alexandra Potter and Katie Fforde won't be able to resist. Nina Elliot is tired of her life. She's not sure how it happened, but somewhere along the way she lost track of where it was all going. So one fateful day, she makes a brave decision: she's going to leave it all behind. Taking a job deep in the English countryside, Nina does just that. Ensconced at the Old Mill, she settles into daily life with the Milton family, where she works as a researcher for author Dudley. With endless summer days stretching out ahead of her, Nina couldn't be happier. But her quiet life is soon interrupted when the handsome Milton boys return home, for they plan to make sure this really is a summer to remember.... Relax and enjoy a breath of warm summer air in the delightful new novel from Victoria Connelly, best-selling author of Wish You Were Here. Perfect for fans of Katie Fforde and Alexandra Potter.
- Narrator: Anna Parker-Naples
- Published: 2015
- Category: Fiction
- Provider: HarperCollins Publishers Limited
- Presented by Audible.co.uk


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- Height: 4
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Collection of poetry, inspirational & motivational quotes, short stories, articles, and educational materials (lesson plans, reading tests, and much more)!
FREE EBOOKS My Books The Little Book of Big Quotes Vol I and The Poems Volume I!
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Thank you for reading and always supporting me, it means more than you know. :)
See you on page one,
Carlos Salinas
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The hexadecimal color code #64298f is a medium dark shade of blue-magenta. In the RGB color model #64298f is comprised of 39.22% red, 16.08% green and 56.08% blue. In the HSL color space #64298f has a hue of 275° (degrees), 55% saturation and 36% lightness. This color has an approximate wavelength of 564.04 nm.
The artist's world is limitless. It can be found anywhere, far from where he lives or a few feet away. It is always on his doorstep.

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Pharmaceutical Research
Journal Prestige (SJR): 1.077
Citation Impact (citeScore): 3
Number of Followers: 145
Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1573-904X - ISSN (Online) 0724-8741
Published by Springer-Verlag [2351 journals]
- Evaluation of Antiproliferative Activity, Safety and Biodistribution of
Oxaliplatin and 5-Fluorouracil Loaded Lactoferrin Nanoparticles for the
Management of Colon Adenocarcinoma: an In Vitro and an In Vivo Study
- Authors: Farhan Ahmed; Sonali Kumari; Anand Kumar Kondapi
Abstract: Purpose Colon adenocarcinoma is the most common form of gastro intestinal tract cancer, predominantly in ageing population. Chemotherapy with 5-Fluorouracil and oxaliplatin is an indispensable treatment regimen, nevertheless having limitation of systemic toxicity and lower therapeutic index. The present study is based on evaluation of anti-proliferative potential, pharmacokinetics parameters, safety profile, biodistribution and efficacy of 5-FU/oxaliplatin loaded lactoferrin nanoparticles in cell lines and wistar rats in order to overcome the above limitation. Methods Nanoparticles were prepared by Water-in-oil process. The anti-proliferative efficacy and mode of cellular entry was evaluated in COLO-205 cells. The pharmacokinetics and biodistribution analysis were performed in healthy rats while efficacy and safety assay were performed in ACF induced rats. Results 5-FU and oxaliplatin loaded nanoparticles shows enhanced antiproliferative activity as compare to free drugs in COLO-205 cells. Lactoferrin nanoparticles also improve the pharmacokinetics profile, safety parameters and efficacy of 5-FU and Oxaliplatin. Conclusion Lactoferrin nanoparticles demonstrated an attractive drug delivery module to manage the colon adenocarcinoma as it has improved the antiproliferative activity of 5-FU and Oxaliplatin against colon adenocarcinoma cells. Moreover, it also improves the pharmacokinetic profile and safety parameters of the same drug in wistar rat.
PubDate: 2018-07-16
DOI: 10.1007/s11095-018-2457-7
Issue No: Vol. 35, No. 9 (2018)
- Authors: Farhan Ahmed; Sonali Kumari; Anand Kumar Kondapi
- Barriers to Effective Drug Treatment for Brain Metastases: A
Multifactorial Problem in the Delivery of Precision Medicine
- Authors: Minjee Kim; Sani H. Kizilbash; Janice K. Laramy; Gautham Gampa; Karen E. Parrish; Jann N. Sarkaria; William F. Elmquist
Abstract: The treatment of metastatic lesions in the brain represents a serious unmet medical need in the field of neuro-oncology. Even though many effective compounds have demonstrated success in treating peripheral (non-CNS) tumors with targeted agents, one aspect of this lack of success in the brain may be related to poor delivery of otherwise effective compounds. Many factors can influence the brain delivery of these agents, but one key barrier is a heterogeneously "leaky" BBB that expresses efflux transporters that limit the BBB permeability for many targeted agents. Future success in therapeutics for brain metastases must take into account the adequate delivery of "active, free drug" to the target, and may include combinations of targeted drugs that are appropriate to address each individual patient's tumor type. This review discusses some issues that are pertinent to precision medicine for brain metastases, using specific examples of tumor types that have a high incidence of brain metastases.
PubDate: 2018-07-12
DOI: 10.1007/s11095-018-2455-9
Issue No: Vol. 35, No. 9 (2018)
- Authors: Minjee Kim; Sani H. Kizilbash; Janice K. Laramy; Gautham Gampa; Karen E. Parrish; Jann N. Sarkaria; William F. Elmquist
- 3D Printing in Pharmaceutical and Medical Applications – Recent
Achievements and Challenges
- Authors: Witold Jamróz; Joanna Szafraniec; Mateusz Kurek; Renata Jachowicz
Abstract: Growing demand for customized pharmaceutics and medical devices makes the impact of additive manufacturing increased rapidly in recent years. The 3D printing has become one of the most revolutionary and powerful tool serving as a technology of precise manufacturing of individually developed dosage forms, tissue engineering and disease modeling. The current achievements include multifunctional drug delivery systems with accelerated release characteristic, adjustable and personalized dosage forms, implants and phantoms corresponding to specific patient anatomy as well as cell-based materials for regenerative medicine. This review summarizes the newest achievements and challenges of additive manufacturing in the field of pharmaceutical and biomedical research that have been published since 2015. Currently developed techniques of 3D printing are briefly described while comprehensive analysis of extrusion-based methods as the most intensively investigated is provided. The issue of printlets attributes, i.e. shape and size is described with regard to personalized dosage forms and medical devices manufacturing. The undeniable benefits of 3D printing are highlighted, however a critical view resulting from the limitations and challenges of the additive manufacturing is also included. The regulatory issue is pointed as well.
PubDate: 2018-07-11
DOI: 10.1007/s11095-018-2454-x
Issue No: Vol. 35, No. 9 (2018)
- Authors: Witold Jamróz; Joanna Szafraniec; Mateusz Kurek; Renata Jachowicz
- Effect of Tumor Relevant Acidic Environment in the Interaction of a N
-hydroxyindole-2-Carboxylic Derivative with the Phospholipid Bilayer
- Authors: Daniela Monti; Silvia Tampucci; Erica Zucchetti; Carlotta Granchi; Filippo Minutolo; Anna Maria Piras
Abstract: Purpose The inhibitors of the human isoform 5 of lactate dehydrogenase (hLDH5) have attracted growing interest as efficient anti-cancer agents. In the present paper, the interactions between an efficient hLDH5 inhibitor (N-hydroxyindole-2-carboxylic derivative) and lipid bilayers based on dipalmitoylphosphatidylcholine (DPPC) were investigated. Additionally, since interstitial acidification plays a key role in tumor pathogenesis and tumor drug therapy, the effect of acidic pH was assessed and correlated to DPPC/drug interaction. Methods Four different techniques were used: differential scanning calorimetry, dynamic light scattering, UV-VIS second derivative spectrometry and attenuated total reflection Fourier transformed infrared spectroscopy. Results All techniques concur in highlighting a structural change of lipid assembly, susceptible both to pH change and to the presence of the antitumor compound. Lipid vesicles appeared more compact at the lower pH, since the thermal pre-transition from the lamellar gel phase to the ripple gel phase was absent at pH 7.4 and the infrared analysis revealed a stronger acyl chain packing as well as a different hydration degree. Drug interaction was mainly detected in the lipid region including the ester linkages and the first portion of the acyl chains. Furthermore, a lower drug partitioning was recorded at pH 6.6. Conclusions The investigated antitumor agent possesses a stable negative charge at the investigated pH values, thus the lower interaction at the acidic pH is mainly ascribable to an environmental effect on lipid assembly. Therefore, drug efficacy under tumor acid conditions may be hampered by the observed lipid membrane constraints, and suggest for the development of suitable prodrugs.
PubDate: 2018-07-09
DOI: 10.1007/s11095-018-2449-7
Issue No: Vol. 35, No. 9 (2018)
- Authors: Daniela Monti; Silvia Tampucci; Erica Zucchetti; Carlotta Granchi; Filippo Minutolo; Anna Maria Piras
- Safety Assessment of Formulation Vehicles Following Intravitreal
Administration in Rabbits
- Authors: Shirley A. Aguirre; Hovhannes J. Gukasyan; Husam S. Younis; Wenhu Huang
Abstract: Purpose Evaluate 21 formulation vehicles administered to rabbits after intravitreal injection for tolerability and safety. Methods Forty-two Dutch Belted rabbits were anesthetized, and the eyes received a single intravitreal injection of the excipient formulation. Clinical signs and ocular irritation responses were recorded twice daily for 7 days and microscopic evaluation of the eyes, optic nerve, and eyelids was completed at 1-week post treatment. Results Saline (≥ 300 mOsm and ≤ 592 mOsm at pH 7.0 or 300 mOsm at pH 8.0) and 10 formulation excipients; (10% w/v PEG 3350 at pH 7.4, 1% polysorbate 21 at pH 7.4, PVA at pH 7.0, 0.2% polysorbate 80 at pH 7.2, 0.2% Pluronic F108® at pH 7.3, 2%, 100 mM sodium sulfate at pH 3.2, 2 mM sodium glycocholate at pH 7.4, and 275 mM D-mannitol pH 7.0 in sterile water, and 100 mM sodium phosphate in combination with 0.9% NaCl 300 mOsm and 0.01% or 0.05% polysorbate 80 at pH 7.4) considered as formulation vehicles for intravitreal injectables, were well-tolerated in rabbits. Clinical signs were transient and microscopic changes were not observed. Conclusions Of the 21 formulation vehicles evaluated, 10 formulation vehicles were well-tolerated in rabbits and feasible candidates for future investigations.
PubDate: 2018-07-09
DOI: 10.1007/s11095-018-2450-1
Issue No: Vol. 35, No. 9 (2018)
- Authors: Shirley A. Aguirre; Hovhannes J. Gukasyan; Husam S. Younis; Wenhu Huang
- A Multiscale Physiologically-Based Pharmacokinetic Model for Doxorubicin
to Explore its Mechanisms of Cytotoxicity and Cardiotoxicity in Human
Physiological Contexts
- Authors: Hua He; Can Liu; Yun Wu; Xinyuan Zhang; Jianghong Fan; Yanguang Cao
Abstract: Purpose The mechanisms underlying doxorubicin cytotoxicity and cardiotoxicity were broadly explored but remain incompletely understood. A multiscale physiologically-based pharmacokinetic (PBPK) model was developed to assess doxorubicin dispositions at levels of system, tissue interstitial, cell, and cellular organelles. This model was adopted to explore the mechanisms-of-action/toxicity of doxorubicin in humans. Methods The PBPK model was developed by analyzing data from mice and the model was verified by scaling up to predict doxorubicin multiscale dispositions in rats and humans. The multiscale dispositions of doxorubicin in human heart and tumors were explicitly simulated to elucidate the potential mechanisms of its cytotoxicity and cardiotoxicity. Results The developed PBPK model was able to adequately describe doxorubicin dispositions in mice, rats and humans. In humans, prolonged infusion, a dosing regimen with less cardiotoxicity, was predicted with substantially reduced free doxorubicin concentrations at human heart interstitium, which were lower than the concentrations associated with oxidative stress. However, prolonged infusion did not reduce doxorubicin-DNA adduct at tumor nucleus, consistent with clinical observations that prolonged infusion did not compromise anti-tumor effect, indicating that one primary anti-tumor mechanism was DNA torsion. Conclusions A multiscale PBPK model for doxorubicin was developed and further applied to explore its cytotoxic and cardiotoxic mechanisms.
PubDate: 2018-07-09
DOI: 10.1007/s11095-018-2456-8
Issue No: Vol. 35, No. 9 (2018)
- Authors: Hua He; Can Liu; Yun Wu; Xinyuan Zhang; Jianghong Fan; Yanguang Cao
- Development of a Virosomal RSV Vaccine Containing 3D-PHAD® Adjuvant:
Formulation, Composition, and Long-Term Stability
- Authors: J. Lederhofer; J. van Lent; F. Bhoelan; Z. Karneva; A. de Haan; J.C. Wilschut; T. Stegmann
Abstract: Purpose Characterization of virosomes, in late stage preclinical development as vaccines for Respiratory Syncytial Virus (RSV), with a membrane-incorporated synthetic monophosphoryl lipid A, 3D-PHAD® adjuvant. Methods Virosomes were initially formed by contacting a lipid film containing 3D-PHAD® with viral membranes solubilized with the short chain phospholipid DCPC, followed by dialysis, later by adding solubilized 3D-PHAD to viral membranes, or to preformed virosomes from DMSO. Results Virosomes formed from lipid films contained the membrane glycoproteins G and F, at similar F to G ratios but lower concentrations than in virus, and the added lipids, but only a fraction of the 3D-PHAD®. By single particle tracking (SPT), the virosome size distribution resembled that seen by cryo-electron microscopy, but dynamic light scattering showed much larger particles. These differences were caused by small virosome aggregates. Measured by SPT, virosomes were stable for 300 days. 3DPHAD ® incorporation in virosomes could be enhanced by providing the adjuvant from DCPC solubilized stock, but also by adding DMSO dissolved adjuvant to pre-formed virosomes. Virosomes with 0.1 mg/mg of 3D-PHAD®/viral protein from DMSO induced antibody titers similar to those by virosomes containing 0.2 mg/mg of DCPC-solubilized 3D-PHAD®. Conclusions Stable 3D-PHAD® adjuvanted RSV virosomes can be formulated.
PubDate: 2018-07-03
DOI: 10.1007/s11095-018-2453-y
Issue No: Vol. 35, No. 9 (2018)
- Authors: J. Lederhofer; J. van Lent; F. Bhoelan; Z. Karneva; A. de Haan; J.C. Wilschut; T. Stegmann
- Combined Used of Rheology and LF-NMR for the Characterization of
PVP-Alginates Gels Containing Liposomes
- Authors: Giulia Fanesi; Michela Abrami; Francesca Zecchin; Irina Giassi; Elena Dal Ferro; Anja Boisen; Gabriele Grassi; Paolo Bertoncin; Mario Grassi; Paolo Marizza
Abstract: Purpose This paper is based on the characterization of the rheological and Low Field NMR (LF-NMR) properties of an interpenetrated hydrogel made up by poly(N-vinyl-2-pyrrolidone) and sodium alginate. The final aim is to use the hydrogel as a delivery matrix for liposomes, widely used tools in the drug delivery field. Methods Rheology, LF-NMR, TEM, cryo-TEM, confocal laser scanning microscopy and release test were employed to characterize the interpenetrated hydrogel. Different theoretical approaches such as Flory, Chui, Scherer and Schurz theories were used to interpret the experimental results. Results We found that the crosslinking mechanisms of the two polymers produced an anti-synergistic effect on the final mechanical properties of the interpenetrated hydrogel. Instead of creating a continuous network, alginate formed isolated, cross-linked, clusters embedded in a continuous network of poly(N-vinyl-2-pyrrolidone). Additionally, gel structure significantly influenced liposome delivery. Conclusions The rheological and LF-NMR characterization were confirmed and supported by the independent techniques TEM, cryo-TEM and release tests Thus, our findings reiterate the potentiality of both rheology and LF-NMR for the characterisation of soft materials such as interpenetrated polymeric networks.
PubDate: 2018-07-02
DOI: 10.1007/s11095-018-2427-0
Issue No: Vol. 35, No. 9 (2018)
- Authors: Giulia Fanesi; Michela Abrami; Francesca Zecchin; Irina Giassi; Elena Dal Ferro; Anja Boisen; Gabriele Grassi; Paolo Bertoncin; Mario Grassi; Paolo Marizza
- Naïve Bayesian Models for Vero Cell Cytotoxicity
- Authors: Alexander L. Perryman; Jimmy S. Patel; Riccardo Russo; Eric Singleton; Nancy Connell; Sean Ekins; Joel S. Freundlich
Abstract: Purpose To advance translational research of potential therapeutic small molecules against infectious microbes, the compounds must display a relative lack of mammalian cell cytotoxicity. Vero cell cytotoxicity (CC50) is a common initial assay for this metric. We explored the development of naïve Bayesian models that can enhance the probability of identifying non-cytotoxic compounds. Methods Vero cell cytotoxicity assays were identified in PubChem, reformatted, and curated to create a training set with 8741 unique small molecules. These data were used to develop Bayesian classifiers, which were assessed with internal cross-validation, external tests with a set of 193 compounds from our laboratory, and independent validation with an additional diverse set of 1609 unique compounds from PubChem. Results Evaluation with independent, external test and validation sets indicated that cytotoxicity Bayesian models constructed with the ECFP_6 descriptor were more accurate than those that used FCFP_6 fingerprints. The best cytotoxicity Bayesian model displayed predictive power in external evaluations, according to conventional and chance-corrected statistics, as well as enrichment factors. Conclusions The results from external tests demonstrate that our novel cytotoxicity Bayesian model displays sufficient predictive power to help guide translational research. To assist the chemical tool and drug discovery communities, our curated training set is being distributed as part of the Supplementary Material. Graphical Naive Bayesian models have been trained with publically available data and offer a useful tool for chemical biology and drug discovery to select for small molecules with a high probability of exhibiting acceptably low Vero cell cytotoxicity.
PubDate: 2018-06-29
DOI: 10.1007/s11095-018-2439-9
Issue No: Vol. 35, No. 9 (2018)
- Authors: Alexander L. Perryman; Jimmy S. Patel; Riccardo Russo; Eric Singleton; Nancy Connell; Sean Ekins; Joel S. Freundlich
- First Infusion Reactions are Mediated by FcγRIIIb and Neutrophils
- Authors: Felix Weber; Daniel Breustedt; Sonja Schlicht; Claas A. Meyer; Jens Niewoehner; Martin Ebeling; Per-Ola Freskgard; Peter Bruenker; Thomas Singer; Michael Reth; Antonio Iglesias
Abstract: Purpose Administration of therapeutic monoclonal antibodies (mAbs) is frequently accompanied by severe first infusion reactions (FIR). The mechanism driving FIR is still unclear. This study aimed to investigate the cellular and molecular mechanisms causing FIR in humanized mouse models and their potential for evaluating FIR risk in patients. Methods Mice humanized for Fc gamma receptors (FcγRs) were generated by recombination-mediated genomic replacement. Body temperature, cytokine release and reactive oxygen species (ROS) were measured to assess FIR to mAbs. Results Infusion of human mAb specific for mouse transferrin receptor (HamTfR) into FcγR-humanized mice, produced marked transient hypothermia accompanied by an increase in inflammatory cytokines KC and MIP-2, and ROS. FIR were dependent on administration route and Fc-triggered effector functions mediated by neutrophils. Human neutrophils also induced FIR in wild type mice infused with HamTfR. Specific knock-in mice demonstrated that human FcγRIIIb on neutrophils was both necessary and sufficient to cause FIR. FcγRIIIb-mediated FIR was abolished by depleting neutrophils or blocking FcγRIIIb with CD11b antibodies. Conclusions Human FcγRIIIb and neutrophils are primarily responsible for triggering FIR. Clinical strategies to prevent FIR in patients should focus on this pathway and may include transient depletion of neutrophils or blocking FcγRIIIb with specific mAbs.
PubDate: 2018-06-27
DOI: 10.1007/s11095-018-2448-8
Issue No: Vol. 35, No. 9 (2018)
- Authors: Felix Weber; Daniel Breustedt; Sonja Schlicht; Claas A. Meyer; Jens Niewoehner; Martin Ebeling; Per-Ola Freskgard; Peter Bruenker; Thomas Singer; Michael Reth; Antonio Iglesias
- Use of Cyclodextrin as a Novel Agent in the SEC-HPLC Mobile Phase to
Mitigate the Interactions of Proteins or Peptide or their Impurities with
the Residual Silanols of Commercial SEC-HPLC Columns with Improved
Separation and Resolution
- Authors: Indu Javeri; Kaliappanadar Nellaiappan; Charles McNemar; Kirill Yakovlevsky; Amina Soukrati; Phanindra Velisetty; Bijay Misra
Abstract: Purpose Accurate quantification of the intact proteins, antibodies or peptides and their impurities without interaction to silanols of HPLC column. Methods Hydroxypropyl ß Cyclodextrin (HPCD) is added in the mobile phase at different concentrations. Different commercial SEC-HPLC columns and biologics with a molecular weight ranging from 5.8 kDa to 150kDa were assessed with and without cyclodextrin. Results Addition of non-ionic sugars such as Hydroxypropyl ß Cyclodextrin in the mobile phase, resulted improved peak performance such as theoretical plates, peak resolution, peak width, peak height, and improved quantification of aggregates in biologics such as antibodies Humira and Actemra, and peptides such as insulin. There is an increase in peak height, reduced retention time, increased plate and reduced peak width with increasing concentration of cyclodextrin studied. Discussion High ionic strength, basic amino acids such as arginine, organic solvents (with a concentration low enough not to precipitate protein), sodium perchlorate and ion pairing agents in the mobile phase used for separation of peptides, proteins and antibodies to prevent silanol interaction. These commonly used solutions are not always successful, as they not only interact with the biologic, but are sometimes, not compatible. The non-ionic cyclodextrin itself does not cause protein aggregation but prevents the nonspecific binding or interaction of protein itself and thereby allowing for improved resolution, and accurate quantification of aggregates in antibodies, and peptides. The data on the separation in presence of cyclodextrin in the mobile phase showed higher peak resolution, improved peak shape, accurate apparent molecular weight, improved efficiency, and less peak tailing for biological products. Conclusion Hydroxypropyl ß Cyclodextrin in the mobile phase, resulted improved SEC-HPLC resolution, and quantitation of aggregates in biologics by preventing the interaction of biologics to silanol of the commercial SEC-HPLC columns.
PubDate: 2018-06-26
DOI: 10.1007/s11095-018-2446-x
Issue No: Vol. 35, No. 9 (2018)
- Authors: Indu Javeri; Kaliappanadar Nellaiappan; Charles McNemar; Kirill Yakovlevsky; Amina Soukrati; Phanindra Velisetty; Bijay Misra
- Continuous Single-Step Wet Granulation with Integrated in-Barrel-Drying
- Authors: Adrian Schmidt; Hans de Waard; Peter Kleinebudde; Markus Krumme
Abstract: Purpose It was investigated if continuous wet granulation and drying could be combined in a twin-screw granulator with the aim to provide (pre-)dried granules in a single-step process, i.e. in-barrel-drying. Methods To have a consistent and robust material propulsion mechanism, a twin-screw granulator was divided into two compartments. One compartment was operated at lower temperature to granulate and to pre-heat the material, while another compartment was operated at very high temperature to evaporate the granulation liquid as rapidly as possible. Design of experiments was used to investigate the in-barrel-drying process in detail. The process was further investigated for twin-screw wet granulation with API suspension feed, and compared against traditional fluidised-bed drying. Granule and compact properties were evaluated to study the process impact on the product quality. Results In-barrel-drying was demonstrated as feasible and yielded completely dried and granulated material at specific settings. The evaporation zone temperature and the processed mass of water were identified as key parameters to balance the evaporation capacity of the process and the material throughput. Granules and compacts showed an acceptable product quality. Conclusions In-barrel-drying can be used to condense the wet granulation and drying process steps into one piece of equipment, thereby limiting or even omitting downstream drying process steps.
PubDate: 2018-06-25
DOI: 10.1007/s11095-018-2451-0
Issue No: Vol. 35, No. 8 (2018)
- Authors: Adrian Schmidt; Hans de Waard; Peter Kleinebudde; Markus Krumme
- Preclinical Development of Cell-Based Products: a European Regulatory
Science Perspective
- Authors: James W. McBlane; Parvinder Phul; Michaela Sharpe
Abstract: Purpose This article describes preclinical development of cell-based medicinal products for European markets and discusses European regulatory mechanisms open to developers to aid successful product development. Cell-based medicinal products are diverse, including cells that are autologous or allogeneic, have been genetically modified, or not, or expanded ex vivo, and applied systemically or to an anatomical site different to that of their origin; comments applicable to one product may not be applicable to others, so bespoke development is needed, for all elements - quality, preclinical and clinical. Methods After establishing how the product is produced, proof of potential for therapeutic efficacy, and then safety, of the product need to be determined. This includes understanding biodistribution, persistence and toxicity, including potential for malignant transformation. These elements need to be considered in the context of the intended clinical development. Results This article describes regulatory mechanisms available to developers to support product development that aim to resolve scientific issues prior to marketing authorization application, to enable patients to have faster access to the product than would otherwise be the case. Conclusions Developers are encouraged to be aware of both the scientific issues and regulatory mechanisms to ensure patients can be supplied with these products.
PubDate: 2018-06-25
DOI: 10.1007/s11095-018-2437-y
Issue No: Vol. 35, No. 8 (2018)
- Authors: James W. McBlane; Parvinder Phul; Michaela Sharpe
- Local Application of Pyrophosphorylated Simvastatin Prevents Experimental
- Authors: Xiaobei Wang; Zhenshan Jia; Yosif Almoshari; Subodh M. Lele; Richard A. Reinhardt; Dong Wang
Abstract: Purpose Simvastatin (SIM), a HMG-CoA reductase inhibitor widely prescribed for hypercholesterolemia, has been reported to ameliorate inflammation and promote osteogenesis. Its clinical applications on these potential secondary indications, however, have been hampered by its lack of osteotropicity and poor water solubility. To address this challenge, we propose to design and evaluate the therapeutic efficacy of a novel simvastatin prodrug with better water solubility and bone affinity. Method The prodrug (SIM-PPi) was synthesized by directly conjugating a SIM trimer to a pyrophosphate (PPi). It was characterized and evaluated in vitro for its water solubility, osteotropicity, toxicity, anti-inflammatory and osteoinductive properties. It was then tested for anti-inflammatory and osteoinductive properties in vivo by three weekly injections into gingiva of a ligature-induced experimental periodontitis rat model. Results In vitro studies showed that SIM-PPi has greatly improved water-solubility of SIM and shows strong binding to hydroxyapatite (HA). In macrophage culture, SIM-PPi inhibited LPS-induced pro-inflammatory cytokines (IL-1β, IL-6). In osteoblast culture, it was found to significantly increase alkaline phosphatase (ALP) activity with accelerated mineral deposition, confirming the osteogenic potential of SIM-PPi. When tested in vivo on an experimental periodontal bone-loss model, SIM-PPi exhibited a superior prophylactic effect compared to dose equivalent SIM in reducing inflammatory cells and in preserving alveolar bone structure, as shown in the histological and micro-CT data. Conclusion SIM-PPi may have the potential to be further developed for better clinical management of bone loss associated with periodontitis.
PubDate: 2018-06-25
DOI: 10.1007/s11095-018-2444-z
Issue No: Vol. 35, No. 8 (2018)
- Authors: Xiaobei Wang; Zhenshan Jia; Yosif Almoshari; Subodh M. Lele; Richard A. Reinhardt; Dong Wang
- Chemotherapeutic Delivery from a Self-Assembling Peptide Nanofiber
Hydrogel for the Management of Glioblastoma
- Authors: Christina Karavasili; Emmanuel Panteris; Ioannis S. Vizirianakis; Sotirios Koutsopoulos; Dimitrios G. Fatouros
Abstract: Purpose Localized chemotherapy has gained significant impetus for the management of malignant brain tumors. In the present study, we appraised the versatility of an in-situ gel forming self-assembling peptide, ac-(RADA)4-CONH2, as a biocompatible delivery depot of the chemotherapeutic drug doxorubicin (DOX) and the anticancer agent curcumin (CUR), respectively. Methods The morphology and mechanical properties of ac-(RADA)4-CONH2 were assessed with scanning electron microscopy (SEM) and rheological studies. The in vitro drug release from ac-(RADA)4-CONH2 was monitored in phosphate-buffered saline pH 7.4. Distribution of the fluorescent actives within the peptide matrix was visualized with confocal laser scanning microscopy (CLSM). The in vitro biological performance of the ac-(RADA)4-CONH2-DOX and ac-(RADA)4-CONH2-CUR was evaluated on the human glioblastoma U-87 MG cell line. Results SEM studies revealed that the ac-(RADA)4-CONH2 hydrogel contains an entangled nanofiber network. Rheology studies showed that the more hydrophobic CUR resulted in a stiffer hydrogel compared with ac-(RADA)4-CONH2 and ac-(RADA)4-CONH2-DOX, due to the interaction of CUR with the hydrophobic domains of the peptide nanofibers as confirmed by CLSM. In vitro release studies showed a complete DOX release from ac-(RADA)4-CONH2 within 4 days and a prolonged release for ac-(RADA)4-CONH2-CUR over 20 days. An increased cellular uptake and a higher cytotoxic effect were observed for ac-(RADA)4-CONH2-DOX, compared with DOX solution. Higher levels of early apoptosis were observed for the cells treated with the ac-(RADA)4-CONH2-CUR, compared to CUR solution. Conclusions The current findings highlight the potential utility of the in-situ depot forming ac-(RADA)4-CONH2 hydrogel for the local delivery of both water soluble and insoluble chemotherapeutic drugs.
PubDate: 2018-06-25
DOI: 10.1007/s11095-018-2442-1
Issue No: Vol. 35, No. 8 (2018)
- Authors: Christina Karavasili; Emmanuel Panteris; Ioannis S. Vizirianakis; Sotirios Koutsopoulos; Dimitrios G. Fatouros
- Development of a Clinically Relevant Dissolution Method for Metaxalone
Immediate Release Formulations Based on an IVIVC Model
- Authors: Lucija Vuletić; M. Zahirul I. Khan; Drago Špoljarić; Maja Radić; Biserka Cetina-Čižmek; Jelena Filipović-Grčić
Abstract: Purpose The aim of the present work was to classify metaxalone according to the Biopharmaceutics Classification System (BCS), to develop a clinically relevant dissolution method that can be used to predict the oral absorption of metaxalone and to establish an in vitro-in vivo correlation (IVIVC). Methods Solubility of the drug was studied in different pH media and permeability studies were performed using a Caco-2 cell model. The in vitro dissolution and in vivo disposition of metaxalone from 3 different immediate release (IR) tablet formulations were investigated using USP 2 apparatus and a single dose, four-way, crossover bioequivalence study in healthy humans along with an oral solution of the drug, respectively. An IVIVC was established by using a direct, differential based method. Results Metaxalone has been confirmed as a Class II drug according to BCS. Bioavailability studies performed in humans demonstrated that dissolution was the rate limiting step for bioavailability of the drug and one of the test products had significantly improved bioavailability compared to the marketed product Skelaxin®. An IVIVC model was developed that demonstrated an acceptable internal predictability. Conclusion The IVIVC demonstrated that formulation factors play a significant role in dissolution and absorption of metaxalone. A pH 4.5 dissolution medium containing 0.5% NaCl with 0.2% SLS (USP apparatus 2 at 50 rpm) is clinically relevant to predict bioavailability of the drug and is superior to the USP method in terms of the Quality by Design (QbD) concept.
PubDate: 2018-06-22
DOI: 10.1007/s11095-018-2434-1
Issue No: Vol. 35, No. 8 (2018)
- Authors: Lucija Vuletić; M. Zahirul I. Khan; Drago Špoljarić; Maja Radić; Biserka Cetina-Čižmek; Jelena Filipović-Grčić
- A Semi-Physiologically Based Pharmacokinetic Model Describing the Altered
Metabolism of Midazolam Due to Inflammation in Mice
- Authors: Ninad Varkhede; Nita Patel; William Chang; Kenneth Ruterbories; M. Laird Forrest
Abstract: Purpose To investigate influence of inflammation on metabolism and pharmacokinetics (PK) of midazolam (MDZ) and construct a semi-physiologically based pharmacokinetic (PBPK) model to predict PK in mice with inflammatory disease. Methods Glucose-6-phosphate isomerase (GPI)-mediated inflammation was used as a preclinical model of arthritis in DBA/1 mice. CYP3A substrate MDZ was selected to study changes in metabolism and PK during the inflammation. The semi-PBPK model was constructed using mouse physiological parameters, liver microsome metabolism, and healthy animal PK data. In addition, serum cytokine, and liver-CYP (cytochrome P450 enzymes) mRNA levels were examined. Results The in vitro metabolite formation rate was suppressed in liver microsomes prepared from the GPI-treated mice as compared to the healthy mice. Further, clearance of MDZ was reduced during inflammation as compared to the healthy group. Finally, the semi-PBPK model was used to predict PK of MDZ after GPI-mediated inflammation. IL-6 and TNF-α levels were elevated and liver-cyp3a11 mRNA was reduced after GPI treatment. Conclusion The semi-PBPK model successfully predicted PK parameters of MDZ in the disease state. The model may be applied to predict PK of other drugs under disease conditions using healthy animal PK and liver microsomal data as inputs.
PubDate: 2018-06-21
DOI: 10.1007/s11095-018-2447-9
Issue No: Vol. 35, No. 8 (2018)
- Authors: Ninad Varkhede; Nita Patel; William Chang; Kenneth Ruterbories; M. Laird Forrest
- Ranking Itraconazole Formulations Based on the Flux through Artificial
Lipophilic Membrane
- Authors: Konstantin Tsinman; Oksana Tsinman; Ram Lingamaneni; Saijie Zhu; Bernd Riebesehl; Arnaud Grandeury; Michael Juhnke; Bernard Van Eerdenbrugh
Abstract: Purpose The goal of the study was to evaluate a miniaturized dissolution-permeation apparatus (μFLUX™ apparatus) for its ability to benchmark several itraconazole (ITZ) formulations for which in vivo PK data was available in the literature. Method Untreated and micronized powders of ITZ and various enabling formulations of ITZ (commercial Sporanox® solid dispersion, a Soluplus®-based solid dispersion and a nanosuspension) were introduced to the donor compartment of μFLUX™ apparatus. Donor and acceptor chambers were divided from each other by a lipophilic membrane. In addition to the flux evaluations, changes in solid state as a function of time were investigated to gain further insight into the flux changes observed over time for the solid dispersion formulations. Results Initial flux values from Sporanox®, the nanosuspension and the micronized ITZ showed ratios of 52/4/1 with a decreasing flux from nanosuspension and both solid dispersions after 2.5–3 h. Although the initial flux from the Soluplus® formulation was 2.2 times lower than the one observed for Sporanox®, the decrease in flux observed was milder and became ~ 2 times higher than Sporanox® after approximately 2.5 h. The total amounts of ITZ in the receiver compartment after 240 min showed the same rank order as the rodent AUCs of these formulations reported in literature. Conclusions It was demonstrated that in vitro flux measurements using lipophilic artificial membranes could correctly reproduce the rank order of PK results for ITZ formulations. The drop in flux over time for solid dispersions could be backed by experimental indications of crystallization.
PubDate: 2018-06-20
DOI: 10.1007/s11095-018-2440-3
Issue No: Vol. 35, No. 8 (2018)
- Authors: Konstantin Tsinman; Oksana Tsinman; Ram Lingamaneni; Saijie Zhu; Bernd Riebesehl; Arnaud Grandeury; Michael Juhnke; Bernard Van Eerdenbrugh
- Fampridine is a Substrate and Inhibitor of Human OCT2, but not of Human
MATE1, or MATE2K
- Authors: Guangqing Xiao; Christopher Rowbottom; Carri Boiselle; Liang-Shang Gan
Abstract: Purpose The renal clearance of fampridine (Fampyra®, or Ampyra®) significantly exceeds the glomerular filtration rate, suggesting active renal secretion is likely the major elimination pathway. The goal of this study was to identify the renal transporters that are involved in the renal active secretion, and elucidate the active renal secretion mechanism of fampridine. Methods The uptake of fampridine to HEK-293 cells overexpressing human OCT2, MATE1 or MATE2K was determined in the absence and presence of Cimetidine, the prototypical inhibitor of the transporters. The inhibition potential of fampridine on the renal transporters was evaluated by determining the uptake of TEA and Metformin, the probe substrates of the transporters of OCT2 and MATEs, respectively, in the absence or presence of fampridine. Results Significant time- and concentration-dependent uptake of fampridine by human OCT2 was observed. The Km and Vmax were determined as 51.0 ± 17.1 μM and 1107 ± 136 pmole/min/106 cells, respectively. Fampridine also inhibited OCT2 mediated uptake of Metformin with estimated IC50 of 66.8 μM. In contrast, there was not significant uptake of fampridine by human MATE1 or MATE2K, and fampridine did not inhibit MATE1 or MATE2K mediated uptake of TEA. Conclusion The studies indicated fampridine is a substrate and inhibitor of OCT2, but not MATE1 or MATE2K. Results from the study suggested the active renal secretion of fampridine is mediated by human OCT2 but not MATE1 or MATE2K. To our knowledge, fampridine is the first reported substrate specific to OCT2 but not to MATE1 or MATE2K.
PubDate: 2018-06-18
DOI: 10.1007/s11095-018-2445-y
Issue No: Vol. 35, No. 8 (2018)
- Authors: Guangqing Xiao; Christopher Rowbottom; Carri Boiselle; Liang-Shang Gan
- Investigation into the Emerging Role of the Basic Amino Acid L-Lysine in
Enhancing Solubility and Permeability of BCS Class II and BCS Class IV
- Authors: Hamdy Abdelkader; Zeinab Fathalla
Abstract: Background The search for a simple and scalable approach that can improve the two key biopharmaceutical processes (solubility and permeability) for BCS Class II and BCS Class IV has still been unmet need. Purpose In this study, L-lysine was investigated as a potential excipient to tackle problems with solubility and permeability. Bendazac (Class II); quercetin and rutin (Class IV) were employed. Methods Drugs-lysine complexes in 1:1 M ratios were prepared by co-precipitation and co-grinding; characterized for solubility, partition coefficient, DSC, FTIR, SEM, dissolution rate and permeability. Chemical stability of quercetin-lysine and rutin-lysine was studied by assessing antioxidant capacity using Trolox and CUPRAC assays. Results and Conclusion Drugs-lysine salt/complexes were confirmed. Solubility enhancement factors ranged from 68- to 433-fold increases and dissolution rates were also significantly enhanced by up to 6-times, compared with drugs alone. With the exception of rutin-lysine, Papp for bendazac-lysine and quercetin-lysine enhanced by 2.3- to 4-fold. Papp for quercetin (Class IV) benefited more than bendazac (Class II) when complexed with lysine. This study warrants the use of L-lysine as a promising excipient for enhanced solubility and permeability of Class II and Class IV, providing that the solubility of the drug is ensured at 'the door step' of absorption sites.
PubDate: 2018-06-18
DOI: 10.1007/s11095-018-2443-0
Issue No: Vol. 35, No. 8 (2018)
- Authors: Hamdy Abdelkader; Zeinab Fathalla


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About Edwin I.Close
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All styles - strumming, single note playing
Improvisation soloing
Proper technique
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About Edwin
I am a professional teacher/studio musician/performer/producer with over 17 years of private teaching experience and a graduate of the University of Miami Studio Music and Jazz program in 2002 specializing in the guitar.
I am available to teach guitar(acoustic, electric, classical) for all levels, ages, and styles(pop to folk, rock to soul, world to classical) in English, Spanish and Japanese.
Other subjects taught include bass guitar, piano/keyboard, ukulele, banjo, mandolin, harmonium, classical percussion, music theory, composition(all styles from pop to classical), ear training, and studio production/engineering/mixing.
Born in Cali, Colombia on April 1979, I began my musical endeavors studying the piano at the age of 6. Early on I had the opportunit
During 1996-98 I studied jazz guitar at the New World School of the Arts music program under the direction of J.B. Dyas and Dr. Roby George. Upon graduation, I was immediately accepted to the University of Miami jazz guitar program under the direction of Randall Dollahan. It was during this time that I also refined my skills as a classical guitarist and as a composer/arranger. In addition, I began passing my knowledge onto friends and eventually began working as a teacher.
My ability to play almost any genre of music is the fruit of past experience playing with an impressive variety of music groups, including jazz combos, symphony orchestras, Andean world music ensembles, and several rock and pop groups as well. As a studio guitarist I have recorded for various artists including Jaci Velasquez, Carlos Ponce, Alexandre Pires, and Noelia.
*** Lesson Details ***
Now also available to teach online video chat lessons through Skype.
Every one of you is unique and there are many possible paths to reach your goals in music.
With my background and music industry experience, I am able to customize my lessons for you so that you can reach your desired goals. We will take some time to find out where your passion lies in music and I will use my experience and knowledge to create a customized lesson-plan that will allow us to focus on reaching your desired goals and at the same time maintain a well rounded music education.
I find this to be key in making the lessons and your practice sessions very enjoyable, fun and laid back - knowing that everything we practice, play and talk about is in line with your goals as a student.
I will also be playing along with you and demonstrating everything that we're working on - music is meant to be shared and played with others and it is important to have that experience of interaction from early on in your lessons.
So whether it's learning to accompany yourself or others, write songs, read music, understand harmony, solo, or just jam out to your favorite songs, you will be well on your way to reaching your goals within 6 months of my lessons.
Look forward to making music with you!
Want to learn a quick exercise for mastering the fretboard on your guitar? Check out my article on the TakeLessons blog here: http://takelessons.com/blog/guitar-fretboard-chart
*** Studio Equipment ***
Living room w/ grand piano and seating for parents.
Room/studio with professional recording equipment - Logic Pro X recording software, Mackie HR824 Studio Monitors, Miktech C4 Tube Microphone, UA6176 Preamp/compressor, Apogee Duet D/A converter.
*** Travel Equipment ***
I provide my instrument and teaching materials.
Students provide their instrument, music folders.
*** Specialties ***
All styles - pop, rock, classical, jazz, blues, folk, ethnic, latin, soul
· · Online
· Mandolin · In studio
· Ukulele · Online
Edwin I.
Edwin I.
About Chris S.Close
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About Chris
I was born into a musical family and have studied classical piano since I was 4 years old! I am very well versed in music theory and proper technique, with an emphasis on avoiding player's injuries, as well as a great knowledge of classical Pieces for any skill level.
As a young teenager I grew rebellious and learned how to play the electric guitar and have since sought teachers outside my family to learn modern styles and 5 other instruments!! I have also worked toward a music degree and have made music the center of my life.
Classical music is not everyone's passion but a good practice routine, attitude and environment is always a good thing to ha
*** Lesson Details ***
Lessons are held with a fun and relaxed attitude. Learning music should always be enjoyable and a good attitude and love for music is cultured and encouraged.
Lessons are structured just like a practice session should be. We will begin with a warm-up exercise designed to acquaint you with the proper technique to meet your personal musical goals. the next activities are highly personalized, but is usually something like reading music or a music theory game. These activities are things that are good for you but may not be your favorite part of learning music. They will, however, go a long way toward your better understanding of how your favorite music is structured.
Examples could be learning about 12 bar blues, common strum patterns (for guitar), scales, sight-reading, or music analysis.
We will spend the rest of class learning and practicing an activity of your choice. This is usually a song but can be anything you wish to improve upon. this is usually a long-term goal of yours. *I've always wanted to learn......*
By structuring our lessons the same as how you will practice, and by keeping good notes, it will be easy for you to take on practice at home and achieve all of your musical goals!
*** Travel Equipment ***
Students should have their own guitar/piano/keyboard etc. Guitar/violin students should also have a music stand and tuner to keep at home. I will bring picks, spare tuner, music, and handouts.
*** Specialties ***
I primarily specialize in classical piano in styles such as Muzio Clementi and Frederic Chopin. I also play Bach and various Spanish classical guitar pieces. I have also extensively studied electric guitar in Blues such ZZ Top, Metal such as Metallica, and rock such as Led Zeppelin. I have also studied Irish and Celtic folk music for instruments such as Mandolin and Violin.
· Bass Guitar · In studio
· Piano · In home
· Piano · In home
Chris S.
Chris S.
About Kelvin L.Close
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I have been teaching mandolin lesson for almost 18 years.
Students will learn everything from the ground up. While they move from one skill level to the next, instruction will include not only learning how to play their mandolin, but instrument and equipment maintenance, passing a proficiency exam at the end of each session
About Kelvin
I am very comfortable with all aspects of the current music syllabus, including teaching musical concepts (such as duration, pitch, dynamics, tone color, texture and structure) as well as performance, composition. I am fully qualified, with a Bachelor of Education in Music, Double Masters in music performance and education from University of Nottingham.
I am proficient in classical, jazz and Celtic fiddle violin and possess solid skills in piano (grade 8-13) Royal conservatory system.
Throughout my teaching career, I have been driven to help students achieve their very best. I str
The most important thing I look for in a student is communication skills, as well as talent. I like to nurture students and help identify their individual strengths, which is a key factor in shaping a musical persona that will make its mark both on and offstage. I do not advocate a uniform technique for all students. Physical differences and learning styles are always taken into consideration. Potential is as important to me as early achievements and experience. My goal is to help students become self-sufficient, discriminating artists. I discuss practice techniques often and develop individualized scale routines. I encourage initiative and expressive musicality as well as precision. Above all, music needs to bring obvious joy to the student, regardless of the difficulties."
*** Lesson Details ***
I use Suzuki and traditional method for my students... for Suzuki beginner they will play a song in four days....
*** Studio Equipment ***
In-Studio- Lessons in separate music lesson room, piano and violin are available. Students and parents will enjoy comfortable and clean studio environment with recent remodeled new hard wood floor and studio patio window over looking at beautiful garden. Free WiFi available for parents while waiting during the lesson appointment.
University of St Francis Joliet- can teach in rehearsal rooms at the university.
Online class at world class teaching studio
*** Travel Equipment ***
violin, viola, cello, piano and guitar
*** Specialties ***
I specialize in Suzuki teaching method for beginners, traditional conservatory method for intermediate and Royal conservatory recital program for advanced level students..I also teach orchestration program to help students prepare their auditions for major symphonies through out the country including Chicago symphony orchestra etc...
· Banjo · In studio
· Photography · Online
· Photography · Online
Kelvin L.
Kelvin L.
About Linda L.Close
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I have over 30 years experience as a music teacher. Although guitar is my main instrument, I play several stringed instruments, including mandolin, well enough to teach beginners of ALL ages - children, teens, and adults. I have played mandolin with bluegrass bands, in the past.
Mandolin is a good first instrument for those who have never played a stringed instrument before, and for young children whose hands are not strong enough to play a larger instrument such as a guitar. It is fairly easy to learn, and fun to play.
About Linda
I do not typically provide any equipment - but I am willing to select and purchase books for the students to learn from (cost of books to be reimbursed by the student/parent) when requested to do so.
I am also willing to provide stick-on note-names for the keyboard, for young children.
The students must have their own instruments, and provide a folder for sheet music and notes/instructions.
*** Specialties ***
Guitar, I specialize in the following styles: jazz, rock, blues, folk, bluegrass, and children's songs.
Piano: I prefer electronic keyboard to acoustic piano, but am happy to teach beginning students on a regular piano as well. I teach note-reading, playing by ear, and theory, with en emphasis on rock, pop, and folk music. I include arranging, chord theory, and use of the many features of an elec
Bass Guitar: I teach rock, pop, funk, and country music on bass.
Banjo: I teach bluegrass, country, and some blues and rock music. I can also teach a bit of old-timey frailing/clawhammer style.
English and Reading: I am highly qualified, to tutor/teach English (spoken, written, and reading comprehension) to both native English speakers and to those learning it as a second language.
*** I am particularly good at working with children who have a.d.h.d. and other learning disabilities!
· Ukulele · Online
· Banjo · In studio
· Banjo · In home
Linda L.
Linda L.
About Dee F.Close
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I have taught mandolin lessons for over 10 years and played mandolin professionally in two bands for over 20 years.
About Dee
Books. Students must have their own instrument (keyboards are acceptable for taking piano lessons). I always council students on brand, quality of instrument they are purchasing before they buy it.
*** Specialties *** I have been a public school music educator for over 28 years, have taught private music lessons for over 30 years. I have taught band, orchestra, and choir which enables me to teach many instruments and voice. I also have been a language and reading tutor for over 6 years and have worked with students with special needs for over 10 years. I studied classical guitar with master guitarist, Christopher Parkening, at Montana State University where I graduated with a B.M.E. I also did graduate work at MSU in composition. I am completing a Masters Degree in Teacher Leadership currently at Gran
Online student requirements: A fast, reliable COMPUTER; HIGH SPEED INTERNET (at least 400 kbps); SKYPE software; WEBCAM (preferably HD); MICROPHONE (most laptops or tablets have mikes built in). Be sure your camera is focused on you and your instrument, if applicable.
· Piano · In home
· Organ · Online
The very first day,Angel,my 12 year old daughter said "Mom--I like her"---plus,look at her qualifications ---and you will know that we found a rare gem in her!
· Violin · Online
Dee F.
Dee F.
About Christopher W.Close
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About Christopher
*** Lesson Details ***
Having been in the student seat throughout my training, I know that the right teacher makes all the difference. That is why I believe it is so important to find a teacher that is invested in your success and understands and values the student/teacher relationship.
My students find me to be a patient teacher who is able to balance the fun and excitement of learning a new instrument and the discipline necessary to develop a new skill and achieve your musical goals.
I tailor all of my les
Music has been my passion as long as I can remember, and teaching others who feel the same is what I love doing. I hope we can work together one day and find out what we can accomplish together!
*** Specialties ***
I am fluent in most popular styles, rock/pop/country/jazz, and also skilled in classical/fingerstyle guitar.
· Guitar ·
I've had a few guitar instructors through out my life and Chris was by far the best one Iâve had. I went to him after taking guitar for a couple years with other instructors and he helped me rediscover my love for it. Heâs motivating, smart, and all around a great instructor. Iâd recommend him to anyone--from beginners to even more advanced guitarists. He really is the best!
· Music Performance ·
Chris was instrumental in me rediscovering my love of guitar through performance. For the band that was assembled we were allowed to pick the songs which made us more motivated as well as making it fun. Chris was excellent at determining your strengths and challenging you. I had never played lead guitar before. Now I expect to be the lead guitarist for the band.
· Guitar ·
I took lessons with Chris for probably a year and a half, maybe two years. He was easily one of the greatest teachers I've ever had. He would let me pick the songs I wanted to learn and then, despite his feelings toward the music, would listen intently to the song, figure out everything about how it's played, and then decide the most appropriate way to go about teaching said song according to what he knew I was and wasn't capable of. He always pushed me to do better and if I couldn't get passed a certain part we would work on it until I nailed it. Not to mention he's a really cool dude so there was never a dull moment. I can't recommend him enough.
Christopher W.
Christopher W.
About Andrew C.Close
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from basic instrument setup, chords, and techniques to various songs and styles
About Andrew
Currently In Las Vegas, Andrew splits his time between his original band, various productions in the casino showrooms, a well-known local country cover band, teaching, running his own music copying, arranging, and orchestration company, various freelance engagements, and spending time with his amazing wife and two sons.
Andrew's original band, "Tin Toy Cars," formed in 2014 and consists of two local Las Vegas musicians and a few musicians from Cirque du Soleil. Their debut album entitle
Andrew currently plays in the orchestra for the weekly production "Brunch to Broadway" at Red Rock Resort and Casino. The show features original members of Broadway's "Smokey Joe's Cafe" and the wonderful music of Jerry Leiber and Mike Stoller. Band members include musicians from "Le Reve" at the beautiful Wynn Resort, as well as long time veterans of Bette Midler's Orchestra and Donnie and Marie Osmond's backing band.
Andrew also performs with local country cover and line dance band "The Voodoo Cowboys." The band can be seen almost any night in Las Vegas between the famed Gilleys at Treasure Island, Toby Keith's I Love This Bar at Harrah's Resort, and one of the three stages at the amazing Fremont Street Experience.
Andrew also plays in the band at a local church on Sunday mornings and Wednesday evenings, and teaches a handful of lessons each week on his various instruments.
*** Lesson Details ***
Music Theory (Building Scales, Harmonizing Scales into Chords)
Ear Training
Single String Concepts (Scales, Arpeggios, Intervals)
Rhythm Concepts (Chords, Blending with a Band)
Learning Songs
Writing Licks, Lines, Chord Progressions, Charts, and Songs
Techniques (Pick vs. Fingers vs. Hybrid Picking)
Acoustic vs. Electric vs. Nylon String
Slide and Steel Guitar
Mandolin, Banjo, Ukulele, and Other Doubling Instruments
Playing in a Stylistically Appropriate Manner
Choosing the Right Equipment for the Gig or Project
Music Reading
How to Practice
How to Market Yourself to Acquire Work
*** Studio Equipment ***
various electric and acoustic guitars, mandolin, ukulele, banjo. A few different amplifiers, and many different pieces of effect and accessory equipment.
*** Travel Equipment ***
various electric and acoustic guitars, mandolin, ukulele, banjo.
*** Specialties ***
All Contemporary Styles (Rock, Blues, Country and Country Rock, Mo-Town, Jazz, Latin, Latin Jazz, Fusion, Metal and Tapping Style, Theater)
· Guitar · In studio
· Banjo · In studio
· Banjo · In studio
Andrew C.
Andrew C.
About Nolan M.Close
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Mandolin is a magical instrument, that livens and spices up any occasion or form of music! The sweet high tones can be found in bluegrass and country music, Irish music, Italian traditionals, and many varied other musics around the world.... Come and explore the joys of mandolin! :-)
About Nolan
· Singing · In home
Nolan M.
Nolan M.
About Vic D.Close
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I can help you to learn chords and improvise in country rock and bluegrass styles
About Vic
· Acoustic Guitar · In studio
· Guitar · In studio
· Acoustic Guitar · In home
Vic D.
Vic D.
About Coleman S.Close
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My lessons are focused on building foundational techniques that can be applied across genres and playing styles. From picking technique that lays the groundwork for intricate melodies and expressive tremolo, to fretboard work that allows for a wide array of chords, you'll learn solid skills to allow comfortable play with any group.
About Coleman
With years of tutoring experience specific to the mandolin, Coleman has the expertise to help you achieve your music goals.
Coleman S.
Coleman S.
How it Works
From finding the perfect teacher to managing payments, scheduling and tracking your progress, we take care of all the details, so you can focus on learning. Learn More
Search for a teacher
Compare hundreds of teachers based on the criteria that matter to you, including background checks, age and experience.
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Your teacher will welcome you with a personalized curriculum to meet your specific goals and you'll be able to manage your entire schedule through our free online account.
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problem: The Error Code Is Error Vlookup ExcelThis error is usually caused by misconfigured system files that create registry errors within your operating system. Windows errors can cause program lock-ups, slow PC performance, system crashes, computer freezing and more.
Cause: Registry errors generally occur when new programs are installed over old ones without the old programs being completely uninstalled. This can cause registry pile-ups and error messages. Another potential cause of these error messages can come from malicious software such as adware, spyware, and viruses.Repair The Error Code Is Error Vlookup Excel Instantly -Windows Media Player DVD: Fixes issues that can prevent DVDs from playing in Windows Media Player.Free hard drive space is incredibly important to a smooth running Windows system.I've tried /bcdedit, /bcdboot and /bootrec, all with no avail.Skip to main content area Sign up for our daily newsletter Newsletter IT PRO Main menu Security Mobile Network/internet Cloud Strategy Server/storage Software More Sections News GDPR Blockchain Machine learning Big data Operating systems Laptops Whitepapers You are here: Home Software operating systems 17 Windows 10 problems - and how to fix them Share twitter linkedin facebook Clare Hopping, Adam Shepherd, Simon Handby, Rene Millman, Lee Bell Tutorials 1 Dec, 2017 Stop tearing your hair out and follow our tips Windows 10 has been hailed by many as a vast improvement over the previous generation, marrying the best features of 'classic' Windows with the best bits of Windows 8.Reduce startup programs Many programs will load when Windows start, even though they don't need to.Read this first!To run a troubleshooter, just click it in the Troubleshooting pane.View of all troubleshooters in Windows 10 Find troubleshooters Email Print Was this information helpful?HomeGroup: Looks for problems with your HomeGroup network and file-sharing settings.To do this, you need to make sure that Windows is taking these snapshots (restore points) on a regular basis.You can expect to learn how to refresh, reset and restore your PC, create a recovery drive, use File History, and how to troubleshoot system errors using the System Configuration tool.Pages 1 2 next › last » Read more about operating systems Software Windows 10 by Taboola Sponsored Links You might like Government Stimulus Plan Saves California HomeownersHARP Quiz If You Have a Car, You Need This New TechnologyFIXD How To Pay Off Your House ASAP (So Simple It's Unbelievable)LowerMyBills Get the ITPro Newsletter Get FREE weekly newsletters from ITPro - delivering the latest news, reviews, insight and case studies.I want to figure out a way to install CS6 without running into these problems.fix windows 10 the six month bedroom makeover spoonful of imagination .
SolutionS: Scan and repair any missing or damaged Windows registry files using RegCure Pro. After the registry issues are resolved, it is recommended to optimize your PC by removing any spyware, adware and viruses with Plumbytes.
STEP 1: Automatically Fix The Error Code Is Error Vlookup Excel with RegCure Pro
STEP 2: Optimize your PC with Plumbytes.
1) Download and install RegCure Pro to fix The Error Code Is Error Vlookup Excel errors.
2) Install program and click Scan button.
3) Click the Fix Errors button when scan is completed.
4) Restart your computer normally to have a check.
Plumbytes is one of the most powerful spyware removal tools on the market. Plumbytes can help you detect and delete various kinds of malware, spyware, viruses and adware from your computer. Follow the removal steps below to automatically remove malicious files.
Step 1: Download removal tool Plumbytes by clicking on the below button.
Step 2: Following the installation wizard to install it on your PC. After the installation, launch Plumbytes and click 'Run a Scan' to perform a full and quick system scan on your PC.
Step 3: As soon as finishing the system scan, choose Select all and then click Remove Now to get rid of all the threats on your PC


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Posted at April 15th, 2016, Aleta Loyola write about Choosing Best Building the Custom Made Entertainment Center. Entertainment center is much needed to be provided in your house. The togetherness with your family will not complete without entertainment center. You can have fun and enjoyment through entertainment center. If you have dealt to build the ...Read More
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Posted at April 12th, 2016, Aleta Loyola talk about Choosing Modern Rustic Bedroom Design Inside of House. At this point of time when everything seems to be modern, rustic bedroom design is in fact something still found to be interesting in the eyes of some people. Moreover, they also creatively combine the rustic theme with modern touches in or...Read More
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Posted at April 13th, 2016, Aleta Loyola share about Interior Designer Modern and How to Create with the Best Design Ideas. In case you are still confused in determining the right decorating ideas for your house, it is highly recommended for you to choose the modern theme. This kind of theme will be so suitable for you, especially if you are a kind of person who...Read More
Posted at April 22nd, 2016, Blenda Eliassen share about How You Get Beautiful Bathroom Shower Remodel Ideas ?. A house can be without a dining room and home office, but it cannot be without a bathroom. In an apartment, you will only find several rooms that are indeed important for the owner. But bathroom will always be a room that every building nee...Read More
Posted at April 25th, 2016, Blenda Eliassen post about Recycled DIY Crafts: Earth Day Recycled Crafts for Kids. Nowadays, people are so busy playing their gadgets and forget about how to do some more meaningful things. They are so busy to check their social network sites and to play many games in their phones. It is not that you have to cut off all t...Read More
Posted at August 2nd, 2016, Blenda Eliassen post about Sheer Curtain Ideas for Living Room: One of the Ideas to Apply to Have Better Living Room. Have you ever found some boredom or inconvenience whenever you are spending the time in the living room? The living room should be a good place for you to enjoy great time there. Therefore, if you face boredom, it is so bad for the living r...Read More
Posted at April 10th, 2016, Aleta Loyola write about Contemporary Designing for Black and White Interior Decorating. It is better for us to design our home based on our own personality and style. If you are eager to create an extraordinary house, why don't you try black and white concept for your interior? Black and white is a symbol of balance and besi...Read More


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Ray Ban Outdoorsman Tortoise
Ray Ban Rb3386
It is important to understand that a broken promise, alone, is not a sufficient basis for a fraud claim. More than a mere broken promise is required. The victim must also prove that the defendant did not intend to perform the promise at the time the promise was made.
Pei designed Bank of America Tower is Sky Grille, a cafeteria mostly inhabited by the building's sizable workforce but open to the public. The corporate handsome dining room follows the famous curve of the building, and a glass wall affords diners a bird's eye view of downtown. An outdoor terrace with umbrella shaded tables is even more picturesque, but the most breathtaking sight might very well be that of the food: It is miles above typical cafeteria fare.
Not every celeb has gone through a breast reduction at an older age. Actress Drew Barrymore was 16 years old when she had the procedure. For her it seems to have been a great choice since now as an adult she does not have to endure the effects of overly large breasts.
"The study emphasizes the role of cultures or norms," Fisman said. "There's a strong norm of legal compliance in, say, Sweden. Less so in Mozambique.". 2) Find and Communicate Your Core Difference Even if your make it up, you've got to find something that makes your business stand out from the pack. Once you do, you've got to build your entire marketing program around this difference. Is it red trucks, is it an unheard of guarantee, is it a very specific market niche.
Fortune Teller Costume: If any costume strikes a balance between sensuous yet dignified, it is this one. There are two variations of this costume and I could not decide which one I like better. One is short and sensuous while the other has a long flowy skirt.
Combine cinnamon, salt pepper, sugar, onion, and garlic. Blend in 1 tablespoon soy sauce. If not spreadable, add another tablespoon of soy sauce. The metropolitan Atlanta chapter of the Red Cross sent boxes of Girl Scout cookies. Tyson Foods shipped 7,000 pounds of canned chicken and chicken salad. ESPN recently delivered fresh copies of ESPN the Magazine..
"Dowd can't defend his own actions here so he is distracting. It's just Dowd attacking Pete instead of defending his own inexplicable accusations on the radio the day before Pete was to be honored in Cincinnati at the All Star Game. His litigation strategy is to further drag Pete's name through the mud.
Almel: And we promote just a simple line any kind of tobacco is bad; any cancer is is also bad. So there is nothing like good tobacco and bad tobacco. So there is no premium and non premium. Rob Lowe (what a naughty boy!) was the ultimate spunk, but some preferred Andrew McCarthy, Tom Cruise or Mel Gibson (that's before insanity). 'The Brat Pack', were the gilded idols of the times and some really, great movies were made like The Breakfast Club (I still love it!) and Back to the Future. Also I just remembered Eddie Murphy, when he used to be funny, so was Chevy Chase (corny is funny sometimes) and Robin Williams was a scream!.