Nutritional Products from Space Research

NASA Technical Reports Server (NTRS)

1996-01-01

Six scientists from Martin Marietta who did research for NASA on algae as food supply, oxygen source and a recycling agent for long duration space travel founded Martek Biosciences Corporation. Martek's main product is Formulaid for infants, an algae-based, vegetable-like oil containing two essential polyunsaturated fatty acids known as DHA (docosahexaenoic acid) and ARA (arachidonic acid). The acids are found in human milk but not in most infant formulas, and they are believed to be associated with mental and visual development. Formulaid is on the market in two European countries and licensed to the Mead Johnson Division of Bristol-Myers Squibb, American Home Products and others.

Case study: impact of technology investment on lead discovery at Bristol-Myers Squibb, 1998-2006.

PubMed

Houston, John G; Banks, Martyn N; Binnie, Alastair; Brenner, Stephen; O'Connell, Jonathan; Petrillo, Edward W

2008-01-01

We review strategic approaches taken over an eight-year period at BMS to implement new high-throughput approaches to lead discovery. Investments in compound management infrastructure and chemistry library production capability allowed significant growth in the size, diversity and quality of the BMS compound collection. Screening platforms were upgraded with robust automated technology to support miniaturized assay formats, while workflows and information handling technologies were streamlined for improved performance. These technology changes drove the need for a supporting organization in which critical engineering, informatics and scientific skills were more strongly represented. Taken together, these investments led to significant improvements in speed and productivity as well a greater impact of screening campaigns on the initiation of new drug discovery programs.

Paclitaxel (3-hour infusion) followed by carboplatin (24 hours after paclitaxel): a phase II study in advanced non-small cell lung cancer.

PubMed

Roychowdhury, D F; Desai, P; Zhu, Y W

1997-08-01

This phase II study was performed to investigate the efficacy of a 3-hour 225 mg/m2 paclitaxel infusion (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) followed 24 hours later by a 30-minute infusion of carboplatin (dosed to an area under the concentration-time curve of 6) in patients with stage IIIA, IIIB, or IV non-small cell lung cancer. Patients received chemotherapy and were monitored for toxicity, response, quality of life, and survival. Paclitaxel and carboplatin pharmacokinetics were also determined with the first cycle of chemotherapy. Eleven men have been treated to date. Eight were white and three black, with a median age of 65 years. All patients had a performance status of 0 or 1. The regimen was well tolerated, with no deaths or grade 4 toxicities noted. The most common grade 3 toxicity was neutropenia, thrombocytopenia, and parasthesias (observed in <10% of cycles). The overall response rate was 57% (14% complete and 43% partial responses). Quality of life improved in most patients. Physical and emotional well-being improved in 57%, functional well-being in 43%, and social/family well-being in 14% of patients. Pharmacokinetic data are being analyzed by limited sampling technique to predict the paclitaxel area under the concentration-time curve. This unique schedule of paclitaxel and carboplatin is well tolerated and active, and is associated with improvements in various aspects of quality of life.

Synthesis of isotopically labeled daclatasvir for use in human clinical studies.

PubMed

Easter, John A; Burrell, Richard C; Bonacorsi, Samuel J

2016-04-01

Daclatasvir is a novel hepatitis C virus NS5A inhibitor developed by Bristol-Myers Squibb and marketed as Daklinza®. The need to support the development of daclatasvir required the synthesis of carbon-14 labeled material for use in human absorption, distribution, metabolism, and excretion studies. A total of 7.53 mCi of [(14) C]-daclatasvir was synthesized in eight steps from commercially available [(14) C]-copper cyanide. The radiochemical purity was 99.6%, and specific activity was 3.86 μCi/mg. To support a human absolute bioavailability study, 5.56 g of [(13) C2 , (15) N4 ]-daclatasvir was synthesized in four steps. Copyright © 2016 John Wiley & Sons, Ltd.

LIFT Tenant Is Off and Running

NASA Technical Reports Server (NTRS)

Steele, Gynelle C.

2001-01-01

Lewis Incubator for Technology (LIFT) tenant, Analiza Inc., graduated from the incubator July 2000. Analiza develops technology and products for the early diagnosis of diseases, quality control of bio-pharmaceutical therapeutics, and other applications involving protein analyses. Technology links with NASA from existing and planned work are in areas of microfluidics and laser light scattering. Since their entry in LIFT in May, 1997, Analiza has: Received a $750,000 grant from the National Institutes of Health. Collaborated with a Nobel Prize winner on drug design. Collaborated with Bristol-Myers Squibb on the characterization of biological therapeutics. Added a Ph.D. senior scientist and several technicians. Received significant interest from major pharmaceutical companies about collaborating and acquiring Analiza technology.

Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience.

PubMed

Markman, M; Kennedy, A; Webster, K; Kulp, B; Peterson, G; Belinson, J

1997-10-01

To examine the toxicity profile and antineoplastic activity of carboplatin (area under the concentration-time curve of 4 to 7.5) plus 3-hour infusional paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (135 or 175 mg/m2) in women with advanced gynecologic malignancies, we retrospectively reviewed the experience of the Gynecologic Cancer Program at The Cleveland Clinic with this combination chemotherapy regimen. To date, 92 patients (median age, 67 years) have received a total of 460 courses (median number per patient, six) of this two-drug combination. The initial paclitaxel dose was 175 mg/m2 and the carboplatin area under the concentration-time curve was > or = 5 in 72% and 73% of patients, respectively. The major toxicity was neutropenia (grade 4 in 9% of patients), resulting in two febrile episodes and a single septic death. Grade 4 thrombocytopenia and grade 3 peripheral neuropathy were noted in one and two patients, respectively. Twelve patients (13%) experienced at least one episode of paclitaxel-associated hypersensitivity, but all were able to continue with the treatment program. Of the 62 patients with ovarian cancer or primary peritoneal carcinoma with carbohydrate antigen-125 levels > or = 60 U/mL before the initiation of chemotherapy, 74% exhibited a > or = 90% decline in the tumor marker following treatment. We conclude that the combination of carboplatin and 3-hour infusional paclitaxel can be administered in the outpatient setting with a highly acceptable toxicity profile and with major activity in patients with ovarian cancer and primary carcinoma of the peritoneum.

Isolation, Purification, and Identification of Taxol and Related Taxanes from Taxol-Producing Fungus Aspergillus niger subsp. taxi.

PubMed

Li, Dan; Fu, Dongwei; Zhang, Yue; Ma, Xueling; Gao, Liguo; Wang, Xioahua; Zhou, Dongpo; Zhao, Kai

2017-08-28

The content of taxol in the bark of yews is very low, and this is not affordable from the environmental point of view. Thus, it is a necessity to look for alternative sources of taxol production to solve its supply. Currently, a large portion of the taxol in the market comes from chemical semi-synthesis, but the semi-synthetic precursors such as baccatin III and 10-deacetyl-baccatin III are extracted from needles and twigs of yew trees. Taxol-producing fungi as a renewable resource is a very promising way to increase the scale of taxol production. Our group has obtained a taxol-producing endophytic fungus, Aspergillus niger subsp. taxi HD86-9, to examine if A. niger can produce the taxanes. Six compounds from the fermentation broth of strain HD86-9 were isolated and identified by 1 H NMR, 13 C NMR, and ESI-MS. The results showed that the six compounds included four taxane diterpenoids (taxol, cephalomannine, baccatin III, and 10-deacetyl-baccatin III) and two non-taxane compounds (β-sitosterol and flavonoid isovitexin). The study verified that the taxanes can be produced by the A. niger , which is very important to taxol production via chemical semi-synthesis. Additionally, the finding is potentially very significant to solve the taxol semi-synthetic precursors extracted from needles and twigs of yew trees, and the precursor production can be easily increased through the culture condition optimization, genetic breeding, and metabolic engineering of the A. niger .

Ketamine: stimulating antidepressant treatment?

PubMed

Malhi, Gin S; Byrow, Yulisha; Cassidy, Frederick; Cipriani, Andrea; Demyttenaere, Koen; Frye, Mark A; Gitlin, Michael; Kennedy, Sidney H; Ketter, Terence A; Lam, Raymond W; McShane, Rupert; Mitchell, Alex J; Ostacher, Michael J; Rizvi, Sakina J; Thase, Michael E; Tohen, Mauricio

2016-05-01

SmithKline, and Sunovion Pharmaceuticals; royalties from American Psychiatric Publishing, Inc. Also, AstraZeneca Pharmaceuticals LP provided publication support to Parexel for preparation of a manuscript. Spouse employee and stockholder of Janssen Pharmaceuticals. R.W.L. Honoraria for speaking/advising/consulting, and/or received research funds: AstraZeneca, Brain Canada, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson and Johnson, Lundbeck, Lundbeck Institute, Pfizer, Servier, St. Jude Medical, Takeda University, Health Network Foundation, and Vancouver Coastal Health Research Institute. R.M. Investigator Janssen trials of esketamine; 'paid-for' ketamine clinic operated by Oxford Health NHS Foundation Trust - fees used to support the Trust. M.J.O. Consultant: Sunovion and Acadia Pharmaceuticals. Full-time employee of U.S. Department of Veterans Affairs. M.E.T. Advisory/Consultant: Alkermes, Allergan, AstraZeneca, Bristol-Myers Squibb Company, Cerecor inc., Eli Lilly & Co., Forest Laboratories, Gerson Lehrman Group, Fabre-Kramer Pharmaceuticals, Inc., GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante Inc., Merck and Co. Inc. (formerly Schering Plough and Organon), Moksha8, Naurex Inc., Neuronetics Inc., Novartis, Ortho-McNeil Pharmaceuticals (Johnson & Johnson; Janssen), Otsuka, Pamlab, L.L.C. (Nestle), Pfizer (formerly Wyeth Ayerst Pharmaceuticals), Shire US Inc., Sunovion Pharmaceuticals Inc., Trius Therapeutical Inc. and Takeda. Grant support: Agency for Healthcare Research and Quality, Alkermes, AssureRx, Avanir, Forest Pharmaceuticals, Janssen, National Institute of Mental Health, and Otsuka Pharmaceuticals. Speakers Bureau: None since June, 2010. Equity Holdings: MedAvante, Inc. Royalties: American Psychiatric Foundation, Guilford Publications, Herald House, W.W. Norton & Company

Effect of Apixaban Versus Warfarin Use on Health Care Resource Utilization and Costs Among Elderly Patients with Nonvalvular Atrial Fibrillation.

PubMed

Deitelzweig, Steven; Luo, Xuemei; Gupta, Kiran; Trocio, Jeffrey; Mardekian, Jack; Curtice, Tammy; Lingohr-Smith, Melissa; Menges, Brandy; Lin, Jay

2017-11-01

apixaban versus warfarin ($17,077 vs. $20,236, P < 0.001). After PSM, 14,214 patients were matched, with 7,107 in each cohort. Mean age, CCI score, and stroke and bleeding risks were similar between matched cohorts, as were total all-cause health care costs during the baseline period. During the follow-up among matched cohorts, apixaban versus warfarin treatment was associated with higher annual pharmacy costs ($5,159 vs. $2,867, P < 0.001) but lower annual inpatient ($8,327 vs. $14,296, P < 0.001), outpatient ($9,655 vs. $11,469, P < 0.001), and total all-cause health care costs ($23,141 vs. $28,633, P < 0.001), which were reflective of lower inpatient, outpatient, and all-cause HCRU among apixaban-treated patients. Furthermore, bleeding-related ($2,101 vs. $3,963, P < 0.001) and stroke-related ($652 vs. $1,178, P = 0.001) annual medical costs were lower for patients treated with apixaban versus warfarin. After controlling for differences in patient characteristics, in the real-world setting apixaban versus warfarin use was associated with less HCRU and lower total all-cause health care costs and costs for bleeding- and stroke-related medical services, but greater pharmacy costs, among elderly NVAF patients. This study was sponsored by Pfizer and Bristol-Myers Squibb. Deitelzweig is a consultant for Pfizer and Bristol-Myers Squibb and has served on their advisory boards and received speaker fees. Deitelzweig also serves as consultant and advisory board member to Portola and Janssen. Luo, Trocio, and Mardekian are employees of Pfizer and own stock in the company. Gupta and Curtice are employees of Bristol-Myers Squibb and own stock in the company. Lingohr-Smith, Menges, and Lin are employees of Novosys Health, which received research funds from Pfizer and Bristol-Myers Squibb to conduct this study and develop the manuscript. Study concept and design were primarily contributed by Deitelzweig, Luo, and Gupta, along with Trocio, Mardekian, Curtice, and Lin. Lin, Menges, and

Clinically significant depressive symptoms and sexual behaviour among men who have sex with men

PubMed Central

Rodger, Alison J.; Sewell, Janey; Speakman, Andrew; Phillips, Andrew N.; Sherr, Lorraine; Gilson, Richard J.; Asboe, David; Nwokolo, Nneka C.; Clarke, Amanda; Gompels, Mark M.; Allan, Sris; Collins, Simon; Lampe, Fiona C.

2017-01-01

Background The relationship between depression and sexual behaviour among men who have sex with men (MSM) is poorly understood. Aims To investigate prevalence and correlates of depressive symptoms (Patient Health Questionnaire-9 score ≥10) and the relationship between depressive symptoms and sexual behaviour among MSM reporting recent sex. Method The Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) is a cross-sectional study of UK genitourinary medicine clinic attendees without diagnosed HIV (2013–2014). Results Among 1340 MSM, depressive symptoms (12.4%) were strongly associated with socioeconomic disadvantage and lower supportive network. Adjusted for key sociodemographic factors, depressive symptoms were associated with measures of condomless sex partners in the past 3 months (≥2 (prevalence ratio (PR) 1.42, 95% CI 1.17–1.74; P=0.001), unknown or HIV-positive status (PR 1.43, 95% CI 1.20–1.71; P<0.001)), sexually transmitted infection (STI) diagnosis (PR 1.46, 95% CI 1.19–1.79; P<0.001) and post-exposure prophylaxis use in the past year (PR 1.83, 95% CI 1.33–2.50; P<0.001). Conclusions Management of mental health may play a role in HIV and STI prevention. Declaration of interest A.N.P. has received payments for presentations made at meetings sponsored by Gilead in spring 2015. N.C.N. has received support for attendance at conferences, speaker fees and payments for attendance at advisory boards from Gilead Sciences, Viiv Healthcare, Janssen Pharmaceuticals and Bristol-Myers Squibb and a research grant from Gilead Sciences. D.A. served on the advisory board for Gilead in January 2016. M.M.G. has had sponsorship to attend conferences by Bristol-Myers Squibb, been on the BioCryst advisory board and run trials for Merck, Gilead, SSAT, BioCryst and Novartis. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives

BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy.

PubMed

Lee, F Y; Borzilleri, R; Fairchild, C R; Kim, S H; Long, B H; Reventos-Suarez, C; Vite, G D; Rose, W C; Kramer, R A

2001-05-01

BMS-247550, a novel epothilone derivative, is being developed by Bristol-Myers Squibb Company (BMS) as an anticancer agent for the treatment of patients with malignant tumors. BMS-247550 is a semisynthetic analogue of the natural product epothilone B and has a mode of action analogous to that of paclitaxel (i.e., microtubule stabilization). In vitro, it is twice as potent as paclitaxel in inducing tubulin polymerization. Like paclitaxel, BMS-247550 is a highly potent cytotoxic agent capable of killing cancer cells at low nanomolar concentrations. Importantly, BMS-247550 retains its antineoplastic activity against human cancers that are naturally insensitive to paclitaxel or that have developed resistance to paclitaxel, both in vitro and in vivo. Tumors for which BMS-247550 demonstrated significant antitumor activity encompass both paclitaxel-sensitive and -refractory categories, i.e., (a) paclitaxel-resistant: HCT116/VM46 colorectal (multidrug resistant), Pat-21 breast and Pat-7 ovarian carcinoma (clinical isolates; mechanisms of resistance not fully known), and A2780Tax ovarian carcinoma (tubulin mutation); (b) paclitaxel-insensitive: Pat-26 human pancreatic carcinoma (clinical isolate) and M5076 murine fibrosarcoma; and (c) paclitaxel sensitive: A2780 ovarian, LS174T, and HCT116 human colon carcinoma. In addition, BMS-247550 is p.o. efficacious against preclinical human tumor xenografts grown in immunocompromised mice or rats. Schedule optimization studies indicate that BMS-247550 is efficacious when administered frequently (every 2 days x 5) or intermittently (every 4 days x 3 or every 8 days x 2). These efficacy data demonstrate that BMS-247550 has the potential to surpass Taxol in both clinical efficacy and ease of use (i.e., less frequent treatment schedule and/or oral administration).

Rethinking production of Taxol® (paclitaxel) using endophyte biotechnology.

PubMed

Kusari, Souvik; Singh, Satpal; Jayabaskaran, Chelliah

2014-06-01

Taxol® (generic name paclitaxel) represents one of the most clinically valuable natural products known to mankind in the recent past. More than two decades have elapsed since the notable discovery of the first Taxol®-producing endophytic fungus, which was followed by a plethora of reports on other endophytes possessing similar biosynthetic potential. However, industrial-scale Taxol® production using fungal endophytes, although seemingly promising, has not seen the light of the day. In this opinion article, we embark on the current state of knowledge on Taxol® biosynthesis focusing on the chemical ecology of its producers, and ask whether it is actually possible to produce Taxol® using endophyte biotechnology. The key problems that have prevented the exploitation of potent endophytic fungi by industrial bioprocesses for sustained production of Taxol® are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vitro TAXOL production, by Pestalotiopsis breviseta--a first report.

PubMed

Kathiravan, Govindarajan; Sri Raman, Vithiyanathan

2010-09-01

Coelomycetous fungi were screened for the production of TAXOL. TAXOL production of Pestalotiopsis breviseta fungi is confirmed by Ultra Violet (UV) spectroscopic analysis, Infra Red (IR) analysis, high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) and LC-MASS spectroscopy. TAXOL isolated from the P. breviseta fungus was identical with authentic TAXOL and produces 0.064 mg/L (0.128% dry weight of fungal mat). Copyright (c) 2010 Elsevier B.V. All rights reserved.

Design of SGLT2 Inhibitors for the Treatment of Type 2 Diabetes: A History Driven by Biology to Chemistry.

PubMed

Cai, Wenqing; Jiang, Linlin; Xie, Yafei; Liu, Yuqiang; Liu, Wei; Zhao, Guilong

2015-01-01

A brief history of the design of sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors is reviewed. The design of O-glucoside SGLT2 inhibitors by structural modification of phlorizin, a naturally occurring O-glucoside, in the early stage was a process mainly driven by biology with anticipation of improving SGLT2/SGLT1 selectivity and increasing metabolic stability. Discovery of dapagliflozin, a pioneering C-glucoside SGLT2 inhibitor developed by Bristol-Myers Squibb, represents an important milestone in this history. In the second stage, the design of C-glycoside SGLT2 inhibitors by modifications of the aglycone and glucose moiety of dapagliflozin, an original structural template for almost all C-glycoside SGLT2 inhibitors, was mainly driven by synthetic organic chemistry due to the challenge of designing dapagliflozin derivatives that are patentable, biologically active and synthetically accessible. Structure-activity relationships (SAR) of the SGLT2 inhibitors are also discussed.

Paclitaxel and carboplatin in early phase studies: Roswell Park Cancer Institute experience in the subset of patients with lung cancer.

PubMed

Creaven, P J; Raghavan, D; Pendyala, L; Loewen, G; Kindler, H L; Berghorn, E J

1997-08-01

The combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given by 3-hour infusion followed by carboplatin infused over 30 minutes has been evaluated in a series of phase I studies and is currently being explored in a phase II study in patients with limited- and extensive-stage small cell lung cancer. Pharmacokinetic measurements were performed at all dose levels in the phase I studies, in which the use of granulocyte colony-stimulating factor in previously treated patients enabled more than twice the dose of paclitaxel to be given with low to moderate doses of carboplatin (dosed to a target area under the concentration-time curve of 4.0 mg x min x mL[-1]). Treatment-naive patients tolerated high paclitaxel doses (270 mg/m2) with carboplatin (dosed to a target area under the curve of 4.5 mg x min x mL[-1]) without granulocyte colony-stimulating factor support. Twenty-three patients (including previously treated and untreated) with non-small cell lung cancer were entered at a variety of paclitaxel doses in the phase I studies. At 100 to 205 mg/m2 paclitaxel, none of nine treated patients responded; at 230 to 290 mg/m2, four (29%) of 14 responded. In the phase II study of paclitaxel 250 mg/m2 in previously untreated patients with small cell lung cancer, two of five evaluable patients with extensive-stage disease have shown a partial response. In a preliminary analysis of the pharmacodynamics of paclitaxel in relation to neurotoxicity (dose limiting in two of three phase I studies), neurotoxicity correlated with the total dose of paclitaxel, the area under the curve, and the peak paclitaxel concentration, but not with the length of time plasma paclitaxel levels remained above 0.05 micromol/L. These correlations were not strong, however, and analysis of these data is ongoing.

76 FR 79701 - Bristol-Myers Squibb Co. et al.; Withdrawal of Approval of 70 New Drug Applications and 97...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-22

...: Florine Purdie, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0411... Drug Applications; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction...

76 FR 33310 - Bristol-Myers Squibb Co. et al.; Withdrawal of Approval of 70 New Drug Applications and 97...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-08

..., Inc. ANDA 074634 Dobutamine Injection Hospira, Inc. USP, 12.5 mg/mL. ANDA 074643 Minoxidil Topical Bausch & Lomb, Inc. Solution, 2%. ANDA 074743 Minoxidil Topical Sight Solution, 2%. Pharmaceuticals, Inc...

Isolation and characterization of endophytic taxol-producing fungi from Taxus chinensis.

PubMed

Liu, Kaihui; Ding, Xiaowei; Deng, Baiwan; Chen, Wenqiang

2009-09-01

This study investigated the endophytic fungi diversity of Taxus chinensis and screened the taxol-producing fungi in the host. A total of 115 endophytic fungi isolates obtained from bark segments of T. chinensis were grouped into 23 genera based on the morphological traits and sequence analysis of the internal transcribed spacers (ITS1-5.8S-ITS2), indicating endophytic fungi in T. chinensis are diverse and abundant. Diaporthe, Phomopsis (anamorph of Diaporthe), Acremonium, and Pezicula were the dominant genera, whereas the remaining genera were infrequent groups. The 13 representative species of the distinct genera were capable of producing taxol verified by reverse-phase high performance liquid chromatography (HPLC). Among the taxol-producing fungi, the yield of taxol produced by the Metarhizium anisopliae, H-27 was 846.1 microg l(-1) in reformative potato dextrose liquid medium, and the fungal taxol was further validated by mass spectrometry (MS). The taxol-producing fungi (92.3%) were infrequent communities, suggesting that infrequent fungi associated with T. chinensis might be a fascinating reservoir of taxol-generating fungi.

Occurrence of taxol and related taxanes in the wood of Pacific yew

Treesearch

John R. Obst

1993-01-01

Maximizing the yield of taxol per tree is important for the best management of the yew resource. Therefore, the possibility of obtaining additional taxol from the wood was explored. Initial reports form our laboratory, in cooperation with the National Cancer Institute, indicated relatively high concentrations of taxol in Pacific yew heartwood. Although these taxol...

A new large-scale process for taxol and related taxanes from Taxus brevifolia.

PubMed

Rao, K V; Hanuman, J B; Alvarez, C; Stoy, M; Juchum, J; Davies, R M; Baxley, R

1995-07-01

In view of the demonstrated antitumor activity of taxol, ready availability of the drug is important. The current isolation methods starting from the bark of Taxus brevifolia involve multiple manipulations, leading to only taxol and in a yield of 0.01%. A new process consisting of a single reverse phase column is introduced here, and the present purpose is to determine its large scale applicability. The chloroform extractable fraction of the bark of T. brevifolia is applied directly on to a C-18 bonded silica column in 25% acetonitrile/water, with elution using a step gradient: 30-50% acetonitrile/water. On standing, eight different taxanes, including taxol, crystallize out directly from different fractions. The crystals are filtered and purified further by recrystallization. Taxol and four other taxanes are purified this way. The other three require a short silica column. Taxol is freed from cephalomannine by selective ozonolysis. The large scale process gave taxol (0.04%), 10-deacetylbaccatin III (0.02%), 10-deacetyl taxol-7-xyloside (0.1%), 10-deacetyl taxol-C-7-xyloside (0.04%), 10-deacetyl cephalomannine-7-xyloside (0.006%), taxol-7-xyloside (0.008%), 10-deacetyl taxol (0.008%) and cephalomannine (0.004%). Processing of the needles of T. brevifolia gave brevifoliol (0.17%), and that of the wood, 10-deacetyl taxol-C-7-xyloside (0.01%) and 10-deacetyl taxol-C. The reverse phase column process is simpler (one column, direct crystallization), more efficient (eight taxanes obtained simultaneously) and also gives higher yields.

The Bristol "Badminton" Airplane

NASA Technical Reports Server (NTRS)

1926-01-01

The Bristol Badminton, Type 99 airplane has a radial aircooled engine (a Bristol Jupiter 9 cylinder 450 HP.) and three fuel tanks. It is a single seat biplane weighing 1,840 lbs. empty and 2,460 lbs. loaded.

Taxol-producing [corrected] fungal endophyte, Pestalotiopsis species isolated from Taxus cuspidata.

PubMed

Kumaran, Rangarajulu Senthil; Kim, Hyung Joo; Hur, Byung-Ki

2010-11-01

The endophytic fungi, Pestalotiopsis versicolor and Pestalotiopsis neglecta, were isolated from the healthy leaves and bark of the Japanese Yew tree, Taxus cuspidata. The fungal species were identified by their characteristic culture morphology and molecular analysis. For the first time, the test fungi were screened for the production of taxol in modified liquid medium. The presence of taxol was confirmed by HPLC, (1)H NMR, and LC-MS methods of analysis. The maximum amount of taxol production in P. versicolor was recorded as 478 μg/l. The production rate was increased to 9560-fold than that found in the culture broth of earlier reported fungus, Taxomyces andreanae. The extracted fungal taxol showed a strong cytotoxic activity in the in vitro culture of tested human cancer cells by apoptotic assay indicating that the increase in taxol concentration induces increased cell death. A PCR-based screening for ts, a unique gene in the formation of the taxane skeleton, confirmed the molecular blueprint for taxol biosynthesis. The results designate that the fungal endophyte, P. versicolor, is an excellent candidate for an alternate source of taxol supply and can also serve as a potential species for genetic engineering to enhance the production of taxol to a higher level. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Direct effect of Taxol on free radical formation and mitochondrial permeability transition.

PubMed

Varbiro, G; Veres, B; Gallyas, F; Sumegi, B

2001-08-15

To elucidate the potential role of mitochondria in Taxol-induced cytotoxicity, we studied its direct mitochondrial effects. In Percoll-gradient purified liver mitochondria, Taxol induced large amplitude swelling in a concentration-dependent manner in the microM range. Opening of the permeability pore was also confirmed by the access of mitochondrial matrix enzymes for membrane impermeable substrates in Taxol-treated mitochondria. Taxol induced the dissipation of mitochondrial membrane potential (DeltaPsi) determined by Rhodamine123 release and induced the release of cytochrome c from the intermembrane space. All these effects were inhibited by 2.5 microM cyclosporine A. Taxol significantly increased the formation of reactive oxygen species (ROS) in both the aqueous and the lipid phase as determined by dihydrorhodamine123 and resorufin derivative. Cytochrome oxidase inhibitor CN(-), azide, and NO abrogated the Taxol-induced mitochondrial ROS formation while inhibitors of the other respiratory complexes and cyclosporine A had no effect. We confirmed that the Taxol-induced collapse of DeltaPsi and the induction of ROS production occurs in BRL-3A cells. In conclusion, Taxol-induced adenine nucleotide translocase-cyclophilin complex mediated permeability transition, and cytochrome oxidase mediated ROS production. Because both cytochrome c release and mitochondrial ROS production can induce suicide pathways, the direct mitochondrial effects of Taxol may contribute to its cytotoxicity.

Investigation of genotoxic effect of taxol plus radiation on mice bone marrow cells.

PubMed

Ozkan, Lütfi; Egeli, Unal; Tunca, Berrin; Aydemir, Nilüfer; Ceçener, Gülşah; Akpinar, Gürler; Ergül, Emel; Cimen, Ciğdem; Ozuysal, Sema; Kahraman-Cetintaş, Sibel; Engin, Kayihan; Ahmed, Mansoor M

2002-01-01

In this study, we investigated the genotoxic effect of taxol, radiation, or taxol plus radiation on highly proliferative normal tissue-bone marrow cells of Swiss albino mice. Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered bolus intravenously through the tail vein. Radiation was given by using a linear accelerator. There were four treatment categories, which had a total of 34 groups. Each group consisted of five animals. The first was the control category that had one group (n = 5). The second treatment category was taxol alone, which had three groups as per taxol dose alone (n = 15). The third treatment category was radiation alone, which had three groups as per the radiation dose (n = 15). The fourth treatment category was taxol plus radiation, which had 27 groups as per combined radiation dose plus taxol dose concentration and as per pre-treatment timing sequence of taxol before radiation (n = 135). Mice were sacrificed 24 h after taxol or radiation or combined administration using ether anesthesia. The cells were then dropped on two labeled slides, flamed, air dried, and stained in 7% Giemsa; 20-30 well-spread mitotic metaphases were analyzed for each animal; the cells with chromosome breaks, acentric fragments, and rearrangements were evaluated on x1,000 magnification with light microscope (Zeiss axioplan). The mitotic index was determined by counting the number of mitotic cells among 1,000 cells per animal. Differences between groups were evaluated with Student's t-test statistically. Taxol caused a dose-dependent increase in chromosomal aberrations (P = 0.027). Similarly, radiation caused a dose-dependent increase in chromosomal aberrations (P = 0.003) and decreased mitotic index (P = 0.002). In combination, there were a small enhancements at the 40 mg/kg taxol dose level and at 0.25 and 0.5 Gy radiation doses in the 48 h group. However, an increase in chromosomal aberrations was observed after 48 hours of taxol exposure

Live morphological analysis of taxol-induced cytoplasmic vacuolization [corrected] in human lung adenocarcinoma cells.

PubMed

Wang, Xiao-Ping; Chen, Tong-Sheng; Sun, Lei; Cai, Ji-Ye; Wu, Ming-Qian; Mok, Martin

2008-12-01

Taxol (paclitaxel), one of the most active cancer chemotherapeutic agents, can cause programmed cell death (PCD) and cytoplasmic vacuolization. The objective of this study was to analyze the morphological characteristics induced by taxol. Human lung adenocarcinoma (ASTC-a-1) cells were exposed to various concentration of taxol. CCK-8 was used to assay the cell viability. Atomic force microscopy (AFM), plasmid transfection and confocal fluorescence microscopy were performed to image the cells morphological change induced by taxol. Fluorescence resonance energy transfer (FRET) was used to monitor the caspase-3 activation in living cells during taxol-induced cell death. Cells treated with taxol exhibited significant swelling and cytoplasmic vacuolization which may be due to endoplasmic reticulum (ER) vacuolization. Caspase-3 was not activated during taxol-induced cytoplasmic vacuolization and cell death. These findings suggest that taxol induces caspase-3-independent cytoplasmic vacuolization, cell swelling and cell death through ER vacuolization.

Myers-Briggs typology and Jungian individuation.

PubMed

Myers, Steve

2016-06-01

Myers-Briggs typology is widely seen as equivalent to and representative of Jungian theory by the users of the Myers-Briggs Type Indicator (MBTI) and similar questionnaires. However, the omission of the transcendent function from the theory, and the use of typological functions as its foundation, has resulted in an inadvertent reframing of the process of individuation. This is despite some attempts to integrate individuation and typology, and reintroduce the transcendent function into Myers-Briggs theory. This paper examines the differing views of individuation in Myers-Briggs and Jungian theory, and some of the challenges of reconciling those differences, particularly in the context of normality. It proposes eight principles, drawn mainly from Jungian and classical post-Jungian work, that show how individuation as a process can be integrated with contemporary Myers-Briggs typology. These principles show individuation as being a natural process that can be encouraged outside of the analytic process. They make use of a wide range of opposites as well as typological functions, whilst being centred on the transcendent function. Central to the process is the alchemical image of the caduceus and a practical interpretation of the axiom of Maria, both of which Jung used to illustrate the process of individuation. © 2016, The Society of Analytical Psychology.

Polysaccharide-based Noncovalent Assembly for Targeted Delivery of Taxol

NASA Astrophysics Data System (ADS)

Yang, Yang; Zhang, Ying-Ming; Chen, Yong; Chen, Jia-Tong; Liu, Yu

2016-01-01

The construction of synthetic straightforward, biocompatible and biodegradable targeted drug delivery system with fluorescent tracking abilities, high anticancer activities and low side effects is still a challenge in the field of biochemistry and material chemistry. In this work, we constructed targeted paclitaxel (Taxol) delivery nanoparticles composed of permethyl-β-cyclodextrin modified hyaluronic acid (HApCD) and porphyrin modified paclitaxel prodrug (PorTaxol), through host-guest and amphiphilic interactions. The obtained nanoparticles (HATXP) were biocompatible and enzymatic biodegradable due to their hydrophilic hyaluronic acid (HA) shell and hydrophobic Taxol core, and exhibited specific targeting internalization into cancer cells via HA receptor mediated endocytosis effects. The cytotoxicity experiments showed that the HATXP exhibited similar anticancer activities to, but much lower side effects than commercial anticancer drug Taxol. The present work would provide a platform for targeted paclitaxel drug delivery and a general protocol for the design of advanced multifunctional nanoscale biomaterials for targeted drug/gene delivery.

Greater taxol yield of fungus Pestalotiopsis hainanensis from dermatitic scurf of the giant panda (Ailuropoda melanoleuca).

PubMed

Gu, Yu; Wang, Yanlin; Ma, Xiaoping; Wang, Chengdong; Yue, Guizhou; Zhang, Yuetian; Zhang, Yunyan; Li, Shanshan; Ling, Shanshan; Liu, Xiaomin; Wen, Xintian; Cao, Sanjie; Huang, Xiaobo; Deng, Junliang; Zuo, Zhicai; Yu, Shumin; Shen, Liuhong; Wu, Rui

2015-01-01

While taxol yields of fungi from non-animal sources are still low, whether Pestalotiopsis hainanensis isolated from the scurf of a dermatitic giant panda, Ailuropoda melanoleuca, provides a greater taxol yield remains unknown. The objective of the study was to determine the corresponding taxol yield. The structure of the taxol produced by the fungus was evaluated by thin layer chromatography (TLC), ultraviolet (UV) spectroscopy, high-performance liquid chromatography (HPLC), (1)H and (13)C nuclear magnetic resonance spectroscopy ((1)H-NMR and (13)C-NMR), and time-of-flight mass spectrometry (TOF-MS), with standard taxol as a control. The results demonstrated that the P. hainanensis fungus produced taxol, which had the same structure as the standard taxol and yield of 1,466.87 μg/L. This fungal taxol yield from the dermatitic giant panda was significantly greater than those of fungus from non-animal sources. The taxol-producing fungus may be a potential candidate for the production of taxol on an industrial scale.

Vacuum decay container closure integrity leak test method development and validation for a lyophilized product-package system.

PubMed

Patel, Jayshree; Mulhall, Brian; Wolf, Heinz; Klohr, Steven; Guazzo, Dana Morton

2011-01-01

A leak test performed according to ASTM F2338-09 Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method was developed and validated for container-closure integrity verification of a lyophilized product in a parenteral vial package system. This nondestructive leak test method is intended for use in manufacturing as an in-process package integrity check, and for testing product stored on stability in lieu of sterility tests. Method development and optimization challenge studies incorporated artificially defective packages representing a range of glass vial wall and sealing surface defects, as well as various elastomeric stopper defects. Method validation required 3 days of random-order replicate testing of a test sample population of negative-control, no-defect packages and positive-control, with-defect packages. Positive-control packages were prepared using vials each with a single hole laser-drilled through the glass vial wall. Hole creation and hole size certification was performed by Lenox Laser. Validation study results successfully demonstrated the vacuum decay leak test method's ability to accurately and reliably detect those packages with laser-drilled holes greater than or equal to approximately 5 μm in nominal diameter. All development and validation studies were performed at Whitehouse Analytical Laboratories in Whitehouse, NJ, under the direction of consultant Dana Guazzo of RxPax, LLC, using a VeriPac 455 Micro Leak Test System by Packaging Technologies & Inspection (Tuckahoe, NY). Bristol Myers Squibb (New Brunswick, NJ) fully subsidized all work. A leak test performed according to ASTM F2338-09 Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method was developed and validated to detect defects in stoppered vial packages containing lyophilized product for injection. This nondestructive leak test method is intended for use in manufacturing as an in-process package integrity

Effects of Taxol plus radiation on the apoptotic and mitotic indices of mouse intestinal crypt cells.

PubMed

Ozkan, L; Ozuysal, S; Egeli, U; Adim, S B; Tunca, B; Aydemir, N; Ceçener, G; Ergül, E; Akpinar, G; Cimen, C; Engin, K; Ahmed, M M

2001-07-01

In this study we investigated the effect of Taxol, radiation, or Taxol plus radiation on highly proliferative normal tissue--the intestinal crypt cells of Swiss albino mice. Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered by bolus intravenously through the tail vein. Radiation was given using a linear accelerator. There were four treatment categories, which comprised a total of 34 groups. Each group consisted of five animals. The first category was a control category which comprised one group (n = 5). The second treatment category was Taxol alone which comprised three groups (n = 15). The third treatment category was radiation alone which comprised three groups (n = 15). The fourth treatment category was Taxol plus radiation which comprised 27 groups (n = 135). Mice were killed 24 h after Taxol or radiation or combined administration using ether anesthesia. Using a light microscope, apoptotic and mitotic indices were counted on jejunal crypt cells of mice that were stained with hematoxylin-eosin. Differences between groups were statistically evaluated with Student's t-test. Taxol caused a dose-dependent increase in apoptosis (P = 0.045) and decreased the mitotic index (P = 0.006) at high doses. Similarly, radiation caused a dose-dependent increase in apoptosis (P = 0.046) and decreased the mitotic index (P = 0.299) at higher radiation doses. Compared to radiation alone, Taxol caused a significant induction of apoptosis (P = 0.010). In combination, no significant radiosensitizing effect of Taxol was observed (enhancement ratio < 1), when compared to radiation alone. However, an increase in apoptosis was observed after 24 h of Taxol exposure when compared to 12 or 48 h of Taxol exposure (P = 0.0001 and P = 0.0001). These findings suggest that Taxol did not cause a radiosensitizing effect in intestinal crypt cells. However, a 24-hour pretreatment of Taxol exposure followed by radiation caused significant induction of apoptosis and

February 18, 2005 Order Responding to Petition Requesting the Administrator Object to Operating Permit for Bristol-Myers Squibb in Syracuse, NY

EPA Pesticide Factsheets

This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Petition Database available at www2.epa.gov/title-v-operating-permits/title-v-petition-database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Bristol Bay Assessment - Final Report (2014)

EPA Pesticide Factsheets

This is the final Bristol Bay assessment developed and peer reviewed by the Office of Research and Development in EPA. The purpose of this assessment is to provide a characterization of the biological and mineral resources of the Bristol Bay watershed.

Induction of taxol metabolism in the rat by dexamethasone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, C.D.; Gondi, K.N.; Walle, T.

1994-12-31

The antitumor drug taxol was metabolized to two major metabolites (RM1 and RM2) in adult male and female rat liver microsomes. The male rats produced RM1 2.6 fold faster than the females, and they produced RM2 3 fold faster than the females. This correlated well with the sex differences noticed in liver microsomal cytochrome P450 (CYP) 3A content (4.4 fold greater in male) and 6{beta}-hydroxylation of testosterone (2.4 fold greater in male). Taxol was metabolized to three major metabolites (RM1, RM2, and RM3) in adult male and female rat liver microsomes from rats pretreated with dexamethasone. Production of RM1 andmore » RM2 was increased in these rats (2.3 and 3.3 fold respectively in males; 6.5 and 8.7 fold respectively in females) as compared to the untreated rats. These results compared well with the induction of CYP 3A proteins (3.5 fold in male, 10 fold in female) and induction of 6{beta}-hydroxylation (1.9 fold in males, 3.8 fold in females). RM3, which was produced only by the rats pretreated with dexamethasone, had a retention time of 0.58 relative to taxol which corresponds to 6{alpha}- hydroxytaxol, the major human metabolite of taxol. This study indicates that taxol metabolism in the rat is likely due to CYP 3A enzymes. Although the evidence points toward CYP 3A1 as the major isoform involved, it does not rule out others. The findings also suggest that CYP 3A1 is responsible for the induced metabolite, RM3.« less

Sustainability of NGO capacity building in southern Africa: successes and opportunities.

PubMed

Humphries, Debbie; Gomez, Ligia; Hartwig, Kari

2011-01-01

Despite an increase in organizational capacity building efforts by external organizations in low and middle income countries, the documentation of these efforts and their effects on health programs and systems remains limited. This paper reviews key frameworks for considering sustainability of capacity building and applies these frameworks to an evaluation of the sustainability of an AIDS non-governmental organization (NGO) capacity building initiative. From 2004-2007 Bristol-Myers Squibb Foundation's Secure the Future(TM) initiative in southern Africa funded a five country program, the NGO Training Institute (NGOTI), to build capacity of NGOs working to address HIV/AIDS. Lessons learned from this project include issues of ownership, the importance of integrating planning for sustainability within capacity-building projects, and the value of identifying primary capacity-building objectives in order to select sustainability strategies that are focused on maintaining program benefits. Sustainability for capacity building projects can be developed by discussing key issues early in the planning process with all primary stakeholders. Copyright © 2010 John Wiley & Sons, Ltd.

Induction therapy with carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal radiotherapy in the treatment of locally advanced, unresectable non-small cell lung cancer: preliminary report of a phase I trial.

PubMed

Socinski, M A; Clark, J A; Halle, J; Steagall, A; Kaluzny, B; Rosenman, J G

1997-08-01

Locally advanced non-small cell lung cancer is optimally managed with chemotherapy and thoracic irradiation, although the most appropriate strategy is not yet defined. In this phase I trial, we use two 21-day cycles of induction chemotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (225 mg/m2 over 3 hours) and carboplatin (area under the concentration-time curve = 6) followed by concurrent weekly paclitaxel (45 mg/m2/wk x 6) and carboplatin (area under the concentration-time curve = 2/wk x 6) and thoracic irradiation. Patients undergo three-dimensional treatment planning (conformal radiotherapy) to define the cancer target volume precisely. The phase I question being addressed in this study is the maximum tolerated radiation dose given concurrently with low-dose paclitaxel and carboplatin. The initial radiation dose is 60 Gy, with dose escalations to 66 Gy, 70 Gy, and 74 Gy being planned. Ten patients have been entered thus far (eight men and two women). Their median age is 67 years (range, 59 to 78 years), and none of the patients has had greater than 5% pretreatment weight loss. Seven of 10 are evaluable for response to induction carboplatin and paclitaxel, with a response rate of 57% (three partial responses and one minor response). Three patients had stable disease and none of the patients had evidence of progressive disease during induction chemotherapy. Three patients have completed all treatment at 60 Gy and one has completed all treatment at 66 Gy. Three of the four patients have had partial responses (75%), with the remaining patient having stable disease. Toxicity in the concurrent chemoradiotherapy portion of the trial thus far has consisted of grade 3 neutropenia in one patient and grade 4 lymphocytopenia in all four patients. No grade 3 or 4 nonhematologic toxicity has been seen. The trial data are not yet mature enough to report on survival. Accrual and treatment is continuing at the 66 Gy radiation dose level.

Transformation of taxol-producing endophytic fungi by restriction enzyme-mediated integration (REMI).

PubMed

Wang, Yechun; Guo, Binhui; Miao, Zhiqi; Tang, Kexuan

2007-08-01

The REMI method was used to introduce the plasmid pV2 harboring the hygromycin B phosphotransferase (hph) gene controlled by the Aspergillus nidulans trpC promoter and the trpC terminator into a taxol-producing endophytic fungus BT2. REMI transformation yielded stable transformants capable of continuing to grow on PDA medium containing 125 mug mL(-1) hygromycin B. The transformation efficiency was about 5-6 transformants mug(-1) plasmid DNA. The presence of hph gene in transformants was confirmed by PCR and Southern blot analyses. To the authors' knowledge, this is the first report on the transformation of taxol-producing endophytic fungi by the REMI technique. This study provides an effective approach for improving taxol production of endophytic fungi by the genetic engineering of taxol biosynthetic pathway genes in the future.

Taxol induces concentration-dependent phosphatidylserine (PS) externalization and cell cycle arrest in ASTC-a-1 cells

NASA Astrophysics Data System (ADS)

Guo, Wen-jing; Chen, Tong-sheng

2010-02-01

Taxol (Paclitaxel) is an important natural product for the treatment of solid tumors. Different concentrations of taxol can trigger distinct effects on both the cellular microtubule network and biochemical pathways. Apoptosis induced by low concentrations (5-30 nM) of taxol was associated with mitotic arrest, alteration of microtubule dynamics and/or G2/M cell cycle arrest, whereas high concentrations of this drug (0.2-30 μM) caused significant microtubule damage, and was found recently to induce cytoplasm vacuolization in human lung adenocarcinoma (ASTC-a-1) cells. In present study, cell counting kit (CCK-8) assay, confocal microscope, and flow cytometry analysis were used to analyze the cell death form induced by 35 nM and 70 μM of taxol respectively in human lung adenocarcinoma (ASTC-a-1) cells. After treatment of 35 nM taxol for 48 h, the OD450 value was 0.80, and 35 nM taxol was found to induce dominantly cell death in apoptotic pathway such as phosphatidylserine (PS) externalization, G2/M phase arrest after treatment for 24 h, and nuclear fragmentation after treatment for 48 h. After 70 μM taxol treated the cell for 24 h, the OD450 value was 1.01, and 70 μM taxol induced cytoplasm vacuolization programmed cell death (PCD) and G2/M phase as well as the polyploidy phase arrest in paraptotic-like cell death. These findings imply that the regulated signaling pathway of cell death induced by taxol is dependent on taxol concentration in ASTC-a-1 cells.

Fluorescence imaging analysis of taxol-induced ASTC-a-1 cell death with cell swelling and cytoplasmic vacuolization

NASA Astrophysics Data System (ADS)

Chen, Tong-sheng; Sun, Lei; Wang, Longxiang; Wang, Huiying

2008-02-01

Taxol (Paclitaxel), an isolated component from the bark of the Pacific yew Taxus brevifolia, exhibits a broad spectrum of clinical activity against human cancers. Taxol can promote microtubule (MT) assembly, inhibit depolymerization, and change MT dynamics, resulting in disruption of the normal reorganization of the microtubule network required for mitosis and cell proliferation. However, the molecular mechanism of taxol-induced cell death is still unclear. In this report, CCK-8 was used to assay the inhibition of taxol on the human lung adenocarcinoma (ASTC-a-1) cells viability, confocal fluorescence microscope was used to monitor the morphology changes of cells with taxol treatment. We for the first time describe the characteristics of taxol-induced cells swelling, cytoplasmic vacuolization and cell death. Taxol induced swelling, cytoplasmatic vacuolization and cell death without cell shrinkage and membrane rupture. These features differ from those of apoptosis and resemble the paraptosis, a novel nonapoptotic PCD.

Selected CNS Outcomes Among INSTI Antiretrovirals

PubMed Central

Wohl, David; Mills, Anthony; Mera, Robertino; Piontkowsky, David

2017-01-01

with different INSTIs. Disclosures D. Wohl, Gilead Sciences: Consultant and Investigator, Consulting fee and Research grant; Viiv: Consultant and Investigator, Consulting fee and Research grant; Janssen: Consultant, Consulting fee; Bristol-Myers Squibb: Consultant, Consulting fee; A. Mills, Gilead Sciences: Consultant, Investigator and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium; Viiv: Consultant and Investigator, Consulting fee and Research grant; Merck: Consultant, Investigator and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium; Janssen: Investigator, Research grant; Bristol-Myers Squibb: Investigator, Research grant; Sangamo Bio Sciences: Investigator, Research grant; R. Mera, Gilead Sciences: Employee and Shareholder, Salary; D. Piontkowsky, Gilead Sciences: Employee and Shareholder, Salary

In vitro cell cultures obtained from different explants of Corylus avellana produce Taxol and taxanes

PubMed Central

Bestoso, Federica; Ottaggio, Laura; Armirotti, Andrea; Balbi, Alessandro; Damonte, Gianluca; Degan, Paolo; Mazzei, Mauro; Cavalli, Francesca; Ledda, Bernardetta; Miele, Mariangela

2006-01-01

Background Taxol is an effective antineoplastic agent, originally extracted from the bark of Taxus brevifolia with a low yield. Many attempts have been made to produce Taxol by chemical synthesis, semi-synthesis and plant tissue cultures. However, to date, the availability of this compound is not sufficient to satisfy the commercial requirements. The aim of the present work was to produce suspension cell cultures from plants not belonging to Taxus genus and to verify whether they produced Taxol and taxanes. For this purpose different explants of hazel (Corylus avellana species) were used to optimize the protocol for inducing in vitro callus, an undifferentiated tissue from which suspension cell cultures were established. Results Calli were successfully induced from stems, leaves and seeds grown in various hormone concentrations and combinations. The most suitable callus to establish suspension cell cultures was obtained from seeds. Media recovered from suspension cell cultures contained taxanes, and showed antiproliferative activity on human tumour cells. Taxol, 10-deacetyltaxol and 10-deacetylbaccatin III were the main taxanes identified. The level of Taxol recovered from the media of hazel cultures was similar to that found in yew cultures. Moreover, the production of taxanes in hazel cell cultures increased when elicitors were used. Conclusion Here we show that hazel cell cultures produce Taxol and taxanes under controlled conditions. This result suggests that hazel possesses the enzymes for Taxol production, which until now was considered to be a pathway particular to Taxus genus. The main benefit of producing taxanes through hazel cell cultures is that hazel is widely available, grows at a much faster rate in vivo, and is easier to cultivate in vitro than yew. In addition, the production of callus directly from hazel seeds shortens the culture time and minimizes the probability of contamination. Therefore, hazel could become a commercial source of Taxol and

Insulin-Like Growth Factor 2 Silencing Restores Taxol Sensitivity in Drug Resistant Ovarian Cancer

PubMed Central

Brouwer-Visser, Jurriaan; Lee, Jiyeon; McCullagh, KellyAnne; Cossio, Maria J.; Wang, Yanhua; Huang, Gloria S.

2014-01-01

Drug resistance is an obstacle to the effective treatment of ovarian cancer. We and others have shown that the insulin-like growth factor (IGF) signaling pathway is a novel potential target to overcome drug resistance. The purpose of this study was to validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and to determine the efficacy of targeting IGF2 in vivo. An analysis of The Cancer Genome Atlas (TCGA) data in the serous ovarian cancer cohort showed that high IGF2 mRNA expression is significantly associated with shortened interval to disease progression and death, clinical indicators of drug resistance. In a genetically diverse panel of ovarian cancer cell lines, the IGF2 mRNA levels measured in cell lines resistant to various microtubule-stabilizing agents including Taxol were found to be significantly elevated compared to the drug sensitive cell lines. The effect of IGF2 knockdown on Taxol resistance was investigated in vitro and in vivo. Transient IGF2 knockdown significantly sensitized drug resistant cells to Taxol treatment. A Taxol-resistant ovarian cancer xenograft model, developed from HEY-T30 cells, exhibited extreme drug resistance, wherein the maximal tolerated dose of Taxol did not delay tumor growth in mice. Blocking the IGF1R (a transmembrane receptor that transmits signals from IGF1 and IGF2) using a monoclonal antibody did not alter the response to Taxol. However, stable IGF2 knockdown using short-hairpin RNA in HEY-T30 effectively restored Taxol sensitivity. These findings validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and show that directly targeting IGF2 may be a preferable strategy compared with targeting IGF1R alone. PMID:24932685

77 FR 3324 - Release of Airport Property: Fort Myers International Airport, Fort Myers, FL

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-23

... north of Daniels Parkway and Chana Court, near the intersection of Chamberlin Parkway, in Fort Myers... appraised Fair Market Value of $41,622. The value of the parcel to be received is $5,000, and the value of...

Bristol Bay Assessment – Supplemental Peer Review Reports ...

EPA Pesticide Factsheets

These reports represent the results of independent peer reviews of several technical reports submitted to the public docket for the May 2012 draft of the Bristol Bay Assessment, An Assessment of Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska. Background In May 2012, the U.S. Environmental Protection Agency (USEPA) released the draft assessment entitled An Assessment of Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska, or the Bristol Bay Assessment. The purpose of the assessment is to provide a characterization of the biological and mineral resources of the Bristol Bay watershed, increase understanding of the potential impacts of large-scale mining on the region’s fish resources, and inform future governmental decisions. During the public comment period for the May 2012 draft, numerous technical reports were submitted to the public docket. The USEPA identified several of these reports as providing information about issues raised by the peer reviewers, but the reports did not show evidence of prior peer review. The USEPA made arrangements for a contractor to conduct independent peer reviews of seven such reports. The reports and the results of these supplemental peer reviews are provided here to document that the reports are of

Growth-inhibiting effects of taxol on human liver cancer in vitro and in nude mice

PubMed Central

Yuan, Jin Hui; Zhang, Ru Ping; Zhang, Ru Gang; Guo, Li Xia; Wang, Xing Wang; Luo, Dan; Xie, Yong; Xie, Hong

2000-01-01

AIM: To investigate the effects of taxol on SMMC-7721 human hepatoma and its mechanisms. METHODS: In vitro cell growth was assessed by trypan blue exclusion method. Experimental hepatoma model was established by seeding SMMC-7721 cells subcutaneously into Balb/c (nu/nu) nude mice. In vivo tumor growth was determined by measurement of tumor diameter with Vernier calipers. The syntheses of DNA, RNA and protein were analyzed by incorporation of 3H-thymidine, 3H-uridine and 3H-leucine respectively. Using light and electron microscopes to observe the morphological changes of cells including mitosis and apoptosis. RESULTS: Taxol was effective against SMMC-7721 human hepatoma cell growth in the ranges of 2.5 nmol/L-10 nmol/L- with mitotic arrest and apoptosis in vitro. DNA, RNA and protein syntheses in cells were also obviously suppressed by in vitro treatment of taxol for 72 h. Taxol at 2.5 nmol/L reduced 3H-thymidine uptake to about 34% of the control value (P ＜ 0.05). Increasing the dose of taxol to 20 nmol/L resulted in a greater decrease in 3H-thymidine incorporation to 60% of the control value (P ＜ 0.01). At a concentration of 20 nmol/L, the 3H-uridine and 3H-leucine uptakes were reduced to 52% (P ＜ 0.05) and 63% (P ＜ 0.01), respectively. In vivo, taxol significantly inhibited SMMC-7721 tumor growth at 10 mg/kg, i.p. once daily for 10 d. A more than 90% decrease in tumor volume was observed by day 11 (P ＜ 0.01) similarly with mitotic arrest and cell apoptosis. CONCLUSION: Taxol has a marked anticancer activity in SMMC-7721 human hepatoma both in vitro and in nude mice. Its mechanisms might be associated with mitotic arrest, subsequently, apoptosis of the hepatoma cells. No obvious toxicity was observed with in vivo administration of taxol. PMID:11819558

Purity Determination by Capillary Electrophoresis Sodium Hexadecyl Sulfate (CE-SHS): A Novel Application For Therapeutic Protein Characterization.

PubMed

Beckman, Jeff; Song, Yuanli; Gu, Yan; Voronov, Sergey; Chennamsetty, Naresh; Krystek, Stanley; Mussa, Nesredin; Li, Zheng Jian

2018-02-20

Capillary gel electrophoresis using sodium dodecyl sulfate (CE-SDS) is used commercially to provide quantitative purity data for therapeutic protein characterization and release. In CE-SDS, proteins are denatured under reducing or nonreducing conditions in the presence of SDS and electrophoretically separated by molecular weight and hydrodynamic radius through a sieving polymer matrix. Acceptable performance of this method would yield protein peaks that are baseline resolved and symmetrical. Nominal CE-SDS conditions and parameters are not optimal for all therapeutic proteins, specifically for Recombinant Therapeutic Protein-1 (RTP-1), where acceptable resolution and peak symmetry were not achieved. The application of longer alkyl chain detergents in the running buffer matrix substantially improved assay performance. Matrix running buffer containing sodium hexadecyl sulfate (SHS) increased peak resolution and plate count 3- and 8-fold, respectively, compared to a traditional SDS-based running gel matrix. At Bristol-Myers Squibb (BMS), we developed and qualified a viable method for the characterization and release of RTP-1 using an SHS-containing running buffer matrix. This work underscores the potential of detergents other than SDS to enhance the resolution and separation power of CE-based separation methods.

Isolation of anticancer drug TAXOL from Pestalotiopsis breviseta with apoptosis and B-Cell lymphoma protein docking studies.

PubMed

Kathiravan, G; Sureban, Sripathi M; Sree, Harsha N; Bhuvaneshwari, V; Kramony, Evelin

2012-12-01

Extraction and investigation of TAXOL from Pestalotiopsis breviseta (Sacc.) using protein docking, which is a computational technique that samples conformations of small molecules in protein-binding sites. Scoring functions are used to assess which of these conformations best complements the protein binding site and active site prediction. Coelomycetous fungi P. breviseta (Sacc.) Steyaert was screened for the production of TAXOL, an anticancer drug. TAXOL PRODUCTION WAS CONFIRMED BY THE FOLLOWING METHODS: Ultraviolet (UV) spectroscopic analysis, Infrared analysis, High performance liquid chromatography analysis (HPLC), and Liquid chromatography mass spectrum (LC-MASS). TAXOL produced by the fungi was compared with authentic TAXOL, and protein docking studies were performed. The BCL2 protein of human origin showed a higher affinity toward the compound paclitaxel. It has the binding energy value of -13.0061 (KJ/Mol) with four hydrogen bonds.

Isolation of anticancer drug TAXOL from Pestalotiopsis breviseta with apoptosis and B-Cell lymphoma protein docking studies

PubMed Central

Kathiravan, G.; Sureban, Sripathi M.; Sree, Harsha N.; Bhuvaneshwari, V.; Kramony, Evelin

2012-01-01

Background: Extraction and investigation of TAXOL from Pestalotiopsis breviseta (Sacc.) using protein docking, which is a computational technique that samples conformations of small molecules in protein-binding sites. Scoring functions are used to assess which of these conformations best complements the protein binding site and active site prediction. Materials and Methods: Coelomycetous fungi P. breviseta (Sacc.) Steyaert was screened for the production of TAXOL, an anticancer drug. Results: TAXOL production was confirmed by the following methods: Ultraviolet (UV) spectroscopic analysis, Infrared analysis, High performance liquid chromatography analysis (HPLC), and Liquid chromatography mass spectrum (LC-MASS). TAXOL produced by the fungi was compared with authentic TAXOL, and protein docking studies were performed. Conclusion: The BCL2 protein of human origin showed a higher affinity toward the compound paclitaxel. It has the binding energy value of −13.0061 (KJ/Mol) with four hydrogen bonds. PMID:24808664

Anti-proliferative effect of fungal taxol extracted from Cladosporium oxysporum against human pathogenic bacteria and human colon cancer cell line HCT 15

NASA Astrophysics Data System (ADS)

Gokul Raj, K.; Manikandan, R.; Arulvasu, C.; Pandi, M.

2015-03-01

Cladosporium oxysporum a new taxol producing endophytic fungus was identified and production of taxol were characterized using UV-visible spectroscopy (UV-vis), high-performance liquid chromatography (HPLC), infrared (IR) nuclear magnetic resonance spectroscopy (NMR (13C and 1H)) and liquid chromatography-mass spectrometry (LC-MS). The taxol biosynthetic gene (dbat) was evaluated for new taxol producing fungus. Antibacterial activity against six different human pathogenic bacteria was done by agar well diffusion method. The anticancer efficacy of isolated fungal taxol were also evaluated in human colon cancer cell HCT 15 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cytotoxicity and nuclear morphology analysis. The isolated fungal taxol showed positive towards biosynthetic gene (dbat) and effective against both Gram positive as well as Gram negative. The fungal taxol suppress growth of cancer cell line HCT 15 with an IC50 value of 3.5 μM concentration by 24 h treatment. Thus, the result reveals that C. oxysporum could be a potential alternative source for production of taxol and have antibacterial as well as anticancer properties with possible clinical applications.

33 CFR 100.717 - Annual Fort Myers Beach Offshore Grand Prix; Fort Myers, FL.

Code of Federal Regulations, 2011 CFR

2011-07-01

...°58.30′ W). All coordinates referenced use datum: NAD 83. (b) Special local regulations. (1) No vessel... coordinates referenced use datum: NAD 83. (3) All vessel traffic, not involved with the Fort Myers Beach... clear of the racecourse. All coordinates referenced use datum: NAD 83. (4) All vessel traffic, not...

33 CFR 100.717 - Annual Fort Myers Beach Offshore Grand Prix; Fort Myers, FL.

Code of Federal Regulations, 2010 CFR

2010-07-01

...°58.30′ W). All coordinates referenced use datum: NAD 83. (b) Special local regulations. (1) No vessel... coordinates referenced use datum: NAD 83. (3) All vessel traffic, not involved with the Fort Myers Beach... clear of the racecourse. All coordinates referenced use datum: NAD 83. (4) All vessel traffic, not...

33 CFR 100.717 - Annual Fort Myers Beach Offshore Grand Prix; Fort Myers, FL.

Code of Federal Regulations, 2013 CFR

2013-07-01

...°58.30′ W). All coordinates referenced use datum: NAD 83. (b) Special local regulations. (1) No vessel... coordinates referenced use datum: NAD 83. (3) All vessel traffic, not involved with the Fort Myers Beach... clear of the racecourse. All coordinates referenced use datum: NAD 83. (4) All vessel traffic, not...

33 CFR 100.717 - Annual Fort Myers Beach Offshore Grand Prix; Fort Myers, FL.

Code of Federal Regulations, 2014 CFR

2014-07-01

...°58.30′ W). All coordinates referenced use datum: NAD 83. (b) Special local regulations. (1) No vessel... coordinates referenced use datum: NAD 83. (3) All vessel traffic, not involved with the Fort Myers Beach... clear of the racecourse. All coordinates referenced use datum: NAD 83. (4) All vessel traffic, not...

33 CFR 100.717 - Annual Fort Myers Beach Offshore Grand Prix; Fort Myers, FL.

Code of Federal Regulations, 2012 CFR

2012-07-01

...°58.30′ W). All coordinates referenced use datum: NAD 83. (b) Special local regulations. (1) No vessel... coordinates referenced use datum: NAD 83. (3) All vessel traffic, not involved with the Fort Myers Beach... clear of the racecourse. All coordinates referenced use datum: NAD 83. (4) All vessel traffic, not...

Alterations in Taxol production in plant cell culture via manipulation of the phenylalanine ammonia lyase pathway.

PubMed

Brincat, Michelle C; Gibson, Donna M; Shuler, Michael L

2002-01-01

One approach to increasing secondary metabolite production in plant cell culture is to manipulate metabolic pathways to utilize more resources toward production of one desired compound or class of compounds, such as diverting carbon flux from competing secondary pathways. Since phenylalanine provides both the phenylisoserine side chain and the benzoyl moiety at C-2 of Taxol, we speculated that blockage of the phenylpropanoid pathway might divert phenylalanine into Taxol biosynthesis. We used specific enzyme inhibitors to target the first enzyme in the phenylpropanoid pathway, phenylalanine ammonia lyase (PAL), the critical control point for conversion of L-phenylalanine to trans-cinnamic acid. Cinnamic acid acted quickly in reducing PAL activity by 40-50%, without affecting total protein levels, but it generally inhibited the taxane pathway, reducing Taxol by 90% of control levels. Of the taxanes produced, 13-acetyl-9-dihydro-baccatin III and 9-dihydrobaccatin III doubled as a percentage of total taxanes in C93AD and CO93P cells treated with 0.20 and 0.25 mM cinnamic acid, when all other taxanes were lowered. The PAL inhibitor alpha-aminooxyacetic acid (AOA) almost entirely shut down Taxol production at both 0.5 and 1.5 mM, whereas L-alpha-aminooxy-beta-phenylpropionic acid (AOPP) had the opposite effect, slightly enhancing Taxol production at 1 microM but having no effect at 10 microM. The discrepancy in the effectiveness of AOA and AOPP and the lack of effect with addition of phenylalanine or benzoic acid derivatives further indicates that the impact of cinnamic acid on Taxol is related not to its effect on PAL but rather to a specific effect on the taxane pathway. On the basis of these results, a less direct route for inhibiting the phenylpropanoid pathway may be required to avoid unwanted side effects and potentially enhance Taxol production.

8. Photocopy of architectural drawing (from blueprint at Fort Myer ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. Photocopy of architectural drawing (from blueprint at Fort Myer Engineer Activity) 'Double set of Non-Commissioned Officers Qrs.' Quartermaster Generals Office, sheets 2 and 3, standard plan 23, June 1891, Lithographed on linen architectural drawing. 1 PLAN, 3 ELEVATIONS - Fort Myer, Non-Commissioned Officers Quarters, Washington Avenue between Johnson Lane & Custer Road, Arlington, Arlington County, VA

Interactions between Co-Habitating fungi Elicit Synthesis of Taxol from an Endophytic Fungus in Host Taxus Plants

PubMed Central

Soliman, Sameh S. M.; Raizada, Manish N.

2012-01-01

Within a plant, there can exist an ecosystem of pathogens and endophytes, the latter described as bacterial and fungal inhabitants that thrive without causing disease to the host. Interactions between microbial inhabitants represent a novel area of study for natural products research. Here we analyzed the interactions between the fungal endophytes of Taxus (yew) trees. Fungal endophytes of Taxus have been proposed to produce the terpenoid secondary metabolite, Taxol, an anti-cancer drug. It is widely reported that plant extracts stimulate endophytic fungal Taxol production, but the underlying mechanism is not understood. Here, Taxus bark extracts stimulated fungal Taxol production 30-fold compared to a 10-fold induction with wood extracts. However, candidate plant-derived defense compounds (i.e., salicylic acid, benzoic acid) were found to act only as modest elicitors of fungal Taxol production from the endophytic fungus Paraconiothyrium SSM001, consistent with previous studies. We hypothesized the Taxus plant extracts may contain elicitors derived from other microbes inhabiting these tissues. We investigated the effects of co-culturing SSM001 with other fungi observed to inhabit Taxus bark, but not wood. Surprisingly, co-culture of SSM001 with a bark fungus (Alternaria) caused a ∼threefold increase in Taxol production. When SSM001 was pyramided with both the Alternaria endophyte along with another fungus (Phomopsis) observed to inhabit Taxus, there was an ∼eightfold increase in fungal Taxol production from SSM001. These results suggest that resident fungi within a host plant interact with one another to stimulate Taxol biosynthesis, either directly or through their metabolites. More generally, our results suggest that endophyte secondary metabolism should be studied in the context of its native ecosystem. PMID:23346084

9. Photocopy of architectural drawing (from blueprint at Fort Myer ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

9. Photocopy of architectural drawing (from blueprint at Fort Myer Engineer Activity) 'Double Set of Non-Commissioned Officers Qrs.' Quartermaster Generals Office, sheet 1 and unnumbered sheet, standard plan 23, June 1891. lithograph on linen architectural drawing 2. PLANS, 1 SECTION, 2 DETAILS - Fort Myer, Non-Commissioned Officers Quarters, Washington Avenue between Johnson Lane & Custer Road, Arlington, Arlington County, VA

Cordyceps sinensis health supplement enhances recovery from taxol-induced leukopenia.

PubMed

Liu, Wei-Chung; Chuang, Wei-Ling; Tsai, Min-Lung; Hong, Ji-Hong; McBride, William H; Chiang, Chi-Shiun

2008-04-01

This study aimed to evaluate the ability of the health food supplement Cordyceps sinensis (CS) to ameliorate suppressive effects of chemotherapy on bone marrow function as a model for cancer treatment. Mice were treated with Taxol (17 mg/kg body wt) one day before oral administration of a hot-water extract of CS (50 mg/kg daily) that was given daily for 3 weeks. White blood cell counts in peripheral blood of mice receiving Taxol were at 50% of normal levels on day 28 but had recovered completely in mice treated with CS. In vitro assays showed that CS enhanced the colony-forming ability of both granulocyte macrophage colony forming unit (GM-CFU) and osteogenic cells from bone marrow preparations and promoted the differentiation of bone marrow mesenchymal stromal cells into adipocytes, alkaline phosphatase-positive osteoblasts, and bone tissue. This result could be attributed to enhanced expression of Cbfa1 (core binding factor a) and BMP-2 (bone morphogenetic protein) with concurrent suppression of ODF (osteoclast differentiation factor/RANK [receptor activator of NF-kappaB]) ligand. In summary, CS enhances recovery of mice from leukopenia caused by Taxol treatment. It appears to do so by protecting both hematopoietic progenitor cells directly and the bone marrow stem cell niche through its effects on osteoblast differentiation.

Bristol Bay Assessment – Supplemental Peer Review Reports (May 2012)

EPA Science Inventory

These reports represent the results of independent peer reviews of several technical reports submitted to the public docket for the May 2012 draft of the Bristol Bay Assessment, An Assessment of Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska.

...

Effect of taxol from Pestalotiopsis mangiferae on A549 cells-In vitro study.

PubMed

Kathiravan, Govindarajan; Sureban, Sripathi M

2009-12-01

Pestalotiopsis mangiferae Coelomycete fungi were used to examine the production of taxol. The taxol isolated from this fungus is biologically active against cancer cell lines were investigated for its antiproliferative activity in human Non Small Cell Lung Cancer A549 cells. The results showed that the methylene chloride extraction of Pestalotiopsis mangiferae inhibited the proliferation of A 549 cells as measured by MTT and Trypan blue assay. Flow cytometric analysis showed that methylene chloride extraction of Pestalotiopsis mangiferae blocked cell cycle progression in G0/G1 phase. In addition fungal taxol induced A549 cell apoptosis as determined by propidium iodide staining. Further the percentage of LDH release was increased at increasing concentrations which is a measure of cell death. The levels of sialic acid levels and DNA, RNA and protein levels were decreased after treatment with methylene chloride extraction of Pestalotiopsis mangiferae. We suggests that methylene chloride extraction of Pestalotiopsis mangiferae might be considered for future therapeutic application with further studies against lung cancer.

Writing through the Labyrinth of Fears: The Legacy of Walter Dean Myers

ERIC Educational Resources Information Center

Tatum, Alfred W.

2015-01-01

This commentary discusses the legacy of Walter Dean Myers in relationship to advancing writing as an intellectual tool of protection for black male teens. Multiple implications are provided for teachers who want to engage black male teens to write fearlessly to extend the legacy of Walter Dean Myers.

Necitumumab, a fully human IgG1 mAb directed against the EGFR for the potential treatment of cancer.

PubMed

Dienstmann, Rodrigo; Tabernero, Josep

2010-12-01

Necitumumab (IMC-11F8), under development by ImClone Systems in collaboration with Bristol-Myers Squibb, is a fully human IgG1 mAb targeting the epidermal growth factor receptor (EGFR), for the potential intravenous treatment of cancer, in particular NSCLC. In vitro studies demonstrate that necitumumab inhibits downstream targets in the EGFR pathway (eg, MAPK), which are important for cellular proliferation, differentiation, invasion and metastasis. Furthermore, because necitumumab is an IgG1 construct, it has the potential to induce antibody-dependent cell-mediated cytotoxicity against tumor cells. Preclinical studies indicated that the antitumor activity of necitumumab is either comparable with or superior to that of ImClone's chimeric anti-EGFR mAb cetuximab. In a phase I clinical trial in patients with advanced solid malignancies, necitumumab displayed nonlinear pharmacokinetic behavior. The toxicity profile of necitumumab is acceptable, with skin toxicity being the most frequently reported adverse event in the phase I and II clinical trials conducted to date. Preliminary data from a phase II clinical trial of necitumumab in combination with chemotherapy for the first-line treatment of advanced colon cancer are promising. Success in the ongoing phase III clinical trials in patients with advanced NSCLC would lead to necitumumab becoming a valuable addition to future therapeutic strategies in oncology.

Access to hepatitis C medicines

PubMed Central

Coppens, Delphi GM; Prasad, Tara L; Rook, Laurien A; Iyer, Jayasree K

2015-01-01

Abstract Hepatitis C is a global epidemic. Worldwide, 185 million people are estimated to be infected, most of whom live in low- and middle-income countries. Recent advances in the development of antiviral drugs have produced therapies that are more effective, safer and better tolerated than existing treatments for the disease. These therapies present an opportunity to curb the epidemic, provided that they are affordable, that generic production of these medicines is scaled up and that awareness and screening programmes are strengthened. Pharmaceutical companies have a central role to play. We examined the marketed products, pipelines and access to medicine strategies of 20 of the world’s largest pharmaceutical companies. Six of these companies are developing medicines for hepatitis C: AbbVie, Bristol-Myers Squibb, Gilead, Johnson & Johnson, Merck & Co. and Roche. These companies employ a range of approaches to supporting hepatitis C treatment, including pricing strategies, voluntary licensing, capacity building and drug donations. We give an overview of the engagement of these companies in addressing access to hepatitis C products. We suggest actions companies can take to play a greater role in curbing this epidemic: (i) prioritizing affordability assessments; (ii) developing access strategies early in the product lifecycle; and (iii) licensing to manufacturers of generic medicines. PMID:26549908

Analysis of Soft Drinks Using Nuclear Magnetic Resonance Spectroscopy: A Mentorship

NASA Astrophysics Data System (ADS)

Wilson, Arkim; Myers, Craig; Crull, George; Curtis, Michael; Pasciak Patterson, Pamela

1999-10-01

This mentorship was designed to expose a student to the laboratory routine for a chemist at Bristol Myers Squibb Company (BMS). The student visited BMS, collaborated with BMS scientists, and actually completed a project on site. He was asked to determine the identity of an unknown sample of soft drink retrieved from a fictitious crime scene using NMR spectroscopy. He designed an experiment to test the unknown sample and used samples of purified sugar, purified caffeine, purified citric acid, Coke, Diet Coke, Pepsi, Mountain Dew, Diet 7-Up, and Sam's Diet Cola as controls. The results were analyzed and presented in a final report. The student was able to determine if the unknown contained sugar, caffeine, Nutrasweet, or sodium benzoate. He learned how to compile relevant information, conduct an experiment, collect and analyze data, draw conclusions, and prepare and edit a formal report. In addition to learning the uses of NMR, he also learned some of its limitations. In the final report, he was encouraged to reflect on the difficulties a scientist might encounter when trying to identify NMR peaks without an "ingredient list" like those of the soft drink cans. The experience was rewarding for the student and all scientists involved.

Government-NGO collaboration and sustainability of orphans and vulnerable children projects in southern Africa.

PubMed

Rosenberg, Alana; Hartwig, Kari; Merson, Michael

2008-02-01

Given current donor attention to orphans and children made vulnerable by HIV/AIDS, and the need for a new framework that recognizes the complementary roles of nations and non-governmental organizations (NGOs), this analysis reviews NGO-operated community-based orphans and vulnerable children (OVC) projects in Botswana, Lesotho, Namibia, South Africa, and Swaziland. There has been a lack of attention within the field of evaluation to inter-organizational relationships, specifically those with government agencies, as a factor in sustainability. We analyzed evaluations of nine OVC projects funded by the Bristol-Myers Squibb Foundation for the influence of government-NGO collaboration on project sustainability. For eight of the nine projects, evaluations provided evidence of the importance of the government partnership for sustainability. Government collaboration was important in projects designed to help families access government grants, initiate community-based solutions, and advocate for OVC rights through legislation. Government partnerships were also critical to the sustainability of two projects involved in placing children in foster care, but these showed signs of tension with government partners. In addition to the more common factors associated with sustainability, such as organizational characteristics, donors and NGOs should concentrate on developing strong partnerships with local and national government agencies for the sustainability of their projects.

Access to hepatitis C medicines.

PubMed

Edwards, Danny J; Coppens, Delphi Gm; Prasad, Tara L; Rook, Laurien A; Iyer, Jayasree K

2015-11-01

Hepatitis C is a global epidemic. Worldwide, 185 million people are estimated to be infected, most of whom live in low- and middle-income countries. Recent advances in the development of antiviral drugs have produced therapies that are more effective, safer and better tolerated than existing treatments for the disease. These therapies present an opportunity to curb the epidemic, provided that they are affordable, that generic production of these medicines is scaled up and that awareness and screening programmes are strengthened. Pharmaceutical companies have a central role to play. We examined the marketed products, pipelines and access to medicine strategies of 20 of the world's largest pharmaceutical companies. Six of these companies are developing medicines for hepatitis C: AbbVie, Bristol-Myers Squibb, Gilead, Johnson & Johnson, Merck & Co. and Roche. These companies employ a range of approaches to supporting hepatitis C treatment, including pricing strategies, voluntary licensing, capacity building and drug donations. We give an overview of the engagement of these companies in addressing access to hepatitis C products. We suggest actions companies can take to play a greater role in curbing this epidemic: (i) prioritizing affordability assessments; (ii) developing access strategies early in the product lifecycle; and (iii) licensing to manufacturers of generic medicines.

Lipid-laden macrophage infiltration of human adenocarcinoma in vivo associated with taxol and GCSF treatment.

PubMed

Abramson, N; Castro, S; Goldstein, J D

1997-01-01

This brief report illustrates the presence of lipid-laden macrophages in proximity to metastatic adenocarcinoma cells within the bone marrow of a patient receiving taxol and GCSF therapy. The pathophysiological mechanism is uncertain. Taxol, which is associated with macrophage function in vitro, may have been responsible for the recruitment of macrophages in this patient. GCSF could have contributed as well; however, GCSF usually has little effect on monocytes and macrophages.

Effect of taxol from Pestalotiopsis mangiferae on A549 cells-In vitro study

PubMed Central

Kathiravan, Govindarajan; Sureban, Sripathi M.

2009-01-01

Pestalotiopsis mangiferae Coelomycete fungi were used to examine the production of taxol. The taxol isolated from this fungus is biologically active against cancer cell lines were investigated for its antiproliferative activity in human Non Small Cell Lung Cancer A549 cells. The results showed that the methylene chloride extraction of Pestalotiopsis mangiferae inhibited the proliferation of A 549 cells as measured by MTT and Trypan blue assay. Flow cytometric analysis showed that methylene chloride extraction of Pestalotiopsis mangiferae blocked cell cycle progression in G0/G1 phase. In addition fungal taxol induced A549 cell apoptosis as determined by propidium iodide staining. Further the percentage of LDH release was increased at increasing concentrations which is a measure of cell death. The levels of sialic acid levels and DNA, RNA and protein levels were decreased after treatment with methylene chloride extraction of Pestalotiopsis mangiferae. We suggests that methylene chloride extraction of Pestalotiopsis mangiferae might be considered for future therapeutic application with further studies against lung cancer. PMID:25206246

The influence of the combined treatment with Vadimezan (ASA404) and taxol on the growth of U251 glioblastoma xenografts

PubMed Central

2012-01-01

Background One of the most important biological characteristics of Glioblastoma multiforme (GBM) is high vascular density. Vadimezan (ASA404, DMXAA) belongs to the class of small molecule vascular disrupting agents (VDA) that cause disruption of established tumor vessels and subsequent tumor hemorrhagic necrosis. Its selective antivascular effect is mediated by intratumoral induction of several cytokines including tumor necrosis factor-α (TNF-α), granulocyte-colony-stimulating factor (G-CSF), interleukin 6 (IL-6) and macrophage inflammatory protein 1α (MIP-1α). Preclinical studies have demonstrated that ASA404 acts synergistically with taxanes. In this study, we investigated if treatment of mice bearing U251 human glioblastoma xenografts with ASA404 and taxol may be synergistic. Therapy response was evaluated by measuring changes in tumor size and metabolic activity using 18F-FDG PET (Fluorodeoxyglucose - positron emision tomography) imaging. Methods U251 cells were inoculated s.c. in the right hind limb of NMRI-Foxn1nu athymic female nude mice. Animals were randomly assigned into 4 groups (7–9 animals/group) for treatment: control, taxol, ASA404, and ASA404 plus taxol. The animals received either a single dose of taxol (10 mg/kg), ASA404 (27.5 mg/kg), or taxol (10 mg/kg) plus ASA404 (27.5 mg/kg) administered i.p.; ASA404 was administred 24 h after the treatment with taxol. 4 and 24 h after treatment with ASA404 (28 and 48 h hours after treatment with taxol) 18 F-FDG PET scans were performed. Results The treatment with taxol did not affect the tumor growth in comparison to untreated controls. The treatment of animals with single dose ASA404 alone or in combination with taxol caused a significant delay in tumor growth. The combined treatment did not decrease the growth of the xenografts significantly more than ASA404 alone, but early changes in tumor 18 F-FDG uptake preceded subsequent growth inhibition. The tumor weights, which were

Telling Stories That Are Needed: An Interview with Christopher Myers. Breakfast Speaker Interview

ERIC Educational Resources Information Center

Adomat, Donna Sayers; Lowery, Ruth McKoy; Fain, Jeanne Gilliam

2016-01-01

Christopher Myers won acclaim at a young age as a vibrant illustrator of children's picturebooks. In this interview, Myers discusses how he has advocated for diversity in children's literature through themes that weave throughout his writing and illustration, collaborations with other artists, and his participation in the communities of artists,…

77 FR 16227 - Frank Myers AutoMaxx, LLC; Analysis of Proposed Consent Order To Aid Public Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

... FEDERAL TRADE COMMISSION [File No. 112 3206] Frank Myers AutoMaxx, LLC; Analysis of Proposed... ``Frank Myers AutoMaxx, File No. 112 3206'' on your comment, and file your comment online at https... April 16, 2012. Write ``Frank Myers AutoMaxx, File No. 112 3206'' on your comment. Your comment...

Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death

PubMed Central

WU, JIANG; JI, FANG; DI, WEN; CHEN, HONGDUO; WAN, YINSHENG

2011-01-01

Acetyl-coenzyme A carboxylase (ACC) is an attractive target for research into the treatment of a variety of human diseases, including diabetes, obesity and cancer. Mounting evidence suggests that the inhibition of ACC induced of cancer cell apoptosis. However, whether the inhibition of ACC regulates apoptosis in CaOV3 cancer cells has yet to be addressed. This study investigated the cytotoxic mechanism of action of ACC inhibition. Results showed that 5-(tetradecyloxy)-2-furoic acid (TOFA), an ACC inhibitor, enhanced Taxol-induced CaOV3 human ovarian cancer cell apoptosis. Notably, when TOFA was administered as a monotherapy, it induced CaOV3 cell apoptosis. Pre-treatment with the EGFR inhibitor PD153035 was found to markedly enhance ACC phosphorylation, whereas AMP-activated protein kinase (AMPK) activator AICAR was found to marginally enhance ACC phosphorylation. Taken together, the data showed ACC is a potential novel molecular target of Taxol. Additionally, ACC inhibition partially contributed to the cytotoxic effect of Taxol in ovarian cancer cells. PMID:22866118

Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death.

PubMed

Wu, Jiang; Ji, Fang; DI, Wen; Chen, Hongduo; Wan, Yinsheng

2011-05-01

Acetyl-coenzyme A carboxylase (ACC) is an attractive target for research into the treatment of a variety of human diseases, including diabetes, obesity and cancer. Mounting evidence suggests that the inhibition of ACC induced of cancer cell apoptosis. However, whether the inhibition of ACC regulates apoptosis in CaOV3 cancer cells has yet to be addressed. This study investigated the cytotoxic mechanism of action of ACC inhibition. Results showed that 5-(tetradecyloxy)-2-furoic acid (TOFA), an ACC inhibitor, enhanced Taxol-induced CaOV3 human ovarian cancer cell apoptosis. Notably, when TOFA was administered as a monotherapy, it induced CaOV3 cell apoptosis. Pre-treatment with the EGFR inhibitor PD153035 was found to markedly enhance ACC phosphorylation, whereas AMP-activated protein kinase (AMPK) activator AICAR was found to marginally enhance ACC phosphorylation. Taken together, the data showed ACC is a potential novel molecular target of Taxol. Additionally, ACC inhibition partially contributed to the cytotoxic effect of Taxol in ovarian cancer cells.

Bioreactor engineering as an enabling technology to tap biodiversity. The case of taxol.

PubMed

Shuler, M L

1994-11-30

One barrier to exploiting the chemical and genetic diversity in nature is the difficulty of cultivating many organisms in a controlled manner. In some cases it is difficult to achieve growth. In many others, good growth is achieved, but the expression of the organism's genetic potential to make a desired product is not realized. The thesis of this paper is that a coupling of an understanding of reactor engineering principles with the basic knowledge of the biology is often necessary to circumvent these barriers. In many cases the construction of appropriate cultivation systems is a necessary step to better understanding of cellular physiology. In some cases the chemical of interest is of high social utility and comes from a natural source that is uncommon and difficult to secure. In these cases a method of controlled cultivation becomes a prerequisite for commercial exploitation. These points were illustrated using a taxol. Taxol is an important new anticancer drug whose development has been greatly impeded by supply problems. Taxol has been derived from the park of the pacific yew tree, a process that kills the tree. The pacific yew is a relatively uncommon tree and very slow growing. One alternative to the natural source is plant cell culture. Such cultures can produce significant levels of taxol with substantial release into the medium. Taxane products not observed in typical extracts from field-grown plants can be found in cell cultures, indicating the potential unmasking of pathways. These cultures are quite responsive to changes in their environments as illustrated by the summary of initial observations. With regard to natural compounds, biochemical engineers can play a major role in the capture and preservation of producing systems, in the discovery of useful compounds, and in providing the basis for commercial production of natural compounds.

33 CFR 100.740 - Annual Offshore Super Series Boat Race; Fort Myers Beach, FL.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Annual Offshore Super Series Boat Race; Fort Myers Beach, FL. 100.740 Section 100.740 Navigation and Navigable Waters COAST GUARD... Annual Offshore Super Series Boat Race; Fort Myers Beach, FL. (a) Regulated area. (1) The regulated area...

33 CFR 100.740 - Annual Offshore Super Series Boat Race; Fort Myers Beach, FL.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Annual Offshore Super Series Boat Race; Fort Myers Beach, FL. 100.740 Section 100.740 Navigation and Navigable Waters COAST GUARD... Annual Offshore Super Series Boat Race; Fort Myers Beach, FL. (a) Regulated area. (1) The regulated area...

33 CFR 100.740 - Annual Offshore Super Series Boat Race; Fort Myers Beach, FL.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Annual Offshore Super Series Boat Race; Fort Myers Beach, FL. 100.740 Section 100.740 Navigation and Navigable Waters COAST GUARD... Annual Offshore Super Series Boat Race; Fort Myers Beach, FL. (a) Regulated area. (1) The regulated area...

33 CFR 100.740 - Annual Offshore Super Series Boat Race; Fort Myers Beach, FL.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Annual Offshore Super Series Boat Race; Fort Myers Beach, FL. 100.740 Section 100.740 Navigation and Navigable Waters COAST GUARD... Annual Offshore Super Series Boat Race; Fort Myers Beach, FL. (a) Regulated area. (1) The regulated area...

Identifying the Right Disease Targets to Develop Better Drugs, Faster | NIH MedlinePlus the Magazine

MedlinePlus

... Association Foundation for the NIH Rheumatoid Arthritis and Lupus The Partners Government NIH Industry AbbVie Bristol-Myers ... Pfizer Sanofi Takeda Non-Profit Organizations Alliance for Lupus Research Foundation for HIH Lupus Research Institute Rheumatology ...

Etoposide phosphate: what, why, where, and how?

PubMed

Schacter, L

1996-12-01

The podophyllotoxin derivatives etoposide and teniposide are active in the treatment of a variety of malignant conditions. Both represent chemical modifications of podophyllin, an extract of Podophyllum peltatum (May apple, mandrake, Indian apple, wild lemon, or duck's foot), a plant long used as a folk remedy and recognized in the 19th century to be effective in the treatment of cancer. While etoposide is active in the treatment of many cancers and is widely used, it has a number of limitations due to its lack of water solubility. Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-soluble prodrug of etoposide that is rapidly and completely converted to the parent compound after intravenous dosing. The pharmacokinetic profile of etoposide after treatment with either etoposide or etoposide phosphate is identical. Toxicity and clinical activity also are the same. Because etoposide phosphate is water soluble and can be made up to a concentration of 20 mg/mL, however, it can be given as a 5-minute bolus, in high doses in small volumes, and as a continuous infusion. Furthermore, it is not formulated with polyethylene glycol, polysorbate 80 (Tween; ICI Americas, Wilmington, DE), and ethanol, and does not cause acidosis when given at high doses. The easier-to-use etoposide phosphate represents an improved formulation of etoposide.

Five-dimensional Myers-Perry black holes cannot be overspun in gedanken experiments

NASA Astrophysics Data System (ADS)

An, Jincheng; Shan, Jieru; Zhang, Hongbao; Zhao, Suting

2018-05-01

We apply the new version of a gedanken experiment designed recently by Sorce and Wald to overspin the five-dimensional Myers-Perry black holes. As a result, the extremal black holes cannot be overspun at the linear order. On the other hand, although the nearly extremal black holes could be overspun at the linear order, this process is shown to be prohibited by the quadratic order correction. Thus, no violation of the weak cosmic censorship conjecture occurs around the five-dimensional Myers-Perry black holes.

The flavonoid quercetin transiently inhibits the activity of taxol and nocodazole through interference with the cell cycle

PubMed Central

Samuel, Temesgen; Fadlalla, Khalda; Turner, Timothy; Yehualaeshet, Teshome E.

2010-01-01

Quercetin is a flavonoid with anticancer properties. In this study, we examined the effects of quercetin on cell cycle, viability and proliferation of cancer cells, either singly or in combination with the microtubule-targeting drugs taxol and nocodazole. Although quercetin induced cell death in a dose dependent manner, 12.5-50μM quercetin inhibited the activity of both taxol and nocodazole to induce G2/M arrest in various cell lines. Quercetin also partially restored drug-induced loss in viability of treated cells for up to 72 hours. This antagonism of microtubule-targeting drugs was accompanied by a delay in cell cycle progression and inhibition of the buildup of cyclin-B1 at the microtubule organizing center of treated cells. However, quercetin did not inhibit the microtubule targeting of taxol or nocodazole. Despite the short-term protection of cells by quercetin, colony formation and clonogenicity of HCT116 cells were still suppressed by quercetin or quercetin-taxol combination. The status of cell adherence to growth matrix was critical in determining the sensitivity of HCT116 cells to quercetin. We conclude that while long-term exposure of cancer cells to quercetin may prevent cell proliferation and survival, the interference of quercetin with cell cycle progression diminishes the efficacy of microtubule-targeting drugs to arrest cells at G2/M. PMID:21058190

An Assessment of the Myers-Briggs Type Indicator

ERIC Educational Resources Information Center

Carlyn, Marcia

1977-01-01

The Myers Briggs Type Indicator is a self-report inventory developed to measure variables in Carl Jung's personality typology. The four personality scales measured by the instrument, and the scoring process are described, and an extensive review of the intercorrelation, reliability, and validity research is presented. (Author/MV)

Selected 1970 Census Data for Alaska Communities. Part 4 - Bristol Bay-Aleutian Region.

ERIC Educational Resources Information Center

Alaska State Dept. of Community and Regional Affairs, Juneau. Div. of Community Planning.

As 1 of 6 regional reports supplying statistical information on Alaska's incorporated and unincorporated communities (those of 25 or more people), this report on Alaska's Bristol Bay-Aleutian Region presents data derived from the 1970 U.S. Census first-count microfilm. Organized via the 3 Bristol Bay-Aleutian census divisions, data are presented…

Career Assessment and the Myers-Briggs Type Indicator.

ERIC Educational Resources Information Center

McCaulley, Mary H.; Martin, Charles R.

1995-01-01

The Myers-Briggs Type Inventory provides a way of determining the fit between individual preferences and potential occupations. It can give people an appreciation of their strengths and weaknesses and awareness of possible blind spots. Recognition of individual types can help in selecting appropriate steps for career planning and lifelong…

Myers-Briggs Type Inventory Personality Preferences and Academic Performance.

ERIC Educational Resources Information Center

Lowenthal, Werner; Meth, Hilda

1989-01-01

A study to determine if there are any relationships between the Myers-Briggs Type Inventory personality preferences and academic performance in schools of pharmacy is discussed. Differences in academic performance that could be related to gender are reported. (Author/MLW)

Personality characteristics of hospice volunteers as measured by Myers-Briggs Type Indicator.

PubMed

Mitchell, C W; Shuff, I M

1995-12-01

A sample of hospice volunteers (n = 99) was administered the Myers-Briggs Type Indicator (Myers & McCaulley, 1985). Frequencies of types observed were compared to population sample (n = 1,105) frequencies. Results indicated that, as a whole, hospice volunteers preferred extraversion over introversion, intuition over sensing, and feeling over thinking. Analysis of four-and two-letter preference combinations also yielded statistically significant differences. Most notably, the sensing-intuitive function appeared pivotal in determining of hospice volunteering. Suggestions are offered as to why the sensing-intuition function appeared central to hospice volunteering. Results appeared consistent with Jungian personality theory.

Sensor and Video Monitoring of Water Quality at Bristol Floating Harbour

NASA Astrophysics Data System (ADS)

Chen, Yiheng; Han, Dawei

2017-04-01

Water system is an essential component in a smart city for its sustainability and resilience. The harbourside is a focal area of​ ​Bristol with new buildings and features redeveloped in the last ten years, attracting numerous visitors by the diversity of attractions and beautiful views. There is a strong​ ​relationship between the satisfactory of the visitors and local people with the water quality in the Harbour. The freshness and beauty of the water body would please people as well as benefit the aquatic ecosystems. As we are entering a data-rich era, this pilot project aims to explore the concept of using​ ​ video cameras and smart sensors to collect and monitor water quality condition at the Bristol harbourside. The video cameras and smart sensors are connected to the Bristol Is Open network, an open programmable city platform. This will be the​ first​ attempt to collect water quality data in real time in the​ ​Bristol urban area with the wireless network. The videos and images of the water body collected by the cameras will be correlated with the in-situ water quality parameters for research​ ​purposes. The successful implementation of the sensors can attract more academic researchers and industrial partners to expand the sensor network to multiple locations​ ​around the city covering the other parts of the Harbour and River Avon, leading to a new generation of urban system infrastructure model.

Transcriptome-wide identification and screening of WRKY factors involved in the regulation of taxol biosynthesis in Taxus chinensis.

PubMed

Zhang, Meng; Chen, Ying; Nie, Lin; Jin, Xiaofei; Liao, Weifang; Zhao, Shengying; Fu, Chunhua; Yu, Longjiang

2018-03-26

WRKY, a plant-specific transcription factor family, plays important roles in pathogen defense, abiotic cues, phytohormone signaling, and regulation of plant secondary metabolism. However, little is known about the roles, functions, and mechanisms of WRKY in taxane biosynthesis in Taxus spp. In this study, 61 transcripts were identified from Taxus chinensis transcriptome datasets by using hidden Markov model search. All of these transcripts encoded proteins containing WRKY domains, which were designated as TcWRKY1-61. After phylogenetic analysis of the WRKY domains of TcWRKYs and AtWRKYs, 16, 8, 10, 14, 5, 7, and 1 TcWRKYs were cladded into Group I, IIa-IIe, and III, respectively. Then, six representative TcWRKYs were selected to classify their effects on taxol biosynthesis. After MeJA (methyl jasmonate acid) and SA (salicylic acid) treatments, all of the six TcWRKYs were upregulated by MeJA treatment. TcWRKY44 (IId) and TcWRKY47 (IIa) were upregulated, whereas TcWRKY8 (IIc), TcWRKY20 (III), TcWRKY26 (I), TcWRKY41 (IIe), and TcWRKY52 (IIb) were downregulated by SA treatment. Overexpression experiments showed that the six selected TcWRKYs exerted different effects on taxol biosynthesis. In specific, TcWRKY8 and TcWRKY47 significantly improved the expression levels of taxol-biosynthesis-related genes. Transcriptome-wide identification of WRKY factors in Taxus not only enhances our understanding of plant WRKY factors but also identifies candidate regulators of taxol biosynthesis.

Androgen and taxol cause cell type-specific alterations of centrosome and DNA organization in androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cells

NASA Technical Reports Server (NTRS)

Schatten, H.; Ripple, M.; Balczon, R.; Weindruch, R.; Chakrabarti, A.; Taylor, M.; Hueser, C. N.

2000-01-01

We investigated the effects of androgen and taxol on the androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cell lines. Cells were treated for 48 and 72 h with 0.05-1 nM of the synthetic androgen R1881 and with 100 nM taxol. Treatment of LNCaP cells with 0.05 nM R1881 led to increased cell proliferation, whereas treatment with 1 nM R1881 resulted in inhibited cell division, DNA cycle arrest, and altered centrosome organization. After treatment with 1 nM R1881, chromatin became clustered, nuclear envelopes convoluted, and mitochondria accumulated around the nucleus. Immunofluorescence microscopy with antibodies to centrosomes showed altered centrosome structure. Although centrosomes were closely associated with the nucleus in untreated cells, they dispersed into the cytoplasm after treatment with 1 nM R1881. Microtubules were only faintly detected in 1 nM R1881-treated LNCaP cells. The effects of taxol included microtubule bundling and altered mitochondria morphology, but not DNA organization. As expected, the androgen-independent prostate cancer cell line DU145 was not affected by R1881. Treatment with taxol resulted in bundling of microtubules in both cell lines. Additional taxol effects were seen in DU145 cells with micronucleation of DNA, an indication of apoptosis. Simultaneous treatment with R1881 and taxol had no additional effects on LNCaP or DU145 cells. These results suggest that LNCaP and DU145 prostate cancer cells show differences not only in androgen responsiveness but in sensitivity to taxol as well. Copyright 2000 Wiley-Liss, Inc.

Association between Twist and multidrug resistance gene-associated proteins in Taxol®-resistant MCF-7 cells and a 293 cell model of Twist overexpression.

PubMed

Wang, Li; Tan, Rui-Zhi; Zhang, Zhi-Xia; Yin, Rui; Zhang, Yong-Liang; Cui, Wei-Jia; He, Tao

2018-01-01

Multidrug resistance (MDR) severely limits the effectiveness of chemotherapy. Previous studies have identified Twist as a key factor of acquired MDR in breast, gastric and prostate cancer. However, the underlying mechanisms of action of Twist in MDR remain unclear. In the present study, the expression levels of MDR-associated proteins, including lung resistance-related protein (LRP), topoisomerase IIα (TOPO IIα), MDR-associated protein (MRP) and P-glycoprotein (P-gp), and the expression of Twist in cancerous tissues and pericancerous tissues of human breast cancer, were examined. In order to simulate Taxol ® resistance in cells, a Taxol ® -resistant human mammary adenocarcinoma cell subline (MCF-7/Taxol ® ) was established by repeatedly exposing MCF-7 cells to high concentrations of Taxol ® (up to 15 µg/ml). Twist was also overexpressed in 293 cells by transfecting this cell line with pcDNA5/FRT/TO vector containing full-length hTwist cDNA to explore the dynamic association between Twist and MDR gene-associated proteins. It was identified that the expression levels of Twist, TOPO IIα, MRP and P-gp were upregulated and LRP was downregulated in human breast cancer tissues, which was consistent with the expression of these proteins in the Taxol ® -resistant MCF-7 cell model. Notably, the overexpression of Twist in 293 cells increased the resistance to Taxol ® , Trichostatin A and 5-fluorouracil, and also upregulated the expression of MRP and P-gp. Taken together, these data demonstrated that Twist may promote drug resistance in cells and cancer tissues through regulating the expression of MDR gene-associated proteins, which may assist in understanding the mechanisms of action of Twist in drug resistance.

78 FR 34093 - An Assessment of Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... scientific and technical information presented in the report, the realistic mining scenario used, the data... Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska AGENCY: Environmental Protection Agency... document titled, ``An Assessment of Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska...

High heterogeneity and low reliability in the diagnosis of major depression will impair the development of new drugs.

PubMed

Lieblich, Samuel M; Castle, David J; Pantelis, Christos; Hopwood, Malcolm; Young, Allan Hunter; Everall, Ian P

2015-10-01

Major depressive disorder is a common diagnosis associated with a high burden of disease that has proven to be highly heterogeneous and unreliable. Treatments currently available demonstrate limited efficacy and effectiveness. New drug development is urgently required but is likely to be hindered by diagnostic limitations. D.J.C. has received grants and personal fees from Eli Lilly, Janssen-Cilag, Roche, Allergen, Bristol-Myers Squibb, Pfizer, Lundbeck, AstraZeneca, Hospira, Organon, Sanofi-Aventis, and Wyeth during the writing of this review. C.P. has received grant support from Janssen-Cilag, Eli Lilly, Hospira (Mayne), AstraZeneca, and received honoraria for consultancy to Janssen-Cilag, Eli Lilly, Hospira (Mayne), AstraZeneca, Pfizer, Schering Plough, and Lundbeck. Over the past 2 years he has participated on advisory boards for Janssen-Cilag and Lundbeck, and received honoraria for talks presented at educational meetings organised by AstraZeneca, Janssen-Cilag and Lundbeck. M.H. has received personal fees or grants from Lundbeck, AstraZeneca and Servier during the writing of this review. A.H.Y. reports personal fees from Lundbeck, Sunovion, AstraZeneca and Janssen outside the submitted work. I.P.E. has received personal fees or grants from Lundbeck, AstraZeneca, and Abbvie during the writing of this review. © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Common to both academia and industry: the challenge of discovery. An interview with Perry Molinoff.

PubMed

Molinoff, P B

2001-06-01

Perry Molinoff recognizes the distinctions between basic and applied science, between academic and industrial research, and between the preclinical and clinical realities of drug development. But he generally discusses these categories in fluid, practical terms, having throughout his career crossed the lines of distinction that have sometimes been rather heavily drawn among pharmacologists. As a third-year medical student at Harvard, he decided "to take a year off" to conduct laboratory research. After receiving his MD and pursuing further clinical and postdoctoral work, he enjoyed an academic career that included fourteen years as the A.N. Richards Professor and Chair of Pharmacology at the University of Pennsylvania School of Medicine. He has just completed six years as Vice President of Neuroscience and Genitourinary Drug Discovery for Bristol-Myers Squibb and will soon return to teaching, in the Departments of Psychiatry and Pharmacology at Yale University. Referring to himself as either pharmacologist or neuroscientist, depending on context, he has made fundamental discoveries in receptor biology, has overseen the discovery and development of drugs and their subsequent clinical trials, and has mentored a host of pharmacologists and neuroscientists who themselves have established careers in industry and academia. The pursuit of discovery as its own reward emerges as a theme that has marked his professional life (and is perhaps reflected also in the images displayed in his office of the Himalayan mountains, photographed by Molinoff himself from the Everest base camp last year).

Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells.

PubMed

Nautiyal, Jyoti; Banerjee, Sanjeev; Kanwar, Shailender S; Yu, Yingjie; Patel, Bhaumik B; Sarkar, Fazlul H; Majumdar, Adhip P N

2011-02-15

Colorectal cancer is the third most common form of malignancy, behind prostate and lung cancers. Despite recent advances in medicine, mortality from colorectal cancer remains high, highlighting the need for improved therapies. Numerous studies have demonstrated increased activation of EGFR and its family members (EGFRs), IGF-1R as well as c-Src in colorectal cancer. The current study was undertaken to examine the effectiveness of combination therapy of dasatinib (BMS-354825; Bristol-Myers Squibb), a highly specific inhibitor of Src family kinases (SFK) and a nontoxic dietary agent; curcumin (diferuloylmethane), in colorectal cancer in in vitro and in vivo experimental models. For the latter, we utilized C57BL/6 APC(Min+/-) mice. Initial in vitro studies revealed synergistic interactions between the two agents. Additionally, we have observed that combination treatment causes a much greater inhibition of the following metastatic processes than either agent alone: (i) colony formation, (ii) invasion through extracellular matrix and (iii) tubule formation by endothelial cells. Dasatinib affects the cell adhesion phenotype of colon cancer HCT-116 cells whereas the combination therapy enhances this effect to a greater extent. Preclinical investigation revealed that the combination therapy to be highly effective causing an over 95% regression of intestinal adenomas in Apc(Min+/-) mice, which could be attributed to decreased proliferation and increased apoptosis. In conclusion, our data suggest that combination treatment of dasatinib and curcumin could be a potential therapeutic strategy for colorectal cancer. Copyright © 2010 UICC.

Curcumin Enhances Dasatinib Induced Inhibition of Growth and Transformation of Colon Cancer Cells

PubMed Central

Nautiyal, Jyoti; Banerjee, Sanjeev; Kanwar, Shailender S; Yu, Yingjie; Patel, Bhaumik B; Sarkar, Fazlul H; Majumdar, Adhip P. N.

2010-01-01

Colorectal cancer is the third most common form of malignancy, behind prostate and lung cancers. Despite recent advances in medicine, mortality from colorectal cancer remains high, highlighting the need for improved therapies. Numerous studies have demonstrated increased activation of EGFR and its family members (EGFRs), IGF-1R as well as c-Src in colorectal cancer. The current study was undertaken to examine the effectiveness of combination therapy of dasatinib (BMS-354825; Bristol-Myers Squibb), a highly specific inhibitor of Src family kinases (SFK) and a non-toxic dietary agent; curcumin (diferuloylmethane), in colorectal cancer in in vitro and in vivo experimental models. For the latter we utilized C57BL/6J-ApcMin+/− mice. Initial in vitro studies revealed synergistic interactions between the two agents. Additionally, we have observed that combination treatment causes a much greater inhibition of the following metastatic processes than either agent alone: (a) colony formation (b) invasion through extracellular matrix (c) tubule formation by endothelial cells. Dasatinib affects the cell adhesion phenotype of colon cancer HCT-116 cells whereas the combination therapy enhances this effect to a greater extent. Preclinical investigation revealed that the combination therapy to be highly effective causing an over 95% regression of intestinal adenomas in ApcMin+/− mice, which could be attributed to decreased proliferation and increased apoptosis. In conclusion, our data suggest that combination treatment of dasatinib and curcumin could be a potential therapeutic strategy for colorectal cancer. PMID:20473900

5. ATTLEBORO VIADUCT: PARK STREET ARCHES. ATTLEBORO,, BRISTOL CO., MA. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. ATTLEBORO VIADUCT: PARK STREET ARCHES. ATTLEBORO,, BRISTOL CO., MA. Sec. 4116, MP 197.38. - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

78 FR 25266 - An Assessment of Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

... information presented in the report, the realistic mining scenario used, the data and information used to... additional data or scientific or technical information about Bristol Bay resources or large-scale mining that... Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska AGENCY: Environmental Protection Agency...

Outreach within the Bristol ChemLabS CETL (Centre for Excellence in Teaching and Learning)

ERIC Educational Resources Information Center

Shallcross, Dudley E.; Harrison, Tim G.; Obey, Tim M.; Croker, Steve J.; Norman, Nick C.

2013-01-01

This paper presents an overview of the Bristol ChemLabS project. In particular, it describes the development and impacts of the outreach project within Bristol ChemLabS, the UK's Centre for Excellence in Teaching and Learning (CETL) in practical chemistry, and its continuation beyond the funded project. The major elements of working with both…

Economics of wild salmon ecosystems: Bristol Bay, Alaska

Treesearch

John W. Duffield; Christopher J. Neher; David A. Patterson; Oliver S. Goldsmith

2007-01-01

This paper provides an estimate of the economic value of wild salmon ecosystems in the major watershed of Bristol Bay, Alaska. The analysis utilizes both regional economic and social benefit-cost accounting frameworks. Key sectors analyzed include subsistence, commercial fishing, sport fishing, hunting, and nonconsumptive wildlife viewing and tourism. The mixed cash-...

Painleve-gullstrand-type Coordinates for the Five-dimensional Myers-Perry Black Hole

NASA Technical Reports Server (NTRS)

Finch, Tehani Kahi

2013-01-01

The Painleve-Gullstrand coordinates provide a convenient framework for presenting the Schwarzschild geometry because of their flat constant-time hypersurfaces, and the fact that they are free of coordinate singularities outside r=0. Generalizations of Painlev´e-Gullstrand coordinates suitable for the Kerr geometry have been presented by Doran and Nat´ario. These coordinate systems feature a time coordinate identical to the proper time of zero-angular-momentum observers that are dropped from infinity. Here, the methods of Doran and Nat´ario are extended to the five-dimensional rotating black hole found by Myers and Perry. The result is a new formulation of the Myers-Perry metric. The properties and physical significance of these new coordinates are discussed.

3. DODGEVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR DODGEVILLE, BRISTOL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. DODGEVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR DODGEVILLE, BRISTOL CO., MA. Sec. 4116, MP 195.55. - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

1. HEBRONVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR. HEBRONVILLE, BRISTOL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. HEBRONVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR. HEBRONVILLE, BRISTOL CO., MA. Sec. 4116, MP 193.75. - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

Over-representation of Myers Briggs Type Indicator introversion in social phobia patients.

PubMed

Janowsky, D S; Morter, S; Tancer, M

2000-01-01

The purpose of this study is to profile the personalities of patients with social phobia. Sixteen patients with social phobia were compared with a normative population of 55,971, and with 24 hospitalized Major Depressive Disorder inpatients, using the Myers Briggs Type Indicator. The Myers Briggs Type Indicator, a popular personality survey, divides individuals into eight categories: Extroverts versus Introverts, Sensors versus Intuitives, Thinkers versus Feelers, and Judgers versus Perceivers. Social phobia patients were significantly more often Introverts (93.7%) than were subjects in the normative population (46.2%). In addition, using continuous scores, the social phobia patients scored as significantly more introverted than did the patients with Major Depressive Disorder, who also scored as Introverted. Introversion is a major component of social phobia, and this observation may have both etiological and therapeutic significance.

The Myers-Briggs Type Indicator and the Teaching-Learning Process.

ERIC Educational Resources Information Center

McCaulley, Mary H.

The Myers-Briggs Type Indicator (MBTI) was developed specifically to make possible the implementation of Carl Jung's theory of type and is concerned mainly with conscious elements of the personality. It assumes that to function well, an individual must have a well-developed system for perception and a well-developed system for making decisions or…

77 FR 10372 - Drawbridge Operation Regulations; The Gut, South Bristol, ME

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... Bristol, Maine. The deviation is necessary to facilitate subsurface test boring at the bridge. This... temporary deviation to facilitate subsurface test borings at the bridge. Under this temporary deviation the...

Microbiological Analysis of the Food Preparation and Dining Facilities at Fort Myer and Bolling Air Force Base

DTIC Science & Technology

1975-02-01

the viewpoint of microbiological safety one would be tempted to conclude that Ft. Myer had a much lower risk hazard than Bolting Air Force Base. The...I TECHNICAL REPORT I I 76·63-FSL MICROBIOLOGICAL ANAL.YSIS OF THE FOOD PREPARATION AND DINING FACILITIES AT FORT MYER AND BOLLING AIR FORCE...RECIPIENT’ S CATALOG NUMBER 75-53-ESL 4. TITLE (and Subtltlo) 5. TYPE OF REPOR T & PERIOD COVERED Microbiological Analysis of the Food Preparation and

Energy savings opportunity survey, Fort Myer, Arlington, Virginia, summer steam shut-down study: Volume 1 - executive summary

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1994-03-01

Fort Myer is a permanent United States Army installation located in Arlington County, Virginia, on a site backing Arlington National Cemetery and overlooking the Potomac River and Washington, D.C. The installation consists of offices, family housing, Army Band facilities, supporting facilities, and barracks buildings including those known as the `Old Guard Barracks` which house soldiers that provide services at Arlington National Cemetery. This report consists of the Summer Steam Shut Down Study of an Energy Savings Opportunity Survey (ESOS) at Fort Myer. The purpose of this study is to improve energy efficiency at Fort Myer by analyzing the effects andmore » benefits of closing the central steam producing boiler facility, Building 447, during the non-heating months from mid-May to mid-October. Currently, the central steam plant operates through this period to provide steam for domestic hot water, steam driven laundry presses, air conditioning system reheat, food preparation and dishwashing demands of twenty-two buildings on the base.« less

Forensic investigation of pavement distress : Old Airport Road in Bristol, Virginia.

DOT National Transportation Integrated Search

2003-01-01

A few years after Old Airport Road in Bristol, Virginia, was reconstructed, inordinate distortions of remarkable uniformity began to appear in the paved asphalt surface directly above concrete pipe culverts, which were buried beneath and across the r...

No ISCOs in Charged Myers Perry Spacetimes by Measuring Lyapunov Exponent

NASA Astrophysics Data System (ADS)

Pradhan, Parthapratim

2015-01-01

By computing coordinate time Lyapunov exponent, we prove that for more than four spacetime dimensions (N ≥ 3), there are no Innermost Stable Circular Orbit (ISCO) in charged Myers Perry blackhole spacetime.Using it, we show that the instability of equatorial circular geodesics, both massive and massless particles for such types of blackhole space-times.

Saccharomyces cerevisiae fungemia: an emerging infectious disease.

PubMed

Muñoz, Patricia; Bouza, Emilio; Cuenca-Estrella, Manuel; Eiros, Jose María; Pérez, María Jesús; Sánchez-Somolinos, Mar; Rincón, Cristina; Hortal, Javier; Peláez, Teresa

2005-06-01

Saccharomyces cerevisiae is well known in the baking and brewing industry and is also used as a probiotic in humans. However, it is a very uncommon cause of infection in humans. During the period of 15-30 April 2003, we found 3 patients with S. cerevisiae fungemia in an intensive care unit (ICU). An epidemiological study was performed, and the medical records for all patients who were in the unit during the second half of April were assessed. The only identified risk factor for S. cerevisiae infection was treatment with a probiotic containing Saccharomyces boulardii (Ultralevura; Bristol-Myers Squibb). This probiotic is used in Europe for the treatment and prevention of Clostridium difficile-associated diarrhea. The 3 patients received the product via nasograstric tube for a mean duration of 8.5 days before the culture result was positive, whereas only 2 of 41 control subjects had received it. Surveillance cultures for the control patients admitted at the same time did not reveal any carriers of the yeast. Strains from the probiotic capsules and the clinical isolates were identified as S. cerevisiae, with identical DNA fingerprinting. Discontinuation of use of the product in the unit stopped the outbreak of infection. A review of the literature identified another 57 cases of S. cerevisiae fungemia. Overall, 60% of these patients were in the ICU, and 71% were receiving enteral or parenteral nutrition. Use of probiotics was detected in 26 patients, and 17 patients died. Use of S. cerevisiae probiotics should be carefully reassessed, particularly in immunosuppressed or critically ill patients.

A Study on The Effectiveness of a Pilot Inquiry-Based Middle School Science Program on Non- Cognitive Outcomes and Academic Achievement

NASA Astrophysics Data System (ADS)

Dionisio, Rui Meira

The randomized research study assessed the effect of an inquiry-based science (IBS) program on non-cognitive outcomes and academic achievement. The study was the result of a grant that was awarded by Professional Resources in Science and Mathematics (PRISM), a program affiliated with Montclair State University in conjunction with Bristol-Myers Squibb, and part of the New Jersey Statewide Systemic Initiative (NJSSI). The NJSSI is a partnership of schools, districts, colleges and universities, science centers, businesses, and museums dedicated to improving the teaching and learning of science, mathematics, and technology in New Jersey. The quantitative research study utilized an IBS instructional program titled Science and Technology Concepts for Middle Schools (STC/MS) and was implemented in two middle schools within the same suburban school district. This study examined the effect of IBS classrooms on learning outcomes specifically related to gender and special education. Evaluation of student learning outcomes was conducted through the administration of three instruments: the Academic Self-Concept (ASC) scale, unit assessments, and NJASK 8 Science. The ASC scale and unit assessments were administered as a pretest and posttest in IBS classrooms. NJASK 8 Science scale scores were obtained through reporting of student performance data from the New Jersey Department of Education to the district. The quantitative analysis in this study provided evidence that IBS classrooms had a positive effect on academic achievement. Overall, students in IBS classrooms performed better than students in traditional classrooms on unit assessments. Additionally, male students and special education students in IBS classrooms outperformed students in traditional classrooms on unit assessments.

The role of chromatographic and chiroptical spectroscopic techniques and methodologies in support of drug discovery for atropisomeric drug inhibitors of Bruton's tyrosine kinase.

PubMed

Dai, Jun; Wang, Chunlei; Traeger, Sarah C; Discenza, Lorell; Obermeier, Mary T; Tymiak, Adrienne A; Zhang, Yingru

2017-03-03

Atropisomers are stereoisomers resulting from hindered bond rotation. From synthesis of pure atropisomers, characterization of their interconversion thermodynamics to investigation of biological stereoselectivity, the evaluation of drug candidates subject to atropisomerism creates special challenges and can be complicated in both early drug discovery and later drug development. In this paper, we demonstrate an array of analytical techniques and systematic approaches to study the atropisomerism of drug molecules to meet these challenges. Using a case study of Bruton's tyrosine kinase (BTK) inhibitor drug candidates at Bristol-Myers Squibb, we present the analytical strategies and methodologies used during drug discovery including the detection of atropisomers, the determination of their relative composition, the identification of relative chirality, the isolation of individual atropisomers, the evaluation of interconversion kinetics, and the characterization of chiral stability in the solid state and in solution. In vivo and in vitro stereo-stability and stereo-selectivity were investigated as well as the pharmacological significance of any changes in atropisomer ratios. Techniques applied in these studies include analytical and preparative enantioselective supercritical fluid chromatography (SFC), enantioselective high performance liquid chromatography (HPLC), circular dichroism (CD), and mass spectrometry (MS). Our experience illustrates how atropisomerism can be a very complicated issue in drug discovery and why a thorough understanding of this phenomenon is necessary to provide guidance for pharmaceutical development. Analytical techniques and methodologies facilitate key decisions during the discovery of atropisomeric drug candidates by characterizing time-dependent physicochemical properties that can have significant biological implications and relevance to pharmaceutical development plans. Copyright © 2017 Elsevier B.V. All rights reserved.

Circumvention of Taxol-Resistance in Human Breast Cancers by Improved Water Soluble Taxanes

DTIC Science & Technology

2001-10-01

possible roles of interferon alpha, tumor necrosis factor alpha and transforming growth factor beta in Mn-SOD induction by polysaccharide K. Cancer ...chemoembolization in combination with local hyperthermia. Japanese Journal of Cancer & Chemotherapy. 16:2957-2960 61. Kidd P. (2000) The use of mushroom glucans ...Circumvention of Taxol-Resistance in Human Breast Cancers by Improved Water Soluble Taxanes PRINCIPAL INVESTIGATOR: Li-Xi Yang, M.D., Ph.D. CONTRACTING

Montelukast is a potent and durable inhibitor of multidrug resistance protein 2 (MRP2)-mediated efflux of taxol and saquinavir

PubMed Central

Roy, Upal; Chakravarty, Geetika; Honer Zu Bentrup, Kerstin; Mondal, Debasis

2009-01-01

The ATP binding cassette (ABC)-transporters are energy dependent efflux pumps which regulate the pharmacokinetics of both anti-cancer chemotherapeutic agents, e.g. taxol, and of HIV-1 protease inhibitors (HPIs), e.g. saquinavir. Increased expression of several ABC-transporters, especially P-gp and MRP2, are observed in multidrug resistant (MDR) tumor cells and on HIV-1 infected lymphocytes. In addition, due to their apical expression on vascular endothelial barriers, both P-gp and MRP2 are of crucial importance towards dictating drug access into sequestered tissues. However, although a number of P-gp inhibitors are currently in clinical trials, possible inhibitors of MRP2 are not being thoroughly investigated. The experimental leukotriene receptor antagonist (LTRA), MK-571 is known to be a potent inhibitor of MRP transporters. Using the MRP2 over-expressing cell line, MDCKII-MRP2, we evaluated whether the clinically approved LTRAs, e.g. montelukast (Singulair™) and zafirlukast (Accolate™), can similarly suppress MRP2-mediated efflux. We compared the efficacy of increasing concentrations (20-100 μM) of MK-571, montelukast, and zafirlukast, in suppressing the efflux of calcein-AM, a fluorescent MRP substrate, and the radiolabeled [3H-] drugs, taxol and saquinavir. Montelukast was the most potent inhibitor (p<0.01) of MRP2-mediated efflux of all three substrates. Montelukast also increased (p<0.01) the duration of intracellular retention of both taxol and saquinavir. More than 50% of the drugs were retained in cells even after 90 mins post removal of montelukast from the medium. Our findings implicate that montelukast, a relatively safe anti-asthmatic agent, may be used as an adjunct therapy to suppress the efflux of taxol and saquinavir from MRP2 overexpressing cells. PMID:19952419

Utilizing the Myers-Briggs Personality Inventory in Employee Assistance Program Workplace Seminars.

ERIC Educational Resources Information Center

Aviles, Christopher B.

Social work educators are being called upon more often to deliver employee workplace seminars for community agencies on a variety of topics ranging from burnout and stress management to improving workplace communication and managing workplace conflicts. One tool that addresses workplace communication is the Myers-Briggs Type Indicator (MBTI). It…

Delaware River water quality Bristol to Marcus Hook, Pennsylvania, August 1949 to December 1963

USGS Publications Warehouse

Keighton, Walter B.

1965-01-01

During the 14-year period from August 1949 to July 1963, the U.S. Geological Survey, in cooperation with the city of Philadelphia, collected samples of river water once each month in the 43-mile reach of the Delaware River from Bristol to Marcus Hook, Pa., and daily at Trenton, 10 miles upstream from Bristol. This part of the Delaware is an estuary into which salt water is brought by tides; fresh water flows into the estuary at Trenton, NJ, and farther downstream from the Schuylkill River and other tributaries of the Delaware. In March, April, and May, when fresh-water flow is high, the average concentration of dissolved solids in the water at Bristol was 76 ppm (parts per million), and at Marcus Hook 112 PPM In August and September, streamflow is lower, and the average concentration of dissolved solids increased to 117 PPM at Bristol and 804 PPM at Marcus Hook. Major salinity invasions of the Delaware River occurred in 1949, 1953, 1954, 1957, and 1963. In each of these years the fresh-water flow into the tidal river at Trenton was low during the period from July to October. The greatest dissolved-solids concentrations in these monthly samples were 160 PPM at Bristol and 4,000 PPM at Marcus Hook. At times the dissolved-oxygen concentration of the river water has become dangerously low, especially in that reach of the river between Wharton Street and League Island. At the Benjamin Franklin Bridge, one-third of the samples of river water were less than 30 percent saturated with oxygen; however, no trend, either for better or for worse, was apparent during the 14-year period. It is useful now to summarize these monthly analyses for the period 1949-63 even though a much more detailed description of water quality in this reach of the estuary will soon become available through the use of recording instrumental conditions. This compendium of water-quality data is useful as an explicit statement of water quality during the 14-year study period and is valuable for directing

Self-Selection Patterns of College Roommates as Identified by the Myers-Briggs Type Indicator.

ERIC Educational Resources Information Center

Anchors, W. Scott; Hale, John, Jr.

1985-01-01

Investigated patterns and processes by which students (N=422) made unassisted roommate pairings within residence halls using the Myers-Briggs Type Indicator. Results indicated introverts, intuitives, feelers, and perceivers each tended to self-select. (BL)

Communicator image and Myers-Briggs Type Indicator extraversion-introversion.

PubMed

Opt, Susan K; Loffredo, Donald A

2003-11-01

This study is an examination of the relationship between communicator image and Myers-Briggs Type Indicator (MBTI) dimensions of extraversion-introversion. The authors found that individuals who prefer extraversion tend to have a more positive communicator image than those who prefer introversion. The results of this study support other research results showing that personality preferences differ in communication behaviors and traits, which could have implications for the individual's comfort and success in society. Results of this research also support the contention that communication behavior has biological aspects.

Opposition from Christians to Myers-Briggs Personality Typing: An Analysis and Evaluation

ERIC Educational Resources Information Center

Lloyd, John B.

2007-01-01

Myers-Briggs personality typing is widely used in the Christian church as an aid to individual self-understanding and spiritual formation. However, some Christian leaders have expressed doubt about its validity in understanding human personality and also opposition to its use in nurturing spiritual growth. The aim of the work reported was to…

Enhancing Student Team Effectiveness: Application of Myers-Briggs Personality Assessment in Business Courses

ERIC Educational Resources Information Center

Amato, Christie H.; Amato, Louis H.

2005-01-01

This article examines the relationship between student perceptions of team learning experience and communication style. Student group learning perceptions were evaluated and team communication style was measured using dyads derived from Myers-Briggs personality profiles. Groups containing similar personalities were classified as compatible,…

Managing out of hours clinical photography at the University Hospitals Bristol.

PubMed

Brinkworth, Simon; Kenny, Alice; Knights, Christina

2018-04-01

In recent years, Medical Illustration at University Hospitals Bristol (UHBristol) NHS Foundation Trust has seen a steady increase in photography requests, including the need for out of hours photography provision. This paper details how Medical Illustration at UHBristol decided to manage an out of hours clinical photography service.

The Influence of Hemispheric Dominance on Scores of the Myers-Briggs Type Indicator.

ERIC Educational Resources Information Center

Hartman, Steve E.; And Others

1997-01-01

Results for 75 medical students and 248 undergraduates suggest that the Myers-Briggs Type Indicator appears to sample only 3 bipolar personality dimensions rather than the 4 that the use of "type tables" implies. One of these dimensions shares substantial variance with the cognitive model of hemispheric dominance. (SLD)

Population structure and genetic diversity of the parasite Trichomonas vaginalis in Bristol, UK.

PubMed

Hawksworth, Joseph; Levy, Max; Smale, Chloe; Cheung, Dean; Whittle, Alice; Longhurst, Denise; Muir, Peter; Gibson, Wendy

2015-08-01

The protozoan parasite Trichomonas vaginalis is the causative agent of trichomoniasis, an extremely common, but non-life-threatening, sexually-transmitted disease throughout the world. Recent population genetics studies of T. vaginalis have detected high genetic diversity and revealed a two-type population structure, associated with phenotypic differences in sensitivity to metronidazole, the drug commonly used for treatment, and presence of T. vaginalis virus. There is currently a lack of data on UK isolates; most isolates examined to date are from the US. Here we used a recently described system for multilocus sequence typing (MLST) of T. vaginalis to study diversity of clinical isolates from Bristol, UK. We used MLST to characterise 23 clinical isolates of T. vaginalis collected from female patients during 2013. Seven housekeeping genes were PCR-amplified for each isolate and sequenced. The concatenated sequences were then compared with data from other MLST-characterised isolates available from http://tvaginalis.mlst.net/ to analyse the population structure and construct phylogenetic trees. Among the 23 isolates from the Bristol population of T. vaginalis, we found 23 polymorphic nucleotide sites, 25 different alleles and 19 sequence types (genotypes). Most isolates had a unique genotype, in agreement with the high levels of heterogeneity observed elsewhere in the world. A two-type population structure was evident from population genetic analysis and phylogenetic reconstruction split the isolates into two major clades. Tests for recombination in the Bristol population of T. vaginalis gave conflicting results, suggesting overall a clonal pattern of reproduction. We conclude that the Bristol population of T. vaginalis parasites conforms to the two-type population structure found in most other regions of the world. We found the MLST scheme to be an efficient genotyping method. The online MLST database provides a useful repository and resource that will prove

Explore the advantage of High-frequency Water Quality Data in Urban Surface Water: A Case Study in Bristol, UK

NASA Astrophysics Data System (ADS)

Chen, Y.; Han, D.

2017-12-01

Water system is an essential component in a smart city for its sustainability and resilience. The freshness and beauty of the water body would please people as well as benefit the local aquatic ecosystems. Water quality monitoring approach has evolved from the manual lab-based monitoring approach to the manual in-situ monitoring approach, and finally to the latest wireless-sensor-network (WSN) based solutions in recent decades. The development of the in-situ water quality sensors enable humans to collect high-frequency and real-time water quality data. This poster aims to explore the advantages of the high-frequency water quality data over the low-frequency data collected manually. The data is collected by a remote real-time high-frequency water quality monitor system based on the cutting edge smart city infrastructure in Bristol - `Bristol Is Open'. The water quality of Bristol Floating Harbour is monitored which is the focal area of Bristol with new buildings and features redeveloped in the past decades. This poster will first briefly introduce the water quality monitoring system, followed by the analysis of the advantages of the sub-hourly water quality data. Thus, the suggestion on the monitoring frequency will be given.

Essentials of Myers-Briggs Type Indicator[R] Assessment. Essentials of Psychological Assessment Series.

ERIC Educational Resources Information Center

Quenk, Naomi L.

This book provides step-by-step guidance on the administration, scoring, and interpretation of the Myers-Briggs Type Indicator[R] (MBTI). The book also contains assessment of the test's strengths and weaknesses, advice on its clinical applications, and several case reports. The chapters are: (1) "Overview"; (2) "How To Administer…

Measuring Education for Sustainable Development: Experiences from the University of Bristol

ERIC Educational Resources Information Center

Tierney, Aisling; Tweddell, Hannah; Willmore, Chris

2015-01-01

Purpose: The purpose of this paper is to explore how education for sustainable development (ESD) was measured in the taught curriculum at the University of Bristol (UoB), providing comparison to other methods of measurement and how measurements were used to engage academics in considering the visibility of the penetration of sustainable…

Predictability of Bristol Bay, Alaska, sockeye salmon returns one to four years in the future

USGS Publications Warehouse

Adkison, Milo D.; Peterson, R.M.

2000-01-01

Historically, forecast error for returns of sockeye salmon Oncorhynchus nerka to Bristol Bay, Alaska, has been large. Using cross-validation forecast error as our criterion, we selected forecast models for each of the nine principal Bristol Bay drainages. Competing forecast models included stock-recruitment relationships, environmental variables, prior returns of siblings, or combinations of these predictors. For most stocks, we found prior returns of siblings to be the best single predictor of returns; however, forecast accuracy was low even when multiple predictors were considered. For a typical drainage, an 80% confidence interval ranged from one half to double the point forecast. These confidence intervals appeared to be appropriately wide.

Undergraduate and graduate education in Volcanology at University of Bristol, UK

NASA Astrophysics Data System (ADS)

Ernst, G.; Mader, H.; Phillips, J.; Lejeune, A.; Sparks, S.

2002-05-01

Volcanology education at Bristol is unique for several reasons. The Bristol group operates within a University Research Centre in Environmental and Geophysical Flows (CEGF), involving over 30 staff-to-PhD-level researchers, centered around close collaboration between 4 depts including Earth Sciences and Applied Maths. The uniquely-multidisciplinary setting supports training in volcanology with strong emphasis on combining field-based physical volcanology, theoretical modelling and simple analogue lab experiments. PhD students gain expertise in at least 2 of these 3 aspects during the PhD. Our dept itself is one of the most multidisciplinary in Earth Sciences and is ranked among the 3 leading ES Depts for its research quality. At dept level, there is a strong focus on understanding physical and chemical processes of magmatic/volcanic systems. Teaching/training of students is thus supported by excellent research, and aims at providing profound insights and practical experience into research. At undergraduate level, key experiences of students include 1.) a week-long field class to textbook-quality field sections on one of the most studied active volcanoes (Santorini, Greece), 2.) an independent project where the aim is to learn about all aspects of research as part of a well-focused study including gaining the experience of producing one potentially-publishable paper, 3.) a hands-on research project centered on using the latest analytical methods to solve a problem - this is most successful for 2 reasons: a.) Bristol hosts the EU Geochemical Facility and coordinates an EU Marie Curie Training Centre and b.) the students operate the instruments themselves (ie. they are not run for them); 4.) fourth-year students are especially challenged on the quantitative front (computer programming, statistical data analyses and hypothesis testing -we have excellent computer labs support for teaching), advanced field work and several independent projects. Students are helped into

Bristol Palin: The Pedagogical Media Spectacle of a Sexual Abstinence Ambassador

ERIC Educational Resources Information Center

DaoJensen, Thuy

2013-01-01

This paper explores the public political media spectacle of Bristol Palin's teenage pregnancy and her status as a single mother through the lens of a critical feminist discourse analysis. The author explores how cultural anxieties over teenage sexuality and unintended pregnancy in America are constructed when the pregnant teen is the daughter…

50 CFR Figure 12 to Part 679 - Bristol Bay Trawl Closure Area

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Bristol Bay Trawl Closure Area 12 Figure 12 to Part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE ECONOMIC ZONE OFF...

[Apoptosis mechanism of taxol combined with resveratrol on human laryngeal carcinoma Hep-2 cells].

PubMed

Lu, Chen-Xin; Sun, Jing-Hui; Wu, Chun-Lian

2016-02-01

Laryngeal cancer is one of the most common malignant tumors in the respiratory tumors, and its incidence ranks second highest in the respiratory tumors. Resveratrol (Res) is a kind of polyphenols, which can inhibit nucleotides can inhibit the growth of liver cancer cells, gastric cancer cells, pancreatic cells and other tumor cells by inhibiting ribonucleotide reductase in the cells. Taxol (Tax) is a kind of secondary metabolites of Taxus chinensis, which has anti-tumor activity for breast cancer, cervical cancer, ovarian cancer and other tumors by inhibiting cellular microtubule depolymerization. But at present the effects of resveratrol combined with taxol on human laryngeal carcinoma cell strain Hep-2 and their underlying molecular mechanisms are rarely reported. After human laryngeal cancer cell Hep-2 cells were processed with resveratrol (Res) and taxol (Tax), CCK-8 assay was used to evaluate the effect of these two herbs on the proliferation of cancer cells; AO/PI staining and JC-1 were used to detect Hep-1 cells apoptosis; the expression of Bax, Bcl-2, PARP, TRIB3, and XIAP genes was detected by real time quantitative PCR; the activity of caspase-3 and caspase-8 was determined with quantitative fluorescence method. The experimental results showed that compared with Tax, Res medication alone, joint group significantly enhanced inhibition of Hep-2 cells activity, decreased the dosage of Tax, increased the expression of Bax and PARP, TRIB3, reduced the expression of the Bcl-2 and XIAP, and promoted the activity of caspase-3 and caspase-8. The test results showed that compared with the single medication, combined group could significantly increase the inhibitory effect on Hep-2 cells, significantly reduce Tax dosage, increase expressions of Bax, PARP, TRIB3, reduce expressions of Bcl-2, XIAP, and promote activity of caspase-3, caspase-8. This indicated apoptosis of human laryngeal carcinoma cell strain Hep-2 may be induced with Res, Tax, and the combination of

Performance Monitoring of a Nearshore Berm at Ft. Myers Beach, Florida

DTIC Science & Technology

2013-08-01

prototype designs. Coastal Zone ’93, American Society of Civil Engineers, pp. 2938 -2950. Andrassy, C . J. 1991. Monitoring of a nearshore disposal mound at...ER D C / CH L TR -1 3 -1 1 Performance Monitoring of a Nearshore Berm at Ft. Myers Beach, Florida: Final Report C oa st al a n d H yd...122  Appendix C : USF-CRL Survey Data: morphologic evolution during the first 2 years post construction

Ernest Victor Davey (1888-1957) a mechanical dentist and dentists in North Bristol at the time of the First World War.

PubMed

Stephens, Chris

2015-01-01

Ernest Davey practised dentistry in Bristol until 1924 when his lack of a dental qualification restricted him to work as a dental technician. He appears to have served in this capacity in France during the First World War before returning to Bristol in 1919 where he spent the rest of his life.

Survey of Librarians Using the Myers-Briggs Type Indicator (Form G Self-Scorable).

ERIC Educational Resources Information Center

Johns, Alan

A survey conducted in February 1990 asked 100 librarians to respond to a mailed Myers-Briggs Type Indicator (MBTI), a widely used personality survey that determines Jungian personality types. The results of the MBTI can be applied to building work teams in the library. Forty-eight librarians responded to the survey. Their responses were tallied…

Redistribution of fluorescently labeled tubulin in the mitotic apparatus of sand dollar eggs and the effects of taxol.

PubMed

Hamaguchi, Y; Toriyama, M; Sakai, H; Hiramoto, Y

1987-02-01

Fluorescently labeled tubulin was quickly incorporated into the mitotic apparatus when injected into a live sand dollar egg. After a rectangular area (1.6 X 16 microns) of the mitotic spindle was photobleached at metaphase or anaphase by the irradiation of a laser microbeam, redistribution of fluorescence was almost complete within 30 sec. The photobleached area did not change in shape during the redistribution. During the period of redistribution, the bleached area moved slightly toward the near pole at metaphase and anaphase (means: 1.6 and 1.8 micron/min, respectively). These results indicate that redistribution was not due to the exchange of tubulin subunits only at the ends of microtubules but to their rapid exchange at sites along the microtubules in the bleached region. Furthermore, treadmilling of tubulin molecules along with the spindle microtubules possibly occurred at the rate of 1.6 micron/min at metaphase. Birefringence of the mitotic apparatus increased with a large increase in both the number and length of astral rays shortly after taxol was injected. However, the microtubules did not all seem to elongate at the same rate but appeared to become equalized in length. Chromosome movement stopped within 60 sec after the injection. Centrospheres became large and the labeled tubulin already incorporated into the centrospheres was excluded from the enlarged centrospheres. Shortly after the labeled tubulin was injected following the injection of taxol, it accumulated in the peripheral region of the centrospheres, suggesting that microtubules first assembled at this region. Fluorescently labeled tubulin in the mitotic apparatus in the egg after injection of taxol was redistributed much more slowly after photobleaching than in uninjected eggs.

A Managerial View of Myers-Briggs Personality Types in the Clinical Laboratory.

DTIC Science & Technology

1982-12-01

of personality on selection of a laboratory specialty controlling for certain demographic variables, and to examine the relationship between...cent of the sample. One index of the personality, judging/perceiving, showed a weak relationship to choice of specialty unaffected by any of the... relationship between personality and job tenure in a sample of 141 medical technologists and medical laboratory technicians using the Myers-Briggs Type

Induction of oxidative stress by Taxol® vehicle Cremophor-EL triggers production of interleukin-8 by peripheral blood mononuclear cells through the mechanism not requiring de novo synthesis of mRNA.

PubMed

Ilinskaya, Anna N; Clogston, Jeffrey D; McNeil, Scott E; Dobrovolskaia, Marina A

2015-11-01

Understanding the ability of cytotoxic oncology drugs, and their carriers and formulation excipients, to induce pro-inflammatory responses is important for establishing safe and efficacious formulations. Literature data about cytokine response induction by the traditional formulation of paclitaxel, Taxol®, are controversial, and no data are available about the pro-inflammatory profile of the nano-albumin formulation of this drug, Abraxane®. Herein, we demonstrate and explain the difference in the cytokine induction profile between Taxol® and Abraxane®, and describe a novel mechanism of cytokine induction by a nanosized excipient, Cremophor EL, which is not unique to Taxol® and is commonly used in the pharmaceutical industry for delivery of a wide variety of small molecular drugs. Advances in nanotechnology have enabled the production of many nano-formulation drugs. The cellular response to drugs has been reported to be different between traditional and nano-formulations. In this article, the authors investigated and compared cytokine response induction profiles between Taxol® and Abraxane®. The findings here provided further understanding to create drugs with better safety profiles. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparative Assessment of Lixisenatide, Exenatide, and Liraglutide Pen Devices: A Pilot User-Based Study.

PubMed

Stauder, Udo; Enginee, Diplom; Elton, Hina; Penfornis, Alfred; Edelman, Steve

2014-01-01

Glucagon-like peptide-1 (GLP-1) receptor agonists are a relatively recent addition to the treatment options for type 2 diabetes mellitus (T2DM) and are administered using prefilled pen devices. In this open-label task and interview-based pilot study, 3 GLP-1 receptor agonist pen devices-exenatide (Byetta ® , Bristol-Myers Squibb/AstraZeneca), liraglutide (Victoza ® , Novo Nordisk), and lixisenatide (Lyxumia ® , Sanofi-Aventis)-were comparatively assessed in a randomized order in 30 participants with T2DM for ease of use, using a series of key performance measures (time taken to complete a series of tasks, number of user errors [successful performance], and user satisfaction rating). Linear and logistic regression analysis was conducted for the lixisenatide and liraglutide pens versus the exenatide pen. Participants' mean age was 60 years; 27% and 20% of the participants had visual impairments and reduced manual dexterity, respectively. Tasks were completed faster (P < .001) and with higher successful performance (P = .001) with the lixisenatide pen than with the exenatide pen, whereas the liraglutide pen was not statistically significant versus the exenatide pen on these parameters. Overall, user satisfaction was statistically higher for the lixisenatide and liraglutide pens versus the exenatide pen (P < .001 for both). Lixisenatide and liraglutide pens are associated with higher user satisfaction compared with the exenatide pen. In addition, the lixisenatide pen is faster and results in fewer errors than its comparator (exenatide). The lixisenatide pen may therefore be a suitable choice for patients with T2DM, including older and pen device-naïve patients, and those with visual impairments and reduced manual dexterity. © 2014 Diabetes Technology Society.

Four children and Yale: the making of a human geneticist: the Grover Powers lecture 2014.

PubMed

Rosenberg, Leon E

2014-09-01

Dr. Leon E. Rosenberg delivered the following presentation as the Grover Powers Lecturer on May 14, 2014, which served as the focal point of his return to his "adult home" as a Visiting Professor in the Department of Pediatrics. Grover F. Powers, MD, was one of the most influential figures in American Pediatrics and certainly the leader who created the modern Department of Pediatrics at Yale when he was recruited in 1921 from Johns Hopkins and then served as its second chairman from 1927 to 1951. Dr. Powers was an astute clinician and compassionate physician and fostered and shaped the careers of countless professors, chairs, and outstanding pediatricians throughout the country. This lectureship has continued yearly since it first honored Dr. Powers in 1956. The selection of Dr. Rosenberg for this honor recognizes his seminal role at Yale and throughout the world in the fostering and cultivating of the field of human genetics. Dr. Rosenberg served as the inaugural Chief of a joint Division of Medical Genetics in the Departments of Pediatrics and Internal Medicine; he became Chair when this attained Departmental status. Then he served as Dean of the Medical School from 1984 to 1991, before he became President of the Pharmaceutical Research Institute at Bristol-Myers Squibb and later Senior Molecular Biologist and Professor at Princeton University, until his recent retirement. Dr. Rosenberg has received numerous honors that include the Borden Award from the American Academy of Pediatrics, the McKusick Leadership Award from the American Society for Human Genetics, and election to the Institute of Medicine and the National Academy of Sciences.

Four Children and Yale: The Making of a Human Geneticist

PubMed Central

Rosenberg, Leon E.

2014-01-01

Dr. Leon E. Rosenberg delivered the following presentation as the Grover Powers Lecturer on May 14, 2014, which served as the focal point of his return to his “adult home” as a Visiting Professor in the Department of Pediatrics. Grover F. Powers, MD, was one of the most influential figures in American Pediatrics and certainly the leader who created the modern Department of Pediatrics at Yale when he was recruited in 1921 from Johns Hopkins and then served as its second chairman from 1927 to 1951. Dr. Powers was an astute clinician and compassionate physician and fostered and shaped the careers of countless professors, chairs, and outstanding pediatricians throughout the country. This lectureship has continued yearly since it first honored Dr. Powers in 1956. The selection of Dr. Rosenberg for this honor recognizes his seminal role at Yale and throughout the world in the fostering and cultivating of the field of human genetics. Dr. Rosenberg served as the inaugural Chief of a joint Division of Medical Genetics in the Departments of Pediatrics and Internal Medicine; he became Chair when this attained Departmental status. Then he served as Dean of the Medical School from 1984 to 1991, before he became President of the Pharmaceutical Research Institute at Bristol-Myers Squibb and later Senior Molecular Biologist and Professor at Princeton University, until his recent retirement. Dr. Rosenberg has received numerous honors that include the Borden Award from the American Academy of Pediatrics, the McKusick Leadership Award from the American Society for Human Genetics, and election to the Institute of Medicine and the National Academy of Sciences. PMID:25191153

Comparative Assessment of Lixisenatide, Exenatide, and Liraglutide Pen Devices

PubMed Central

Enginee, Diplom; Elton, Hina; Penfornis, Alfred; Edelman, Steve

2014-01-01

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists are a relatively recent addition to the treatment options for type 2 diabetes mellitus (T2DM) and are administered using prefilled pen devices. Method: In this open-label task and interview-based pilot study, 3 GLP-1 receptor agonist pen devices—exenatide (Byetta®, Bristol-Myers Squibb/AstraZeneca), liraglutide (Victoza®, Novo Nordisk), and lixisenatide (Lyxumia®, Sanofi-Aventis)—were comparatively assessed in a randomized order in 30 participants with T2DM for ease of use, using a series of key performance measures (time taken to complete a series of tasks, number of user errors [successful performance], and user satisfaction rating). Linear and logistic regression analysis was conducted for the lixisenatide and liraglutide pens versus the exenatide pen. Participants’ mean age was 60 years; 27% and 20% of the participants had visual impairments and reduced manual dexterity, respectively. Results: Tasks were completed faster (P < .001) and with higher successful performance (P = .001) with the lixisenatide pen than with the exenatide pen, whereas the liraglutide pen was not statistically significant versus the exenatide pen on these parameters. Overall, user satisfaction was statistically higher for the lixisenatide and liraglutide pens versus the exenatide pen (P < .001 for both). Conclusions: Lixisenatide and liraglutide pens are associated with higher user satisfaction compared with the exenatide pen. In addition, the lixisenatide pen is faster and results in fewer errors than its comparator (exenatide). The lixisenatide pen may therefore be a suitable choice for patients with T2DM, including older and pen device-naïve patients, and those with visual impairments and reduced manual dexterity. PMID:24876548

Analysis of Breast Cell-Lineage Response Differences to Taxol Using a Novel Co-Culture System

DTIC Science & Technology

2005-06-01

as the Hayflick limit [159], is thought to be a "mitotic clock" preventing cumulative cell damage from progressing to tumorigenesis [164-166] and...TERMS Breast cancer, co-culture, gene expression profiles, Taxol, transport mechanisms 16. SECURITY CLASSIFICATION OF: 17. LIMITATION 18. NUMBER 19a...proteins have been shown to bind and inactivate p53 and pRb respectively [25]. While the mortal cells have limited replicative potential in culture and

Engineering with Nature: Nearshore Berm Placements at Fort Myers Beach and Perdido Key, Florida, USA

DTIC Science & Technology

2015-05-15

may be winnowed from the placement sediment and ideally move offshore. In the case of Fort Myers Beach, this design proved to be successful. The...material and subsequent dredging of material once the undesirable fine fraction has winnowed out. Conclusions Although quite different designs, both

Differences in Myers-Briggs Personality Types among High School Band, Orchestra, and Choir Members

ERIC Educational Resources Information Center

MacLellan, Christin Reardon

2011-01-01

The purpose of this study was to explore personality type differences among high school band, string orchestra, and choir students according to ensemble membership. Participants (N = 355) were high school students who had participated in their school's band, orchestra, or choir for 1 year or more. The author administered the Myers-Briggs Type…

Extracellular biosynthesis of gadolinium oxide (Gd2O3) nanoparticles, their biodistribution and bioconjugation with the chemically modified anticancer drug taxol

PubMed Central

Khan, Shadab Ali; Gambhir, Sanjay

2014-01-01

Summary As a part of our programme to develop nanobioconjugates for the treatment of cancer, we first synthesized extracellular, protein-capped, highly stable and well-dispersed gadolinium oxide (Gd2O3) nanoparticles by using thermophilic fungus Humicola sp. The biodistribution of the nanoparticles in rats was checked by radiolabelling with Tc-99m. Finally, these nanoparticles were bioconjugated with the chemically modified anticancer drug taxol with the aim of characterizing the role of this bioconjugate in the treatment of cancer. The biosynthesized Gd2O3 nanoparticles were characterized by UV–vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoemission spectroscopy (XPS). The Gd2O3–taxol bioconjugate was confirmed by UV–vis spectroscopy and fluorescence microscopy and was purified by using high performance liquid chromatography (HPLC). PMID:24778946

Validation of a modified Bristol stool scale - inter-rater reliability amongst pediatric gastroenterologists

USDA-ARS?s Scientific Manuscript database

Stool form and changes in stool form are important criteria in both clinical practice and clinical research. However, descriptions of stool form from both patients and physicians alike may be subjective and objective measurements of stool form are not well developed. Although the Bristol stool scale...

Myers-Briggs Type Indicator (MBTI) Personality Profiling and General Weighted Average (GWA) of Nursing Students

ERIC Educational Resources Information Center

Mallari, Shedy Dee C.; Pelayo, Jose Maria G., III

2017-01-01

The study focused on the investigation of the existing dynamics between the Myers Briggs Type Indicator personality profiling (MBTI), and General Weighted Average (GWA) of nursing students. The participants were 48 college students in Angeles City, Philippines. All the students were administered with the MBTI instrument. Descriptive…

78 FR 63148 - Approval and Promulgation of Implementation Plans; Tennessee; Bristol; 2010 Lead Base Year...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-23

... per year within the Bristol Area is Exide Technologies Facility, a lead acid battery manufacturing and recycling facility which processes lead and reclaimed lead into batteries for the auto industry. Pursuant to...

Bouse Formation in the Bristol basin near Amboy, California, USA

USGS Publications Warehouse

Miller, David M.; Reynolds, Robert E.; Bright, Jordan E.; Starratt, Scott W.

2014-01-01

Limestone beds underlain and overlain by alluvial fan conglomerate near Amboy, California, are very similar in many respects to parts of the Bouse Formation, suggesting that an arm of the Pliocene Bouse water body extended across a wide part of the southern Mojave Desert. The deposits are north of the town of Amboy at and below an elevation of 290 m, along the northern piedmont of the Bristol “dry” Lake basin. The Amboy outcrops contain the Lawlor Tuff (4.83 Ma), which is also found in an outcrop of the Bouse Formation in the Blythe basin near Buzzards Peak in the Chocolate Mountains, 180 km southeast of Amboy. Bouse exposures near Amboy are ∼3.4 m thick, white, distinctly bedded, with limestone and calcareous sandstone as well as stromatolite mounds; we interpret these as nearshore deposits. The Bouse at Amboy contains ostracodes, diatoms, and mollusks that indicate saline lake or estuarine environments with an admixture of fresh-water forms. Along with wading bird tracks and a spine from a marine fish, these fossils suggest that the deposits formed in saline waters near a fresh-water source such as a perennial stream. Beds of the outcrop dip southward and are 113 m above the surface of Bristol Playa, where similar age sediments are buried 270+ m deep, indicating significant faulting and vertical tectonics in this part of the Eastern California Shear Zone during the past 5 m.y. Confirmation of the Bouse Formation at Amboy strengthens previous assignments to the Bouse Formation for mudstones in driller logs at Danby “dry” Lake, California, and suggests that areally extensive arms of the Bouse water body were west of the Blythe basin. The Bristol basin arm of the lower Bouse basin probably was restricted from the main water body by narrow passages, but Bouse sediment there is similar to that in the Blythe basin, suggesting generally similar water chemistry and environmental conditions. Examining the degree to which Bouse deposits in the western arms

Efficacy, safety, bone and metabolic effects of HIV nucleoside reverse transcriptase inhibitor BMS-986001 (AI467003): a phase 2b randomised, controlled, partly blinded trial.

PubMed

Gupta, Samir K; McComsey, Grace A; Lombaard, John; Echevarría, Juan; Orrell, Catherine; Avihingsanon, Anchalee; Osiyemi, Olayemi; Santoscoy, Mario; Ray, Neelanjana; Stock, David A; Joshi, Samit R; Hanna, George J; Lataillade, Max

2016-01-01

%) of 65 patients for whom there were data in the 100 mg group, 54 (81%) of 67 in the 200 mg group, 62 (94%) of 66 in the 400 mg group achieved HIV-1 RNA less than 50 copies per mL, compared with 88 (89%) of 99 in the tenofovir disoproxil fumarate group (modified intention-to-treat population). BMS-986001 was generally well tolerated through week 48. Two patients had BMS-986001-related serious adverse events (atypical drug eruption and thrombocytopenia) and two in the tenofovir disoproxil fumarate group had study drug-related serious adverse events (potential drug-induced liver injury and depression or lipodystrophy) that led to discontinuation. NRTI resistance-associated mutations were reported in four (2%) of 198 patients, and non-NRTI mutations in 17 (9%) of 198 patients receiving BMS-986001 versus none of 99 and one (1%) of 99 patients receiving tenofovir disoproxil fumarate, respectively. Compared with tenofovir disoproxil fumarate, individuals in the BMS-986001 groups showed a smaller decrease in lumbar spine and hip bone mineral density but greater accumulation of limb and trunk fat, subcutaneous and visceral adipose tissue, and increased total cholesterol. BMS-986001 had similar efficacy to that of tenofovir disoproxil fumarate and was associated with a smaller decrease in bone mineral density; however, greater resistance and gains in both peripheral and central fat accumulation were recorded for the investigational drug. Bristol-Myers Squibb has discontinued its involvement in the development of BMS-986001, and future decisions on development will be made by Oncolys BioPharma. Bristol-Myers Squibb. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Complex and Elusive Nature of Religious Prosociality: Reply to Myers (2012) and Saroglou (2012)

ERIC Educational Resources Information Center

Galen, Luke W.

2012-01-01

This reply explores issues raised in comments by Myers (2012) and Saroglou (2012) on Galen (2012) regarding whether religiosity has any influence on prosociality. Areas of contention include (a) the distinction between religious belief and other influences, mainly the socialization effects of group behavior; (b) whether behavior largely restricted…

University-School Partnerships: On the Impact on Students of Summer Schools (for School Students Aged 17-18) Run by Bristol ChemLabs

ERIC Educational Resources Information Center

Shaw, A. J.; Harrison, T. G.; Croker, S. J.; Medley, M.; Sellou, L.; Shallcross, K. L.; Williams, S, J.; Grayson, D. J.; Shallcross, D. E.

2010-01-01

Chemistry summer schools for 17-18 year old school students in the UK were run by Bristol ChemLabS, a Centre for Excellence in Teaching and Learning in Chemistry at the University of Bristol. Students attending were all studying Chemistry at post-16 level (A level in the UK) and experienced not only new practical techniques but also lectures on…

Geology and ground-water resources of the Bristol-Plainville-Southington area, Connecticut

USGS Publications Warehouse

La Sala, A. M.

1964-01-01

The Bristol-Plainville-Southington area straddles the boundary between the New England Upland and the Connecticut Valley Lowland sections of the New England physiographic province. The western parts of Bristol are Southington lie in the New England Upland section, an area of rugged topography underlain by metamorphic rocks of Palezoic age. The eastern part of the area, to the east of a prominent scarp marking the limit of the metamorphic rocks, is in the Connecticut Valley Lowland and is underlain by sedimentary rocks and interbedded basaltic lava flows of Triassic age. The lowland is characterized for the most part by broad valleys and low intervening linear hills, but in the eastern parts of Plainville and Southington, basaltic rocks form a rugged highland. The bedrock is largely mantled by glacial deposits of Wisconsin age. On hills the glacial deposits are mainly ground moraine, and in valleys mainly stratified. The metamorphic rocks comprise the Hartland Formation, Bristol Granite Gneiss of Gregory (1906), and Prospect Gneiss. These formations contain water in fractures, principally joints occurring in regular sets. The rocks generally yield supplies of 5 to 15 gpm (gallons per minute) to drilled wells averaging about 140 feet in depth. The rocks of Triassic age in the area are the New Haven Arkose, Talcott Basalt, Shuttle Meadow Formation, Holyoke Basalt, and East Berlin Formation. The formations contain water principally in joints and other fractures and, to a lesser extent, in bedding-plane openings and pore spaces. Drilled wells penetrating these rocks generally range from 100 to 200 feet in depth and yield an average of nearly 20 gpm. The maximum yield obtained from a well in these rocks is 180 gpm. The ground moraine of Pleistocene age is composed principally of till. The deposit averages about 24 feet in thickness, and wells penetrating it average about 16 feet in depth. The ground moraine yields small supplier of water suitable for household use when

The Multifactorial Nature of Extraversion-Introversion in the Myers-Briggs Type Indicator and Eysenck Personality Inventory.

ERIC Educational Resources Information Center

Sipps, Gary J.; Alexander, Ralph A.

1987-01-01

The construct validity of extraversion-introversion was explored, as measured by the Myers Briggs Type Indicator (MBTI) and the Eysenck Personality Inventory. Findings supported the complexity of extraversion-introversion. Two MBTI scales, Extraversion Introversion and Judging Perceiving, were factorially valid measures of impulsivity…

Personality Characteristics of South Korean Students with Visual Impairments Using the Myers-Briggs Type Indicator

ERIC Educational Resources Information Center

Bak, Sunhi

2012-01-01

Introduction: The study presented here was designed to determine whether there were significant differences in the frequency and preference scores of personality functions and the frequency of personality types, as measured by the Myers-Briggs Type Indicator (MBTI), by gender, school level, and level of visual function, of students with visual…

Alternative models of climatic effects on sockeye salmon (Oncorhynchus nerka) productivity in Bristol Bay, Alaska, and the Fraser River, British Columbia

USGS Publications Warehouse

Adkison, M.; Peterman, R.; Lapointe, M.; Gillis, D.; Korman, J.

1996-01-01

We compare alternative models of sockeye salmon (Oncorhynchus nerka) productivity (returns per spawner) using more than 30 years of catch and escapement data for Bristol Bay, Alaska, and the Fraser River, British Columbia. The models examined include several alternative forms of models that incorporate climatic influences as well as models not based on climate. For most stocks, a stationary stock-recruitment relationship explains very little of the interannual variation in productivity. In Bristol Bay, productivity co-varies among stocks and appears to be strongly related to fluctuations in climate. The best model for Bristol Bay sockeye involved a change in the 1970s in the parameters of the Ricker stock-recruitment curve; the stocks generally became more productive. In contrast, none of the models of Fraser River stocks that we examined explained much of the variability in their productivity.

Re-Engineering Your Office Environment: Matching Careers and Personality via the Myers-Briggs Type Indicator.

ERIC Educational Resources Information Center

McPherson, Bill

1995-01-01

Provides a summary of the research on the use of the Myers-Briggs Type Indicator (MBTI) in the workplace with implications for the practical uses of the MBTI. Suggests using the MBTI to aid the office professional, office manager, and office employee in training, career counseling and planning, team building, organizational development, and…

Notification: Review of the EPA’s Assessment of Potential Mining Impacts in Bristol Bay, Alaska

EPA Pesticide Factsheets

Project #OPE-FY14-0039, May 2, 2014. The EPA OIG plans to begin preliminary research to determine whether the EPA adhered to laws in developing its assessment of potential mining impacts on ecosystems in Bristol Bay, Alaska.

A Review of the Myers-Briggs Type Inventory: A Potential Training Tool for Human Services Organizations.

ERIC Educational Resources Information Center

Aviles, Christopher B.

The Myers-Briggs Type Inventory (MBTI) can be helpful in personal, career, and marriage counseling; conflict and stress management; team building; and understanding managerial and learning styles. It has great potential to be utilized in human services organizations for training purposes because it offers a way to conceptualize employee…

Integrability of geodesics in near-horizon extremal geometries: Case of Myers-Perry black holes in arbitrary dimensions

NASA Astrophysics Data System (ADS)

Demirchian, Hovhannes; Nersessian, Armen; Sadeghian, Saeedeh; Sheikh-Jabbari, M. M.

2018-05-01

We investigate dynamics of probe particles moving in the near-horizon limit of extremal Myers-Perry black holes in arbitrary dimensions. Employing ellipsoidal coordinates we show that this problem is integrable and separable, extending the results of the odd dimensional case discussed by Hakobyan et al. [Phys. Lett. B 772, 586 (2017)., 10.1016/j.physletb.2017.07.028]. We find the general solution of the Hamilton-Jacobi equations for these systems and present explicit expressions for the Liouville integrals and discuss Killing tensors and the associated constants of motion. We analyze special cases of the background near-horizon geometry were the system possesses more constants of motion and is hence superintegrable. Finally, we consider a near-horizon extremal vanishing horizon case which happens for Myers-Perry black holes in odd dimensions and show that geodesic equations on this geometry are also separable and work out its integrals of motion.

An Assessment of Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska (Final Report)

EPA Science Inventory

The Bristol Bay watershed in southwestern Alaska supports the largest sockeye salmon fishery in the world, is home to 25 federally recognized tribal governments, and contains large mineral resources. The potential for large-scale mining activities in the watershed has raised conc...

Comparing University Students and Community College Students Learning Styles and Myers-Briggs Type Indicator (MBTI) Preferences.

ERIC Educational Resources Information Center

Herbster, Douglas L.; And Others

This document reports on a study to determine if there is a pattern between specific learning styles and Myers-Briggs Type Indicator preferences. The learning style inventory used for the study, "The Teaching and Learning Styles Survey for Adolescents (TLC)," is based on Jungian style preferences--thinker, feeler, sensor, and…

Clopidogrel in infants with systemic-to-pulmonary-artery shunts.

PubMed

Wessel, David L; Berger, Felix; Li, Jennifer S; Dähnert, Ingo; Rakhit, Amit; Fontecave, Sylvie; Newburger, Jane W

2013-06-20

Infants with cyanotic congenital heart disease palliated with placement of a systemic-to-pulmonary-artery shunt are at risk for shunt thrombosis and death. We investigated whether the addition of clopidogrel to conventional therapy reduces mortality from any cause and morbidity related to the shunt. In a multicenter, double-blind, event-driven trial, we randomly assigned infants 92 days of age or younger with cyanotic congenital heart disease and a systemic-to-pulmonary-artery shunt to receive clopidogrel at a dose of 0.2 mg per kilogram of body weight per day (467 infants) or placebo (439 infants), in addition to conventional therapy (including aspirin in 87.9% of infants). The primary efficacy end point was a composite of death or heart transplantation, shunt thrombosis, or performance of a cardiac procedure due to an event considered to be thrombotic in nature before 120 days of age. The rate of the composite primary end point did not differ significantly between the clopidogrel group (19.1%) and the placebo group (20.5%) (absolute risk difference, 1.4 percentage points; relative risk reduction with clopidogrel, 11.1%; 95% confidence interval, -19.2 to 33.6; P=0.43), nor did the rates of the three components of the composite primary end point. There was no significant benefit of clopidogrel treatment in any subgroup, including subgroups defined by shunt type. Clopidogrel recipients and placebo recipients had similar rates of overall bleeding (18.8% and 20.2%, respectively) and severe bleeding (4.1% and 3.4%, respectively). Clopidogrel therapy in infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary-artery shunt, most of whom received concomitant aspirin therapy, did not reduce either mortality from any cause or shunt-related morbidity. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00396877.).

Clinically relevant reductions in HbA1c without hypoglycaemia: results across four studies of saxagliptin.

PubMed

Karyekar, C S; Frederich, R; Ravichandran, S

2013-08-01

In four 24-week controlled studies, the antihyperglycaemic efficacy of saxagliptin was demonstrated in patients with type 2 diabetes mellitus as add-on therapy to glyburide, a thiazolidinedione, or metformin, and when used in initial combination with metformin vs. metformin monotherapy in drug-naive patients. Data from these studies were analysed to compare the proportions of patients who achieved specific reductions from baseline in glycated haemoglobin [HbA(1c); reductions of ≥ 0.5% and ≥ 0.7% in all studies (prespecified); reductions ≥ 1.0% in the add-on studies and ≥ 1.0% to ≥ 2.5% in the initial combination study (post hoc)] for saxagliptin vs. comparator at week 24. We report overall rates of glycaemic response defined by these reductions in HbA(1c) and rates of response without experiencing hypoglycaemia. Large glycaemic response rates were higher with saxagliptin 2.5 and 5 mg/day than with comparator (HbA(1c) ≥ 1.0%, 31.7-50.3% vs. 10.3-20.0%) as add-on therapy and higher with saxagliptin 5 mg/day as initial combination with metformin than with metformin monotherapy (HbA(1c) ≥ 2.0%, 68.3% vs. 49.8%) in drug-naive patients. Addition of saxagliptin was associated with a low incidence of hypoglycaemia; overall response rates and response rates excluding patients who experienced hypoglycaemia were similar. Analysis of several demographic and baseline clinical variables revealed no consistent correlations with response to saxagliptin. Whether receiving saxagliptin as an add-on therapy to glyburide, a thiazolidinedione, or metformin or in initial combination with metformin, a greater percentage of patients achieve clinically relevant large reductions in HbA(1c) vs. comparator, with a low incidence of hypoglycaemia. © 2013 Bristol-Myers Squibb Co. International Journal of Clinical Practice published by John Wiley & Sons Ltd.

Randomized, placebo-controlled window trial of EGFR, Src, or combined blockade in head and neck cancer.

PubMed

Bauman, Julie E; Duvvuri, Umamaheswar; Gooding, William E; Rath, Tanya J; Gross, Neil D; Song, John; Jimeno, Antonio; Yarbrough, Wendell G; Johnson, Faye M; Wang, Lin; Chiosea, Simion; Sen, Malabika; Kass, Jason; Johnson, Jonas T; Ferris, Robert L; Kim, Seungwon; Hirsch, Fred R; Ellison, Kimberly; Flaherty, John T; Mills, Gordon B; Grandis, Jennifer R

2017-03-23

BACKGROUND. EGFR and Src family kinases are upregulated in head and neck squamous cell carcinoma (HNSCC). EGFR interacts with Src to activate STAT3 signaling, and dual EGFR-Src targeting is synergistic in HNSCC preclinical models. pSrc overexpression predicted resistance to the EGFR inhibitor, erlotinib, in a prior window trial. We conducted a 4-arm window trial to identify biomarkers associated with response to EGFR and/or Src inhibition. METHODS. Patients with operable stage II-IVa HNSCC were randomized to 7-21 days of neoadjuvant erlotinib, the Src inhibitor dasatinib, the combination of both, or placebo. Paired tumor specimens were collected before and after treatment. Pharmacodynamic expression of EGFR and Src pathway components was evaluated by IHC of tissue microarrays and reverse-phase protein array of tissue lysates. Candidate biomarkers were assessed for correlation with change in tumor size. RESULTS. From April 2009 to December 2012, 58 patients were randomized and 55 were treated. There was a significant decrease in tumor size in both erlotinib arms ( P = 0.0014); however, no effect was seen with dasatinib alone ( P = 0.24). High baseline pMAPK expression was associated with response to erlotinib ( P = 0.03). High baseline pSTAT3 was associated with resistance to dasatinib ( P = 0.099). CONCLUSIONS. Brief exposure to erlotinib significantly decreased tumor size in operable HNSCC, with no additive effect from dasatinib. Baseline pMAPK expression warrants further study as a response biomarker for anti-EGFR therapy. Basal expression of pSTAT3 may be independent of Src, explain therapeutic resistance, and preclude development of dasatinib in biomarker-unselected cohorts. TRIAL REGISTRATION. NCT00779389. FUNDING. National Cancer Institute, American Cancer Society, Pennsylvania Department of Health, V Foundation for Cancer Research, Bristol-Myers Squibb, and Astellas Pharma.

Randomized, placebo-controlled window trial of EGFR, Src, or combined blockade in head and neck cancer

PubMed Central

Bauman, Julie E.; Duvvuri, Umamaheswar; Gooding, William E.; Rath, Tanya J.; Gross, Neil D.; Song, John; Jimeno, Antonio; Yarbrough, Wendell G.; Johnson, Faye M.; Wang, Lin; Chiosea, Simion; Sen, Malabika; Kass, Jason; Johnson, Jonas T.; Ferris, Robert L.; Kim, Seungwon; Hirsch, Fred R.; Ellison, Kimberly; Flaherty, John T.; Mills, Gordon B.

2017-01-01

BACKGROUND. EGFR and Src family kinases are upregulated in head and neck squamous cell carcinoma (HNSCC). EGFR interacts with Src to activate STAT3 signaling, and dual EGFR-Src targeting is synergistic in HNSCC preclinical models. pSrc overexpression predicted resistance to the EGFR inhibitor, erlotinib, in a prior window trial. We conducted a 4-arm window trial to identify biomarkers associated with response to EGFR and/or Src inhibition. METHODS. Patients with operable stage II–IVa HNSCC were randomized to 7–21 days of neoadjuvant erlotinib, the Src inhibitor dasatinib, the combination of both, or placebo. Paired tumor specimens were collected before and after treatment. Pharmacodynamic expression of EGFR and Src pathway components was evaluated by IHC of tissue microarrays and reverse-phase protein array of tissue lysates. Candidate biomarkers were assessed for correlation with change in tumor size. RESULTS. From April 2009 to December 2012, 58 patients were randomized and 55 were treated. There was a significant decrease in tumor size in both erlotinib arms (P = 0.0014); however, no effect was seen with dasatinib alone (P = 0.24). High baseline pMAPK expression was associated with response to erlotinib (P = 0.03). High baseline pSTAT3 was associated with resistance to dasatinib (P = 0.099). CONCLUSIONS. Brief exposure to erlotinib significantly decreased tumor size in operable HNSCC, with no additive effect from dasatinib. Baseline pMAPK expression warrants further study as a response biomarker for anti-EGFR therapy. Basal expression of pSTAT3 may be independent of Src, explain therapeutic resistance, and preclude development of dasatinib in biomarker-unselected cohorts. TRIAL REGISTRATION. NCT00779389. FUNDING. National Cancer Institute, American Cancer Society, Pennsylvania Department of Health, V Foundation for Cancer Research, Bristol-Myers Squibb, and Astellas Pharma. PMID:28352657

Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma.

PubMed

Lonial, Sagar; Dimopoulos, Meletios; Palumbo, Antonio; White, Darrell; Grosicki, Sebastian; Spicka, Ivan; Walter-Croneck, Adam; Moreau, Philippe; Mateos, Maria-Victoria; Magen, Hila; Belch, Andrew; Reece, Donna; Beksac, Meral; Spencer, Andrew; Oakervee, Heather; Orlowski, Robert Z; Taniwaki, Masafumi; Röllig, Christoph; Einsele, Hermann; Wu, Ka Lung; Singhal, Anil; San-Miguel, Jesus; Matsumoto, Morio; Katz, Jessica; Bleickardt, Eric; Poulart, Valerie; Anderson, Kenneth C; Richardson, Paul

2015-08-13

Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma. In this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate. Final results for the coprimary end points are reported on the basis of a planned interim analysis of progression-free survival. Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group. After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68%, as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively. Median progression-free survival in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio for progression or death in the elotuzumab group, 0.70; 95% confidence interval, 0.57 to 0.85; P<0.001). The overall response rate in the elotuzumab group was 79%, versus 66% in the control group (P<0.001). Common grade 3 or 4 adverse events in the two groups were lymphocytopenia, neutropenia, fatigue, and pneumonia. Infusion reactions occurred in 33 patients (10%) in the elotuzumab group and were grade 1 or 2 in 29 patients. Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-2 ClinicalTrials.gov number, NCT01239797.).

"Center punch" and "whole spot" bioanalysis of apixaban in human dried blood spot samples by UHPLC-MS/MS.

PubMed

Zheng, Naiyu; Yuan, Long; Ji, Qin C; Mangus, Heidi; Song, Yan; Frost, Charles; Zeng, Jianing; Aubry, Anne-Françoise; Arnold, Mark E

2015-04-15

Apixaban (Eliquis™) was developed by Bristol-Myers Squibb (BMS) and Pfizer to use as an antithrombotic/anticoagulant agent and has been recently approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. A clinical study of apixaban, sponsored by BMS and Pfizer, included a pilot exploratory portion to evaluate the potential for future drug concentration monitoring using dried blood spot (DBS) sample collection. For DBS sample collection, a fixed blood volume was dispensed onto a DBS card by either regular volumetric pipette (venous blood collection) or capillary dispenser (finger prick blood collection). A 96-well semi-automated liquid-liquid extraction sample preparation procedure was developed to provide clean extracts for UHPLC-MS/MS quantitation. Assays using both partial-spot center punch and whole spot punch were developed and validated. The linear dynamic ranges for all the analyses were from 0.5 to 500 ng/mL. The coefficient of determination (r(2)) values was >0.9944 for all the validation runs. For the center punch approach, the intra-assay precision (%CV) was within 4.4% and inter-assay precision was within 2.6%. The assay accuracy, expressed as %Dev., was within ± 5.4% of the nominal concentrations. One accuracy and precision run was performed using the whole spot approach, the intra-assay precision (%CV) was within 7.1% and the accuracy was within ± 8.0% of the nominal concentrations. In contrast to the center punch approach, the whole spot approach eliminated the effect of hematocrit and high lipids on the analysis of apixaban in human DBS when an accurate sample blood volume was collected on DBS cards. Copyright © 2015 Elsevier B.V. All rights reserved.

Bristol Stool Form Scale reliability and agreement decreases when determining Rome III stool form designations

USDA-ARS?s Scientific Manuscript database

Rater reproducibility of the Bristol Stool Form Scale (BSFS), which categorizes stools into one of seven types, is unknown. We sought to determine reliability and agreement by individual stool type and when responses are categorized by Rome III clinical designation as normal or abnormal (constipatio...

76 FR 37002 - Drawbridge Operation Regulation; Delaware River, Between Burlington, NJ and Bristol, PA

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... the operating lift cables. DATES: This deviation is effective from 12:01 a.m. July 9, 2011, until 11.... SUPPLEMENTARY INFORMATION: The Burlington County Bridge Commission, who owns and operates this vertical-lift... 33 CFR 117.5 and 117.716(b) to facilitate the replacement of the lift cables. The Burlington-Bristol...

Risk-adjusted sequential probability ratio tests: applications to Bristol, Shipman and adult cardiac surgery.

PubMed

Spiegelhalter, David; Grigg, Olivia; Kinsman, Robin; Treasure, Tom

2003-02-01

To investigate the use of the risk-adjusted sequential probability ratio test in monitoring the cumulative occurrence of adverse clinical outcomes. Retrospective analysis of three longitudinal datasets. Patients aged 65 years and over under the care of Harold Shipman between 1979 and 1997, patients under 1 year of age undergoing paediatric heart surgery in Bristol Royal Infirmary between 1984 and 1995, adult patients receiving cardiac surgery from a team of cardiac surgeons in London,UK. Annual and 30-day mortality rates. Using reasonable boundaries, the procedure could have indicated an 'alarm' in Bristol after publication of the 1991 Cardiac Surgical Register, and in 1985 or 1997 for Harold Shipman depending on the data source and the comparator. The cardiac surgeons showed no significant deviation from expected performance. The risk-adjusted sequential probability test is simple to implement, can be applied in a variety of contexts, and might have been useful to detect specific instances of past divergent performance. The use of this and related techniques deserves further attention in the context of prospectively monitoring adverse clinical outcomes.

The Myers-Briggs Type Indicator[R] and Mainstream Psychology: Analysis and Evaluation of an Unresolved Hostility

ERIC Educational Resources Information Center

Lloyd, John B.

2012-01-01

The Myers-Briggs Type Indicator (MBTI[R]) is widely used as a staff-development tool in the business and voluntary sectors. Its Psychological Type approach is found to be a valuable aid to understanding self and others and thus to enhancing effective team-working. This continuing and growing popularity is surprising in view of the disdain with…

Small deformations of extreme five dimensional Myers-Perry black hole initial data

NASA Astrophysics Data System (ADS)

Alaee, Aghil; Kunduri, Hari K.

2015-02-01

We demonstrate the existence of a one-parameter family of initial data for the vacuum Einstein equations in five dimensions representing small deformations of the extreme Myers-Perry black hole. This initial data set has `' symmetry and preserves the angular momenta and horizon geometry of the extreme solution. Our proof is based upon an earlier result of Dain and Gabach-Clement concerning the existence of -invariant initial data sets which preserve the geometry of extreme Kerr (at least for short times). In addition, we construct a general class of transverse, traceless symmetric rank 2 tensors in these geometries.

Chemistry Provision for Primary Pupils: The Experiences of 10 Years of Bristol ChemLabs Outreach

ERIC Educational Resources Information Center

Harrison, Timothy G.; Shallcross, Dudley E.

2016-01-01

Bristol ChemLabS, the UK's Centre for Excellence in Teaching and Learning in practical chemistry, delivers numerous outreach activity days per year for thousands of primary school pupils annually. These mainly comprise demonstration assemblies and hands on workshops for pupils in the main. The activities support the UK's Key Stage 2 science…

Teaching Eskimo Culture to Eskimo Students: A Special Program for Secondary Schools in Bristol Bay.

ERIC Educational Resources Information Center

Holthaus, Gary H.

Eskimo youth in Bristol Bay, Alaska, caught between the clash of native and white cultures, have difficulty identifying with either culture. The curriculum in Indian schools in the area, geared primarily to white middle-class standards, is not relevant to the students, Textbooks and standardized tests, based on experiences common to a white…

Literacy in a Business Context: Literacy Practices of Some Bristol Merchants in the Sixteenth Century

ERIC Educational Resources Information Center

Takeda, Reiko

2011-01-01

This article considers the education and literacy practices of Bristol merchants involved in overseas trade in the sixteenth century by focusing on their business concerns. It argues that these demanded complex literacy skills and the discussion explores why writing was so central to their work. The merchants required specific training in order to…

How Zoos Are Meeting the Challenges Facing Biodiversity: Bristol Zoo Gardens as a Case Study

ERIC Educational Resources Information Center

Garrett, Simon

2010-01-01

As ideas about effective conservation of biodiversity develop, zoos are adapting their roles to meet the new challenges. This article considers these changes, using the work of Bristol and other UK zoos as a case study. The significance of zoos in both global and local conservation of biodiversity, their role in promoting public engagement and…

77 FR 31353 - An Assessment of Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, AK

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-25

... prepared by the EPA's Region 10 (Pacific Northwest and Alaska), EPA's Office of Water, and EPA's Office of Research and Development. The EPA conducted this assessment to determine the significance of Bristol Bay's... under the Clean Water Act. The assessment is intended to provide a scientific and technical foundation...

Considering Personality Type in Adult Learning: Using the Myers-Briggs Type Indicator in Instructor Preparation at PricewaterhouseCoopers

ERIC Educational Resources Information Center

Daisley, Richard J.

2011-01-01

This article explores the feasibility of using the Myers-Briggs Type Indicator (MBTI) as a framework for instructor development in a professional services training environment. It explores the consistency of MBTI with common adult learning theory, addresses questions on MBTI's reliability and validity, and explores the applicability of MBTI to the…

An Assessment of Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska (First External Review Draft)

EPA Science Inventory

[UPDATE] In March 2014, EPA released a response to public comments on the draft document, "An Assessment of the Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska" (see downloads). In Jan 2014, EPA released a response to peer review comments on ...

An Assessment of Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska (Second External Review Draft)

EPA Science Inventory

[UPDATE] In March 2014, EPA released a response to public comments on the second draft document, "An Assessment of the Potential Mining Impacts on Salmon Ecosystems of Bristol Bay, Alaska" (see downloads). In Jan 2014, EPA released a response to peer review comme...

Tidally generated sea-floor lineations in Bristol Bay, Alaska, USA

USGS Publications Warehouse

Marlow, M. S.; Stevenson, A.J.; Chezar, H.; McConnaughey, R.A.

1999-01-01

Highly reflective linear features occur in water depths of 20-30 m in northern Bristol Bay (Alaska, USA) and are, in places, over 600 m in length. Their length-to-width ratio is over 100:1. The lineations are usually characterized by large transverse ripples with wavelengths of 1-2 m. The lineations trend about N60??E, and are spaced between 20 and 350 m. Main tidal directions near the lineations are N60??E (flood) and S45??W (ebb), which are parallel to subparallel to the lineations. They suggest that the lineations may be tidally generated. The lineations may be bright sonar reflections from a winnowed lag concentrate of coarse sand.

The Myers-Briggs Type Indicator as a Tool to Facilitate Learning Outcomes for Team Building in the Classroom

ERIC Educational Resources Information Center

Berry, Priscilla; Wood, Cindy; Thornton, Barry

2007-01-01

Globalization and domestic competition are forcing businesses to rethink the human resources utilization process, and one method for considering again this challenge is creating a team culture. One key to this process for human resources development is the understanding of how to create the most successful teams. The use of the Myers-Briggs Type…

Synthesis Laboratory for the U.S. Army Medical Research Institute of Infectious Diseases Selection Panel

DTIC Science & Technology

1991-01-14

McCain 27 1 M. D. Ochs 73.5 4 C Richards 203.25 11 Dr. J. M. Riordan 108.5 6 Glassware Technicians: A. D. Jackson 322 18 W. Johnson 172 10 R...Kissinger. L. W.; Von. 1. / Med. Chem., 1*4*. 68, 1220- 1225. 3. Robins, R. K; Christensen, L. F. /. Med. Chem., 1978, 21, 742 4. Branson , J. (Bristol...Myers), personal communication. 5. Branson , Joanne J.; Ghazzouli, I.; Hitchcock, M. J. M; Webb, R. R.; Martin, J. C, J. Med. Chem., 1989. 32, 1457-1463

The Relationship of the Myers-Briggs Type Indicator to Scores on the National Teacher's Examination. AIR Forum 1981 Paper.

ERIC Educational Resources Information Center

Pratt, Linda K.; And Others

The relationship of the dimensions of the Myers-Briggs Type Indicator (MBTI) to scores on the National Teacher's Examination (NTE) was examined. The MBTI classifies people on each of four indices: extraversion/introversion, sensing/intuition, thinking/feeling, and judgment/perception. A sample of 111 students, 90 percent of whom were black,…

77 FR 14011 - Assessment of Potential Large-Scale Mining on the Bristol Bay Watershed of Alaska: Nomination of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-08

... Bristol Bay watershed provides habitat for one of the largest wild salmon populations in the world. In... resident fish populations of the Kvichak and Nushagak River drainages, and if these effects are likely to affect wildlife and human populations in the region. Additional information describing the assessment...

An Evaluation of Food Service Systems at Fort Myer, Bolling Air Force Base and Fort Benjamin Harrison

DTIC Science & Technology

1974-09-01

A comparative evaluation of the food service operations at Fort Myer, Virginia; Bolling Air Force Base, Maryland; and Fort Benjamin Harrison, Indiana...was conducted. These three bases each represent different types of food service systems, which are respectively: contract provided food and labor...Operations Research and Systems Analysis Office had the responsibility for comparing the costs, nutritional aspects and consumer attitudes involved in these three different systems of food service .

77 FR 11111 - Assessment of Potential Large-Scale Mining on the Bristol Bay Watershed of Alaska: Nomination of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... populations in the world. In February 2011, EPA began a scientific assessment of the Bristol Bay watershed to... on salmon and resident fish populations of the Kvichak and Nushagak River drainages, and if these effects are likely to affect wildlife and human populations in the region. Additional information...

Third Response to "The Teacher as a Service Professional," by Donald A. Myers: Defining "Professionalism" Does Not Make It So

ERIC Educational Resources Information Center

Houston, W. Robert

2008-01-01

It has been generally accepted that teaching does not meet the criteria of a profession, at least as exemplified by the more mature professions of medicine and law (Abbott, 1988; Darling-Hammond & Youngs, 2002; Etzioni, 1969; Howsam, Corrigan, Denemark, & Nash, 1976). Teaching is most often referred to as a semiprofession; Myers's (2008 [this…

Individualized Communications

NASA Technical Reports Server (NTRS)

1997-01-01

IntelliWeb and IntelliPrint, products from MicroMass Communications, utilize C Language Integrated Production System (CLIPS), a development and delivery expert systems tool developed at Johnson Space Center. IntelliWeb delivers personalized messages by dynamically creating single web pages or entire web sites based on information provided by each website visitor. IntelliPrint is a product designed to create tailored, individualized messages via printed media. The software uses proprietary technology to generate printed messages that are personally relevant and tailored to meet each individual's needs. Intelliprint is in use in many operations including Brystol-Myers Squibb's personalized newsletter, "Living at Your Best," geared to each recipient based on a health and lifestyle survey taken earlier; and SmithKline Beecham's "Nicorette Committed Quitters Program," in which customized motivational materials support participants in their attempt to quit smoking.

World sheet instantons via the Myers effect and Script N = 1* quiver superpotentials

NASA Astrophysics Data System (ADS)

Hollowood, Timothy J.; Kumar, S. Prem

2002-10-01

In this note we explore the stringy interpretation of non-perturbative effects in Script N = 1* deformations of the Ak-1 quiver models. For certain types of deformations we argue that the massive vacua are described by Nk fractional D3-branes at the orbifold polarizing into k concentric 5-brane spheres each carrying fractional brane charge. The polarization of the D3-branes induces a polarization of D-instantons into string world-sheets wrapped on the Myers spheres. We show that the superpotentials in these models are indeed generated by these world-sheet instantons. We point out that for certain parameter values the condensates yield the exact superpotential for a relevant deformation of the Klebanov-Witten conifold theory.

Bristol girls dance project feasibility study: using a pilot economic evaluation to inform design of a full trial

PubMed Central

Powell, Jane E; Carroll, Fran E; Sebire, Simon J; Haase, Anne M; Jago, Russell

2013-01-01

Background There is currently little guidance for pilot trial economic evaluation where health outcomes and costs are influenced by a range of wider determinants and factors. Objectives This article presents the findings of a pilot economic evaluation study running alongside the Bristol Girls Dance Project (BGDP) feasibility study. Design 3-arm, cluster randomised, controlled pilot trial and economic evaluation. 7 schools (n=210) from the Bristol and greater Bristol area, UK were randomly allocated to the intervention arm 3 schools (n=90) and the control arm 4 schools (n=120). Intervention Girls aged 11–12 years with parental consent were provided with two, 90 min dance sessions per week for 9 weeks at school facilities. Economic outcome measures Programme costs and girls’ preferences for attributes of dance and preferences for competing leisure time activities were measured. Results The mainstream average cost of the BGDP programme (not including research, control and dance teacher training costs) per school was $2126.40, £1329 and €1555 and per participant was $70.90, £44.31 and €51.84 in 2010–2011 prices. Discrete choice experiment (DCE) methods are acceptable to girls of this age indicating time available for other leisure activities on dance class days is the attribute girls valued most and 2 h leisure time remaining preferred to 3 h. Conclusions This pilot study indicates that providing full cost data for a future trial of the BGDP programme is feasible and practical. There is no evidence from preference data to support adjustment to intervention design. A future economic evaluation is likely to be successful utilising the resource use checklist developed. The importance of categorising separately resources used to develop, prepare, deliver and maintain the programme to estimate mainstream costs accurately is demonstrated. PMID:24362013

THE EFFECT OF TOTAL AND PARTIAL NEPHRECTOMY ON THE PHARMACOKINETICS OF INTRAVENOUS PARACETAMOL IN HUMANS.

PubMed

Karbownik, Agnieszka; Polom, Wojciech; Porazka, Joanna; Szalek, Edyta; Grabowski, Tomasz; Wolc, Anna; Matuszewski Marcin; Grzesowiak, Edmund

2017-05-01

Paracetamol is one of the most common analgesic and antipyretic drugs. Recently intravenous paracetamol has been widely used to treat moderate postoperative pain. Surgery is the main method of treatment of renal cancer. Total or partial nephrectomy can be performed, depending on the size and location of the tumor. Pharmacokinetics of drugs may depend on the type of surgery. The aim of the study was to compare the postinfusion pharmacokinetics of paracetamol in patients after total nephrectomy (TN) and nephron sparing surgery (NSS).The research was carried out on two groups of patients after nephrectomy: total (TN n = 37; mean [SD], age, 60.4 [10.9] years; BMI, 26.5 [3.8] kg/m2; creatinine clearance, Cl, 80.9 [37.1] mL/min) and nephron sparing surgery (NSS n = 17; 57.9 [16.5] years; BMI, 29.5 [5.3] kg/m2; Cl, 97.6 [27.8] mL/min). The patients were treated with paracetamol (PerfalganO Bristol-Myers Squibb) at an intravenous dose of 1.000 mg, which was infused for 15 minutes after surgery. The concentrations of paracetamol in the patients' plasma were determined by the HPLC method with UV detection (X = 261 run). The main pharmacokinetic parameters of paracetamol in the TN vs. NSS group were as follows: C.. 29.08 [17.39] vs. 27.54 [15.70] pg/mL (p = 0.6692); AUC5, 29.24 [13.86] vs. 34.85 [14.28] pg.h/mL (p = 0.2896); AUMC5,,,, 47.58 [26.08] vs. 62.02 [27.64] pg-h/mL (p = 0.1345); to. 2.34 [0.96] vs. 1.93 [0.50] h (p = 0.1415), respectively. In both groups the exposure to paracetamol was comparable. The t1/2 after nephron sparing surgery was shorter than after total nephrectomy. Therefore, these patients may demand more frequent drug administration. In the NSS group the C. of the analgesic was considerably reduced in men.

Apixaban for extended treatment of venous thromboembolism.

PubMed

Agnelli, Giancarlo; Buller, Harry R; Cohen, Alexander; Curto, Madelyn; Gallus, Alexander S; Johnson, Margot; Porcari, Anthony; Raskob, Gary E; Weitz, Jeffrey I

2013-02-21

Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism. In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months. A total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group. Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol-Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893.).

Strength in Amalgamation: Newer Combination Agents for HIV and Implications for Practice.

PubMed

McCoy, Christopher; Badowski, Melissa; Sherman, Elizabeth; Crutchley, Rustin; Smith, Ethan; Chastain, Daniel B

2018-01-01

Antiretroviral (ART) therapy for the treatment of human immunodeficiency virus (HIV) infection has undergone significant changes over the past 30 years. Many single-tablet regimens (STRs), including newer fixed-dose combination (FDC) tablets, are available, offering patients several options for choosing a treatment regimen that works best for them. Given these changes, patients are more likely to adhere to treatment, achieve better clinical outcomes, and experience both fewer side effects and drug-drug interactions. Newer STRs include dolutegravir (DTG)/lamivudine (3TC)/abacavir (ABC) (Triumeq; Viiv Healthcare, Research Triangle Park, NC), rilpivirine (RPV)/emtricitabine (FTC)/tenofovir alafenamide (TAF) (Odefsey; Gilead, Foster City, CA), RPV/FTC/tenofovir disoproxil fumarate (TDF) (Complera; Gilead), elvitegravir (EVG)/cobicistat (COBI)/FTC/TDF (Stribild; Gilead), and EVG/COBI/FTC/TAF (Genvoya; Gilead). Recently approved FDCs, such as atazanavir (ATV)/COBI (Evotaz; Bristol-Myers Squibb, Princeton, NJ), darunavir (DRV)/COBI (Prezcobix; Janssen Products, Titusville NJ), and FTC/TAF (Descovy; Gilead), are also now available. The Department of Health and Human Services treatment guidelines for HIV recommend many of these integrase strand transfer inhibitor (INSTI) STRs as a preferred choice for initiation of treatment in both ART-naive and -experienced patients because they offer comparably faster rates of virologic suppression, reduced rates of resistance development (especially with DTG), and overall better adherence than protease inhibitors or NNRTIs. Numerous phase 3 clinical trials support these recommendations including several switch or simplification clinical trials. Notably, the novel pharmacokinetic booster COBI, with its water soluble properties, has enabled the development and coformulation of a few of these STRs and FDCs. Also, a newer tenofovir salt formulation, TAF, has an advantageous pharmacokinetic profile, contributing to better overall renal and

Hypolipidemic and antioxidant potentials of Xylopia aethiopica seed extract in hypercholesterolemic rats.

PubMed

Nwozo, Sarah O; Orojobi, Bosede F; Adaramoye, Oluwatosin A

2011-01-01

A short-term study was carried out on Wistar strain rats to determine the effects of Xylopia aethiopica extract on serum and postmitochondrial fractions (PMFs) of visceral organs in experimental hypercholesterolemia. Animals received normal diet and were administered cholesterol orally by intubations at a dose of 40 mg/kg/0.3 mL, plant extracts at 250 mg/kg, and cholestyramine (Questran®, Bristol-Myers Squibb, Hounslow, United Kingdom) at 0.26 g/kg five times a week for 8 consecutive weeks. Thereafter the hypolipidemic effects were assessed by measuring total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol, and triglycerides, whereas the extent of oxidative stress was assayed by measuring thiobarbituric acid-reactive substances and enzymatic antioxidants such as superoxide dismutase, catalase, and reduced glutathione (GSH) in serum and PMF of liver and kidney. We assayed two liver biomarkers-alanine aminotransferase and aspartate aminotransferase-for safety of X. aethiopica at the dose given in this experiment. Cholesterol feeding resulted in a significant increase (P < .05) in body weight of the hypercholesterolemic animals relative to control animals, and administration of X. aethiopica (250 mg/kg) caused a more than 60% reduction in body weight. Simultaneous treatment with X. aethiopica and Questran elicited 33.75% and 23.94% reductions, respectively, in serum cholesterol levels of hypercholesterolemic rats. In addition, the LDL-C level decreased significantly (P < .05) by 49.09% and 78.92% in serum and by 64.97% and 37.29% in the liver with cotreatment with the plant extract and Questran, respectively, compared to untreated hypercholesterolemic rats. X. aethiopica counteracted the decreases in enzymatic antioxidants, especially in GSH, where there was a greater than 300% increase compared with hypercholesterolemic animals. This study has shown that intake of X. aethiopica reduced the composition

New perspectives on the pharmacotherapy of ischemic stroke.

PubMed

Bradberry, J Chris; Fagan, Susan C; Gray, David R; Moon, Yong S K

2004-01-01

To provide an overview of the impact of ischemic stroke and the steps that can be taken to reduce its burden through greater awareness of the disease, improved diagnosis and better treatment, with emphasis on the use of antiplatelet agents. Recent (1995-2003) published scientific literature, as identified by the authors through Medline searches, using the terms stroke, transient ischemic attack, cerebrovascular disease, atherothrombosis, risk factors, pharmacotherapy, prevention, and reviews on treatment. Recent systematic English-language review articles and reports of controlled randomized clinical trials were screened for inclusion. Ischemic stroke is generally the result of an atherothrombotic process leading to vessel obstruction or narrowing. Of the two types of ischemic stroke, thrombotic stroke is caused by a thrombus that develops within the cerebral vasculature, while embolic stroke arises from a distant embolus that lodges in a cerebral artery. The neurologic manifestations of stroke depend on the location of injury in the brain and the degree of ischemia or infarction. Symptoms may be reversible or irreversible and range from sensory deficits to hemiplegia. Risk factors for development of ischemic stroke include hypertension, diabetes, dyslipidemia, smoking, atrial fibrillation, prior stroke, and transient ischemic attack. Tissue plasminogen activator is currently the only available drug treatment for acute ischemic stroke. Stroke recurrence rates are high (about 40% over 5 years), and all ischemic stroke patients should receive antithrombotic therapy (unless contraindicated) for secondary prevention. Of the oral antiplatelet therapies, aspirin, clopidogrel (Plavix--Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership), and the extended-release dipyridamole plus aspirin combination are acceptable first-line agents, while anticoagulants (warfarin) are preferred in patients with atrial fibrillation. Lifestyle changes and drug therapy are important

SU-E-J-134: Optimizing Technical Parameters for Using Atlas Based Automatic Segmentation for Evaluation of Contour Accuracy Experience with Cardiac Structures From NRG Oncology/RTOG 0617

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, J; Gong, Y; Bar-Ad, V

Purpose: Accurate contour delineation is crucial for radiotherapy. Atlas based automatic segmentation tools can be used to increase the efficiency of contour accuracy evaluation. This study aims to optimize technical parameters utilized in the tool by exploring the impact of library size and atlas number on the accuracy of cardiac contour evaluation. Methods: Patient CT DICOMs from RTOG 0617 were used for this study. Five experienced physicians delineated the cardiac structures including pericardium, atria and ventricles following an atlas guideline. The consistency of cardiac structured delineation using the atlas guideline was verified by a study with four observers and seventeenmore » patients. The CT and cardiac structure DICOM files were then used for the ABAS technique.To study the impact of library size (LS) and atlas number (AN) on automatic contour accuracy, automatic contours were generated with varied technique parameters for five randomly selected patients. Three LS (20, 60, and 100) were studied using commercially available software. The AN was four, recommended by the manufacturer. Using the manual contour as the gold standard, Dice Similarity Coefficient (DSC) was calculated between the manual and automatic contours. Five-patient averaged DSCs were calculated for comparison for each cardiac structure.In order to study the impact of AN, the LS was set 100, and AN was tested from one to five. The five-patient averaged DSCs were also calculated for each cardiac structure. Results: DSC values are highest when LS is 100 and AN is four. The DSC is 0.90±0.02 for pericardium, 0.75±0.06 for atria, and 0.86±0.02 for ventricles. Conclusion: By comparing DSC values, the combination AN=4 and LS=100 gives the best performance. This project was supported by NCI grants U24CA12014, U24CA180803, U10CA180868, U10CA180822, PA CURE grant and Bristol-Myers Squibb and Eli Lilly.« less

Acute mortality in hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent: results in 18,671 consecutive studies.

PubMed

Kusnetzky, Lisa L; Khalid, Adnan; Khumri, Taiyeb M; Moe, Tabitha G; Jones, Philip G; Main, Michael L

2008-04-29

We sought to define acute mortality in hospitalized patients undergoing clinically indicated echocardiography with and without use of an ultrasound contrast agent. The U.S. Food and Drug Administration recently issued a boxed warning and new contraindications for the perflutren-containing ultrasound contrast agents following post-marketing reports of 4 patient deaths that were temporally related to Definity (Bristol-Myers Squibb Medical Imaging, Billerica, Massachusetts) administration. To appreciate the incremental risk of any medical procedure, the ambient risk of untoward outcome in the population in question must first be defined. There are no published data on short-term major adverse cardiac events in hospitalized patients undergoing echocardiography, either with or without administration of an ultrasound contrast agent. A retrospective analysis of hospitalized patients undergoing clinically indicated echocardiography between January 2005 and October 2007, within Saint Luke's Health System, Kansas City, Missouri, was performed. Studies were separated into 2 groups, those performed without contrast enhancement (n = 12,475) and those performed with Definity (n = 6,196). Vital status within 24 h of the echocardiographic study was available for all patients using a combination of the Social Security Death Master File and Saint Luke's Health System medical records. Incidence of death within 24 h was compared by chi-square test between Definity and unenhanced procedures. Of the 18,671 patient events, 72 patients died within 24 h. Of those that underwent unenhanced echocardiography, 46 died within 24 h (0.37%). Of patients receiving Definity during the echocardiogram, 26 died within 24 h (0.42%). There was no statistical difference between these 2 groups (p = 0.60). No patient died within 1 h of the echocardiographic study. In a random sampling from the unenhanced (n = 201) and Definity groups (n = 202), patients who underwent Definity-enhanced echocardiography

Financial Relationships With Industry of Editorial Board Members of the Three Journals of the American Society for Radiation Oncology.

PubMed

Verma, Vivek

2017-10-01

To quantitate financial conflicts of interest (FCOIs) among radiation oncology peer-reviewers, specifically editorial board members of the 3 American Society for Radiation Oncology journals. The public Centers for Medicare and Medicaid Services Open Payments database delineates payments in 3 categories (general payments, research funding, and company ownership). After excluding non-US and non-MDs, names of board members were searched. Values of each FCOI were extracted for 2013 to 2015 and compiled. Of 85 board members, 65 (76%) received any form of payment during the overall period. The majority of delivered payments were general payments: 59 (69%) received at least 1 general payment during these 3 years. In each year, 9 board members (11%) received research funding, and 3 board members (4%) reported company ownership. Over the studied period, all board members received a sum total of $5,387,985; this was composed of $665,801 (12%) in general payments, $3,758,968 (70%) in research funding, and $963,216 (18%) in company ownership. The mean general payment and research funding amounts (all members) were $2,621 and $14,741, respectively. Median (interquartile range) general payments and research funding only in board members receiving payments were $419 ($91-$5072) and $56,250 ($13,345-$200,000), respectively. When assessing general payments according to amount, the vast majority of editorial board members received lower-quantity or no such payments, along with a smaller proportion that received higher-volume payments. The most frequent sources of general payments were Varian, Elekta, and Bristol-Myers Squibb. Merck and Varian were the most frequent funding sources for research payments. In this population, the majority of FCOIs were general payments, but research funding comprised the highest monetary sums. Large-volume FCOIs do not apply to the vast majority of editorial board members, implying that the maintained integrity of academic peer-review is likely not

Apixaban with antiplatelet therapy after acute coronary syndrome.

PubMed

Alexander, John H; Lopes, Renato D; James, Stefan; Kilaru, Rakhi; He, Yaohua; Mohan, Puneet; Bhatt, Deepak L; Goodman, Shaun; Verheugt, Freek W; Flather, Marcus; Huber, Kurt; Liaw, Danny; Husted, Steen E; Lopez-Sendon, Jose; De Caterina, Raffaele; Jansky, Petr; Darius, Harald; Vinereanu, Dragos; Cornel, Jan H; Cools, Frank; Atar, Dan; Leiva-Pons, Jose Luis; Keltai, Matyas; Ogawa, Hisao; Pais, Prem; Parkhomenko, Alexander; Ruzyllo, Witold; Diaz, Rafael; White, Harvey; Ruda, Mikhail; Geraldes, Margarida; Lawrence, Jack; Harrington, Robert A; Wallentin, Lars

2011-08-25

Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome. We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events. The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P=0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P=0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo. The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 ClinicalTrials.gov number, NCT00831441.).

Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.

PubMed

Brahmer, Julie R; Tykodi, Scott S; Chow, Laura Q M; Hwu, Wen-Jen; Topalian, Suzanne L; Hwu, Patrick; Drake, Charles G; Camacho, Luis H; Kauh, John; Odunsi, Kunle; Pitot, Henry C; Hamid, Omid; Bhatia, Shailender; Martins, Renato; Eaton, Keith; Chen, Shuming; Salay, Theresa M; Alaparthy, Suresh; Grosso, Joseph F; Korman, Alan J; Parker, Susan M; Agrawal, Shruti; Goldberg, Stacie M; Pardoll, Drew M; Gupta, Ashok; Wigginton, Jon M

2012-06-28

Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. In this multicenter phase 1 trial, we administered intravenous anti-PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. As of February 24, 2012, a total of 207 patients--75 with non-small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer--had received anti-PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non-small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.).

On modeling the sound propagation through a lined duct with a modified Ingard-Myers boundary condition

NASA Astrophysics Data System (ADS)

Yang, Cheng; Fang, Yi; Zhao, Chao; Zhang, Xin

2018-06-01

A duct acoustics model is an essential component of an impedance eduction technique and its computation cost determines the impedance measurement efficiency. In this paper, a model is developed for the sound propagation through a lined duct carrying a uniform mean flow. In contrast to many existing models, the interface between the liner and the duct field is defined with a modified Ingard-Myers boundary condition that takes account of the effect of the boundary layer above the liner. A mode-matching method is used to couple the unlined and lined duct segments for the model development. For the lined duct segment, the eigenvalue problem resulted from the modified boundary condition is solved by an integration scheme which, on the one hand, allows the lined duct modes to be computed in an efficient manner, and on the other hand, orders the modes automatically. The duct acoustics model developed from the solved lined duct modes is shown to converge more rapidly than the one developed from the rigid-walled duct modes. Validation against the experiment data in the literature shows that the proposed model is able to predict more accurately the liner performance measured by the two-source method. This, however, cannot be made by a duct acoustics model associated with the conventional Ingard-Myers boundary condition. The proposed model has the potential to be integrated into an impedance eduction technique for more reliable liner measurement.

Sea level trends and NAO influences: The Bristol Channel/Severn Estuary

NASA Astrophysics Data System (ADS)

Phillips, M. R.; Crisp, S.

2010-09-01

Fifteen years, 1993 (earliest available) to 2007 inclusive of monthly mean and extreme (maximum and minimum) sea level data were assessed for four tide gauges located in the Bristol Channel (Mumbles and Ilfracombe) and Severn Estuary (Newport and Hinkley Point). Results showed decreasing maximum sea level trends and increasing minimum sea level trends, resulting in convergence. However, maximum extreme sea levels on the Welsh shoreline (Mumbles and Newport) were higher than corresponding locations on the English coast (Ilfracombe and Hinkley Point). Analysis showed that from 1995 to 1998 inclusive, maximum extreme sea levels were significantly higher at Mumbles (t = 2.342; df = 10; p < 0.05), Newport (t = 5.034; df = 13; p < 0.01) and Hinkley Point (t = 3.570; df = 13; p < 0.01) and were correlated to increased storm frequencies during these years. However, Ilfracombe (t = 1.472; df = 12; p > 0.05) did not demonstrate similar significance, possibly due to tide gauge location and coastal aspect, while tidal influences became more dominant as the tidal prism moved up the estuary. Actual mean sea levels (MSL) at Newport (t = 2.880; df = 14; p < 0.05) and Hinkley Point (t = 5.282; df = 14; p < 0.01) were significantly higher than predicted; at Mumbles (t = 2.673; df = 11; p < 0.05) they were significantly lower than predicted; while Ilfracombe (t = 1.989; df = 13; p > 0.05) once again showed no significant difference. Mumbles is the only location with off-shore sand waves and analysis suggested these as the cause of opposite trends. Sea level variation was strongly correlated to the North Atlantic Oscillation (NAO) Index, especially for maximum extreme sea levels during positive phases (R 2 = 86%), and higher positive or negative NAO Index values resulted in larger sea level ranges. Further analysis showed a rising Bristol Channel and Severn Estuary MSL trend of 2.4 mm yr - 1 and a 2050 MSL of 0.370 m is projected to inform future management. However, continuous

The Relationship between Personality Type and Software Usability Using the Myers-Briggs Type Indicator (MBTI) and the Software Usability Measurement Inventory (SUMI)

ERIC Educational Resources Information Center

Lindsey, William H.

2011-01-01

The study attempted to determine if there is a relationship between user's psychological personality types, measured by the Myers Briggs Type Indicator[R] (MBTI[R]) and distinct measures of usability measured by the Software Usability Measurement Inventory (SUMI). The study was expected to provide an answer to the following basic research…

Progress on the Journey to Total Quality Management: Using the Myers-Briggs Type Indicator and the Adjective Check List in Management Development.

ERIC Educational Resources Information Center

Mani, Bonnie G.

1995-01-01

In an Internal Revenue Service office using total quality management (TQM), the management development program uses Myers Briggs Type Indicator and Adjective Check List for manager self-assessment. Because management commitment is essential to TQM, the process is a way of enhancing leadership skills and demonstrating appreciation of diversity. (SK)

Interobserver agreement between primary graders and an expert grader in the Bristol and Weston diabetic retinopathy screening programme: a quality assurance audit.

PubMed

Patra, S; Gomm, E M W; Macipe, M; Bailey, C

2009-08-01

To assess the quality and accuracy of primary grading in the Bristol and Weston diabetic retinopathy screening programme and to set standards for future interobserver agreement reports. A prospective audit of 213 image sets from six fully trained primary graders in the Bristol and Weston diabetic retinopathy screening programme was carried out over a 4-week period. All the images graded by the primary graders were regraded by an expert grader blinded to the primary grading results and the identity of the primary grader. The interobserver agreement between primary graders and the blinded expert grader and the corresponding Kappa coefficient was determined for overall grading, referable, non-referable and ungradable disease. The audit standard was set at 80% for interobserver agreement with a Kappa coefficient of 0.7. The interobserver agreement bettered the audit standard of 80% in all the categories. The Kappa coefficient was substantial (0.7) for the overall grading results and ranged from moderate to substantial (0.59-0.65) for referable, non-referable and ungradable disease categories. The main recommendation of the audit was to provide refresher training for the primary graders with focus on ungradable disease. The audit demonstrated an acceptable level of quality and accuracy of primary grading in the Bristol and Weston diabetic retinopathy screening programme and provided a standard against which future interobserver agreement can be measured for quality assurance within a screening programme. Diabet. Med. 26, 820-823 (2009).

33 CFR 334.1280 - Bristol Bay, Alaska; air-to-air weapon range, Alaskan Air Command, U.S. Air Force.

Code of Federal Regulations, 2012 CFR

2012-07-01

... weapon range, Alaskan Air Command, U.S. Air Force. 334.1280 Section 334.1280 Navigation and Navigable... REGULATIONS § 334.1280 Bristol Bay, Alaska; air-to-air weapon range, Alaskan Air Command, U.S. Air Force. (a... enforced by the Commander, Alaskan Air Command, U.S. Air Force, Seattle, Washington, or such agencies as he...

33 CFR 334.1280 - Bristol Bay, Alaska; air-to-air weapon range, Alaskan Air Command, U.S. Air Force.

Code of Federal Regulations, 2013 CFR

2013-07-01

... weapon range, Alaskan Air Command, U.S. Air Force. 334.1280 Section 334.1280 Navigation and Navigable... REGULATIONS § 334.1280 Bristol Bay, Alaska; air-to-air weapon range, Alaskan Air Command, U.S. Air Force. (a... enforced by the Commander, Alaskan Air Command, U.S. Air Force, Seattle, Washington, or such agencies as he...

33 CFR 334.1280 - Bristol Bay, Alaska; air-to-air weapon range, Alaskan Air Command, U.S. Air Force.

Code of Federal Regulations, 2014 CFR

2014-07-01

... weapon range, Alaskan Air Command, U.S. Air Force. 334.1280 Section 334.1280 Navigation and Navigable... REGULATIONS § 334.1280 Bristol Bay, Alaska; air-to-air weapon range, Alaskan Air Command, U.S. Air Force. (a... enforced by the Commander, Alaskan Air Command, U.S. Air Force, Seattle, Washington, or such agencies as he...

33 CFR 334.1280 - Bristol Bay, Alaska; air-to-air weapon range, Alaskan Air Command, U.S. Air Force.

Code of Federal Regulations, 2010 CFR

2010-07-01

... weapon range, Alaskan Air Command, U.S. Air Force. 334.1280 Section 334.1280 Navigation and Navigable... REGULATIONS § 334.1280 Bristol Bay, Alaska; air-to-air weapon range, Alaskan Air Command, U.S. Air Force. (a... enforced by the Commander, Alaskan Air Command, U.S. Air Force, Seattle, Washington, or such agencies as he...

33 CFR 334.1280 - Bristol Bay, Alaska; air-to-air weapon range, Alaskan Air Command, U.S. Air Force.

Code of Federal Regulations, 2011 CFR

2011-07-01

... weapon range, Alaskan Air Command, U.S. Air Force. 334.1280 Section 334.1280 Navigation and Navigable... REGULATIONS § 334.1280 Bristol Bay, Alaska; air-to-air weapon range, Alaskan Air Command, U.S. Air Force. (a... enforced by the Commander, Alaskan Air Command, U.S. Air Force, Seattle, Washington, or such agencies as he...

Analyzing the Relationship of Strengths to Personality Preferences and Vocational Interests Utilizing Clifton StrengthsFinder, Myers-Briggs Type Indicator, and Strong Interest Inventory

ERIC Educational Resources Information Center

Schenck, Paulette M.

2009-01-01

Throughout the history of vocational psychology, career counselors have constantly searched for, devised, and implemented practices and techniques to best prepare clients for the world of work. The purpose of this study was to explore the relationship between strengths to personality preference and vocational interests utilizing the Myers-Briggs…

Beyond taxol: microtubule-based treatment of disease and injury of the nervous system

PubMed Central

Ahmad, Fridoon J.

2013-01-01

Contemporary research has revealed a great deal of information on the behaviours of microtubules that underlie critical events in the lives of neurons. Microtubules in the neuron undergo dynamic assembly and disassembly, bundling and splaying, severing, and rapid transport as well as integration with other cytoskeletal elements such as actin filaments. These various behaviours are regulated by signalling pathways that affect microtubule-related proteins such as molecular motor proteins and microtubule severing enzymes, as well as a variety of proteins that promote the assembly, stabilization and bundling of microtubules. In recent years, translational neuroscientists have earmarked microtubules as a promising target for therapy of injury and disease of the nervous system. Proof-of-principle has come mainly from studies using taxol and related drugs to pharmacologically stabilize microtubules in animal models of nerve injury and disease. However, concerns persist that the negative consequences of abnormal microtubule stabilization may outweigh the positive effects. Other potential approaches include microtubule-active drugs with somewhat different properties, but also expanding the therapeutic toolkit to include intervention at the level of microtubule regulatory proteins. PMID:23811322

The rigorous bound on the transmission probability for massless scalar field of non-negative-angular-momentum mode emitted from a Myers-Perry black hole

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ngampitipan, Tritos, E-mail: tritos.ngampitipan@gmail.com; Particle Physics Research Laboratory, Department of Physics, Faculty of Science, Chulalongkorn University, Phayathai Road, Patumwan, Bangkok 10330; Boonserm, Petarpa, E-mail: petarpa.boonserm@gmail.com

Hawking radiation is the evidence for the existence of black hole. What an observer can measure through Hawking radiation is the transmission probability. In the laboratory, miniature black holes can successfully be generated. The generated black holes are, most commonly, Myers-Perry black holes. In this paper, we will derive the rigorous bounds on the transmission probabilities for massless scalar fields of non-negative-angular-momentum modes emitted from a generated Myers-Perry black hole in six, seven, and eight dimensions. The results show that for low energy, the rigorous bounds increase with the increase in the energy of emitted particles. However, for high energy,more » the rigorous bounds decrease with the increase in the energy of emitted particles. When the black holes spin faster, the rigorous bounds decrease. For dimension dependence, the rigorous bounds also decrease with the increase in the number of extra dimensions. Furthermore, as comparison to the approximate transmission probability, the rigorous bound is proven to be useful.« less

The rigorous bound on the transmission probability for massless scalar field of non-negative-angular-momentum mode emitted from a Myers-Perry black hole

NASA Astrophysics Data System (ADS)

Ngampitipan, Tritos; Boonserm, Petarpa; Chatrabhuti, Auttakit; Visser, Matt

2016-06-01

Hawking radiation is the evidence for the existence of black hole. What an observer can measure through Hawking radiation is the transmission probability. In the laboratory, miniature black holes can successfully be generated. The generated black holes are, most commonly, Myers-Perry black holes. In this paper, we will derive the rigorous bounds on the transmission probabilities for massless scalar fields of non-negative-angular-momentum modes emitted from a generated Myers-Perry black hole in six, seven, and eight dimensions. The results show that for low energy, the rigorous bounds increase with the increase in the energy of emitted particles. However, for high energy, the rigorous bounds decrease with the increase in the energy of emitted particles. When the black holes spin faster, the rigorous bounds decrease. For dimension dependence, the rigorous bounds also decrease with the increase in the number of extra dimensions. Furthermore, as comparison to the approximate transmission probability, the rigorous bound is proven to be useful.

The BRIDGE HadCM3 family of climate models: HadCM3@Bristol v1.0

NASA Astrophysics Data System (ADS)

Valdes, Paul J.; Armstrong, Edward; Badger, Marcus P. S.; Bradshaw, Catherine D.; Bragg, Fran; Crucifix, Michel; Davies-Barnard, Taraka; Day, Jonathan J.; Farnsworth, Alex; Gordon, Chris; Hopcroft, Peter O.; Kennedy, Alan T.; Lord, Natalie S.; Lunt, Dan J.; Marzocchi, Alice; Parry, Louise M.; Pope, Vicky; Roberts, William H. G.; Stone, Emma J.; Tourte, Gregory J. L.; Williams, Jonny H. T.

2017-10-01

Understanding natural and anthropogenic climate change processes involves using computational models that represent the main components of the Earth system: the atmosphere, ocean, sea ice, and land surface. These models have become increasingly computationally expensive as resolution is increased and more complex process representations are included. However, to gain robust insight into how climate may respond to a given forcing, and to meaningfully quantify the associated uncertainty, it is often required to use either or both ensemble approaches and very long integrations. For this reason, more computationally efficient models can be very valuable tools. Here we provide a comprehensive overview of the suite of climate models based around the HadCM3 coupled general circulation model. This model was developed at the UK Met Office and has been heavily used during the last 15 years for a range of future (and past) climate change studies, but has now been largely superseded for many scientific studies by more recently developed models. However, it continues to be extensively used by various institutions, including the BRIDGE (Bristol Research Initiative for the Dynamic Global Environment) research group at the University of Bristol, who have made modest adaptations to the base HadCM3 model over time. These adaptations mean that the original documentation is not entirely representative, and several other relatively undocumented configurations are in use. We therefore describe the key features of a number of configurations of the HadCM3 climate model family, which together make up HadCM3@Bristol version 1.0. In order to differentiate variants that have undergone development at BRIDGE, we have introduced the letter B into the model nomenclature. We include descriptions of the atmosphere-only model (HadAM3B), the coupled model with a low-resolution ocean (HadCM3BL), the high-resolution atmosphere-only model (HadAM3BH), and the regional model (HadRM3B). These also include

Seasonal marine growth of Bristol Bay sockeye salmon (Oncorhynchus nerka) in relation to competition with Asian pink salmon (O. gorbuscho) and the 1977 ocean regime shift

USGS Publications Warehouse

Ruggerone, Gregory T.; Farley, Ed; Nielsen, Jennifer L.; Hagen, Peter

2005-01-01

Recent research demonstrated significantly lower growth and survival of Bristol Bay sockeye salmon (Oncorhynchus nerka) during odd-numbered years of their second or third years at sea (1975, 1977, etc.), a trend that was opposite that of Asian pink salmon (O. gorbuscha) abundance. Here we evaluated seasonal growth trends of Kvichak and Egegik river sockeye salmon (Bristol Bay stocks) during even- and odd-numbered years at sea by measuring scale circuli increments within each growth zone of each major salmon age group between 1955 and 2000. First year scale growth was not significantly different between odd- and even-numbered years, but peak growth of age-2. smolts was significantly higher than age-1 smolts. Total second and third year scale growth of salmon was significantly lower during odd- than during even-numbered years. However, reduced scale growth in odd-numbered years began after peak growth in spring and continued through summer and fall even though most pink salmon had left the high seas by late July (10-18% growth reduction in odd vs. even years). The alternating odd and even year growth pattern was consistent before and after the 1977 ocean regime shift. During 1977-2000, when salmon abundance was relatively great, sockeye salmon growth was high during specific seasons compared with that during 1955-1976, that is to say, immediately after entry to Bristol Bay, after peak growth in the first year, during the middle of the second growing season, and during spring of the third season. Growth after the spring peak in the third year at sea was relatively low during 1977-2000. We hypothesize that high consumption rates of prey by pink salmon during spring through mid-July of odd-numbered years, coupled with declining zooplankton biomass during summer and potentially cyclic abundances of squid and other prey, contributed to reduced prey availability and therefore reduced growth of Bristol Bay sockeye salmon during late spring through fall of odd-numbered years.

Aripiprazole for autism spectrum disorders (ASD).

PubMed

Hirsch, Lauren E; Pringsheim, Tamara

2016-06-26

use of aripiprazole for a duration of eight weeks in 316 children/adolescents with ASD. Meta-analysis of study results revealed a mean improvement of -6.17 points on the Aberrant Behavior Checklist (ABC) - Irritability subscale (95% confidence intervals (CIs) -9.07 to -3.26, two studies, 308 children/adolescents, moderate-quality evidence), -7.93 points on the ABC - Hyperactivity subscale (95% CI -10.98 to -4.88, two studies, 308 children/adolescents, moderate-quality evidence) and -2.66 points on the ABC - Stereotypy subscale (95% CI -3.55 to -1.77, two studies, 308 children/adolescents, moderate-quality evidence) in children/adolescents taking aripiprazole relative to children/adolescents taking placebo. In terms of side effects, children/adolescents taking aripiprazole had a greater increase in weight, with a mean increase of 1.13 kg relative to placebo (95% CI 0.71 to 1.54, two studies, 308 children/adolescents, moderate-quality evidence), and had a higher risk ratio (RR) for sedation (RR 4.28, 95% CI 1.58 to 11.60, two studies, 313 children/adolescents, moderate-quality evidence) and tremor (RR 10.26, 95% CI 1.37 to 76.63, two studies, 313 children/adolescents, moderate-quality evidence). A randomised, placebo-controlled discontinuation study found that 35% of children/adolescents randomised to continue intervention with aripiprazole relapsed with respect to their symptoms of irritability, compared with 52% of children/adolescents randomised to placebo, for a hazard ratio of 0.57 (95% CI 0.28 to 1.12, 85 children/adolescents, low-quality evidence).All three included trials were supported by Bristol-Myers Squibb (Princeton, NJ) and Otsuka Pharmaceutical Company, Ltd. (Tokyo, Japan), with editorial support provided by Ogilvy Healthworld Medical Education and Bristol-Myers Squibb. Evidence from two RCTs suggests that aripiprazole can be effective as a short-term medication intervention for some behavioural aspects of ASD in children/adolescents. After a short

[Clinical efficacy and adverse effects of taxol plus carboplatin or gemcitabine plus carboplatin in patients with advanced non-small-cell lung carcinoma].

PubMed

Wang, Xiao-Yun; Zhao, Yu-Liang

2010-12-21

To observe the clinical efficacy and adverse effects of taxol plus carboplatin (TP) or gemcitabine plus carboplatin (GP) in patients with advanced non-small-cell lung carcinoma. A total of 86 patients with advanced non-small-cell lung carcinoma with a histologically confirmed diagnosis at our department were treated with at least two cycles of drug therapy according to the WHO standard. There were 43 cases in TP group and 43 cases in GP group. TP group: taxol 150 mg/m(2), d1, carboplatin 300 mg/m(2) in d1; GP group: gemcitabine 1000 mg/m(2), 30 min, d1, 8, carboplatin 300 mg/m(2) in d1, 3 weeks a cycle. The efficacy and side effects were analyzed after two cycles of chemotherapy. When TP and GP groups were compared, the effective rate was 44.2% vs 39.5%; disease control rate (CR + PR + SD): 81.4% vs 74.4%; median time to progress (TTP): 4.6 vs 4.5 months; medium survivals: 8.6 vs 8.8 months; 1-year survival rates: 17.2% vs 18.1%; 2-year survival rates: 8% vs 10%. The statistic analysis showed that the two groups had no significant difference. The main cytotoxicities of GP and TP groups were predominantly thrombocytopenia and leucopenia respectively. The two groups had no significant statistical difference. The incidences of allergen, alopecia and peripheral neurotoxicity were higher in the TP group. The two groups had statistical difference. Tolerance was excellent in both groups. The therapeutic effect and tolerance are excellent for advanced non-small cell lung carcinoma. The efficacy and survival rate of two groups show no statistical difference.

National Program for Inspection of Non-Federal Dams. Bristol Reservoir Number 5 Dam (CT 00366), Farmington River Basin, Harwinton, Connecticut. Phase I Inspection Report.

DTIC Science & Technology

1980-07-01

age control and/or monitoring measures as needed. 2. Investigate the condition of the corrugated metal outlet pipe and make any necessary repairs. 3...BACKGROUND. USARMY ENGINEER DIV NEW ENGLAND BRISTOL RES. NO. 5 DAM Coll O .ENIER NATIONAL PROGRAM OF TR. TO POLAND R IVER WALTHAM ! ASCUE INSPECTION

Maps and tables showing data and analyses of semiquantitative emmission spectrometry and atomic-absorption spectrophotometry of rock samples, Ugashik, Bristol Bay, and part of Karluk quadrangles, Alaska

USGS Publications Warehouse

Wilson, Frederic H.; O'Leary, R. M.

1986-01-01

The accompanying maps and tables show analytical data and data analyses from rock samples collected in conjunction with geologic mapping in the Ugashik, Bristol Bay and western Karluck quadrangles from 1979 through 1981. This work was conducted under the auspices of the Alaska Mineral Resource Assessment Program (AMRAP). A total of 337 samples were collected for analysis, primarily in areas of surficial alteration. The sample locations are shown on sheet 1: they are concentrated along the Pacific Ocean side of the area because the Bristol Bay lowlands part of the map is predominantly unconsolidated Quaternary deposits. Sample collection was by the following people, with their respective two letter identifying code shown in parentheses: W.H. Allaway (AY), J.E. Case (CE), D.P. Cox (CX), R.L. Detterman, (DT), T.G. Theodore (MK), F.H. Wilson (WS), and M.E. Yount (YB).

Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.

PubMed

Scirica, Benjamin M; Bhatt, Deepak L; Braunwald, Eugene; Steg, P Gabriel; Davidson, Jaime; Hirshberg, Boaz; Ohman, Peter; Frederich, Robert; Wiviott, Stephen D; Hoffman, Elaine B; Cavender, Matthew A; Udell, Jacob A; Desai, Nihar R; Mosenzon, Ofri; McGuire, Darren K; Ray, Kausik K; Leiter, Lawrence A; Raz, Itamar

2013-10-03

glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes. (Funded by AstraZeneca and Bristol-Myers Squibb; SAVOR-TIMI 53 ClinicalTrials.gov number, NCT01107886.).

A phase I study of etoposide phosphate plus paclitaxel.

PubMed

Brooks, D J; Alberts, D S

1996-12-01

Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-soluble derivative of etoposide, a semisynthetic podophyllotoxin that is important in the treatment of a variety of malignancies, including lung cancer, germ cell tumors, non-Hodgkin's lymphoma, Hodgkin's lymphoma, acute leukemia, etc. Because etoposide is poorly water soluble, it must be dissolved in a polysorbate 80-based solvent mixture, which is moderately allergenic and requires a large volume of saline for administration. Etoposide phosphate is water soluble and is rapidly converted in vivo to etoposide by endogenous phosphatases. Because it is water soluble, etoposide phosphate can be administered in volumes much smaller than those required with etoposide therapy, permitting rapid intravenous administration in the outpatient setting. We recently reported the results of a phase I study using etoposide phosphate on a bolus, daily x 5 schedule. Like others, we demonstrated that etoposide phosphate has pharmacokinetic properties virtually identical to those of etoposide. Our dose-finding study indicated that etoposide phosphate can be used in doses up to 100 mg/m2/d x 5 every 3 weeks in patients who have not had extensive prior chemotherapy, and that a dose of 75 mg/m2 would be appropriate for patients who had undergone multiple prior therapies or who had prior radiotherapy. The dose-limiting toxicity was neutropenia. Paclitaxel, a microtubule-stabilizing agent, is active against a variety of solid and hematopoietic malignancies that overlap with those against which etoposide is active. Because the mechanisms of action of these two agents differ, it is logical to suppose that the combination of the two agents might produce some additive effect when used to treat cancers that respond to both individual agents. We therefore undertook a phase I study using paclitaxel as a 3-hour infusion in combination with a 5-minute infusion of etoposide phosphate daily x 3 every 21 days. We

AMCP Partnership Forum: Driving Value and Outcomes in Oncology.

PubMed

2017-05-01

arrangements. Addressing these challenges could lead to improving cancer treatment. The AMCP Partnership Forum titled "Driving Value and Outcomes in Oncology" and the development of this report were supported by AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Foundation Medicine, IntrinsiQ Specialty Solutions, Janssen Oncology and Johnson and Johnson Health Systems, Eli Lilly and Company, National Pharmaceutical Council, Novartis Pharmaceuticals Corporation, Pharmaceutical Research and Manufacturers of America, Sanofi, Takeda Oncology, and Xcenda.

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis.

PubMed

Larkin, James; Chmielowski, Bartosz; Lao, Christopher D; Hodi, F Stephen; Sharfman, William; Weber, Jeffrey; Suijkerbuijk, Karijn P M; Azevedo, Sergio; Li, Hewei; Reshef, Daniel; Avila, Alexandre; Reardon, David A

2017-06-01

Despite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune-related adverse events (irAEs), including neurologic events ranging from mild headache to potentially life-threatening encephalitis. Here, we summarize neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment, present cases of treatment-related encephalitis, and provide practical guidance on diagnosis and management. We searched a Global Pharmacovigilance and Epidemiology database for neurologic irAEs reported over an 8-year period in patients with advanced melanoma receiving nivolumab with or without ipilimumab from 12 studies sponsored by Bristol-Myers Squibb. Serious neurologic irAEs were reviewed, and relationship to nivolumab or ipilimumab was assigned. In our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious neurologic irAEs, including neuropathy ( n  = 22), noninfective meningitis ( n  = 5), encephalitis ( n  = 6), neuromuscular disorders ( n  = 3), and nonspecific adverse events ( n  = 7). Study drug was discontinued ( n  = 20), interrupted ( n  = 8), or unchanged ( n  = 7). Most neurologic irAEs resolved (26/35 patients; 75%). Overall, median time to onset was 45 days (range 1-170) and to resolution was 32 days (2-809+). Median time to onset of encephalitis was 55.5 days (range 18-297); four cases resolved and one was fatal. Both oncologists and neurologists need to be aware of signs and symptoms of serious but uncommon neurologic irAEs associated with checkpoint inhibitors. Prompt diagnosis and management using an established algorithm are critical to minimize serious complications from these neurologic irAEs. With increasing use of checkpoint inhibitors in cancer, practicing oncologists need to be aware of the potential risk of neurologic immune-related adverse events and be able to provide prompt treatment of this uncommon, but

Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

PubMed Central

Brahmer, Julie R.; Tykodi, Scott S.; Chow, Laura Q.M.; Hwu, Wen-Jen; Topalian, Suzanne L.; Hwu, Patrick; Drake, Charles G.; Camacho, Luis H.; Kauh, John; Odunsi, Kunle; Pitot, Henry C.; Hamid, Omid; Bhatia, Shailender; Martins, Renato; Eaton, Keith; Chen, Shuming; Salay, Theresa M.; Alaparthy, Suresh; Grosso, Joseph F.; Korman, Alan J.; Parker, Susan M.; Agrawal, Shruti; Goldberg, Stacie M.; Pardoll, Drew M.; Gupta, Ashok; Wigginton, Jon M.

2013-01-01

BACKGROUND Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host’s immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti–PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS As of February 24, 2012, a total of 207 patients — 75 with non–small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer — had received anti–PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non–small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non–small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.) PMID:22658128

Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1.

PubMed

Wyles, David L; Ruane, Peter J; Sulkowski, Mark S; Dieterich, Douglas; Luetkemeyer, Anne; Morgan, Timothy R; Sherman, Kenneth E; Dretler, Robin; Fishbein, Dawn; Gathe, Joseph C; Henn, Sarah; Hinestrosa, Federico; Huynh, Charles; McDonald, Cheryl; Mills, Anthony; Overton, Edgar Turner; Ramgopal, Moti; Rashbaum, Bruce; Ray, Graham; Scarsella, Anthony; Yozviak, Joseph; McPhee, Fiona; Liu, Zhaohui; Hughes, Eric; Yin, Philip D; Noviello, Stephanie; Ackerman, Peter

2015-08-20

all genotypes was 97.0% after 12 weeks of treatment and 76.0% after 8 weeks. (Funded by Bristol-Myers Squibb; ALLY-2 ClinicalTrials.gov number, NCT02032888.).

Dose comparisons of clopidogrel and aspirin in acute coronary syndromes.

PubMed

Mehta, Shamir R; Bassand, Jean-Pierre; Chrolavicius, Susan; Diaz, Rafael; Eikelboom, John W; Fox, Keith A A; Granger, Christopher B; Jolly, Sanjit; Joyner, Campbell D; Rupprecht, Hans-Jurgen; Widimsky, Petr; Afzal, Rizwan; Pogue, Janice; Yusuf, Salim

2010-09-02

stroke. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00335452.)

Planning, Development, and Change in Bristol Bay: A High School Curriculum. Teacher Guide and Student Text. Unit I: Introduction. Unit II: Village Corporations. Revised.

ERIC Educational Resources Information Center

Lipka, Jerry; Willer, Cristy

This combined teacher guide and student text is written with the broad goal of involving high school students in Bristol Bay, Alaska, in the planning and design of their region's future. Unit I introduces changes occurring on village and regional levels, discusses planning strategies for community development, and presents village profiles for…

A cross-sectional investigation of public attitudes toward dementia in Bristol and South Gloucestershire using the approaches to dementia questionnaire.

PubMed

Cheston, Richard; Hancock, Jude; White, Paul

2016-10-01

To date, surveys of attitudes toward dementia have largely been conducted using unvalidated materials or have focused on healthcare professionals supporting people affected by dementia. The aim of this study was to carry out a survey of public attitudes toward people affected by dementia in Bristol and South Gloucestershire. A survey was carried out using a modified version of the Approaches to Dementia Questionnaire (ADQ). Data from people living outside the area, and people who were working with people affected by dementia were omitted from the analysis. Responses from the remaining 794 ADQ questionnaires were weighted to correct for under-represented age, gender, and ethnic groups. Younger people held more positive attitudes toward dementia than older people. Individuals who identified themselves as White held more positive attitudes than non-White individuals. Individuals with personal experience of dementia held more positive attitudes than those with no experience of dementia. When considering age differences, gender played a role, with younger men having more positive scores than other groups. This is one of the first surveys of public attitudes to dementia to use a validated questionnaire such as the ADQ. The study provides a baseline of attitudes toward dementia for the Bristol and South Gloucestershire areas, against which we will be able to compare changes over time. This is important due to the emphasis in public health campaigns on improving attitudes toward dementia.

Patent Survey of Resveratrol, Taxol, Podophyllotoxin, Withanolides and Their Derivatives Used in Anticancer Therapy.

PubMed

Routh, Shreya; Nandagopal, Krishnadas

2017-01-01

Resveratrol, taxol, podophyllotoxin, withanolides and their derivatives find applications in anti-cancer therapy. They are plant-derived compounds whose chemical structures and synthesis limit their natural availability and restrict a large-scale industrial production. Hence, their production by various biotechnological approaches may hold promise for a continuous and reliable mode of supply. We review process and product patents in this regard. Accordingly, we provide a general outline to search the freely accessible WIPO, EPO, USPTO and Cambia databases with several keywords and patent codes. We have tabulated both granted and filed patents from the said databases. We retrieved ~40 patents from these databases. Novel biotechnological processes for production of these anticancer compounds include Agrobacterium rhizogenes-mediated hairy root culture, suspension culture, cell culture with elicitors, use of recombinant microorganisms, and bioreactors among others. The results are indicative of being both database-specific as well as queryspecific. A ten-year search window yielded 33 patents. The utility of the search strategy is discussed in the light of biotechnological developments in the field. Those who examine patent literature using similar search strategies may complement their knowledge obtained from perusal of mainstream journal resources. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Walrus foraging marks on the seafloor in Bristol Bay, Alaska: A reconnaissance survey

USGS Publications Warehouse

Bornhold, Brian D.; Jay, Chadwick V.; McConnaughey, Robert; Rathwell, Glenda; Rhynas, Karl; Collins, William

2005-01-01

A reconnaissance sidescan sonar survey in Bristol Bay, Alaska revealed extensive areas of seafloor with features related to walrus foraging. They are similar to those seen in areas such as the outer Bering Sea and Chukchi Sea. Two types of feature were observed: (a) small (≪1 m diameter) shallow pits, often in clusters ranging in density from 5 pits per hectare to 35 pits per hectare; and, (b) more abundant, narrow, sinuous furrows, typically 5 to 10 m long with some reaching 20 m or more. Most foraging marks were in less than 60 m water depth in areas of sandy seafloor that were smooth, hummocky or characterized by degraded bedforms; the absence of foraging marks in other areas may be related, in part, to their more dynamic nature. The distribution of foraging marks was consistent in a general way with walrus locations from satellite telemetry studies.

Movements of walruses radio-tagged in Bristol Bay, Alaska

USGS Publications Warehouse

Jay, C.V.; Hills, Susan

2005-01-01

Satellite radio-location data from 57 adult male Pacific walruses (Odobenus rosmarus divergens) were used to estimate haul-out fidelity, broadly describe seasonal foraging distributions, and determine the approximate timing of autumn migration from Bristol Bay, Alaska. Data were collected intermittently during 1987-91 and 1995-2000, primarily during the period from May to October. Transmitter longevity ranged from less than 1 day to 560 days (median 75 d). The four tagging sites were the only haul-outs that were commonly used in the bay from spring through autumn. Mean fidelity, defined as the chance that an animal will return to an area where it previously hauled out, was 0.56 (SE = 0.09). However, small sample sizes precluded comparisons of fidelity among years and among haul-outs by season. No tagged animals migrated out of the bay between spring and early autumn. Combined monthly locations suggest that foraging occurred primarily in the southern and eastern areas of the bay in spring and gradually shifted towards northwestern areas in late autumn and winter. Ninety-eight percent of the in-water locations were in waters under 60 m deep, which account for 76% of the study area. Some animals migrated out of the bay in late autumn and winter; others remained within the bay throughout the year. Those making long-range migrations departed the bay during November and December. ?? The Arctic Institute of North America.

The Loneliness of the Long-Distance Learner: Social Networking and Student Support. A Case Study of the Distance-Learning MA in Translation at Bristol University

ERIC Educational Resources Information Center

Duranton, Helene; Mason, Adrienne

2012-01-01

Using the translation programme at the University of Bristol as a case study, we shall argue in this paper that distance delivery can have a very positive impact on recruitment but that the quality of the students' experience depends upon the capacity of the organisation to support course development and delivery, both in terms of instructional…

Bristol Ridge: A 28-nm $$\\times$$ 86 Performance-Enhanced Microprocessor Through System Power Management

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sundaram, Sriram; Grenat, Aaron; Naffziger, Samuel

Power management techniques can be effective at extracting more performance and energy efficiency out of mature systems on chip (SoCs). For instance, the peak performance of microprocessors is often limited by worst case technology (Vmax), infrastructure (thermal/electrical), and microprocessor usage assumptions. Performance/watt of microprocessors also typically suffers from guard bands associated with the test and binning processes as well as worst case aging/lifetime degradation. Similarly, on multicore processors, shared voltage rails tend to limit the peak performance achievable in low thread count workloads. In this paper, we describe five power management techniques that maximize the per-part performance under the before-mentionedmore » constraints. Using these techniques, we demonstrate a net performance increase of up to 15% depending on the application and TDP of the SoC, implemented on 'Bristol Ridge,' a 28-nm CMOS, dual-core x 86 accelerated processing unit.« less

Paleobotany and palynology of the Bristol Hill Coal Member (Bond Formation) and Friendsville Coal Member (Mattoon Formation) of the Illinois Basin (Upper Pennsylvanian)

USGS Publications Warehouse

Willard, D.A.; Phillips, T.L.

1993-01-01

Late Pennsylvanian coal swamps of the Illinois Basin were dominated by Psarnius tree ferns with a spatially heterogeneous distribution of medullosan pteridosperms (subdominant), calamites, sigillarian lycopsids, and cordaites. Miospore and coal-ball plant assemblages from the Missourian-age Bristol Hill Coal Member (Mattoon Formation) of southeastern Illinois were quantified to analyze vegetational patterns in Late Pennsylvanian peat swamps and to compare vegetational composition of the coals. -from Authors

Planning, Development, and Change in Bristol Bay: A High School Curriculum. Teacher Guide and Student Text. Unit III: 1991 and Beyond. Unit IV: International Perspective. Revised.

ERIC Educational Resources Information Center

Lipka, Jerry; Willer, Cristy

Written with the broad goal of involving high school students in Bristol Bay, Alaska, in the planning and design of their region's future, this combined teacher guide and student text contains the third and fourth units of a seven-unit curriculum. Unit III covers the terms of the Alaska Native Claims Settlement Act and the complicated issues…

Characterization and destruction of Definity® microbubbles used for ultrasound imaging and drug delivery

NASA Astrophysics Data System (ADS)

Sarkar, Kausik; Chatterjee, Dhiman; Jain, Pankaj

2004-11-01

Intravenously injected encapsulated microbubbles improve the contrast of an ultrasound image. Their destruction is used in measuring blood flow, stimulating arteriogenesis, and drug delivery. We measure attenuation and scattering of ultrasound through solution of contrast agent Definity (Bristol Meyer-Squibb Imaging, North Ballerina, MA). We have developed an interfacial rheology model for the stabilizing encapsulation of such microbubbles. By matching with attenuation data, we obtain the characteristic rheological parameters for Definity. We compare model predictions with measured scattering. We investigate microbubble destruction under acoustic excitation by measuring time-varying attenuation data. Three regions of acoustic pressure amplitudes are found: at low pressure, there is no destruction; at slightly higher pressure bubbles are destroyed, and the rate of destruction depends on a combination of PRF and amplitude. At a still higher pressure amplitude, the attenuation decreases catastrophically. The last two regimes correspond respectively to 1) slow destruction of bubbles due to increased gas diffusion and 2) complete bubble destruction leading to release of free bubbles. (Supported by DOD, NSF and University of Delaware Research Foundation)

Using self-determination theory to promote adolescent girls' physical activity: Exploring the theoretical fidelity of the Bristol Girls Dance Project.

PubMed

Sebire, Simon J; Kesten, Joanna M; Edwards, Mark J; May, Thomas; Banfield, Kathryn; Tomkinson, Keeley; Blair, Peter S; Bird, Emma L; Powell, Jane E; Jago, Russell

2016-05-01

To report the theory-based process evaluation of the Bristol Girls' Dance Project, a cluster-randomised controlled trial to increase adolescent girls' physical activity. A mixed-method process evaluation of the intervention's self-determination theory components comprising lesson observations, post-intervention interviews and focus groups. Four intervention dance lessons per dance instructor were observed, audio recorded and rated to estimate the use of need-supportive teaching strategies. Intervention participants (n = 281) reported their dance instructors' provision of autonomy-support. Semi-structured interviews with the dance instructors (n = 10) explored fidelity to the theory and focus groups were conducted with participants (n = 59) in each school to explore their receipt of the intervention and views on the dance instructors' motivating style. Although instructors accepted the theory-based approach, intervention fidelity was variable. Relatedness support was the most commonly observed need-supportive teaching behaviour, provision of structure was moderate and autonomy-support was comparatively low. The qualitative findings identified how instructors supported competence and developed trusting relationships with participants. Fidelity was challenged where autonomy provision was limited to option choices rather than input into the pace or direction of lessons and where controlling teaching styles were adopted, often to manage disruptive behaviour. The successes and challenges to achieving theoretical fidelity in the Bristol Girls' Dance Project may help explain the intervention effects and can more broadly inform the design of theory-based complex interventions aimed at increasing young people's physical activity in after-school settings.

Using self-determination theory to promote adolescent girls' physical activity: Exploring the theoretical fidelity of the Bristol Girls Dance Project

PubMed Central

Sebire, Simon J.; Kesten, Joanna M.; Edwards, Mark J.; May, Thomas; Banfield, Kathryn; Tomkinson, Keeley; Blair, Peter S.; Bird, Emma L.; Powell, Jane E.; Jago, Russell

2016-01-01

Objectives To report the theory-based process evaluation of the Bristol Girls' Dance Project, a cluster-randomised controlled trial to increase adolescent girls' physical activity. Design A mixed-method process evaluation of the intervention's self-determination theory components comprising lesson observations, post-intervention interviews and focus groups. Method Four intervention dance lessons per dance instructor were observed, audio recorded and rated to estimate the use of need-supportive teaching strategies. Intervention participants (n = 281) reported their dance instructors' provision of autonomy-support. Semi-structured interviews with the dance instructors (n = 10) explored fidelity to the theory and focus groups were conducted with participants (n = 59) in each school to explore their receipt of the intervention and views on the dance instructors' motivating style. Results Although instructors accepted the theory-based approach, intervention fidelity was variable. Relatedness support was the most commonly observed need-supportive teaching behaviour, provision of structure was moderate and autonomy-support was comparatively low. The qualitative findings identified how instructors supported competence and developed trusting relationships with participants. Fidelity was challenged where autonomy provision was limited to option choices rather than input into the pace or direction of lessons and where controlling teaching styles were adopted, often to manage disruptive behaviour. Conclusion The successes and challenges to achieving theoretical fidelity in the Bristol Girls' Dance Project may help explain the intervention effects and can more broadly inform the design of theory-based complex interventions aimed at increasing young people's physical activity in after-school settings. PMID:27175102

Overcoming heterologous protein interdependency to optimize P450-mediated Taxol precursor synthesis in Escherichia coli

PubMed Central

Biggs, Bradley Walters; Lim, Chin Giaw; Sagliani, Kristen; Shankar, Smriti; Stephanopoulos, Gregory; Ajikumar, Parayil Kumaran

2016-01-01

Recent advances in metabolic engineering have demonstrated the potential to exploit biological chemistry for the synthesis of complex molecules. Much of the progress to date has leveraged increasingly precise genetic tools to control the transcription and translation of enzymes for superior biosynthetic pathway performance. However, applying these approaches and principles to the synthesis of more complex natural products will require a new set of tools for enabling various classes of metabolic chemistries (i.e., cyclization, oxygenation, glycosylation, and halogenation) in vivo. Of these diverse chemistries, oxygenation is one of the most challenging and pivotal for the synthesis of complex natural products. Here, using Taxol as a model system, we use nature’s favored oxygenase, the cytochrome P450, to perform high-level oxygenation chemistry in Escherichia coli. An unexpected coupling of P450 expression and the expression of upstream pathway enzymes was discovered and identified as a key obstacle for functional oxidative chemistry. By optimizing P450 expression, reductase partner interactions, and N-terminal modifications, we achieved the highest reported titer of oxygenated taxanes (∼570 ± 45 mg/L) in E. coli. Altogether, this study establishes E. coli as a tractable host for P450 chemistry, highlights the potential magnitude of protein interdependency in the context of synthetic biology and metabolic engineering, and points to a promising future for the microbial synthesis of complex chemical entities. PMID:26951651

Overcoming heterologous protein interdependency to optimize P450-mediated Taxol precursor synthesis in Escherichia coli.

PubMed

Biggs, Bradley Walters; Lim, Chin Giaw; Sagliani, Kristen; Shankar, Smriti; Stephanopoulos, Gregory; De Mey, Marjan; Ajikumar, Parayil Kumaran

2016-03-22

Recent advances in metabolic engineering have demonstrated the potential to exploit biological chemistry for the synthesis of complex molecules. Much of the progress to date has leveraged increasingly precise genetic tools to control the transcription and translation of enzymes for superior biosynthetic pathway performance. However, applying these approaches and principles to the synthesis of more complex natural products will require a new set of tools for enabling various classes of metabolic chemistries (i.e., cyclization, oxygenation, glycosylation, and halogenation) in vivo. Of these diverse chemistries, oxygenation is one of the most challenging and pivotal for the synthesis of complex natural products. Here, using Taxol as a model system, we use nature's favored oxygenase, the cytochrome P450, to perform high-level oxygenation chemistry in Escherichia coli. An unexpected coupling of P450 expression and the expression of upstream pathway enzymes was discovered and identified as a key obstacle for functional oxidative chemistry. By optimizing P450 expression, reductase partner interactions, and N-terminal modifications, we achieved the highest reported titer of oxygenated taxanes (∼570 ± 45 mg/L) in E. coli. Altogether, this study establishes E. coli as a tractable host for P450 chemistry, highlights the potential magnitude of protein interdependency in the context of synthetic biology and metabolic engineering, and points to a promising future for the microbial synthesis of complex chemical entities.

In vitro synergistic efficacy of conjugated linoleic acid, oleic acid, safflower oil and taxol cytotoxicity on PC3 cells.

PubMed

Kızılşahin, Sadi; Nalbantsoy, Ayşe; Yavaşoğlu, N Ülkü Karabay

2015-01-01

The aim of this study was to determine in vitro synergistic efficacy of conjugated linoleic acid (CLA), oleic acid (OLA), safflower oil and taxol (Tax) cytotoxicity on human prostate cancer (PC3) cell line. To determine synergistic efficacy of oil combinations, PC3 treated with different doses of compounds alone and combined with 10 μg/mL Tax. The MTT results indicated that OLA-Tax combinations exhibited cytotoxicity against PC3 at doses of 30 nM+10 μg-Tax, 15 nM+5 μg-Tax and 7.5 nM+2.5 μg-Tax. The treatment of OLA or Tax did not show significant inhibition on PC3, while OLA-Tax combinations showed effective cytotoxicity at treated doses. CLA-Tax combinations demonstrated the same effect on PC3 as combined form with 45.72% versus the alone form as 74.51% viability. Cytotoxic synergy between Tax, OLA and CLA shows enhanced cytotoxicity on PC3 which might be used in the therapy of prostate cancer.

Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

PubMed Central

Wolchok, J.D.; Chiarion-Sileni, V.; Gonzalez, R.; Rutkowski, P.; Grob, J.-J.; Cowey, C.L.; Lao, C.D.; Wagstaff, J.; Schadendorf, D.; Ferrucci, P.F.; Smylie, M.; Dummer, R.; Hill, A.; Hogg, D.; Haanen, J.; Carlino, M.S.; Bechter, O.; Maio, M.; Marquez-Rodas, I.; Guidoboni, M.; McArthur, G.; Lebbé, C.; Ascierto, P.A.; Long, G.V.; Cebon, J.; Sosman, J.; Postow, M.A.; Callahan, M.K.; Walker, D.; Rollin, L.; Bhore, R.; Hodi, F.S.; Larkin, J.

2017-01-01

melanoma, significantly longer overall survival occurred with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab alone. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.) PMID:28889792

Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma.

PubMed

Weber, Jeffrey; Mandala, Mario; Del Vecchio, Michele; Gogas, Helen J; Arance, Ana M; Cowey, C Lance; Dalle, Stéphane; Schenker, Michael; Chiarion-Sileni, Vanna; Marquez-Rodas, Ivan; Grob, Jean-Jacques; Butler, Marcus O; Middleton, Mark R; Maio, Michele; Atkinson, Victoria; Queirolo, Paola; Gonzalez, Rene; Kudchadkar, Ragini R; Smylie, Michael; Meyer, Nicolas; Mortier, Laurent; Atkins, Michael B; Long, Georgina V; Bhatia, Shailender; Lebbé, Celeste; Rutkowski, Piotr; Yokota, Kenji; Yamazaki, Naoya; Kim, Tae M; de Pril, Veerle; Sabater, Javier; Qureshi, Anila; Larkin, James; Ascierto, Paolo A

2017-11-09

3 or 4 adverse events than adjuvant therapy with ipilimumab. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 238 ClinicalTrials.gov number, NCT02388906 ; Eudra-CT number, 2014-002351-26 .).

Apixaban in patients with atrial fibrillation.

PubMed

Connolly, Stuart J; Eikelboom, John; Joyner, Campbell; Diener, Hans-Christoph; Hart, Robert; Golitsyn, Sergey; Flaker, Greg; Avezum, Alvaro; Hohnloser, Stefan H; Diaz, Rafael; Talajic, Mario; Zhu, Jun; Pais, Prem; Budaj, Andrzej; Parkhomenko, Alexander; Jansky, Petr; Commerford, Patrick; Tan, Ru San; Sim, Kui-Hian; Lewis, Basil S; Van Mieghem, Walter; Lip, Gregory Y H; Kim, Jae Hyung; Lanas-Zanetti, Fernando; Gonzalez-Hermosillo, Antonio; Dans, Antonio L; Munawar, Muhammad; O'Donnell, Martin; Lawrence, John; Lewis, Gayle; Afzal, Rizwan; Yusuf, Salim

2011-03-03

significantly increasing the risk of major bleeding or intracranial hemorrhage. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00496769.).

The use of clopidogrel (Plavix) in patients undergoing nonelective orthopaedic surgery.

PubMed

Nydick, Jason A; Farrell, Eric D; Marcantonio, Andrew J; Hume, Eric L; Marburger, Robert; Ostrum, Robert F

2010-06-01

To assess the effects of Plavix on patients requiring nonelective orthopaedic surgery. Retrospective cohort study. University-affiliated teaching institutions. The orthopaedic trauma registry was used to retrospectively identify all patients taking clopidogrel (Plavix; Bristol-Myers Squibb/Sanofi Pharmaceuticals, Bridgewater, NJ) who required nonelective orthopaedic surgery from 2004 to 2008. Twenty-nine patients were identified on Plavix (PG) and 32 matched patients in the control group not taking Plavix (NPG). The Plavix group was separated into those with a surgical delay less than 5 days of the last dose (PG < 5) (n = 28) and a delay greater than 5 days (PG > 5) (n = 1). A randomized age- and injury-matched control group not on Plavix was separated with surgical delay less than 5 days (NPG < 5) (n = 29) and delay greater than 5 days (NPG > 5) (n = 3). A retrospective review was performed comparing pre- and postoperative hemoglobin, blood transfusion requirements, surgical delay, 30-day mortality, and postoperative complications. Statistical analyses were performed using the Student t test and chi square test to identify differences between the groups. : The mean preoperative hemoglobin of the PG and the NPG was 11.2 g/dL and 12.3 g/dL (P = 0.03). Transfusion rates were similar with 18 of 28 in the PG compared with 13 of 29 in the NPG (P = 0.22). The mean surgical delay between the PG and NPG was 1.88 and 1.68 days (P = 0.64). Overall complications between the PG and NPG was nine of 28 and nine of 29 (P = 0.92). In both groups, two patients had postoperative wound drainage, which resolved without intervention. One patient in each group required revision surgery for nonunion. The 30-day mortality in the Plavix group was zero of 28 (0%) compared with one of 29 (3%) in the control group (cardiac arrest) (P = 0.32). In this study, there were no serious complications or increased transfusion requirements in the Plavix group. Avoiding surgical delay for patients on

Apixaban versus warfarin in patients with atrial fibrillation.

PubMed

Granger, Christopher B; Alexander, John H; McMurray, John J V; Lopes, Renato D; Hylek, Elaine M; Hanna, Michael; Al-Khalidi, Hussein R; Ansell, Jack; Atar, Dan; Avezum, Alvaro; Bahit, M Cecilia; Diaz, Rafael; Easton, J Donald; Ezekowitz, Justin A; Flaker, Greg; Garcia, David; Geraldes, Margarida; Gersh, Bernard J; Golitsyn, Sergey; Goto, Shinya; Hermosillo, Antonio G; Hohnloser, Stefan H; Horowitz, John; Mohan, Puneet; Jansky, Petr; Lewis, Basil S; Lopez-Sendon, Jose Luis; Pais, Prem; Parkhomenko, Alexander; Verheugt, Freek W A; Zhu, Jun; Wallentin, Lars

2011-09-15

Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb

The association between Myers-Briggs Type Indicator and Psychiatry as the specialty choice.

PubMed

Yang, Chong; Richard, George; Durkin, Martin

2016-02-06

The purpose of this pilot study is to examine the association between Myers-Briggs Type Indicator (MBTI) and prospective psychiatry residents. Forty-six American medical schools were contacted and asked to participate in this study. Data were collected and an aggregated list was compiled that included the following information: date of MBTI administration, academic year, MBTI form/version, residency match information and student demographic information. The data includes 835 American medical students who completed the MBTI survey and matched into a residency training program in the United States. All analyses were performed using R 3.1.2. The probability of an introvert matching to a psychiatry residency is no different than that of an extravert (p= 0.30). The probability of an intuitive individual matching to a psychiatry residency is no different than that of a sensing type (p=0.20). The probability of a feeling type matching to a psychiatry residency is no different than that of a thinking type (p= 0.50). The probability of a perceiving type matching to a psychiatry residency is no different than that of a judging type (p= 0.60). Further analyses may elicit more accurate information regarding the personality profile of prospective psychiatry residents. The improvement in communication, team dynamics, mentor-mentee relationships and reduction in workplace conflicts are possible with the awareness of MBTI personality profiles.

The association between Myers-Briggs Type Indicator and Psychiatry as the specialty choice

PubMed Central

Richard, George; Durkin, Martin

2016-01-01

Objectives The purpose of this pilot study is to examine the association between Myers-Briggs Type Indicator (MBTI) and prospective psychiatry residents. Methods Forty-six American medical schools were contacted and asked to participate in this study. Data were collected and an aggregated list was compiled that included the following information: date of MBTI administration, academic year, MBTI form/version, residency match information and student demographic information. The data includes 835 American medical students who completed the MBTI survey and matched into a residency training program in the United States. All analyses were performed using R 3.1.2. Results The probability of an introvert matching to a psychiatry residency is no different than that of an extravert (p= 0.30). The probability of an intuitive individual matching to a psychiatry residency is no different than that of a sensing type (p=0.20). The probability of a feeling type matching to a psychiatry residency is no different than that of a thinking type (p= 0.50). The probability of a perceiving type matching to a psychiatry residency is no different than that of a judging type (p= 0.60). Conclusions Further analyses may elicit more accurate information regarding the personality profile of prospective psychiatry residents. The improvement in communication, team dynamics, mentor-mentee relationships and reduction in workplace conflicts are possible with the awareness of MBTI personality profiles. PMID:26851600

A comparison of music education and music therapy majors: personality types as described by the Myers-Briggs Type Indicator and demographic profiles.

PubMed

Steele, Anita Louise; Young, Sylvester

2008-01-01

The purpose of this study was to develop both personality and demographic profiles for students who are interested in majoring in music education or music therapy. Two primary questions were addressed in the study: (a) Are there similarities and differences in the personality types of music education and music therapy majors as measured by the Myers Briggs Type Indicator (MBTI )? (b) Are there similarities and differences in demographic characteristics of music education and music therapy majors in regard to (i) principal instrument studied in college, (ii) grade point average, (iii) scholarship awards, (iv) high school participation in private study and (v) ensembles, (vi) church/community participation, and (vii) volunteerism in high school?

Topotecan, pegylated liposomal doxorubicin hydrochloride, paclitaxel, trabectedin and gemcitabine for advanced recurrent or refractory ovarian cancer: a systematic review and economic evaluation.

PubMed

Edwards, Steven J; Barton, Samantha; Thurgar, Elizabeth; Trevor, Nicola

2015-01-01

Ovarian cancer is the fifth most common cancer in the UK, and the fourth most common cause of cancer death. Of those people successfully treated with first-line chemotherapy, 55-75% will relapse within 2 years. At this time, it is uncertain which chemotherapy regimen is more clinically effective and cost-effective for the treatment of recurrent, advanced ovarian cancer. To determine the comparative clinical effectiveness and cost-effectiveness of topotecan (Hycamtin(®), GlaxoSmithKline), pegylated liposomal doxorubicin hydrochloride (PLDH; Caelyx(®), Schering-Plough), paclitaxel (Taxol(®), Bristol-Myers Squibb), trabectedin (Yondelis(®), PharmaMar) and gemcitabine (Gemzar(®), Eli Lilly and Company) for the treatment of advanced, recurrent ovarian cancer. Electronic databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluations Database) and trial registries were searched, and company submissions were reviewed. Databases were searched from inception to May 2013. A systematic review of the clinical and economic literature was carried out following standard methodological principles. Double-blind, randomised, placebo-controlled trials, evaluating topotecan, PLDH, paclitaxel, trabectedin and gemcitabine, and economic evaluations were included. A network meta-analysis (NMA) was carried out. A de novo economic model was developed. For most outcomes measuring clinical response, two networks were constructed: one evaluating platinum-based regimens and one evaluating non-platinum-based regimens. In people with platinum-sensitive disease, NMA found statistically significant benefits for PLDH plus platinum, and paclitaxel plus platinum for overall survival (OS) compared with platinum monotherapy. PLDH plus platinum significantly prolonged progression-free survival (PFS) compared with paclitaxel plus platinum. Of the non-platinum-based treatments, PLDH monotherapy and trabectedin plus PLDH

The missing history of Bohm's hidden variables theory: The Ninth Symposium of the Colston Research Society, Bristol, 1957

NASA Astrophysics Data System (ADS)

Kožnjak, Boris

2018-05-01

In this paper, I analyze the historical context, scientific and philosophical content, and the implications of the thus far historically largely neglected Ninth Symposium of the Colston Research Society held in Bristol at the beginning of April 1957, the first major international event after World War II gathering eminent physicists and philosophers to discuss the foundational questions of quantum mechanics, in respect to the early reception of the causal quantum theory program mapped and defended by David Bohm during the five years preceding the Symposium. As will be demonstrated, contrary to the almost unanimously negative and even hostile reception of Bohm's ideas on hidden variables in the early 1950s, in the close aftermath of the 1957 Colston Research Symposium Bohm's ideas received a more open-minded and ideologically relaxed critical rehabilitation, in which the Symposium itself played a vital and essential part.

The revised Bristol Rheumatoid Arthritis Fatigue measures and the Rheumatoid Arthritis Impact of Disease scale: validation in six countries

PubMed Central

Kirwan, John; Bode, Christina; Cramp, Fiona; Carmona, Loreto; Dures, Emma; Englbrecht, Matthias; Fransen, Jaap; Greenwood, Rosemary; Hagel, Sofia; van de Laar, Maart; Molto, Anna; Nicklin, Joanna; Petersson, Ingemar F; Redondo, Marta; Schett, Georg; Gossec, Laure

2018-01-01

Abstract Objective To evaluate the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), the revised Bristol Rheumatoid Arthritis Numerical Rating Scales (BRAF-NRS V2) and the Rheumatoid Arthritis Impact of Disease (RAID) scale in six countries. Methods We surveyed RA patients in France, Germany, The Netherlands, Spain, Sweden and the UK, including the HAQ, 36-item Short Form Health Survey (SF-36) and potential revisions of the BRAF-NRS coping and Spanish RAID coping items. Factor structure and internal consistency were examined by factor analysis and Cronbach’s α and construct validity by Spearman’s correlation. Results A total of 1276 patients participated (76% female, 25% with a disease duration <5 years, median HAQ 1.0). The original BRAF-MDQ four-factor structure and RAID single-factor structure were confirmed in every country with ⩾66% of variation in items explained by each factor and all item factor loadings of 0.71–0.98. Internal consistency for the BRAF-MDQ total and subscales was a Cronbach’s α of 0.75–0.96 and for RAID, 0.93–0.96. Fatigue construct validity was shown for the BRAF-MDQ and BRAF-NRS severity and effect scales, correlated internally with SF-36 vitality and with RAID fatigue (r = 0.63–0.93). Broader construct validity for the BRAFs and RAID was shown by correlation with each other, HAQ and SF-36 domains (r = 0.46–0.82), with similar patterns in individual countries. The revised BRAF-NRS V2 Coping item had stronger validity than the original in all analyses. The revised Spanish RAID coping item performed as well as the original. Conclusion Across six European countries, the BRAF-MDQ identifies the same four aspects of fatigue, and along with the RAID, shows strong factor structure and internal consistency and moderate–good construct validity. The revised BRAF-NRS V2 shows improved construct validity and replaces the original. PMID:29087507

The revised Bristol Rheumatoid Arthritis Fatigue measures and the Rheumatoid Arthritis Impact of Disease scale: validation in six countries.

PubMed

Hewlett, Sarah; Kirwan, John; Bode, Christina; Cramp, Fiona; Carmona, Loreto; Dures, Emma; Englbrecht, Matthias; Fransen, Jaap; Greenwood, Rosemary; Hagel, Sofia; van de Laar, Maart; Molto, Anna; Nicklin, Joanna; Petersson, Ingemar F; Redondo, Marta; Schett, Georg; Gossec, Laure

2018-02-01

To evaluate the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), the revised Bristol Rheumatoid Arthritis Numerical Rating Scales (BRAF-NRS V2) and the Rheumatoid Arthritis Impact of Disease (RAID) scale in six countries. We surveyed RA patients in France, Germany, The Netherlands, Spain, Sweden and the UK, including the HAQ, 36-item Short Form Health Survey (SF-36) and potential revisions of the BRAF-NRS coping and Spanish RAID coping items. Factor structure and internal consistency were examined by factor analysis and Cronbach's α and construct validity by Spearman's correlation. A total of 1276 patients participated (76% female, 25% with a disease duration <5 years, median HAQ 1.0). The original BRAF-MDQ four-factor structure and RAID single-factor structure were confirmed in every country with ⩾66% of variation in items explained by each factor and all item factor loadings of 0.71-0.98. Internal consistency for the BRAF-MDQ total and subscales was a Cronbach's α of 0.75-0.96 and for RAID, 0.93-0.96. Fatigue construct validity was shown for the BRAF-MDQ and BRAF-NRS severity and effect scales, correlated internally with SF-36 vitality and with RAID fatigue (r = 0.63-0.93). Broader construct validity for the BRAFs and RAID was shown by correlation with each other, HAQ and SF-36 domains (r = 0.46-0.82), with similar patterns in individual countries. The revised BRAF-NRS V2 Coping item had stronger validity than the original in all analyses. The revised Spanish RAID coping item performed as well as the original. Across six European countries, the BRAF-MDQ identifies the same four aspects of fatigue, and along with the RAID, shows strong factor structure and internal consistency and moderate-good construct validity. The revised BRAF-NRS V2 shows improved construct validity and replaces the original. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

An evaluation of primary care led dementia diagnostic services in Bristol.

PubMed

Dodd, Emily; Cheston, Richard; Fear, Tina; Brown, Ellie; Fox, Chris; Morley, Clare; Jefferies, Rosalyn; Gray, Richard

2014-11-29

Typically people who go to see their GP with a memory problem will be initially assessed and those patients who seem to be at risk will be referred onto a memory clinic. The demographic forces mean that memory services will need to expand to meet demand. An alternative may be to expand the role of primary care in dementia diagnosis and care. The aim of this study was to contrast patient, family member and professional experience of primary and secondary (usual) care led memory services. A qualitative, participatory study. A topic guide was developed by the peer and professional panels. Data were collected through peer led interviews of people with dementia, their family members and health professionals. Eleven (21%) of the 53 GP practices in Bristol offered primary care led dementia services. Three professional panels were held and were attended by 9 professionals; nine carers but no patients were involved in the three peer panels. These panels identified four main themes: GPs rarely make independent dementia diagnosis; GPs and memory nurses work together; patients and carers generally experience a high quality diagnostic service; an absence of post diagnostic support. Evidence relating to these themes was collected through a total of 46 participants took part; 23 (50%) in primary care and 23 (50%) in the memory service. Patients and carers were generally satisfied with either primary or secondary care led approaches to dementia diagnosis. Their major concern, shared with many health care professionals, was a lack of post diagnostic support.

Investigations of belukha whales in coastal waters of western and northern Alaska, 1982-1983: marking and tracking of whales in Bristol Bay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frost, K.J.; Lowry, L.F.; Nelson, R.R.

1983-12-01

A 2-year study was conducted in Bristol Bay, Alaska, to develop and test techniques for marking belukha whales with visual and radio tags. Information was also gathered on belukha distribution and abundance, foods and feeding, and rates and causes of mortality. Two types of radio packages were developed: an OAR backpack designed to be bolted through the dorsal ridge, and a Telonics barnacle tag with an umbrella-stake attachment. Testing of tags and attachments revealed that the more-powerful OAR radio could be received at longer distances and lower antenna heights, and the the umbrella-stake attachment penetrated too deeply for reliable usemore » on belukhas.« less

Planning, Development, and Change in Bristol Bay: A High School Curriculum. Teacher Guide and Student Text. Unit V: Oil and Gas Development. Unit VI: Minerals and Mining. Unit VII: State Land Disposal. Revised

ERIC Educational Resources Information Center

Lipka, Jerry; Willer, Cristy

Written with the broad goal of involving high school students in Bristol Bay, Alaska, in the planning and design of their region's future, this combined teacher guide and student text contains the final three units of a seven-unit curriculum. Unit V looks at oil development in the Bering Sea, covering topics such as Alaska's dependence on oil,…

Lessons learnt from the Bristol Girls Dance Project cluster RCT: implications for designing and implementing after-school physical activity interventions

PubMed Central

Edwards, Mark J; May, Thomas; Kesten, Joanna M; Banfield, Kate; Bird, Emma L; Powell, Jane E; Sebire, Simon J; Jago, Russell

2016-01-01

Objective To consider implementation issues associated with the delivery of Bristol Girls Dance Project (BGDP) and to identify improvements that may aid the design of after-school physical activity (PA) interventions. Design Two-armed cluster randomised control trial. The BGDP was a 20-week school-based intervention, consisting of two 75 min after-school dance sessions per week, which aimed to support Year 7 girls to be more physically active. Setting 18 secondary schools (nine intervention, nine control) in the Greater Bristol area (as an indication of deprivation, children eligible for the pupil premium in participant schools ranged from 6.9 to 53.3%). Participants 571 Year 7 girls. This article reports on qualitative data collected from 59 girls in the intervention arm of the trial, 10 dance instructors and 9 school contacts involved in the delivering of the BGDP. Methods Data were obtained from nine focus groups with girls (one per intervention school), and interviews with dance instructors and school contacts. Focus groups sought views of girls’ motivation to participate, teaching styles and experiences of the intervention. Interviews explored views on implementation and dissemination. Framework analysis was used to analyse data. Results Qualitative data elicited three themes associated with the delivery of BGDP that affected implementation: project design, session content and project organisation. ‘Project design’ found issues associated with recruitment, timetabling and session quantity to influence the effectiveness of BGDP. ‘Session content’ found that dance instructors delivered a range of content and that girls enjoyed a variety of dance. Themes within ‘project organisation’ suggested an ‘open enrolment’ policy and greater parental involvement may facilitate better attendance. Conclusions After-school PA interventions have potential for increasing PA levels among adolescent girls. There is a need to consider the context in which

Development and initial validation of the Bristol Impact of Hypermobility questionnaire.

PubMed

Palmer, S; Cramp, F; Lewis, R; Gould, G; Clark, E M

2017-06-01

Stage 1 - to identify the impact of joint hypermobility syndrome (JHS) on adults; Stage 2 - to develop a questionnaire to assess the impact of JHS; and Stage 3 - to undertake item reduction and establish the questionnaire's concurrent validity. A mixed methods study employing qualitative focus groups and interviews (Stage 1); a working group of patients, clinicians and researchers, and 'think aloud' interviews (Stage 2); and quantitative analysis of questionnaire responses (Stage 3). Stages 1 and 2 took place in one secondary care hospital in the UK. Members of a UK-wide patient organisation were recruited in Stage 3. In total, 15, four and 615 participants took part in Stages 1, 2 and 3, respectively. Inclusion criteria were: age ≥18 years; diagnosis of JHS; no other conditions affecting physical function; able to give informed consent; and able to understand and communicate in English. None. The development of a questionnaire to assess the impact of JHS. Stage 1 identified a wide range of impairments, activity limitations and participation restrictions In Stage 2, a draft questionnaire was developed and refined following 'think aloud' analysis, leaving 94 scored items. In Stage 3, items were removed on the basis of low severity and/or high correlation with other items. The final Bristol Impact of Hypermobility (BIoH) questionnaire had 55 scored items, and correlated well with the physical component score of the Short Form 36 health questionnaire (r=-0.725). The BIoH questionnaire demonstrated good concurrent validity. Further psychometric properties need to be established. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Tables showing analyses of semiquantitative spectrometry and atomic-absorption spectrophotometry of rock samples collected in the Ugashik, Bristol Bay, and western part of the Karluk quadrangles, Alaska

USGS Publications Warehouse

Wilson, Frederic H.; O'Leary, Richard M.

1987-01-01

The accompanying tables list chemical analyses of 337 rock samples that were collected in 1979, 1980, and 1981 in conjunction with geologic mapping in the Ugashik, Bristol Bay, and part of Karluk quadrangles. This work was conducted under the auspices of the Alaska Mineral Resource Assessment Program (AMRAP). This report is to accompany Wilson and O'Leary (1986) which inadvertently is missing most of the data tables listed here. Together the two reports contain the complete data from all samples collected for the Ugashik AMRAP.

South Asian grandmothers' influence on breast feeding in Bristol.

PubMed

Ingram, Jenny; Johnson, Debbie; Hamid, Nishat

2003-12-01

To assess South Asian grandmothers' health beliefs and cultural practices around baby feeding, knowledge of breast feeding and their ability to support successful breast feeding. To design a suitable antenatal intervention for grandmothers to support their breast-feeding daughters/in-law in an area of low exclusive breast feeding and to assess the acceptability and feasibility of the initiative by means of structured interviews. Qualitative focus groups and interviews. Evaluation of an intervention. Community health centre and family homes in Easton, Bristol, where 32% of women having babies are South Asian. 14 Pakistani, Bangladeshi or Indian grandmothers in focus groups or interviews. 16 South Asian families in the intervention. An intervention for grandmothers to support exclusive breast feeding was based around a leaflet, which covered the health benefits of breast feeding, good positioning and attachment, feed management, and how families can support breast feeding. The intervention was delivered to mother and grandmother pairs at around 36 weeks gestation, and was translated into three languages. South Asian women are not a homogeneous group and differences were seen in cultural and religious practices and in breast-feeding rates between the Pakistani, Bangladeshi and Indian communities. To ensure that the health education message of exclusive breast feeding, how to overcome problems and the importance of family support reaches all women, linkworkers with appropriate training should be available to speak the languages relevant to the ethnic groups in the area. An antenatal educational intervention for extended family members to promote good breast-feeding practice was appreciated by the South Asian families involved and seemed to be influencing behaviour, particularly in giving colostrum, water or artificial milk and the use of dummies/pacifiers. Recording details of baby-feeding method at eight weeks systematically by ethnic group will enable local rates to

Distinct Roles of Velvet Complex in the Development, Stress Tolerance, and Secondary Metabolism in Pestalotiopsis microspora, a Taxol Producer

PubMed Central

Akhberdi, Oren; Zhang, Qian; Wang, Dan; Wang, Haichuan; Hao, Xiaoran; Liu, Yanjie; Wei, Dongsheng; Zhu, Xudong

2018-01-01

The velvet family proteins have been shown to play critical roles in fungal secondary metabolism and development. However, variations of the roles have been observed in different fungi. We report here the observation on the role of three velvet complex components VeA, VelB, and LaeA in Pestalotiopsis microspora, a formerly reported taxol-producing fungus. Deletion of individual members led to the retardation of vegetative growth and sporulation and pigmentation, suggesting critical roles in these processes. The mutant strain △velB appeared hypersensitive to osmotic stress and the dye Congo red, whereas △veA and △laeA were little affected by the pressures, suggesting only velB was required for the integrity of the cell wall. Importantly, we found that the genes played distinct roles in the biosynthesis of secondary metabolites in P. microspora. For instance, the production of pestalotiollide B, a previously characterized polyketide, required velB and laeA. In contrast, the veA gene appeared to inhibit the pestalotiollide B (PB) role in its biosynthesis. This study suggests that the three components of the velvet complex are important global regulators, but with distinct roles in hyphal growth, asexual production, and secondary metabolism in P. microspora. This work provides information for further understanding the biosynthesis of secondary metabolism in the fungus. PMID:29538316

Roles of phospholipid methyltransferases in pycnidia development, stress tolerance and secondary metabolism in the taxol-producing fungus Pestalotiopsis microspore.

PubMed

Akhberdi, Oren; Zhang, Qian; Wang, Haichuan; Li, Yingying; Chen, Longfei; Wang, Dan; Yu, Xi; Wei, Dongsheng; Zhu, Xudong

2018-05-01

Phosphatidylcholine (PC) is an important membrane component of the eukaryotic cell. In yeast fungi, two phospholipid methyltransferases catalyze consecutive steps of methylation in the formation of phosphatidylcholine from phosphatidylethanolamine. However, roles of phospholipid methyltransferases in filamentous fungi remains less investigated. We report here the characterization of two genes, choA and choC, that putatively encoded phospholipid methyltransferases in the taxol-producing fungus Pestalotiopsis microspora. Deletion of choC resulted in defects in PC production, vegetative growth and development of asexual structure. The mutant strains exhibited multiple morphological abnormalities, e.g. swollen hyphal tips and enhanced hyphal branching, and even mycelial autolysis. Some novel roles for the genes were also revealed, for instance, the deletion of either choC or choA impaired the development of pycnidia and conidia, the cell wall integrity. The mutant strains displayed a hypersensitivity to stress conditions, e.g. osmotic stress, cold and metal ions. The osmotic hypersensitivity indicates a crosstalk of PC pathways to other signaling pathways, such as the HOG pathway. Still more, choA, but not choC, was required for the production of secondary metabolites, e.g. pestalotiollide B, suggesting distinct roles of the two genes. This work would contribute to better understanding the function of phospholipid methyltransferases in fungi. Copyright © 2018 Elsevier GmbH. All rights reserved.

Distinct Roles of Velvet Complex in the Development, Stress Tolerance, and Secondary Metabolism in Pestalotiopsis microspora, a Taxol Producer.

PubMed

Akhberdi, Oren; Zhang, Qian; Wang, Dan; Wang, Haichuan; Hao, Xiaoran; Liu, Yanjie; Wei, Dongsheng; Zhu, Xudong

2018-03-14

The velvet family proteins have been shown to play critical roles in fungal secondary metabolism and development. However, variations of the roles have been observed in different fungi. We report here the observation on the role of three velvet complex components VeA, VelB, and LaeA in Pestalotiopsis microspora , a formerly reported taxol-producing fungus. Deletion of individual members led to the retardation of vegetative growth and sporulation and pigmentation, suggesting critical roles in these processes. The mutant strain △velB appeared hypersensitive to osmotic stress and the dye Congo red, whereas △veA and △laeA were little affected by the pressures, suggesting only velB was required for the integrity of the cell wall. Importantly, we found that the genes played distinct roles in the biosynthesis of secondary metabolites in P. microspora . For instance, the production of pestalotiollide B, a previously characterized polyketide, required velB and laeA . In contrast, the veA gene appeared to inhibit the pestalotiollide B (PB) role in its biosynthesis. This study suggests that the three components of the velvet complex are important global regulators, but with distinct roles in hyphal growth, asexual production, and secondary metabolism in P. microspora . This work provides information for further understanding the biosynthesis of secondary metabolism in the fungus.

Medicine As a Corporate Enterprise, Patient Welfare Centered Profession, or Patient Welfare Centered Professional Enterprise?

PubMed Central

Singh, Ajai; Singh, Shakuntala

2005-01-01

There is an alarming trend in the field of medicine, whose portents are ominous but do not seem to shake the complacency and merry making doing the rounds. The wants of the medical man have multiplied beyond imagination. The cost of organizing conferences is no longer possible on delegate fees. The bottom-line is: Crores for a Conference Millions for a Mid-Term. However, the problem is that sponsors keep a discreet but careful tab on docs. All in all, costs of medicines escalate, and quality medical care becomes a luxury. The whole brunt of this movement is borne by the patient. Companies like GlaxoSmithKline, Bayer, Pfizer, Bristol-Myers Squibb, AstraZeneca, Schering-Plough, Abbott Labs, TAP Pharmaceuticals, Wyeth and Merck have paid millions of dollars each as compensation in the last few years. The financial condition of many pharmaceutical majors is not buoyant either. Price deflation, increased Rand D spending, and litigation costs are the main reasons. In the future, the messy lawsuits situation would no longer be restricted to industry. It would involve academia and practising doctors as well. Indian pharma industry captains, who were busy raking in the profits at present, would also come under the scanner. If nothing else, it means industry and docs will have to sit down and do some soul searching. Both short and long-term measures will have to be put into place. Short-term measures involve reduction in i) pharma spending over junkets and trinkets; ii) hype over ‘me too’ drugs; iii) manipulation of drug trials; iv) getting pliant researchers into drug trials; iv) manipulation of Journal Editors to publish positive findings about their drug trials and launches; v) and for Indian Pharma, to conduct their own unbiased clinical trial of the latest drug projected as a blockbuster in the West, before pumping in their millions. The long-term measures are related to the way biomedical advance is to be charted. We have to decide whether medicine is to become a

Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial.

PubMed

Ruperto, Nicolino; Lovell, Daniel J; Quartier, Pierre; Paz, Eliana; Rubio-Pérez, Nadina; Silva, Clovis A; Abud-Mendoza, Carlos; Burgos-Vargas, Ruben; Gerloni, Valeria; Melo-Gomes, Jose A; Saad-Magalhães, Claudia; Sztajnbok, Flavio; Goldenstein-Schainberg, Claudia; Scheinberg, Morton; Penades, Immaculada Calvo; Fischbach, Michael; Orozco, Javier; Hashkes, Philip J; Hom, Christine; Jung, Lawrence; Lepore, Loredana; Oliveira, Sheila; Wallace, Carol A; Sigal, Leonard H; Block, Alan J; Covucci, Allison; Martini, Alberto; Giannini, Edward H

2008-08-02

who continued abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups. Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, both in controls (p=0.50). Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis. Bristol-Myers Squibb.

Peripheral blood stem cell mobilization and engraftment after autologous stem cell transplantation with biosimilar rhG-CSF.

PubMed

Reményi, Péter; Gopcsa, László; Marton, Imelda; Réti, Marienn; Mikala, Gábor; Pető, Mónika; Barta, Anikó; Bátai, Arpád; Farkas, Zita; Borbényi, Zita; Csukly, Zoltán; Bodó, Imre; Fábián, János; Király, Agnes; Lengyel, Lilla; Piukovics, Klára; Torbágyi, Eva; Masszi, Tamás

2014-04-01

Biosimilar versions of filgrastim [recombinant human granulocyte colony-stimulating factor (rhG-CSF)] are now widely available. To date, biosimilar rhG-CSF has demonstrated a comparable quality, safety and efficacy profile to the originator product (filgrastim [Neupogen(®)], Amgen Inc., CA, USA) in the prevention and management of neutropenia. Biosimilar rhG-CSFs have also been used to induce peripheral blood stem cell (PBSC) mobilization in patients undergoing autologous stem cell transplantation (AHSCT). The authors have examined the effectiveness of a biosimilar rhG-CSF (Zarzio(®), Sandoz Biopharmaceuticals, Holzkirchen, Germany) in two retrospective studies across two medical centers in Hungary. In Study 1, 70 patients with hematological malignancies scheduled to undergo AHSCT received chemotherapy followed by biosimilar rhG-CSF (2 × 5 μg) for facilitating neutrophil, leukocyte, and platelet engraftment. In study 2, 40 additional patients with lymphoid malignancies and planned AHSCT received chemotherapy followed by biosimilar rhG-CSF for PBSC mobilization. The effectiveness of treatment was assessed by the average yield of cluster of differentiation (CD) 34+ cells and the number of leukaphereses required. In Study 1 (patients undergoing AHSCT), the median age was 56 years and most patients were male (60%). The conditioning regimens were mainly high-dose melphalan (n = 41) and carmustine (BiCNU(®), Bristol-Myers Squibb, NJ, USA), etoposide, cytarabine and melphalan BEAM (n = 21). Median times to absolute neutrophil and leukocyte engraftment were 9 (range 8-11 days) and 10 (8-12) days, respectively. Median time to platelet engraftment was 10.5 days (7-19 days). In Study 2, the patients' median age was 54 years and the majority (57.5%) were female. The median time interval between day 1 of mobilizing chemotherapy and first leukapheresis was 12 (9-27) days. In the autologous PBSC grafts, the median number of CD34+ cells harvested was 5.2 × 10(6)/kg (2

Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial.

PubMed

Diener, Hans-Christoph; Eikelboom, John; Connolly, Stuart J; Joyner, Campbell D; Hart, Robert G; Lip, Gregory Y H; O'Donnell, Martin; Hohnloser, Stefan H; Hankey, Graeme J; Shestakovska, Olga; Yusuf, Salim

2012-03-01

patients with atrial fibrillation, apixaban is similarly effective whether or not patients have had a previous stroke or TIA. Given that those with previous stroke or TIA have a higher risk of stroke, the absolute benefits might be greater in these patients. Bristol-Myers Squibb and Pfizer. Copyright © 2012 Elsevier Ltd. All rights reserved.

Medicine as a corporate enterprise, patient welfare centered profession, or patient welfare centered professional enterprise?

PubMed

Singh, Ajai; Singh, Shakuntala

2005-11-01

There is an alarming trend in the field of medicine, whose portents are ominous but do not seem to shake the complacency and merry making doing the rounds.The wants of the medical man have multiplied beyond imagination. The cost of organizing conferences is no longer possible on delegate fees. The bottom-line is: Crores for a Conference Millions for a Mid-Term. However, the problem is that sponsors keep a discreet but careful tab on docs. All in all, costs of medicines escalate, and quality medical care becomes a luxury. The whole brunt of this movement is borne by the patient.Companies like GlaxoSmithKline, Bayer, Pfizer, Bristol-Myers Squibb, AstraZeneca, Schering-Plough, Abbott Labs, TAP Pharmaceuticals, Wyeth and Merck have paid millions of dollars each as compensation in the last few years. The financial condition of many pharmaceutical majors is not buoyant either. Price deflation, increased Rand D spending, and litigation costs are the main reasons. In the future, the messy lawsuits situation would no longer be restricted to industry. It would involve academia and practising doctors as well. Indian pharma industry captains, who were busy raking in the profits at present, would also come under the scanner. If nothing else, it means industry and docs will have to sit down and do some soul searching.Both short and long-term measures will have to be put into place. Short-term measures involve reduction in i) pharma spending over junkets and trinkets; ii) hype over 'me too' drugs; iii) manipulation of drug trials; iv) getting pliant researchers into drug trials; iv) manipulation of Journal Editors to publish positive findings about their drug trials and launches; v) and for Indian Pharma, to conduct their own unbiased clinical trial of the latest drug projected as a blockbuster in the West, before pumping in their millions.The long-term measures are related to the way biomedical advance is to be charted. We have to decide whether medicine is to become a corporate

The Science on Saturday Program at Princeton Plasma Physics Laboratory

NASA Astrophysics Data System (ADS)

Bretz, N.; Lamarche, P.; Lagin, L.; Ritter, C.; Carroll, D. L.

1996-11-01

The Science on Saturday Program at Princeton Plasma Physics Laboratory consists of a series of Saturday morning lectures on various topics in science by scientists, engineers, educators, and others with an interesting story. This program has been in existence for over twelve years and has been advertised to and primarily aimed at the high school level. Topics ranging from superconductivity to computer animation and gorilla conservation to pharmaceutical design have been covered. Lecturers from the staff of Princeton, Rutgers, AT and T, Bristol Meyers Squibb, and many others have participated. Speakers have ranged from Nobel prize winners, astronauts, industrialists, educators, engineers, and science writers. Typically, there are eight to ten lectures starting in January. A mailing list has been compiled for schools, science teachers, libraries, and museums in the Princeton area. For the past two years AT and T has sponsored buses for Trenton area students to come to these lectures and an effort has been made to publicize the program to these students. The series has been very popular, frequently overfilling the 300 seat PPPL auditorium. As a result, the lectures are videotaped and broadcast to a large screen TV for remote viewing. Lecturers are encouraged to interact with the audience and ample time is provided for questions.

Modeling and Characterization of Encapsulated Microbubbles for Ultrasound Imaging and Drug Delivery

NASA Astrophysics Data System (ADS)

Sarkar, Kausik; Jain, Pankaj; Chatterjee, Dhiman

2008-07-01

Intravenously injected encapsulated microbubbles improve the contrast of an ultrasound image. Their destruction is used in measuring blood flow, stimulating arteriogenesis, and drug delivery. We measure attenuation and scattering of ultrasound through solution of commercial contrast agents such as Optison (GE Health Care, Princeton, NJ) and Definity (Bristol Meyer-Squibb Imaging, North Ballerina, MA). We have developed an interfacial rheology model for the encapsulation of such microbubbles. By matching with experimental data, we obtain the characteristic rheological parameters. We compare model predictions with other experiments. We also investigate microbubble destruction under acoustic excitation by measuring time-varying attenuation data. Three regions of acoustic pressure amplitudes are found: at low pressure, there is no destruction; at slightly higher pressure bubbles are destroyed, and the rate of destruction depends on a combination of PRF and amplitude. At a still higher pressure amplitude, the attenuation decreases catastrophically. The last two regimes correspond respectively to 1) slow destruction of bubbles due to increased gas diffusion and 2) complete bubble destruction leading to release of free bubbles. An analytical model for the bubble growth and dissolution will be presented. The effects of membrane permeability and elasticity on the stability of microbubbles are investigated. (Supported by DOD, NSF and NIH).

An endophytic Basidiomycete, Grammothele lineata, isolated from Corchorus olitorius, produces paclitaxel that shows cytotoxicity

PubMed Central

Das, Avizit; Rahman, Mohammad Imtiazur; Ferdous, Ahlan Sabah; Amin, Al-; Rahman, Mohammad Mahbubur; Nahar, Nilufar; Uddin, Md. Aftab; Islam, Mohammad Riazul; Khan, Haseena

2017-01-01

Grammothele lineata, an endophyte isolated in our laboratory from jute (Corchorus olitorius acc. 2015) was found to be a substantial paclitaxel producer. Taxol and its related compounds, produced by this endophyte were extracted by growing the fungus in simple nutrient media (potato dextrose broth, PDB). Taxol was identified and characterized by different analytical techniques (TLC, HPLC, FTIR, LC-ESI-MS/MS) following its extraction by ethyl acetate. In PDB media, this fungus was found to produce 382.2 μgL-1 of taxol which is about 7.6 x103 fold higher than the first reported endophytic fungi, Taxomyces andreanae. The extracted taxol exhibited cytotoxic activity in an in vitro culture of HeLa cancer cell line. The fungal extract also exhibited antifungal and antibacterial activities against different pathogenic strains. This is the first report of a jute endophytic fungus harboring the capacity to produce taxol and also the first reported taxol producing species that belongs to the Basidiomycota phylum, so far unknown to be a taxol producer. These findings suggest that the fungal endophyte, Grammothele lineata can be an excellent source of taxol and can also serve as a potential species for chemical and genetic engineering to enhance further the production of taxol. PMID:28636663

An endophytic Basidiomycete, Grammothele lineata, isolated from Corchorus olitorius, produces paclitaxel that shows cytotoxicity.

PubMed

Das, Avizit; Rahman, Mohammad Imtiazur; Ferdous, Ahlan Sabah; Amin, Al-; Rahman, Mohammad Mahbubur; Nahar, Nilufar; Uddin, Md Aftab; Islam, Mohammad Riazul; Khan, Haseena

2017-01-01

Grammothele lineata, an endophyte isolated in our laboratory from jute (Corchorus olitorius acc. 2015) was found to be a substantial paclitaxel producer. Taxol and its related compounds, produced by this endophyte were extracted by growing the fungus in simple nutrient media (potato dextrose broth, PDB). Taxol was identified and characterized by different analytical techniques (TLC, HPLC, FTIR, LC-ESI-MS/MS) following its extraction by ethyl acetate. In PDB media, this fungus was found to produce 382.2 μgL-1 of taxol which is about 7.6 x103 fold higher than the first reported endophytic fungi, Taxomyces andreanae. The extracted taxol exhibited cytotoxic activity in an in vitro culture of HeLa cancer cell line. The fungal extract also exhibited antifungal and antibacterial activities against different pathogenic strains. This is the first report of a jute endophytic fungus harboring the capacity to produce taxol and also the first reported taxol producing species that belongs to the Basidiomycota phylum, so far unknown to be a taxol producer. These findings suggest that the fungal endophyte, Grammothele lineata can be an excellent source of taxol and can also serve as a potential species for chemical and genetic engineering to enhance further the production of taxol.

Amino Acid Sensor Kinase Gcn2 Is Required for Conidiation, Secondary Metabolism, and Cell Wall Integrity in the Taxol-Producer Pestalotiopsis microspora

PubMed Central

Wang, Dan; Akhberdi, Oren; Hao, Xiaoran; Yu, Xi; Chen, Longfei; Liu, Yanjie; Zhu, Xudong

2017-01-01

The canonical Gcn2/Cpc1 kinase in fungi coordinates the expression of target genes in response to amino acid starvation. To investigate its possible role in secondary metabolism, we characterized a gcn2 homolog in the taxol-producing fungus Pestalotiopsis microspora. Deletion of the gene led to severe physiological defects under amino acid starvation, suggesting a conserved function of gcn2 in amino acid sensing. The mutant strain Δgcn2 displayed retardation in vegetative growth. It generated dramatically fewer conidia, suggesting a connection between amino acid metabolism and conidiation in this fungus. Importantly, disruption of the gene altered the production of secondary metabolites by HPLC profiling. For instance, under amino acid starvation, the deletion strain Δgcn2 barely produced secondary metabolites including the known natural product pestalotiollide B. Even more, we showed that gcn2 played critical roles in the tolerance to several stress conditions. Δgcn2 exhibited a hypersensitivity to Calcofluor white and Congo red, implying a role of Gcn2 in maintaining the integrity of the cell wall. This study suggests that Gcn2 kinase is an important global regulator in the growth and development of filamentous fungi and will provide knowledge for the manipulation of secondary metabolism in P. microspora. PMID:29021785

Amino Acid Sensor Kinase Gcn2 Is Required for Conidiation, Secondary Metabolism, and Cell Wall Integrity in the Taxol-Producer Pestalotiopsis microspora.

PubMed

Wang, Dan; Akhberdi, Oren; Hao, Xiaoran; Yu, Xi; Chen, Longfei; Liu, Yanjie; Zhu, Xudong

2017-01-01

The canonical Gcn2/Cpc1 kinase in fungi coordinates the expression of target genes in response to amino acid starvation. To investigate its possible role in secondary metabolism, we characterized a gcn2 homolog in the taxol-producing fungus Pestalotiopsis microspora . Deletion of the gene led to severe physiological defects under amino acid starvation, suggesting a conserved function of gcn2 in amino acid sensing. The mutant strain Δgcn2 displayed retardation in vegetative growth. It generated dramatically fewer conidia, suggesting a connection between amino acid metabolism and conidiation in this fungus. Importantly, disruption of the gene altered the production of secondary metabolites by HPLC profiling. For instance, under amino acid starvation, the deletion strain Δgcn2 barely produced secondary metabolites including the known natural product pestalotiollide B. Even more, we showed that gcn2 played critical roles in the tolerance to several stress conditions. Δgcn2 exhibited a hypersensitivity to Calcofluor white and Congo red, implying a role of Gcn2 in maintaining the integrity of the cell wall. This study suggests that Gcn2 kinase is an important global regulator in the growth and development of filamentous fungi and will provide knowledge for the manipulation of secondary metabolism in P . microspora .

Baseline survey of root-associated microbes of Taxus chinensis (Pilger) Rehd.

PubMed

Zhang, Qian; Liu, Hongwei; Sun, Guiling; Wilson, Iain W; Wu, Jianqiang; Hoffman, Angela; Cheng, Junwen; Qiu, Deyou

2015-01-01

Taxol (paclitaxel) a diterpenoid is one of the most effective anticancer drugs identified. Biosynthesis of taxol was considered restricted to the Taxus genera until Stierle et al. discovered that an endophytic fungus isolated from Taxus brevifolia could independently synthesize taxol. Little is known about the mechanism of taxol biosynthesis in microbes, but it has been speculated that its biosynthesis may differ from plants. The microbiome from the roots of Taxus chinensis have been extensively investigated with culture-dependent methods to identify taxol synthesizing microbes, but not using culture independent methods.,Using bar-coded high-throughput sequencing in combination with a metagenomics approach, we surveyed the microbial diversity and gene composition of the root-associated microbiomefrom Taxus chinensis (Pilger) Rehd. High-throughput amplicon sequencing revealed 187 fungal OTUs which is higher than any previously reported fungal number identified with the culture-dependent method, suggesting that T. chinensis roots harbor novel and diverse fungi. Some operational taxonomic units (OTU) identified were identical to reported microbe strains possessing the ability to synthesis taxol and several genes previously associated with taxol biosynthesis were identified through metagenomics analysis.

Population regulation in a changing environment: Long-term changes in growth, condition and survival of sprat, Sprattus sprattus L. in the Bristol Channel, UK

NASA Astrophysics Data System (ADS)

Henderson, Peter A.; Henderson, Rowena C.

2017-02-01

Sprat, Sprattus sprattus, is the dominant pelagic species in British inshore and estuarine waters. Within the Bristol Channel the population is almost totally composed of fish < 3 years old with the adults overwintering in Bridgwater Bay. Sprat follow regular seasonal migrations and occasionally form huge aggregations which together generate considerable between sample variability. Using a 36-year monthly time series collected in the Bristol Channel since 1980, together with two periods of intensive daily and weekly sampling, sprat growth is shown to have declined almost linearly over the last 36 years coincident with increasing late summer-autumn seawater temperatures. Longevity has also declined, with age 3 + sprat > 140 mm standard length lost to the population by 1999. Further, adult condition, measured as the average weight of a 103 mm standard length adult, declined rapidly from 13.7 g in 2007 to 9 g in 2011. Despite these changes, which would have reduced age-specific fecundity, a sign-rank test showed abundance of adult sprat has shown no long-term trend and Bulmer's test indicates density-dependent regulation is operating. While sprat recruitment is shown to be responding to the sunspot cycle, the North Atlantic Oscillation and sea water temperature, the impact of these variables on adult population density is damped because of density-dependent regulation. The result is that sprat respond to environmental change with large changes in their growth and condition, but the adult abundance is constrained and shows no long-term trend. Recruitment was modelled by combining a Ricker curve with terms for the response of sprat to solar activity, the North Atlantic Oscillation and spring temperature. It is shown that the stock-recruitment relationship does not form a simple curve, but is bounded within a region in which the upper and lower constraints are defined by environmental conditions. Within this bounded region the population trajectory under differing

Birds of the Severn Estuary and Bristol Channel: their current status and key environmental issues.

PubMed

Burton, N H K; Musgrove, A J; Rehfisch, M M; Clark, N A

2010-01-01

The Severn Estuary and Bristol Channel encompass a number of designated sites supporting populations of waterbirds and seabirds that are of national or international importance, including the Severn Estuary and Burry Inlet Special Protection Areas (SPAs)/Ramsar Sites and Carmarthen Bay, the UK's first marine SPA. Here, we provide an overview of the present numbers and trends of the waterbirds and seabirds using these sites, updating previous reviews undertaken prior to these designations. We further provide a summary of the main issues that have affected the status of the area's bird populations. Declines in the numbers of waders on the Severn Estuary and the southwest over the last two decades have been linked to climate change. The Sea Empress oil-spill impacted both breeding seabirds and the wintering Common Scoters in Carmarthen Bay, though numbers of the latter recovered 3years after the spill. At the Burry Inlet, Oystercatcher numbers have fallen over the last 25years and considerable research has been undertaken into the conflict with cockle and mussel fisheries. A long-term study at Cardiff Bay, at the mouth of the Severn, revealed a significant impact on the survival of Redshanks following its impoundment and has helped to further understanding of responses of waterbirds to estuarine habitat loss. The potential impacts of the construction of a tidal power scheme on the Severn Estuary are also discussed. (c) 2009 Elsevier Ltd. All rights reserved.

Gastro-intestinal poisoning due to consumption of daffodils mistaken for vegetables at commercial markets, Bristol, United Kingdom.

PubMed

Matulkova, Petra; Gobin, Maya; Evans, Mark; Parkyn, Phil Charles; Palmer, Casey; Oliver, Isabel

2012-09-01

In February 2012, we investigated a cluster of people who presented at a local emergency department with sudden onset of vomiting after mistaken consumption of daffodils. We interviewed patients to collect information on daffodil purchase and consumption. With Local Authority we investigated points of sale to understand the source of confusion. We identified 11 patients (median age: 23 years, range 5-60 years, eight females) among Bristol (UK) residents of Chinese origin. The most commonly reported symptoms were vomiting (n = 11) and nausea (n = 9) that developed within 12 h of daffodil consumption. There were no hospitalisations or deaths. Patients were clustered in two family dinners and one party. Bunches of pre-bloom daffodil stalks were purchased in two stores of one supermarket chain, which displayed daffodils next to vegetables, not marked as non-edible. Patients cooked and consumed daffodils mistaking them for Chinese chives/onions. Gastro-intestinal poisoning should be considered in differential diagnoses of gastroenteritis. Multi-cultural societies are at risk of confusion between non-edible and edible plants. Supermarket presentation of daffodils may have contributed to mistaken consumption. We recommended explicit labelling and positioning of daffodils, away from produce. The supermarket chain introduced graphic 'non-edible' labels. No further patients were reported following action.

Seasonal hematology and serum chemistry of wild beluga whales (Delphinapterus leucas) in Bristol Bay, Alaska, USA.

PubMed

Norman, Stephanie A; Goertz, Caroline E C; Burek, Kathy A; Quakenbush, Lori T; Cornick, Leslie A; Romano, Tracy A; Spoon, Tracey; Miller, Woutrina; Beckett, Laurel A; Hobbs, Roderick C

2012-01-01

We collected blood from 18 beluga whales (Delphinapterus leucas), live-captured in Bristol Bay, Alaska, USA, in May and September 2008, to establish baseline hematologic and serum chemistry values and to determine whether there were significant differences in hematologic values by sex, season, size/age, or time during the capture period. Whole blood was collected within an average of 19 min (range=11-30 min) after the net was set for capture, and for eight animals, blood collection was repeated in a later season after between 80-100 min; all blood was processed within 12 hr. Mean hematocrit, chloride, creatinine, total protein, albumin, and alkaline phosphatase were significantly lower in May than they were in September, whereas mean corpuscular hemoglobin concentration, monocytes, phosphorous, magnesium, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltranspeptidase, and creatinine kinase were significantly higher. Mean total protein, white blood cell count, neutrophils, and lymphocytes were significantly higher early in the capture period than they were later. No significant differences in blood analyte values were noted between males and females. Using overall body length as a proxy for age, larger (older) belugas had lower white blood cell, lymphocyte, and eosinophil counts as well as lower sodium, potassium, and calcium levels but higher creatinine levels than smaller belugas. These data provide values for hematology and serum chemistry for comparisons with other wild belugas.

Diversity of endophytic fungi and screening of fungal paclitaxel producer from Anglojap yew, Taxus x media

PubMed Central

2013-01-01

Background Endophytic fungi represent underexplored resource of novel lead compounds and have a capacity to produce diverse class of plant secondary metabolites. Here we investigated endophytic fungi diversity and screening of paclitaxel-producing fungi from Taxus x media. Results Eighty-one endophytic fungi isolated from T. media were grouped into 8 genera based on the morphological and molecular identification. Guignardia and Colletotrichum were the dominant genera, whereas the remaining genera were infrequent groups. The genera Glomerella and Gibberella were first reported in Taxus. Three representative species of the distinct genera gave positive hits by molecular marker screening and were capable of producing taxol which were validated by HPLC-MS. Among these 3 taxol-producing fungi, the highest yield of taxol was 720 ng/l by Guignardia mangiferae HAA11 compared with those of Fusarium proliferatum HBA29 (240 ng/l) and Colletotrichum gloeosporioides TA67 (120 ng/l). This is the first report of taxol producer from Guignardia. Moreover, the lower similarities of ts and bapt between microbial and plant origin suggested that fungal taxol biosynthetic cluster might be repeatedly invented during evolution, nor horizontal gene transfer from Taxus species. Conclusions Taxol-producing endophytic fungi could be a fascinating reservoir to generate taxol-related drug lead and to elucidate the remained 5 unknown genes or the potential regulation mechanism in the taxol biosynthesis pathway. PMID:23537181

Baseline Survey of Root-Associated Microbes of Taxus chinensis (Pilger) Rehd

PubMed Central

Sun, Guiling; Wilson, Iain W.; Wu, Jianqiang; Hoffman, Angela; Cheng, Junwen; Qiu, Deyou

2015-01-01

Taxol (paclitaxel) a diterpenoid is one of the most effective anticancer drugs identified. Biosynthesis of taxol was considered restricted to the Taxus genera until Stierle et al. discovered that an endophytic fungus isolated from Taxus brevifolia could independently synthesize taxol. Little is known about the mechanism of taxol biosynthesis in microbes, but it has been speculated that its biosynthesis may differ from plants. The microbiome from the roots of Taxus chinensis have been extensively investigated with culture-dependent methods to identify taxol synthesizing microbes, but not using culture independent methods.,Using bar-coded high-throughput sequencing in combination with a metagenomics approach, we surveyed the microbial diversity and gene composition of the root-associated microbiomefrom Taxus chinensis (Pilger) Rehd. High-throughput amplicon sequencing revealed 187 fungal OTUs which is higher than any previously reported fungal number identified with the culture-dependent method, suggesting that T. chinensis roots harbor novel and diverse fungi. Some operational taxonomic units (OTU) identified were identical to reported microbe strains possessing the ability to synthesis taxol and several genes previously associated with taxol biosynthesis were identified through metagenomics analysis. PMID:25821956

Bristol Girls Dance Project Feasibility Trial: outcome and process evaluation results

PubMed Central

2012-01-01

Background Many adolescent girls do not engage in sufficient physical activity (PA). This study examined the feasibility of conducting a cluster randomized controlled trial (RCT) to evaluate an after-school dance program to increase PA among 11–12 year old girls in Bristol, UK. Methods Three-arm, cluster RCT. Three secondary schools were assigned to intervention arm. Intervention participants received a 9-week dance program with 2, 90-minute dance classes per week. Participants at 2 control schools received incentives for data collection. Participants at 2 additional control schools received incentives and a delayed dance workshop. Accelerometer data were collected at baseline (time 0), during the last week of the dance program (time 1) and 20 weeks after the start of the study (time 2). Weekly attendance, enjoyment and perceived exertion were assessed in intervention participants. Post-study qualitative work was conducted with intervention participants and personnel. Results 40.1% of girls provided consent to be in the study. The mean number of girls attending at least one dance session per week ranged from 15.4 to 25.9. There was greater number of participants for whom accelerometer data were collected in control arms. The mean attendance was 13.3 sessions (maximum = 18). Perceived exertion ratings indicated that the girls did not find the sessions challenging. The dance teachers reported that the program content would benefit from revisions including less creative task time, a broader range of dance genres and improved behavioral management policies. At time 2, the 95% confidence intervals suggest between 5 and 12 minutes more weekday MVPA in the intervention group compared with the control incentives only group, and between 6 minutes fewer and 1 minute more compared with the control incentives plus workshop group. Between 14 and 24 schools would be required to detect a difference of 10 minutes in mean weekday MVPA between intervention and control

Bristol girls dance project feasibility trial: outcome and process evaluation results.

PubMed

Jago, Russell; Sebire, Simon J; Cooper, Ashley R; Haase, Anne M; Powell, Jane; Davis, Laura; McNeill, Jade; Montgomery, Alan A

2012-07-02

Many adolescent girls do not engage in sufficient physical activity (PA). This study examined the feasibility of conducting a cluster randomized controlled trial (RCT) to evaluate an after-school dance program to increase PA among 11-12 year old girls in Bristol, UK. Three-arm, cluster RCT. Three secondary schools were assigned to intervention arm. Intervention participants received a 9-week dance program with 2, 90-minute dance classes per week. Participants at 2 control schools received incentives for data collection. Participants at 2 additional control schools received incentives and a delayed dance workshop. Accelerometer data were collected at baseline (time 0), during the last week of the dance program (time 1) and 20 weeks after the start of the study (time 2). Weekly attendance, enjoyment and perceived exertion were assessed in intervention participants. Post-study qualitative work was conducted with intervention participants and personnel. 40.1% of girls provided consent to be in the study. The mean number of girls attending at least one dance session per week ranged from 15.4 to 25.9. There was greater number of participants for whom accelerometer data were collected in control arms. The mean attendance was 13.3 sessions (maximum=18). Perceived exertion ratings indicated that the girls did not find the sessions challenging. The dance teachers reported that the program content would benefit from revisions including less creative task time, a broader range of dance genres and improved behavioral management policies. At time 2, the 95% confidence intervals suggest between 5 and 12 minutes more weekday MVPA in the intervention group compared with the control incentives only group, and between 6 minutes fewer and 1 minute more compared with the control incentives plus workshop group. Between 14 and 24 schools would be required to detect a difference of 10 minutes in mean weekday MVPA between intervention and control groups. It is possible to recruit 11

Satraplatin: BMS 182751, BMY 45594, JM 216.

PubMed

2007-01-01

Satraplatin [BMS 182751, BMY 45594, JM 216] belongs to a series of orally-active platinum compounds with anticancer activity. It was jointly originated by Bristol-Myers Squibb, Johnson Matthey and the Institute of Cancer Research in the UK; however, Johnson Matthey has since ceased involvement with drug development. Subsequently, the agent has been licensed to and is under development with GPC Biotech, Pharmion and Spectrum Pharmaceuticals. Clinical trials are underway to evaluate satraplatin among patients with different tumour types, including prostate, breast, cervical and lung cancers. The compound is under regulatory review with the US FDA for the treatment of hormone-refractory prostate cancer. NeoTherapeutics (now Spectrum Pharmaceuticals) granted GPC Biotech an exclusive worldwide licence to develop and market satraplatin in October 2002. Under the terms of the agreement, GPC Biotech is fully funding development costs and commercialisation requirements for the drug. The deal also involves GPC Biotech paying a signing fee, milestone and royalty payments. Spectrum is a member of a joint development committee headed by GPC Biotech to govern development of satraplatin. Previously in October 2001, NeoOncoRx (Spectrum Pharmaceuticals) gained the rights to develop and market the compound worldwide. In December 2005, GPC Biotech and Pharmion Corporation entered into a co-development and license agreement for satraplatin. Under the agreement terms, Pharmion has exclusive commercialisation rights for Europe, Turkey, the Middle East, Australia and New Zealand, while GPC Biotech retains rights to North America and all other territories. Pharmion made an upfront payment of $US37.1 million to GPC Biotech, which included reimbursement for past clinical development costs plus funding for ongoing and certain clinical development activities to be jointly conducted by the companies. In addition, both parties will pursue a joint development plan for satraplatin in a variety of

Bristol girls dance project (BGDP): protocol for a cluster randomised controlled trial of an after-school dance programme to increase physical activity among 11-12 year old girls.

PubMed

Jago, Russell; Edwards, Mark J; Sebire, Simon J; Cooper, Ashley R; Powell, Jane E; Bird, Emma L; Simon, Joanne; Blair, Peter S

2013-10-24

Many children do not meet current UK physical activity (PA) guidelines. Girls are less active than boys throughout childhood, and the age-related decline in PA, particularly from early adolescence, is steeper for girls than for boys. Dance is the favourite form of PA among UK secondary school aged girls. Delivering dance sessions after school could make a significant contribution to girls' PA. Therefore, after-school dance sessions may be an appropriate and cost-effective activity through which adolescent girls' PA levels can be increased. Two-arm cluster randomised control trial and economic evaluation conducted in 18 secondary schools across the greater Bristol area. All Year 7 girls in participating schools will receive a 'taster' dance session and subsequently be invited to participate in the project. There is space for up to 33 girls to participate in each school. Schools will be randomly assigned in equal numbers to intervention or control arms after baseline data has been collected. The nine intervention schools will receive a 20 week after-school dance-based intervention, consisting of 40 × 75 minute sessions, delivered by external dance instructors. Control schools will not receive the dance intervention. All measures will be assessed at baseline (time 0), at the end of the intervention period (time 1) and six months after the intervention has ended (time 2). Our primary interest is to determine the effectiveness and cost-effectiveness of the intervention to affect the objectively-assessed (accelerometer) mean weekday minutes of moderate-to-vigorous PA (MVPA) accumulated by Year 7 girls one year after the baseline measurement (time 2). This paper describes the protocol for the Bristol Girls Dance Project cluster randomized controlled trial and economic evaluation, which is attempting to increase MVPA among Year 7 girls in UK secondary schools. ISRCTN52882523.

The Gα1-cAMP signaling pathway controls conidiation, development and secondary metabolism in the taxol-producing fungus Pestalotiopsis microspora.

PubMed

Yu, Xi; Liu, Heng; Niu, Xueliang; Akhberdi, Oren; Wei, Dongsheng; Wang, Dan; Zhu, Xudong

2017-10-01

G-protein-mediated signaling pathways regulate fungal morphogenesis, development and secondary metabolism. In this study, we report a gene, pgα1, that putatively encodes the α-subunit of a group I G protein in Pestalotiopsis microspora NK17, which is known to produce various secondary metabolites, including the antitumor drug taxol and pestalotiollide B (PB). Mutants of pgα1 showed retarded vegetative growth, aging of the mycelium, premature conidiation, deformed conidia, significantly increased melanin production, and a sharp decrease in PB production. The introduction of extra copies of pgα1 led to a different phenotype that was characterized by enhanced production of PB. qRT-PCR revealed that the expression of pks1, which encodes melanin polyketide synthase, an enzyme that is involved in 1, 8-dihydroxynaphthalene (DHN) melanin biosynthesis, was up regulated by 55-fold in the absence of pgα1. Changes in conidiation and PB production in pgα1 mutants were able to be restored by the addition of exogenous cAMP. The deficiencies of PB production and conidiation in Δpgα1 were not able to be rescued by deletion or overexpression of a previously reported histone deacetylase gene (hid1), suggesting that pgα1 is able to override the effect of hid1 on PB production and conidiation. Our results suggested that the G protein-cAMP pathway plays a critical role in vegetative growth as well as in asexual development of P. microspora. Copyright © 2017 Elsevier GmbH. All rights reserved.

Sea level rise in the Severn Estuary and Bristol Channel and impacts of a Severn Barrage

NASA Astrophysics Data System (ADS)

Ahmadian, Reza; Olbert, Agnieszka I.; Hartnett, Michael; Falconer, Roger A.

2014-05-01

Many research projects in recent years have focused on marine renewable energy devices and structures due to the growing interest in marine renewable energy. These devices and structures have very different life spans. Schemes such as the Severn Barrage in the UK, as originally proposed by the Severn Tidal Power Group (STPG), would be the largest tidal renewable energy generation project in the world and would be operational for well over a century if built. Due to the long working life of some of these marine renewable energy schemes, it is important to study the impacts of climate change on such schemes, and particularly sea level rise. This study focuses on investigating the impacts of sea level rise due to climate change on the largest macro-tidal estuary in the UK, namely the Severn Estuary and Bristol Channel, and the alterations of the impacts and the performance of the Severn Barrage as a result of climate change. A hierarchy of computer models was implemented to identify the more localised impacts of climate change in the region of the study. Moreover, the potential benefits of the barrage on reducing flood risk, as well as the impact of climate change and the barrage on intertidal mudflats were investigated. The model predictions showed that the barrage would reduce flood risk due to the sea level rise. Furthermore, annual power output and the initial reduction in flood risk of the barrage would not be affected by sea level rise.

Helminth communities of three sympatric species of shorebirds (Charadrii) from four summer seasons at Bristol Bay, Alaska.

PubMed

Canaris, Albert G; Kinsella, John M

2007-06-01

Helminth communities in sympatric black turnstones (Arenaria melanocephala), ruddy turnstones (Arenaria interpres), and dunlin (Calidris alpina) were examined over 4 summers in Bristol Bay, Alaska. The compound community, made up of component communities of all 3 species of hosts for 4 summer seasons (n=164), consisted of 43 helminth species, with cestodes, especially Anomotaenia clavigera, accounting for 47% of the helminth species and 95% of the abundance. The black turnstone had significantly higher species richness and abundance than either the ruddy turnstone or dunlin. The congeneric black and ruddy turnstone component communities were the most similar, and the dunlin's was the least similar. New helminth species continued to be acquired in all 3 host species during years 2 to 4. There was no significant difference for abundance among sample years for each of the 3 species of host. The 3 component communities all included a predictable suite of helminths with 1 dominant species and 4 to 5 associates, a large number of less-predictable species, and a greater prevalence and abundance of cestode species. Consistencies over time included high diversity, low evenness, low species richness (<5), and continued recruitment of small numbers of helminth species with low prevalence and abundance. There was minimal circulation of helminth species between the dunlin and the 2 turnstone species, indicating a considerable degree of specialization, particularly among species of cestodes.

Commentary on: "Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): A multicentre, randomised, double-blind, phase 3 trial." Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, Krainer M, Houede N, Santos R, Mahammedi H, Ng S, Maio M, Franke FA, Sundar S, Agarwal N, Bergman AM, Ciuleanu TE, Korbenfeld E, Sengeløv L, Hansen S, Logothetis C, Beer TM, McHenry MB, Gagnier P, Liu D, Gerritsen WR, CA184-043 Investigators. Departments of Urology and Immunology and Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, MN, USA, Electronic address: kwon.eugene@mayo.edu; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and Brady Urological Institute, Baltimore, MD, USA; Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA; Institut Gustave Roussy, University of Paris-Sud, Villejuif, France; Institut Gustave Roussy, Villejuif, France; VU University Medical Centre, Amsterdam, Netherlands; Vienna General Hospital, Medical University Vienna, Vienna, Austria; Institut Bergonié, Bordeaux, France; CHU Caremeau, Nimes, France; Centro Médico Austral, Buenos Aires, Argentina; Centre Jean Perrin, Clermont-Ferrand, France; St John of God Hospital, Subiaco, WA, Australia; University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy; Hospital de Caridade de Ijuí, Ijuí, Brazil; Nottingham University Hospital, Nottingham, UK; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; Netherlands Cancer Institute and Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands; Institute of Oncology Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania; Hospital Británico de Buenos Aires, Buenos Aires, Argentina; Herlev Hospital, Herlev, Denmark; Odense University Hospital, Odense, Denmark; University of Texas MD Anderson Cancer Center, Houston,

PubMed

Trump, Donald

2016-05-01

-4 adverse events were immune-related, occurring in 101 (26%) patients in the ipilimumab group and 11 (3%) of patients in the placebo group. The most frequent grade 3-4 adverse events included diarrhoea (64 [16%] of 393 patients in the ipilimumab group vs seven [2%] of 396 in the placebo group), fatigue (40 [11%] vs 35 [9%]), anaemia (40 [10%] vs 43 [11%]), and colitis (18 [5%] vs 0). Four (1%) deaths occurred because of toxic effects of the study drug, all in the ipilimumab group. Although there was no significant difference between the ipilimumab group and the placebo group in terms of overall survival in the primary analysis, there were signs of activity with the drug that warrant further investigation. Bristol-Myers Squibb. Copyright © 2016 Elsevier Inc. All rights reserved.

Promising new developments in cancer chemotherapy.

PubMed

Ferrante, K; Winograd, B; Canetta, R

1999-01-01

attractive target for intervention in several aspects of tumor progression. Local production of MMPs with subsequent degradation of the extracellular matrix is implicated in supporting tumor growth, invasion, and angiogenesis. The development of orally active, nontoxic MMP inhibitors is critical since these compounds will likely require chronic administration in conjunction with other therapies. Oncogenes and tumor suppressor genes are appealing targets for therapy since they are thought to be responsible for a significant number of cancers. Mutations in the Ras oncogene occur with great frequency in a number of human cancers including lung, pancreas, and colon cancer. Clinical development of potent and selective inhibitors of farnesyltransferase, the Ras-processing enzyme, is ongoing. These compounds uncouple Ras activity, affect tumor growth, and have demonstrated significant antitumor activity against experimental models of human cancer. The exciting compounds and novel therapeutic approaches currently under investigation by Bristol-Myers Squibb Pharmaceutical Research Institute offer great potential as effective cancer chemotherapy agents for the near future.

Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial.

PubMed

Younes, Anas; Santoro, Armando; Shipp, Margaret; Zinzani, Pier Luigi; Timmerman, John M; Ansell, Stephen; Armand, Philippe; Fanale, Michelle; Ratanatharathorn, Voravit; Kuruvilla, John; Cohen, Jonathon B; Collins, Graham; Savage, Kerry J; Trneny, Marek; Kato, Kazunobu; Farsaci, Benedetto; Parker, Susan M; Rodig, Scott; Roemer, Margaretha G M; Ligon, Azra H; Engert, Andreas

2016-09-01

common drug-related grade 3 or 4 adverse events were neutropenia (four [5%] patients) and increased lipase concentrations (four [5%]). The most common serious adverse event (any grade) was pyrexia (three [4%] patients). Three patients died during the study; none of these deaths were judged to be treatment related. Nivolumab resulted in frequent responses with an acceptable safety profile in patients with classical Hodgkin's lymphoma who progressed after autologous stem-cell transplantation and brentuximab vedotin. Therefore, nivolumab might be a new treatment option for a patient population with a high unmet need. Ongoing follow-up will help to assess the durability of response. Bristol-Myers Squibb. Copyright © 2016 Elsevier Ltd. All rights reserved.

Randomised controlled trial of effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux: Bristol helicobacter project

PubMed Central

Harvey, Richard F; Lane, J Athene; Murray, Liam J; Harvey, Ian M; Donovan, Jenny L; Nair, Prakash

2004-01-01

Objectives To investigate the effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux. Design Cross sectional study, followed by a randomised placebo controlled trial. Setting Seven general practices in Bristol, England. Participants 10 537 people, aged 20-59 years, with and without H pylori infection (determined by the 13C-urea breath test). Main outcome measures Prevalence of heartburn and gastro-oesophageal acid reflux at baseline and two years after treatment to eradicate H pylori infection. Results At baseline, H pylori infection was associated with increased prevalence of heartburn (odds ratio 1.14, 95% confidence interval 1.05 to 1.23) but not reflux (1.05, 0.97 to 1.14). In participants with H pylori infection, active treatment had no effect on the overall prevalence of heartburn (0.99, 0.88 to 1.12) or reflux (1.04, 0.91 to 1.19) and did not improve pre-existing symptoms of heartburn or reflux. Conclusions H pylori infection is associated with a slightly increased prevalence of heartburn but not reflux. Treatment to eradicate H pylori has no net benefit in patients with heartburn or gastro-oesophageal reflux. PMID:15126313

[Relationships between Myers-Briggs Type Indicator (MBTI) psychological type and marital satisfaction, divorce proneness, positive affect, and conflict regulation in clinic couples].

PubMed

Kong, Seong Sook

2010-06-01

The purpose of the study was to investigate the relationships between the Myers-Briggs Type Indicator (MBTI) psychological type and marital satisfaction, divorce proneness, positive affect, and conflict regulation in couple visiting a clinic. Couples (n=62) who visited "M" couple clinic participated in the study. Data were collected from March to June 2009 using the Marital Satisfaction Scale, Marital Status Inventory, Positive Affect Inventory, and Conflict Regulation Inventory. The couples showed no significant differences in marital satisfaction, positive affect, and conflict regulation according to similarities between spouses in MBTI types. However, they showed significant differences in divorce proneness of husband according to a similarity in the Sensing/Intuition indicator. They also showed significant differences in divorce proneness, positive affect, and conflict regulation between the couples for ISTJ (Introversion, Sensing, Thinking, Judging) or ESTJ (Extraversion, Sensing, Thinking, Judging) types compared to other couples. When nurses counsel couples, they should understand that differences in psychological type between spouses affects their marital relationship. In addition, nurses should educate couples on the characteristics of each type according to the couple's types and help them to understand each other, especially for couples where one spouse is the ISTJ/ESTJ type. These interventions will improve marital satisfaction and prevent the divorce in these couples.

Target-oriented discovery of a new esterase-producing strain Enterobacter sp. ECU1107 for whole cell-catalyzed production of (2S,3R)-3-phenylglycidate as a chiral synthon of Taxol.

PubMed

Zhou, Dong-Jie; Pan, Jiang; Yu, Hui-Lei; Zheng, Gao-Wei; Xu, Jian-He

2013-07-01

A new strain, Enterobacter sp. ECU1107, was identified among over 200 soil isolates using a two-step screening strategy for the enantioselective synthesis of (2S,3R)-3-phenylglycidate methyl ester (PGM), a key intermediate for production of a potent anticancer drug Taxol®. An organic-aqueous biphasic system was employed to reduce spontaneous hydrolysis of the substrate PGM and isooctane was found to be the most suitable organic solvent. The temperature and pH optima of the whole cell-mediated bioreaction were 40 °C and 6.0, respectively. Under these reaction conditions, the enantiomeric excess (ee(s)) of (2S,3R)-PGM recovered was greater than 99 % at approximately 50 % conversion. The total substrate loading in batch reaction could reach 600 mM. By using whole cells of Enterobacter sp. ECU1107, (2S,3R)-PGM was successfully prepared in decagram scale in a 1.0-l mechanically stirred reactor, affording the chiral epoxy ester in >99 % ee s and 43.5 % molar yield based on the initial load of racemic substrate.

Test-retest reliability and smallest detectable change of the Bristol Impact of Hypermobility (BIoH) questionnaire.

PubMed

Palmer, S; Manns, S; Cramp, F; Lewis, R; Clark, E M

2017-12-01

The Bristol Impact of Hypermobility (BIoH) questionnaire is a patient-reported outcome measure developed in conjunction with adults with Joint Hypermobility Syndrome (JHS). It has demonstrated strong concurrent validity with the Short Form-36 (SF-36) physical component score but other psychometric properties have yet to be established. This study aimed to determine its test-retest reliability and smallest detectable change (SDC). A test-retest reliability study. Participants were recruited from the Hypermobility Syndromes Association, a patient organisation in the United Kingdom. Recruitment packs were sent to 1080 adults who had given permission to be contacted about research. BIoH and SF-36 questionnaires were administered at baseline and repeated two weeks later. An 11-point global rating of change scale (-5 to +5) was also administered at two weeks. Test-retest analysis and calculation of the SDC was conducted on 'stable' patients (defined as global rating of change -1 to +1). 462 responses were received. 233 patients reported a 'stable' condition and were included in analysis (95% women; mean (SD) age 44.5 (13.9) years; BIoH score 223.6 (54.0)). The BIoH questionnaire demonstrated excellent test-retest reliability (ICC 0.923, 95% CI 0.900-0.940). The SDC was 42 points (equivalent to 19% of the mean baseline score). The SF-36 physical and mental component scores demonstrated poorer test-retest reliability and larger SDCs (as a proportion of the mean baseline scores). The results provide further evidence of the potential of the BIoH questionnaire to underpin research and clinical practice for people with JHS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Paclitaxel-resistant HeLa cells have up-regulated levels of reactive oxygen species and increased expression of taxol resistance gene 1.

PubMed

Bi, Wenxiang; Wang, Yuxia; Sun, Gaoying; Zhang, Xiaojin; Wei, Yongqing; Li, Lu; Wang, Xiaoyuan

2014-07-01

This study is to establish a paclitaxel (PTX)-resistant human cervical carcinoma HeLa cell line (HeLa/PTX) and to investigate its redox characteristics and the expression of taxol resistance gene 1 (Txr1). HeLa cells were treated with PTX and effects of PTX on cell proliferation were detected through cell counting and the MTT assay. Levels of cellular reactive oxygen species (ROS), reduced glutathione (GSH), and oxidized glutathione (GSSG) as well as the ratio of GSH to GSSG were measured by the 2,7-difluorescein diacetate (DCFH-DA) method and the 5,5'dithiobis(2-nitrobenzoic acid) (DTNB) method. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined by the nitrite formation method, the molybdate colorimetric method, and the DTNB colorimetric method, respectively. The level of Txr1 mRNA was determined by real-time PCR. Compared with the regular HeLa cells, HeLa/PTX cells were larger in size and had more cytoplasmic granules. The population doubling time for HeLa/PTX cells was 1.32 times of that of HeLa cells (P<0.01). HeLa/PTX cells showed stronger resistance to PTX than HeLa cells with a resistance index of 122.69. HeLa/PTX cells had higher levels of ROS (P<0.01) and Txr1 mRNA (P<0.01), lower level of GSH (P < 0.05), and lower activities of SOD (P<0.01) and GPx (P < 0.05) than HeLa cells. HeLa/PTX cells, with higher levels of ROS and Txr1 mRNA expression, are more resistant to PTX than HeLa cells.

The career intentions, work-life balance and retirement plans of dental undergraduates at the University of Bristol.

PubMed

Puryer, J; Patel, A

2016-02-26

Aim To investigate the career intentions, work-life balance and retirement plans of dental undergraduates at the University of Bristol in 2015.Method Cross-sectional survey of 210 clinical undergraduates using an anonymous self-report questionnaire.Results The response rate was 79%. The majority (81.7%) were 'satisfied' or 'extremely satisfied' with their choice of career. The majority (78.7%) felt men and women are equally likely to succeed in dentistry, although 42.9% felt men had an advantage over women with regards to career success. The majority (81.6%) intend on working within general practice, 11.3% within hospital dental services and 2.1% within community dental services. The majority (70.5%) intend to specialise within dentistry. Only 1.8% of participants intend on providing only National Health Service (NHS) dental treatment whereas the 86.5% would provide both NHS and private dental treatment. Fifteen years after qualifying, 52.2% plan to work part-time, and 37.8% intend on retiring at the age of 60 or below. The majority (86.6%) felt that childcare should be shared equally between both parents. Female students intend to take more time out of their career to concentrate on childcare and felt that having a child would affect their career more than males.Conclusion The anticipated career plans, work-life balance and retirement plans of undergraduates change over time, and further research should be carried out to monitor future career intentions of dental students in order to help with dental workforce planning.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Xiao-han; Deng, Suo; Li, Meng

Highlights: Black-Right-Pointing-Pointer HB-EGF over-expression in A2780/Taxol, A2780/CDDP cells and the matched xenografts. Black-Right-Pointing-Pointer CRM197 induces enhanced apoptosis in A2780/Taxol and A2780/CDDP cells. Black-Right-Pointing-Pointer CRM197 arrests A2780/Taxol and A2780/CDDP cells at G0/G1 phase. Black-Right-Pointing-Pointer CRM197 suppressed the A2780/Taxol and A2780/CDDP growth of xenografts. -- Abstract: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. Cross-reacting material 197 (CRM197), a specific HB-EGF inhibitor, has been proven to represent possible chemotherapeutic agent for ovarian cancer. However, the effect of CRM197 on the resistant ovarian carcinoma cells has not been sufficiently elucidated. Here, we found that HB-EGF wasmore » over-expressed in a paclitaxel-resistant human ovarian carcinoma cell line (A2780/Taxol) and a cisplatin-resistant cell line (A2780/CDDP), as well as the xenograft mouse tissue samples with these cells. To investigate the possible significance of the HB-EGF over-expression in A2780/Taxol and A2780/CDDP cells, we inhibited HB-EGF expression by CRM197 to investigate the effect of CRM197 treatment on these cells. We observed that CRM197 significantly induced anti-proliferative activity in a dose-dependent manner with the cell-cycle arrest at the G0/G1 phase and enhanced apoptosis in A2780/Taxol and A2780/CDDP cells. The sensitive ovarian carcinoma parental cell line (A2780), A2780/Taxol and A2780/CDDP cells formed tumors in nude mice, and enhanced tumorigenicity was observed in drug-resistant tumors. Furthermore, we observed that CRM197 significantly suppressed the growth of drug-resistant ovarian cancer xenografts in vivo (p < 0.001). These results suggest that CRM197 as an HB-EGF-targeted agent has potent anti-tumor activity in paclitaxel- and cisplatin-resistant ovarian cancer which over-express HB-EGF.« less

Geochemical evolution of Jurassic diorites from the Bristol Lake region, California, USA, and the role of assimilation

USGS Publications Warehouse

Young, E.D.; Wooden, J.L.; Shieh, Y.-N.; Farber, D.

1992-01-01

Late Jurassic dioritic plutons from the Bristol Lake region of the eastern Mojave Desert share several geochemical attributes with high-alumina basalts, continental hawaiite basalts, and high-K are andesites including: high K2O concentrations; high Al2O3 (16-19 weight %); elevated Zr/TiO2; LREE (light-rare-earth-element) enrichment (La/YbCN=6.3-13.3); and high Nb. Pearce element ratio analysis supported by petrographic relations demonstrates that P, Hf, and Zr were conserved during differentiation. Abundances of conserved elements suggest that dioritic plutons from neighboring ranges were derived from similar parental melts. In the most voluminous suite, correlated variations in elemental concentrations and (87Sr/86Sr)i indicate differentiation by fractional crystallization of hornblende and plagioclase combined with assimilation of a component characterized by abundant radiogenic Sr. Levenberg-Marquardt and Monte Carlo techniques were used to obtain optimal solutions to non-linear inverse models for fractional crystallization-assimilation processes. Results show that the assimilated material was chemically analogous to lower crustal mafic granulites and that the mass ratio of contaminant to parental magma was on the order of 0.1. Lack of enrichment in 18O with differentiation is consistent with the model results. Elemental concentrations and O, Sr, and Nd isotopic data point to a hydrous REE-enriched subcontinental lithospheric source similar to that which produced some Cenozoic continental hawaiites from the southern Cordillera. Isotopic compositions of associated granitoids suggest that partial melting of this subcontinental lithosphere may have been an important process in the development of the Late Jurassic plutonic arc of the eastern Mojave Desert. ?? 1992 Springer-Verlag.

Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial

PubMed Central

Kwon, Eugene D; Drake, Charles G; Scher, Howard I; Fizazi, Karim; Bossi, Alberto; van den Eertwegh, Alfons J M; Krainer, Michael; Houede, Nadine; Santos, Ricardo; Mahammedi, Hakim; Ng, Siobhan; Maio, Michele; Franke, Fabio A; Sundar, Santhanam; Agarwal, Neeraj; Bergman, Andries M; Ciuleanu, Tudor E; Korbenfeld, Ernesto; Sengeløv, Lisa; Hansen, Steinbjorn; Logothetis, Christopher; Beer, Tomasz M; McHenry, M Brent; Gagnier, Paul; Liu, David; Gerritsen, Winald R

2015-01-01

beyond 12 months was 0·60 (0·43–0·86). The most common grade 3–4 adverse events were immune-related, occurring in 101 (26%) patients in the ipilimumab group and 11 (3%) of patients in the placebo group. The most frequent grade 3–4 adverse events included diarrhoea (64 [16%] of 393 patients in the ipilimumab group vs seven [2%] of 396 in the placebo group), fatigue (40 [11%] vs 35 [9%]), anaemia (40 [10%] vs 43 [11%]), and colitis (18 [5%] vs 0). Four (1%) deaths occurred because of toxic effects of the study drug, all in the ipilimumab group. Interpretation Although there was no significant difference between the ipilimumab group and the placebo group in terms of overall survival in the primary analysis, there were signs of activity with the drug that warrant further investigation. Funding Bristol-Myers Squibb. PMID:24831977

Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial.

PubMed

Kwon, Eugene D; Drake, Charles G; Scher, Howard I; Fizazi, Karim; Bossi, Alberto; van den Eertwegh, Alfons J M; Krainer, Michael; Houede, Nadine; Santos, Ricardo; Mahammedi, Hakim; Ng, Siobhan; Maio, Michele; Franke, Fabio A; Sundar, Santhanam; Agarwal, Neeraj; Bergman, Andries M; Ciuleanu, Tudor E; Korbenfeld, Ernesto; Sengeløv, Lisa; Hansen, Steinbjorn; Logothetis, Christopher; Beer, Tomasz M; McHenry, M Brent; Gagnier, Paul; Liu, David; Gerritsen, Winald R

2014-06-01

common grade 3-4 adverse events were immune-related, occurring in 101 (26%) patients in the ipilimumab group and 11 (3%) of patients in the placebo group. The most frequent grade 3-4 adverse events included diarrhoea (64 [16%] of 393 patients in the ipilimumab group vs seven [2%] of 396 in the placebo group), fatigue (40 [11%] vs 35 [9%]), anaemia (40 [10%] vs 43 [11%]), and colitis (18 [5%] vs 0). Four (1%) deaths occurred because of toxic effects of the study drug, all in the ipilimumab group. Although there was no significant difference between the ipilimumab group and the placebo group in terms of overall survival in the primary analysis, there were signs of activity with the drug that warrant further investigation. Bristol-Myers Squibb. Copyright © 2014 Elsevier Ltd. All rights reserved.

AMCP Partnership Forum: Advancing Value-Based Contracting.

PubMed

2017-11-01

of a VBC for facilitating discussion with key policy makers and regulators; (b) determine strategies for advancing the development and utilization of performance benchmarks; (c) identify best practices in evaluating, implementing, and monitoring VBCs; and (d) develop action plans to mitigate legal and regulatory barriers to VBCs. More than 30 national and regional health care leaders representing health plans, integrated delivery systems, pharmacy benefit managers, employers, data and analytics companies, and biopharmaceutical companies participated. Speakers, panelists, and stakeholders attended the forum and explored the current environment for VBCs, identified challenges to the expansion of VBCs, offered potential solutions to those challenges, and developed an action plan for addressing selected challenges. The forum recommendations will be used by AMCP to establish a coalition of organizations to seek broader acceptance of VBCs in the marketplace and by policymakers. The recommendations will also help AMCP provide tools and resources to stakeholders in managing VBCs. This Partnership Forum was supported by Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, the National Pharmaceutical Council, Novo Nordisk, Premier, the Pharmaceutical Research and Manufacturers of America, RxAnte, Takeda, and Xcenda.

Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial.

PubMed

Easton, J Donald; Lopes, Renato D; Bahit, M Cecilia; Wojdyla, Daniel M; Granger, Christopher B; Wallentin, Lars; Alings, Marco; Goto, Shinya; Lewis, Basil S; Rosenqvist, Mårten; Hanna, Michael; Mohan, Puneet; Alexander, John H; Diener, Hans-Christoph

2012-06-01

and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA. The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. Bristol-Myers Squibb and Pfizer. Copyright © 2012 Elsevier Ltd. All rights reserved.

Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study.

PubMed

Long, Georgina V; Atkinson, Victoria; Lo, Serigne; Sandhu, Shahneen; Guminski, Alexander D; Brown, Michael P; Wilmott, James S; Edwards, Jarem; Gonzalez, Maria; Scolyer, Richard A; Menzies, Alexander M; McArthur, Grant A

2018-05-01

(46%; 95% CI 29-63) of 35 patients in cohort A, five (20%; 7-41) of 25 in cohort B, and one (6%; 0-30) of 16 in cohort C. Intracranial complete responses occurred in six (17%) patients in cohort A, three (12%) in cohort B, and none in cohort C. Treatment-related adverse events occurred in 34 (97%) of 35 patients in cohort A, 17 (68%) of 25 in cohort B, and eight (50%) of 16 in cohort C. Grade 3 or 4 treatment-related adverse events occurred in 19 (54%) patients in cohort A, four (16%) in cohort B, and two (13%) in cohort C. No treatment-related deaths occurred. Nivolumab combined with ipilimumab and nivolumab monotherapy are active in melanoma brain metastases. A high proportion of patients achieved an intracranial response with the combination. Thus, nivolumab combined with ipilimumab should be considered as a first-line therapy for patients with asymptomatic untreated brain metastases. Melanoma Institute Australia and Bristol-Myers Squibb. Copyright © 2018 Elsevier Ltd. All rights reserved.

Atom-probe tomography and transmission electron microscopy of the kamacite-taenite interface in the fast-cooled Bristol IVA iron meteorite

NASA Astrophysics Data System (ADS)

Rout, Surya S.; Heck, Philipp R.; Isheim, Dieter; Stephan, Thomas; Zaluzec, Nestor J.; Miller, Dean J.; Davis, Andrew M.; Seidman, David N.

2017-12-01

We report the first combined atom-probe tomography (APT) and transmission electron microscopy (TEM) study of a kamacite-tetrataenite (K-T) interface region within an iron meteorite, Bristol (IVA). Ten APT nanotips were prepared from the K-T interface with focused ion beam scanning electron microscopy (FIB-SEM) and then studied using TEM followed by APT. Near the K-T interface, we found 3.8 ± 0.5 wt% Ni in kamacite and 53.4 ± 0.5 wt% Ni in tetrataenite. High-Ni precipitate regions of the cloudy zone (CZ) have 50.4 ± 0.8 wt% Ni. A region near the CZ and martensite interface has <10 nm sized Ni-rich precipitates with 38.4 ± 0.7 wt% Ni present within a low-Ni matrix having 25.5 ± 0.6 wt% Ni. We found that Cu is predominantly concentrated in tetrataenite, whereas Co, P, and Cr are concentrated in kamacite. Phosphorus is preferentially concentrated along the K-T interface. This study is the first precise measurement of the phase composition at high spatial resolution and in 3-D of the K-T interface region in a IVA iron meteorite and furthers our knowledge of the phase composition changes in a fast-cooled iron meteorite below 400 °C. We demonstrate that APT in conjunction with TEM is a useful approach to study the major, minor, and trace elemental composition of nanoscale features within fast-cooled iron meteorites.

Encapsulation of anticancer drug and magnetic particles in biodegradable polymer nanospheres

NASA Astrophysics Data System (ADS)

Koneracká, M.; Múčková, M.; Závišová, V.; Tomašovičová, N.; Kopčanský, P.; Timko, M.; Juríková, A.; Csach, K.; Kavečanský, V.; Lancz, G.

2008-05-01

In this study, we have prepared PLGA (poly-D,L-lactide-co-glycolide) nanospheres loaded with biocompatible magnetic fluid and anticancer drug taxol by a modified nanoprecipitation technique and investigated their magnetic properties. A magnetic fluid, MF-PEG, with a biocompatible layer of polyethylene glycol (PEG), was chosen as a magnetic carrier. The PLGA, whose copolymer ratio of D,L-lactide to glycolide is 85:15, was utilized as a capsulation material. Taxol, as an important anticancer drug, was chosen for its significant role against a wide range of tumours. The morphology and particle size distributions of the prepared nanospheres were investigated by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and showed a spherical shape of prepared nanospheres with size 250 nm. Infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetry (TGA) analysis confirmed incorporation of magnetic particles and taxol into the PLGA polymer. The results showed good encapsulation with magnetite content 21.5 wt% and taxol 0.5 wt%. Magnetic properties of magnetic fluids and taxol within the PLGA polymer matrix were investigated by SQUID magnetometry from 4.2 to 300 K. The SQUID measurements showed superparamagnetism of prepared nanospheres with a blocking temperature of 160 K and saturation magnetization 1.4 mT.

Can Verbally Aggressive Messages in the Instructor-Student Relationship Be Constructive?

ERIC Educational Resources Information Center

Martin, Matthew M.; Dunleavy, Katie Neary; Kennedy-Lightsey, Carrie

2010-01-01

How instructors communicate with their students impacts their students' instructional attitudes, motivations, and behaviors. Verbal aggression in the classroom often leads to negative instructional and relational outcomes (Infante, 1995; Myers, 2001; Myers & Knox, 2000; Myers & Rocca, 2001). This study investigated whether verbally aggressive…

Incorporation of organic tritium (3H) by marine organisms and sediment in the severn estuary/Bristol channel (UK).

PubMed

McCubbin, D; Leonard, K S; Bailey, T A; Williams, J; Tossell, P

2001-10-01

Discharges of tritium (3H) into the Severn estuary/Bristol Channel (UK) arise from the authorized release of wastes from nuclear power plants at Hinkley Point and Berkley/Oldbury and from the Nycomed-Amersham radiochemical plant, via the sewer system, at Cardiff. The wastes from the nuclear power plants probably consist almost entirely of 3H2O, whereas those from the radiochemical plant also include uncharacterized 3H labelled organic compounds. The total 3H concentrations in demersal fish and other benthic organisms in the vicinity of the Cardiff Eastern sewer outfall are significantly elevated compared to those observed around other UK nuclear establishments. Concentrations in filtered seawater were approximately 10 Bq kg(-1) whilst levels in surface sediment, seaweed (Fucus vesiculosis) and mussels (Mytilus edulis)/flounder (Platichthys flesus) were in the order of 6 x 10(2), 2 x 10(3), and 10(5) Bq kg(-1) (dry weight), respectively. Almost all the 3H found in sediment and biota were organically bound tritium (OBT). The high concentration in these materials, relative to that in seawater, is due to the presence of bioavailable organic 3H labelled compounds in the radiochemical waste. It is suggested that bioaccumulation of 3H by benthic organisms and demersal fish occurs primarily via a pathway of physico-chemical sorption/bacterial transformation of dissolved 3H labelled organic compounds into particulate organic matter, and subsequent transfer up a web of sediment dwelling microbes and meiofauna. Variations in 3H accumulation between individual organisms have been interpreted in terms of their different feeding behaviour. Relatively low concentrations were observed in the herbivorous winkle (Littorina littorea) and the pelagic Sprat (Spratus spratus) compared with other benthic organisms and demersal fish. The elevated 3H concentrations in seafood, due to bioaccumulation of OBT, have low radiological significance even for the local critical group of seafood

Magnetic polymer nanospheres for anticancer drug targeting

NASA Astrophysics Data System (ADS)

Juríková, A.; Csach, K.; Koneracká, M.; Závišová, V.; Múčková, M.; Tomašovičová, N.; Lancz, G.; Kopčanský, P.; Timko, M.; Miškuf, J.

2010-01-01

Poly(D,L-lactide-co-glycolide) polymer (PLGA) nanospheres loaded with biocom-patible magnetic fluid as a magnetic carrier and anticancer drug Taxol were prepared by the modified nanoprecipitation method with size of 200-250 nm in diameter. The PLGA polymer was utilized as a capsulation material due to its biodegradability and biocompatibility. Taxol as an important anticancer drug was chosen for its significant role against a wide range of tumours. Thermal properties of the drug-polymer system were characterized using thermal analysis methods. It was determined the solubility of Taxol in PLGA nanospheres. Magnetic properties investigated using SQUID magnetometry showed superparamagnetism of the prepared magnetic polymer nanospheres.

Successful Aging Through the eyes of Alaska Native Elders. What It Means to Be an Elder in Bristol Bay, AK

PubMed Central

Lewis, Jordan P.

2011-01-01

Purpose: Alaska Natives (ANs) view aging from a holistic perspective, which is not typical of the existing successful aging literature. One of the challenges of conducting research with cultural groups (e.g., ANs) is the lack of data, or research, on culture and aging and its impact on how we view successful aging. This research explores successful aging from an AN perspective or what it means to reach “Eldership” in rural Alaskan communities, which is an area of successful aging where there is very little research. Design and Methods: Data were gathered from 26 elders aged 61–93 years in 6 Bristol Bay communities in Southwest Alaska. An Explanatory Model approach was used and adapted to gain a sense of the beliefs about aging and establish an indigenous understanding of successful aging or what it means to attain “Eldership.” Results: Rather than establishing a definition of successful aging for AN Elders, this study highlights the four elements of “Eldership” or what AN Elders believe are important characteristics to becoming a respected elder. The four elements of “Eldership” are emotional well-being, community engagement, spirituality, and physical health, which are the characteristics of ANs who have reached “Eldership” and become a respected Elder in their community. Implications: This research seeks to inform studies on indigenous aging that prioritizes the perspectives of elders to affect positively on the delivery of health care services in rural Alaska. PMID:21357658

How collaborative governance can facilitate quality learning for sustainability in cities: A comparative case study of Bristol, Kitakyushu and Tongyeong

NASA Astrophysics Data System (ADS)

Ofei-Manu, Paul; Didham, Robert J.; Byun, Won Jung; Phillips, Rebecca; Dickella Gamaralalage, Premakumara Jagath; Rees, Sian

2017-09-01

Quality learning for sustainability can have a transformative effect in terms of promoting empowerment, leadership and wise investments in individual and collective lives and regenerating the local economies of cities, making them more inclusive, safe, resilient and sustainable. It can also help cities move towards achieving the United Nations Sustainable Development Goals (SDGs). Effecting the transformation of cities into Learning Cities, however, requires changes in the structure of governance. Drawing on interviews with key informants as well as secondary data, this article examines how collaborative governance has facilitated quality learning for sustainability in Bristol (United Kingdom), Kitakyushu (Japan) and Tongyeong (Republic of Korea). Focusing on a conceptual framework and practical application of learning initiatives, this comparative study reveals how these cities' governance mechanisms and institutional structures supported initiatives premised on cooperative learning relationships. While recognising differences in the scope and depth of the learning initiatives and the need for further improvements, the authors found evidence of general support for the governance structures and mechanisms for learning in these cities. The authors conclude by recommending that (1) to implement the Learning Cities concept based on UNESCO's Key Features of Learning Cities, recognition should be given to existing sustainability-related learning initiatives in cities; (2) collaborative governance of the Learning Cities concept at both local and international levels should be streamlined; and (3) UNESCO's Global Network of Learning Cities could serve as a hub for sharing education/learning resources and experiences for other international city-related programmes as an important contribution to the implementation of the SDGs.

The microtubule cytoskeleton does not integrate auxin transport and gravitropism in maize roots

NASA Technical Reports Server (NTRS)

Hasenstein, K. H.; Blancaflor, E. B.; Lee, J. S.

1999-01-01

The Cholodny-Went hypothesis of gravitropism suggests that the graviresponse is controlled by the distribution of auxin. However, the mechanism of auxin transport during the graviresponse of roots is still unresolved. To determine whether the microtubule (MT) cytoskeleton is participating in auxin transport, the cytoskeleton was examined and the movement of 3H-IAA measured in intact and excised taxol, oryzalin, and naphthylphthalamic acid (NPA)-treated roots of Zea mays cv. Merit. Taxol and oryzalin did not inhibit the graviresponse of roots but the auxin transport inhibitor NPA greatly inhibited both auxin transport and graviresponse. NPA had no effect on MT organization in vertical roots, but caused MT reorientation in horizontally placed roots. Regardless of treatment, the organization of MTs in intact roots differed from that in root segments. The MT inhibitors, taxol and oryzalin had opposite effects on the MTs, namely, depolymerization (oryzalin) and stabilization and thickening (taxol), but both treatments caused swelling of the roots. The data indicate that the MT cytoskeleton does not directly interfere with auxin transport or auxin-mediated growth responses in maize roots.

Taxol: a review

Treesearch

Walter C. Shortle; Rakesh Minocha

1999-01-01

Cancer is one of the most feared diseases. It involves the rapid and uncontrolled proliferation of "abnormal" cells in the body. The cancerous cell mass disrupts normal functioning of the organ or tissue in which it is found. Current treatments involve surgery, radiotherapy, and chemotherapy often applied in some combination. Naturally occurring...

Codeswitching and Generative Grammar: A Critique of the MLF Model and Some Remarks on "Modified Minimalism"

ERIC Educational Resources Information Center

MacSwan, Jeff

2005-01-01

This article presents an empirical and theoretical critique of the Matrix Language Frame (MLF) model (Myers-Scotton, 1993; Myers-Scotton and Jake, 2001), and includes a response to Jake, Myers-Scotton and Gross's (2002) (JMSG) critique of MacSwan (1999, 2000) and reactions to their revision of the MLF model as a "modified minimalist approach." The…

Ionic-Liquid-Based Paclitaxel Preparation: A New Potential Formulation for Cancer Treatment.

PubMed

Chowdhury, Md Raihan; Moshikur, Rahman Md; Wakabayashi, Rie; Tahara, Yoshiro; Kamiya, Noriho; Moniruzzaman, Muhammad; Goto, Masahiro

2018-06-04

Paclitaxel (PTX) injection (i.e., Taxol) has been used as an effective chemotherapeutic treatment for various cancers. However, the current Taxol formulation contains Cremophor EL, which causes hypersensitivity reactions during intravenous administration and precipitation by aqueous dilution. This communication reports the preliminary results on the ionic liquid (IL)-based PTX formulations developed to address the aforementioned issues. The formulations were composed of PTX/cholinium amino acid ILs/ethanol/Tween-80/water. A significant enhancement in the solubility of PTX was observed with considerable correlation with the density and viscosity of the ILs, and with the side chain of the amino acids used as anions in the ILs. Moreover, the formulations were stable for up to 3 months. The driving force for the stability of the formulation was hypothesized to be the involvement of different types of interactions between the IL and PTX. In vitro cytotoxicity and antitumor activity of the IL-based formulations were evaluated on HeLa cells. The IL vehicles without PTX were found to be less cytotoxic than Taxol, while both the IL-based PTX formulation and Taxol exhibited similar antitumor activity. Finally, in vitro hypersensitivity reactions were evaluated on THP-1 cells and found to be significantly lower with the IL-based formulation than Taxol. This study demonstrated that specially designed ILs could provide a potentially safer alternative to Cremophor EL as an effective PTX formulation for cancer treatment giving fewer hypersensitivity reactions.

Relationship of self-management to personality types and indices.

PubMed

Williams, R L; Verble, J S; Price, D E; Layne, B H

1995-06-01

This study addressed the relationship between self-management (as measured by the Lifestyle Approaches Inventory, Williams, Moore, Pettibone, & Thomas, 1992) and personality types and indexes (as measured by the Myers-Briggs Type Indicator, Myers & McCaulley, 1985) in a sample of 347 university students. Correlational analyses indicated that the self-management factor most consistently linked to the Myers-Briggs indices was Organization of Physical Space. The Myers-Briggs index most consistently correlated with the self-management factors was Judgment-Perception. Overall, male and female subjects showed similar patterns of relationships between the self-management and personality indices. When the self-management scores were compared for the various Myers-Briggs types, the analysis indicated that types having a J (planful and organized) or S (precise and practical) in the typology tended to score higher than those having a P (spontaneous and flexible) or N (imaginative and insightful).

Patent Pooling for Promoting Access to Antiretroviral Drugs (ARVs) – A Strategic Option for India

PubMed Central

Satyanarayana, Kanikaram; Srivastava, Sadhana

2010-01-01

The current HIV/AIDS scenario in India is quite grim with an estimated 2.4 million people living with HIV/AIDS (PLHA) in 2008, just behind South Africa and Nigeria. The anti-retroviral drugs (ARVs) remain the main stay of global HIV/AIDS treatment. Over 30 ARVs (single and FDCs) available under six categories viz., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), Protease inhibitors, the new Fusion inhibitors, Entry inhibitors-CCR5 co-receptor antagonists and HIV integrase strand transfer inhibitors. The major originator companies for these ARVs are: Abbott, Boehringer Ingelheim (BI), Bristol-Myers Squibb (BMS), Gilead, GlaxoSmithKline (GSK), Merck, Pfizer, Roche, and Tibotec. Beginning with zidovidine in 1987, all the drugs are available in the developed countries. In India, about 30 ARVs are available as generics manufactured by Aurobindo, Hyderabad, Andhra Pradesh; Cipla Limited, Goa; Emcure Pharmaceuticals, Pune, Maharashtra; Hetero Drugs, Hyderabad, Andhra Pradesh; Macleods Pharmaceuticals, Daman; Matrix Laboratories, Nashik, Maharashtra; Ranbaxy, Sirmour, Himachal Pradesh; and Strides Arcolab, Bangalore, Karnataka. The National AIDS Control Organization (NACO) set up in 1992 by the Govt. of India provides free ARVs to HIV positive patients in India since 2004. The drugs available in India include both single drugs and FDCs covering both first line and second line ARVs. Even while there are claims of stabilization of the disease load, there is still huge gap of those who require ARVs as only about 150,000 PLHA receive the ARVs from the Govt. and other sources. Access to ARVs therefore is still a cause of serious concern ever since India became fully Trade Related Aspects of Intellectual Property Rights (TRIPS)-complaint in 2005. Therefore, the Indian pharmaceutical companies cannot make generics for those for drugs introduced post-2005 due to product patent regime. Other concerns include heat stable

Patent Pooling for Promoting Access to Antiretroviral Drugs (ARVs) - A Strategic Option for India.

PubMed

Satyanarayana, Kanikaram; Srivastava, Sadhana

2010-01-19

The current HIV/AIDS scenario in India is quite grim with an estimated 2.4 million people living with HIV/AIDS (PLHA) in 2008, just behind South Africa and Nigeria. The anti-retroviral drugs (ARVs) remain the main stay of global HIV/AIDS treatment. Over 30 ARVs (single and FDCs) available under six categories viz., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), Protease inhibitors, the new Fusion inhibitors, Entry inhibitors-CCR5 co-receptor antagonists and HIV integrase strand transfer inhibitors. The major originator companies for these ARVs are: Abbott, Boehringer Ingelheim (BI), Bristol-Myers Squibb (BMS), Gilead, GlaxoSmithKline (GSK), Merck, Pfizer, Roche, and Tibotec. Beginning with zidovidine in 1987, all the drugs are available in the developed countries. In India, about 30 ARVs are available as generics manufactured by Aurobindo, Hyderabad, Andhra Pradesh; Cipla Limited, Goa; Emcure Pharmaceuticals, Pune, Maharashtra; Hetero Drugs, Hyderabad, Andhra Pradesh; Macleods Pharmaceuticals, Daman; Matrix Laboratories, Nashik, Maharashtra; Ranbaxy, Sirmour, Himachal Pradesh; and Strides Arcolab, Bangalore, Karnataka. The National AIDS Control Organization (NACO) set up in 1992 by the Govt. of India provides free ARVs to HIV positive patients in India since 2004. The drugs available in India include both single drugs and FDCs covering both first line and second line ARVs. Even while there are claims of stabilization of the disease load, there is still huge gap of those who require ARVs as only about 150,000 PLHA receive the ARVs from the Govt. and other sources. Access to ARVs therefore is still a cause of serious concern ever since India became fully Trade Related Aspects of Intellectual Property Rights (TRIPS)-complaint in 2005. Therefore, the Indian pharmaceutical companies cannot make generics for those for drugs introduced post-2005 due to product patent regime. Other concerns include heat stable

Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial.

PubMed

Perez-Molina, José A; Rubio, Rafael; Rivero, Antonio; Pasquau, Juan; Suárez-Lozano, Ignacio; Riera, Melcior; Estébanez, Miriam; Santos, Jesús; Sanz-Moreno, José; Troya, Jesús; Mariño, Ana; Antela, Antonio; Navarro, Jordi; Navarro, José; Esteban, Herminia; Moreno, Santiago

2015-07-01

%] to each group). At week 48 in the per-protocol population, 112 (84%) of 133 patients had virological response in the dual-treatment group versus 105 (78%) of 135 in the triple-treatment group (difference 6% [95% CI -5 to 16%), showing non-inferiority at the prespecified level. 14 (5%) patients developed severe adverse events (dual treatment six [4%]; triple treatment eight [6%]), none of which we deemed related to the study drug. Grade 3-4 adverse events were similar between groups (dual treatment 77 [55%] of 140; triple treatment 78 [55%] of 141). Treatment discontinuations were less frequent in the dual-treatment group (three [2%]) than in the triple-treatment group (ten [7%]; p=0·047). In our trial, dual treatment was effective, safe, and non-inferior to triple treatment in patients with an HIV-1 infection who are virologically suppressed who switch antiretroviral therapy because of toxic effects, intolerance, or simplification. This combination has the potential to suppress some of the long-term toxic effects associated with nucleos(t)ide reverse transcriptase inhibitors, preserve future treatment options, and reduce the cost of antiretroviral therapy. Bristol Myers-Squibb and Fundación SEIMC-GESIDA. Copyright © 2015 Elsevier Ltd. All rights reserved.

All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study.

PubMed

Manns, Michael; Pol, Stanislas; Jacobson, Ira M; Marcellin, Patrick; Gordon, Stuart C; Peng, Cheng-Yuan; Chang, Ting-Tsung; Everson, Gregory T; Heo, Jeong; Gerken, Guido; Yoffe, Boris; Towner, William J; Bourliere, Marc; Metivier, Sophie; Chu, Chi-Jen; Sievert, William; Bronowicki, Jean-Pierre; Thabut, Dominique; Lee, Youn-Jae; Kao, Jia-Horng; McPhee, Fiona; Kopit, Justin; Mendez, Patricia; Linaberry, Misti; Hughes, Eric; Noviello, Stephanie

2014-11-01

intolerant patients. Daclatasvir plus asunaprevir provided sustained virological response in 182 (90%, 95% CI 85-94) patients in the treatment-naive cohort, 168 (82%, 77-87) in the non-responder cohort, and 192 (82%, 77-87) in the ineligible, intolerant, or ineligible and intolerant cohort. Serious adverse events occurred in 12 (6%) patients in the treatment-naive group; 11 (5%) non-responders, and 16 (7%) ineligible, intolerant, or ineligible and intolerant patients; adverse events leading to discontinuation (most commonly reversible increases in alanine or aspartate aminotransferase) occurred in six (3%), two (1%), and two (1%) patients, respectively, with no deaths recorded. Grade 3 or 4 laboratory abnormalities were uncommon, with low incidences of aminotransferase increases during the first 12 weeks with daclatasvir plus asunaprevir and placebo in treatment-naive patients (≤2% each). Daclatasvir plus asunaprevir provided high sustained virological response rates in treatment-naive, non-responder, and ineligible, intolerant, or ineligible and intolerant patients, and was well tolerated in patients with HCV genotype 1b infection. These results support the use of daclatasvir plus asunaprevir as an all-oral, interferon-free and ribavirin-free treatment option for patients with HCV genotype 1b infection, including those with cirrhosis. Bristol-Myers Squibb. Copyright © 2014 Elsevier Ltd. All rights reserved.

De novo transcriptome assembly and RNA-Seq expression analysis in blood from beluga whales of Bristol Bay, AK.

PubMed

Morey, Jeanine S; Burek Huntington, Kathy A; Campbell, Michelle; Clauss, Tonya M; Goertz, Caroline E; Hobbs, Roderick C; Lunardi, Denise; Moors, Amanda J; Neely, Marion G; Schwacke, Lori H; Van Dolah, Frances M

2017-10-01

Assessing the health of marine mammal sentinel species is crucial to understanding the impacts of environmental perturbations on marine ecosystems and human health. In Arctic regions, beluga whales, Delphinapterus leucas, are upper level predators that may serve as a sentinel species, potentially forecasting impacts on human health. While gene expression profiling from blood transcriptomes has widely been used to assess health status and environmental exposures in human and veterinary medicine, its use in wildlife has been limited due to the lack of available genomes and baseline data. To this end we constructed the first beluga whale blood transcriptome de novo from samples collected during annual health assessments of the healthy Bristol Bay, AK stock during 2012-2014 to establish baseline information on the content and variation of the beluga whale blood transcriptome. The Trinity transcriptome assembly from beluga was comprised of 91,325 transcripts that represented a wide array of cellular functions and processes and was extremely similar in content to the blood transcriptome of another cetacean, the bottlenose dolphin. Expression of hemoglobin transcripts was much lower in beluga (25.6% of TPM, transcripts per million) than has been observed in many other mammals. A T12A amino acid substitution in the HBB sequence of beluga whales, but not bottlenose dolphins, was identified and may play a role in low temperature adaptation. The beluga blood transcriptome was extremely stable between sex and year, with no apparent clustering of samples by principle components analysis and <4% of genes differentially expressed (EBseq, FDR<0.05). While the impacts of season, sexual maturity, disease, and geography on the beluga blood transcriptome must be established, the presence of transcripts involved in stress, detoxification, and immune functions indicate that blood gene expression analyses may provide information on health status and exposure. This study provides a wealth

[Bristol Stool Chart: Prospective and monocentric study of "stools introspection" in healthy subjects].

PubMed

Amarenco, G

2014-09-01

The Bristol Stool Chart (BSC) allows patients to identify their stool form using seven different images with accompanying written descriptors. Stool form was found to correlate better than stool frequency with whole-gut transit as measured by a radio-opaque marker study. This score is widely used in order to verify the presence of a constipation and to evaluate the therapeutic impact of various treatments. In our clinical practice, we was strongly surprised by the facility and the great precision of the patients to report their stool form, meaning that they usually and daily verify these stools. We wanted to precise the goals of a such attitude. Two questionnaires were proposed to healthy and voluntary subjects. Q1 was supposedly presented in order to verify the sensibility of a French version of BSC in a healthy population. Thus, Q1 precised the difficulties or not to understand pictures and written descriptors, asked about exhaustive analysis by means of BSC of stool form and bowel condition. All subjects with history of ano-rectal disorders or specific treatment for bowel dysfunction were excluded. After Q1 fulfilled, Q2 was proposed to the subjects. Q2 was designed to precise the goals of the patient when he look at his stool and the frequency of such an investigation. Finally a specific question concerning the subject opinion about this behavior in terms of bothersome, shame, or metaphysic interrogation. Eighty-five healthy subjects were recruited (42 female and 43 male). Mean age was 37.2 (sd = 15.7). Mean score of BCS was 2.07 (sd =1.05) (2.07 for female and 1.81 for male, P = 0.22). Number of categories of stool form was only 1 in 40%, 2 categories in 31%, 3 in 19%, 4 in 10%. Presence of a constipation defined by category 1 or 2 was found in 17% (23% in F, 12% in M, P = 0.075). Precision of BSC was noted as excellent in 68%, moderated in 18% and poor in 14%. BSC was considered as easy to use in 75%. Frequency of inspection of feces was systematic for 37%, 1

Therapeutic cure against human tumor xenografts in nude mice by a microtubule stabilization agent, fludelone, via parenteral or oral route.

PubMed

Chou, Ting-Chao; Dong, Huajin; Zhang, Xiuguo; Tong, William P; Danishefsky, Samuel J

2005-10-15

Epothilones, 16-membered macrolides isolated from a myxobacterium in soil, exert their antitumor effect, like Taxol, by induction of microtubule polymerization and microtubule stabilization. They are effective against tumor cells that are resistant to Taxol or vinblastine. We recently designed, via molecular editing and total synthesis, a new class of epothilones represented by 26-trifluoro-(E)-9,10-dehydro-12,13-desoxy-epothilone B (Fludelone), which has emerged as a lead candidate for clinical development. Treatment of nude mice bearing MX-1 human mammary carcinoma xenografts (as large as 3.4% body weight) with Fludelone (6-hour i.v. infusion, 25 mg/kg, q3d x 5, q3d x 4) led to complete disappearance and de facto "cure" (i.e., remission without a relapse for over 15% of the average life span of 2 years). The toxicities induced by bolus i.v. injection could be avoided through prolonged i.v. infusion, which allowed for a 10-fold increase in maximal tolerated dose. Complete remission of MX-1 xenografts was achieved with only one third of this maximal tolerated dose. Parallel studies with Taxol and Fludelone [20 mg/kg, 6-hour i.v. infusion (q2d x 4) x3] against HCT-116 human colon carcinoma xenografts revealed that both drugs achieved tumor remission; however, all Taxol-treated mice relapsed in approximately 1.3 months, whereas the Fludelone-treated mice were cured without any relapse for over 7 months. Furthermore, tumor remission was achieved by Fludelone against SK-OV-3 (ovary), PC-3 (prostate), and the Taxol-resistant CCRF-CEM/Taxol (leukemia) xenograft tumors. Most remarkably, p.o. administration of Fludelone (30 mg/kg, q2d x 7, q2d x 9, q2d x 5) against MX-1 xenografts achieved a nonrelapsing cure for as long as 8.4 months. The above results indicate that Fludelone is a highly promising compound for cancer chemotherapeutics.

Blockade of epidermal growth factor receptor signaling leads to inhibition of renal cell carcinoma growth in the bone of nude mice.

PubMed

Weber, Kristy L; Doucet, Michele; Price, Janet E; Baker, Cheryl; Kim, Sun Jin; Fidler, Isaiah J

2003-06-01

Renal cell carcinoma (RCC) frequently produces metastases to the musculoskeletal system that are a major source of morbidity in the form of pain, immobilization, fractures, neurological compromise, and a decreased ability to perform activities of daily living. Patients with metastatic RCC therefore have a dismal prognosis because there is no effective adjuvant treatment for this disease. Because the epidermal growth factor receptor (EGF-R) signaling cascade is important in the growth and metastasis of RCC, its blockade has been hypothesized to inhibit tumor growth and hence prevent resultant bone destruction. We determined whether blockade of EGF-R by the tyrosine kinase inhibitor PKI 166 inhibited the growth of RCC in bone. We use a novel cell line, RBM1-IT4, established from a human RCC bone metastasis. Protein and mRNA expression of the ligands and receptors was assessed by Western and Northern blots. The stimulation of RBM1-IT4 cells with epidermal growth factor or transforming growth factor alpha resulted in increased cellular proliferation and tyrosine kinase autophosphorylation. PKI 166 prevented these effects. First, RBM1-IT4 cells were implanted into the tibia of nude mice, where they established lytic, progressively growing lesions, after which the mice were treated with PKI 166 alone or in combination with paclitaxel (Taxol). Immunohistochemical analysis revealed that tumor cells and tumor-associated endothelial cells in control mice expressed activated EGF-R. Treatment of mice with PKI 166 alone or in combination with Taxol produced a significant decrease in the incidence and size of bone lesions as compared with the results in control or Taxol-treated mice (P < 0.001). Treatment with PKI 166 also decreased the expression of phosphorylated EGF-R by tumor cells and tumor-associated endothelial cells, and this was even more pronounced with PKI 166 plus Taxol treatment. The PKI 166 plus Taxol combination produced apoptosis of tumor cells and tumor

76 FR 2109 - Methomyl: Cancellation Order for Amendments to Terminate Use of Methomyl on Grapes; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-12

...: Tom Myers, Pesticide Re-evaluation Division (7508P), Office of Pesticide Programs, Environmental...; e-mail address: myers.tom@epa.gov . SUPPLEMENTARY INFORMATION: I. General Information A. Does this...

A test of flushing procedures to control salt-water intrusion at the W. P. Franklin Dam near Ft. Myers, Florida and The magnitude and extent of salt-water contamination in the Caloosahatchee River between La Belle and Olga, Florida

USGS Publications Warehouse

Boggess, Durward H.

1970-01-01

During low-flow periods, salty water from the tidal part of the Caloosahatchee River moves upstream during boat lockages at the W. P. Franklin Darn near Ft. Myers, Florida, as shown on figure L Salty water enters the lock chamber through openings of the downstream sector gates which separate tidal and fresh water; when the upstream gates open, some of the salty water moves into the upper pool, probably as a density current. Repeated injections of salty water cause a progressive increase in the salinity of the upstream water. The salty water moves upstream within the deeper parts of the river channel as far as 5 or more miles above the lock. Some mixing of the high-chloride deeper water and the fresher shallow water occurs in the affected reach above the lock, probably as a result of wind and waves, and turbulence created by boat traffic.

Preclinical Evaluation of Genexol-PM, a Nanoparticle Formulation of Paclitaxel, as a Novel Radiosensitizer for the Treatment of Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Werner, Michael E.; Cummings, Natalie D.; Sethi, Manish

2013-07-01

Purpose: A key research objective in radiation oncology is to identify agents that can improve chemoradiation therapy. Nanoparticle (NP) chemotherapeutics possess several properties, such as preferential accumulation in tumors, that are uniquely suited for chemoradiation therapy. To facilitate the clinical translation of NP chemotherapeutics in chemoradiation therapy, we conducted preclinical evaluation of Genexol-PM, the only clinically approved NP chemotherapeutic with a controlled drug release profile, as a radiosensitizer using non-small cell lung cancer (NSCLC) as a model disease. Methods and Materials: The physical characteristics and drug release profile of Genexol-PM were characterized. Genexol-PM's efficacy as a radiosensitizer was evaluated inmore » vitro using NSCLC cell lines and in vivo using mouse xenograft models of NSCLC. Paclitaxel dose to normal lung and liver after Genexol-PM administration were quantified and compared with that after Taxol administration. Results: Genexol-PM has a size of 23.91 ± 0.41 nm and surface charge of −8.1 ± 3.1 mV. It releases paclitaxel in a controlled release profile. In vitro evaluation of Genexol-PM as a radiosensitizer showed it is an effective radiosensitizer and is more effective than Taxol, its small molecule counterpart, at the half maximal inhibitory concentration. In vivo study of Genexol-PM as a radiosensitizer demonstrated that it is more effective as a radiosensitizer than Taxol. We also found that Genexol-PM leads to lower paclitaxel exposure to normal lung tissue than Taxol at 6 hours postadministration. Conclusions: We have demonstrated that Genexol-PM is more effective than Taxol as a radiosensitizer in the preclinical setting and holds high potential for clinical translation. Our data support the clinical evaluation of Genexol-PM in chemoradiation therapy for NSCLC.« less

Functional analysis of a WRKY transcription factor involved in transcriptional activation of the DBAT gene in Taxus chinensis.

PubMed

Li, S; Zhang, P; Zhang, M; Fu, C; Yu, L

2013-01-01

Although the regulation of taxol biosynthesis at the transcriptional level remains unclear, 10-deacetylbaccatin III-10 β-O-acetyl transferase (DBAT) is a critical enzyme in the biosynthesis of taxol. The 1740 bp fragment 5'-flanking sequence of the dbat gene was cloned from Taxus chinensis cells. Important regulatory elements needed for activity of the dbat promoter were located by deletion analyses in T. chinensis cells. A novel WRKY transcription factor, TcWRKY1, was isolated with the yeast one-hybrid system from a T. chinensis cell cDNA library using the important regulatory elements as bait. The gene expression of TcWRKY1 in T. chinensis suspension cells was specifically induced by methyl jasmonate (MeJA). Biochemical analysis indicated that TcWRKY1 protein specifically interacts with the two W-box (TGAC) cis-elements among the important regulatory elements. Overexpression of TcWRKY1 enhanced dbat expression in T. chinensis suspension cells, and RNA interference (RNAi) reduced the level of transcripts of dbat. These results suggest that TcWRKY1 participates in regulation of taxol biosynthesis in T. chinensis cells, and that dbat is a target gene of this transcription factor. This research also provides a potential candidate gene for engineering increased taxol accumulation in Taxus cell cultures. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

Production of taxadiene by engineering of mevalonate pathway in Escherichia coli and endophytic fungus Alternaria alternata TPF6.

PubMed

Bian, Guangkai; Yuan, Yujie; Tao, Hui; Shi, Xiaofei; Zhong, Xiaofang; Han, Yichao; Fu, Shuai; Fang, Chengxiang; Deng, Zixin; Liu, Tiangang

2017-04-01

Taxol (paclitaxel) is a diterpenoid compound with significant and extensive applications in the treatment of cancer. The production of Taxol and relevant intermediates by engineered microbes is an attractive alternative to the semichemical synthesis of Taxol. In this study, based on a previously developed platform, the authors first established taxadiene production in mutant E. coli T2 and T4 by engineering of the mevalonate (MVA) pathway. The authors then developed an Agrobacterium tumefaciens-mediated transformation (ATMT) method and verified the strength of heterologous promoters in Alternaria alternata TPF6. The authors next transformed the taxadiene-producing platform into A. alternata TPF6, and the MVA pathway was engineered, with introduction of the plant taxadiene-forming gene. Notably, by co-overexpression of isopentenyl diphosphate isomerase (Idi), a truncated version of 3-hydroxy-3-methylglutaryl-CoA reductase (tHMG1), and taxadiene synthase (TS), the authors could detect 61.9 ± 6.3 μg/L taxadiene in the engineered strain GB127. This is the first demonstration of taxadiene production in filamentous fungi, and the approach presented in this study provides a new method for microbial production of Taxol. The well-established ATMT method and the known promoter strengths facilitated further engineering of taxaenes in this fungus. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stabilized micelles as delivery vehicles for paclitaxel.

PubMed

Yoncheva, Krassimira; Calleja, Patricia; Agüeros, Maite; Petrov, Petar; Miladinova, Ivanka; Tsvetanov, Christo; Irache, Juan M

2012-10-15

Paclitaxel is an antineoplastic drug used against a variety of tumors, but its low aqueous solubility and active removal caused by P-glycoprotein in the intestinal cells hinder its oral administration. In our study, new type of stabilized Pluronic micelles were developed and evaluated as carriers for paclitaxel delivery via oral or intravenous route. The pre-stabilized micelles were loaded with paclitaxel by simple solvent/evaporation technique achieving high encapsulation efficiency of approximately 70%. Gastrointestinal transit of the developed micelles was evaluated by oral administration of rhodamine-labeled micelles in rats. Our results showed prolonged gastrointestinal residence of the marker encapsulated into micelles, compared to a solution containing free marker. Further, the oral administration of micelles in mice showed high area under curve of micellar paclitaxel (similar to the area of i.v. Taxol(®)), longer mean residence time (9-times longer than i.v. Taxol(®)) and high distribution volume (2-fold higher than i.v. Taxol(®)) indicating an efficient oral absorption of paclitaxel delivered by micelles. Intravenous administration of micelles also showed a significant improvement of pharmacokinetic parameters of micellar paclitaxel vs. Taxol(®), in particular higher area under curve (1.2-fold), 5-times longer mean residence time and lower clearance, indicating longer systemic circulation of the micelles. Copyright © 2012 Elsevier B.V. All rights reserved.

Summary of Federal Aviation Administration Responses to National Transportation Safety Board Safety Recommendations.

DTIC Science & Technology

1980-10-01

strike A-80-45 Beech C-18S electrical 63 terminal studs A-80-46 Redcoat Air Cargo, Ltd., 69 Bristol Britannia 253 crash Billerica, Massachusetts...Ltd., Bristol Britannia 253, which crashed about 7 minutes after takeoff from Boston’s Logan International Airport on February 16, 1980. We...1980. This recommendation resulted from the Board’s investigation of a Redcoat Air Cargo, Ltd., Bristol Britannia 253 which crashed at Billerica

Risk Factors, Health Care Resource Utilization, and Costs Associated with Nonadherence to Antiretrovirals in Medicaid-Insured Patients with HIV.

PubMed

Dunn, Keith; Lafeuille, Marie-Hélène; Jiao, Xiaolong; Romdhani, Hela; Emond, Bruno; Woodruff, Kimberly; Pesa, Jacqueline; Tandon, Neeta; Lefebvre, Patrick

2018-06-07

adherence. Nonadherence to ARVs was observed in 60%-80% of Medicaid patients, depending on the adherence measure used, and was associated with incremental HCRU and costs. Age, insurance type and coverage, previous ARV treatment, and HIV symptoms were predictors of adherence. Treatment options that enhance adherence and prevent developing virologic failure with drug resistance should be considered for HIV patients. This study was supported by Janssen Scientific Affairs, which was involved in the study design, data collection, data analysis, manuscript preparation, and publication decisions. Emond, Lafeuille, Romdhani, and Lefebvre are employees of Analysis Group, a consulting company that received research grants from Janssen Scientific Affairs to conduct this study. Dunn, Woodruff, Pesa, and Tandon are current employees and stockholders of Johnson & Johnson, owner of Janssen Scientific Affairs. Jiao was an employee of Janssen at the time of the study. Emond has received grants from Novartis, Regeneron, Aegerion, Lundbeck, Bristol-Myers Squibb, Bayer, Millennium, Allergan, AbbVie, and GlaxoSmithKline unrelated to this study. Part of the material in this study was presented at the Academy of Managed Care Pharmacy 2017 Annual Meeting, March 27-30, 2017, in Denver, Colorado, and at the 9th International AIDS Society Conference, July 23-26, 2017, in Paris, France.

Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial.

PubMed

El-Khoueiry, Anthony B; Sangro, Bruno; Yau, Thomas; Crocenzi, Todd S; Kudo, Masatoshi; Hsu, Chiun; Kim, Tae-You; Choo, Su-Pin; Trojan, Jörg; Welling, Theodore H; Meyer, Tim; Kang, Yoon-Koo; Yeo, Winnie; Chopra, Akhil; Anderson, Jeffrey; Dela Cruz, Christine; Lang, Lixin; Neely, Jaclyn; Tang, Hao; Dastani, Homa B; Melero, Ignacio

2017-06-24

. This study is registered with ClinicalTrials.gov, number NCT01658878. Between Nov 26, 2012, and Aug 8, 2016, 262 eligible patients were treated (48 patients in the dose-escalation phase and 214 in the dose-expansion phase). 202 (77%) of 262 patients have completed treatment and follow-up is ongoing. During dose escalation, nivolumab showed a manageable safety profile, including acceptable tolerability. In this phase, 46 (96%) of 48 patients discontinued treatment, 42 (88%) due to disease progression. Incidence of treatment-related adverse events did not seem to be associated with dose and no maximum tolerated dose was reached. 12 (25%) of 48 patients had grade 3/4 treatment-related adverse events. Three (6%) patients had treatment-related serious adverse events (pemphigoid, adrenal insufficiency, liver disorder). 30 (63%) of 48 patients in the dose-escalation phase died (not determined to be related to nivolumab therapy). Nivolumab 3 mg/kg was chosen for dose expansion. The objective response rate was 20% (95% CI 15-26) in patients treated with nivolumab 3 mg/kg in the dose-expansion phase and 15% (95% CI 6-28) in the dose-escalation phase. Nivolumab had a manageable safety profile and no new signals were observed in patients with advanced hepatocellular carcinoma. Durable objective responses show the potential of nivolumab for treatment of advanced hepatocellular carcinoma. Bristol-Myers Squibb. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials.

PubMed

D'Angelo, Sandra P; Mahoney, Michelle R; Van Tine, Brian A; Atkins, James; Milhem, Mohammed M; Jahagirdar, Balkrishna N; Antonescu, Cristina R; Horvath, Elise; Tap, William D; Schwartz, Gary K; Streicher, Howard

2018-03-01

patients) in the nivolumab group and six (16% [7-30] of 38 patients) in the nivolumab plus ipilimumab group. The most common grade 3 or worse adverse events were anaemia (four [10%] patients), decreased lymphocyte count (three [7%]), and dehydration, increased lipase, pain, pleural effusion, respiratory failure, secondary benign neoplasm, and urinary tract obstruction (two [5%] patients each) among the 42 patients in the nivolumab group and anaemia (eight [19%] patients), hypotension (four [10%] patients), and pain and urinary tract infection (three [7%] patients each) among the 42 patients in the nivolumab plus ipilimumab group. Serious treatment-related adverse events occurred in eight (19%) of 42 patients receiving monotherapy and 11 (26%) of 42 patients receiving combination therapy, and included anaemia, anorexia, dehydration, decreased platelet count, diarrhoea, fatigue, fever, increased creatinine, increased alanine aminotransferase, increased aspartate aminotransferase, hyponatraemia, pain, pleural effusion, and pruritus. There were no treatment-related deaths. Nivolumab alone does not warrant further study in an unselected sarcoma population given the limited efficacy. Nivolumab combined with ipilimumab demonstrated promising efficacy in certain sarcoma subtypes, with a manageable safety profile comparable to current available treatment options. The combination therapy met its predefined primary study endpoint; further evaluation of nivolumab plus ipilimumab in a randomised study is warranted. Alliance Clinical Trials in Oncology, National Cancer Institute Cancer Therapy Evaluation Program, Bristol-Myers Squibb, Cycle for Survival. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prescription Drug Utilization and Reimbursement Increased Following State Medicaid Expansion in 2014.

PubMed

Mahendraratnam, Nirosha; Dusetzina, Stacie B; Farley, Joel F

2017-03-01

health care resources, specifically prescription drugs. Although this hypothesis would benefit from further testing, it aligns with previous studies that have shown that Medicaid expansion has led to increased access to coverage and care. While enrollment contributes to the increase in prescription utilization and reimbursement, the drop in PMPQ utilization suggests that the patients entering the program are healthier than existing patients. This shows that risk pooling is working. However, the increase in PMPQ reimbursement suggests that new enrollment may not be the only factor driving reimbursement changes. Factors such as changes in product mix, risk pool composition, and drug pricing and their effects on total and per-member reimbursement should be evaluated in future studies. No outside funding supported this study. Mahendraratnam is currently a Worldwide Health Economics and Outcomes Research Pre-doctoral Fellow at Bristol-Myers Squibb and previously provided advisory services to public and private sector clients while employed at Avalere Health, an Inovalon Company, as well as completed an internship at Genentech, a member of the Roche Group. Farley and Dusetzina have no conflicts of interest to report. Preliminary results of this study were presented at the 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 21st Annual Meeting in Washington, DC, on May 21-25, 2016, and the 2016 AcademyHealth Annual Research Meeting (ARM) in Boston, Massachusetts, on June 26-28, 2016. Study concept and design were contributed by Farley, Mahendraratnam, and Dusetzina. Mahendraratnam, Farley, and Dusetzina collected the data, and data interpretation was performed by all the authors. The manuscript was written by Mahendraratnam, Farley, and Dusetzina and revised by Farley, Dusetzina, and Mahendraratnam.

Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration.

PubMed

Smith, Colette J; Ryom, Lene; Weber, Rainer; Morlat, Philippe; Pradier, Christian; Reiss, Peter; Kowalska, Justyna D; de Wit, Stephane; Law, Matthew; el Sadr, Wafaa; Kirk, Ole; Friis-Moller, Nina; Monforte, Antonella d'Arminio; Phillips, Andrew N; Sabin, Caroline A; Lundgren, Jens D

2014-07-19

disease (0.33 [0.20-0.53) death rates still decreased over time. The percentage of all deaths that were AIDS-related (87/256 [34%] in 1999-2000 and 141/627 [22%] in 2009-11) and liver-related (40/256 [16%] in 1999-2000 and 64/627 [10%] in 2009-11) decreased over time, whereas non-AIDS cancers increased (24/256 [9%] in 1999-2000 to 142/627 [23%] in 2009-11). Recent reductions in rates of AIDS-related deaths are linked with continued improvement in CD4 cell count. We hypothesise that the substantially reduced rates of liver disease and cardiovascular disease deaths over time could be explained by improved use of non-HIV-specific preventive interventions. Non-AIDS cancer is now the leading non-AIDS cause and without any evidence of improvement. Oversight Committee for the Evaluation of Metabolic Complications of HAART, with representatives from academia, patient community, US Food and Drug Administration, European Medicines Agency and consortium of AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, Merck, Pfizer, F Hoffmann-La Roche, and Janssen Pharmaceuticals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ipilimumab for Previously Untreated Unresectable Malignant Melanoma: A Critique of the Evidence.

PubMed

Giannopoulou, Christina; Sideris, Eleftherios; Wade, Ros; Moe-Byrne, Thirimon; Eastwood, Alison; McKenna, Claire

2015-12-01

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of ipilimumab (Bristol-Myers Squibb Pharmaceuticals Limited) to submit clinical and cost-effectiveness evidence for previously untreated advanced (unresectable or metastatic) melanoma as part of the Institute's Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article presents a summary of the manufacturer's submission of ipilimumab, the ERG review and the resulting NICE guidance TA319, issued in July 2014. Ipilimumab at a recommended dose of 3 mg/kg monotherapy was previously granted marketing authorisation by the European Medicines Agency in adult patients who had received prior therapy and was recommended by NICE in guidance TA268. In October 2013, the EMA approved the extension of this indication to previously untreated advanced melanoma patients. NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the NICE Appraisal Committee was whether ipilimumab at a recommended dose of 3 mg/kg monotherapy was effective and cost effective compared with first-line standard of care involving dacarbazine (DTIC) and vemurafenib (for BRAF V600 mutation-positive patients). The CA184-024 trial was the primary source of clinical evidence for ipilimumab. However, this was based on a dose of 10 mg/kg with concomitant DTIC. The results over a 5-year period indicated that ipilimumab 10 mg/kg plus DTIC demonstrated a significant increase in median overall survival (OS) of 2.1 months compared with DTIC plus placebo (11.2 vs. 9.1 months). The BRIM-3 trial, which was an open-label randomised controlled trial (RCT) in BRAF V600 mutation-positive patients, was the primary source of evidence for an indirect comparison with vemurafenib. The results showed that vemurafenib increased median OS by 3

FAA Aviation Forecasts, Fiscal Years 1994-2005

DTIC Science & Technology

1994-03-01

ID (BOI) Fort Lauderdale Executive, FL (FXE) Idaho Falls Fanning Field, ID (IDA) Fort Myers Page Field, FL (FMY) Lewiston , ID (LWS) Fort Myers...Pacoima/Whitman, California (WHP) 3. Lakeland, Florida (LAL) 4. Valdosta Municipal, Georgia (VLD) 5. Halley, Idaho (SUN) 6. Marion Williamson County

Final Report of the KAPSE (Kernal Ada Programming Support Environment) Interface Team (KIT)

DTIC Science & Technology

1988-10-15

Corporation Hans Mumm Naval Ocean Systems Center Bob Munck MITRE Margaret Murray Compusec Gil Myers Naval Ocean Systems Center LCDR Philip Myers NAVELEX-812...Data Corporation Steve Huseth Honeywell Ron Johnson Boeing Aerospace Corporation Mike Kamrad Honeywell , Reed Kotler Lockheed Missile and Space Pekka

Characterizing the successful student in general chemistry and physical science classes in terms of Jung's personality types as identified by the Myers-Briggs Type Indicator

NASA Astrophysics Data System (ADS)

Riley, Wayne David

1998-11-01

A student's success in a science class can depend upon previous experiences, motivation, and the level of interest in the subject. Since psychological type is intrinsic to a person's whole being, it can be influential upon the student's motivation and interests. Thus, a study of student psychological types versus the level of success in a class, as measured by a percentage, has potential to uncover certain personality characteristics which may be helpful to or which may hinder a student's learning environment. This study was initiated, using the Myers-Briggs Type Indicator, to evaluate any correlation between a student's personality type and his/her performance in a science class. A total of 1041 students from three classes: Chemistry 121/122, Chemistry 112, Physical Science 100, volunteered for the study. An analysis of variance (ANOVA) was used to determine the levels of significance among sixteen personality types' averages. The results reveal that for the Chemistry 1121/122 course, the average score of the INTJ personality type was 5.1 to 12.6 points higher than every other personality type. The ANOVA identifies 3 personality types with averages significantly below the INTJ at the p < 0.05 significance level. The ANOVA analysis for the Chemistry 112 course identified significances between student scores at p = 0.08. The significance level for the differences among scores for the Physical Science 100 course was determined at a level of p = 0.02. Significance levels for p < 0.05 and <0.01 were identified between several groups in this course. The data suggest, that although personality type may not predict a particular student's success in a science class, students with certain personality traits may be favored in a chemistry class due the structure of the instruction and the presentation of the subject matter.

A mixed methods evaluation of peer support in Bristol, UK: mothers', midwives' and peer supporters' views and the effects on breastfeeding.

PubMed

Ingram, Jenny

2013-10-20

International studies suggest that breastfeeding interventions in primary care are more effective than usual care in increasing short and long term breastfeeding rates. Interventions that combine pre- and postnatal components have larger effects than either alone, and those that including lay support in a multicomponent intervention may be more beneficial. Despite the mixed reports of the effectiveness of breastfeeding peer support in the UK, targeted peer support services are being established in many areas of the UK. In 2010, NHS Bristol Primary Care Trust commissioned a targeted breastfeeding peer support service for mothers in 12 lower socio-economic areas of the city, with one antenatal visit and postnatal contact for up to 2 weeks. Mothers receiving the peer support service were invited to complete an on-line survey covering infant feeding; breastfeeding support; and confidence in breastfeeding (using the Breastfeeding Self-Efficacy Scale). Semi-structured interviews and a focus group explored perceptions of mothers, midwives and peer supporters. The effects of the service on breastfeeding rates were documented and compared. 163 mothers completed the on-line survey; 25 participants were interviewed (14 mothers, 7 peer supporters and 4 maternity health professionals); exclusive and total breastfeeding rates for initiation and at 8 weeks were compared for 12 months before and after the service started.The targeted peer support service was associated with small non-significant increases in breastfeeding rates, (particularly exclusive breastfeeding), compared to the rest of the city. The service was very positively evaluated by mothers, health professionals and peer supporters. Mothers felt that peer support increased their confidence to breastfeed; peer supporters found the contacts rewarding, enjoyable and important for mothers; midwives and maternity support workers were positive about the continuity of an antenatal visit and postnatal support from the same

Publications - GMC 355 | Alaska Division of Geological & Geophysical

Science.gov Websites

DGGS GMC 355 Publication Details Title: Bristol Bay Native Corp iron, titanium, platinum Kemuk Mountain ): Alaska Statewide Bibliographic Reference ALS Chemex, 2008, Bristol Bay Native Corp iron, titanium

SMIFH2-mediated mDia formin functional inhibition potentiates chemotherapeutic targeting of human ovarian cancer spheroids.

PubMed

Ziske, Megan A; Pettee, Krista M; Khaing, MaNada; Rubinic, Kaitlin; Eisenmann, Kathryn M

2016-03-25

Due to a lack of effective screening or prevention protocol for epithelial ovarian cancer (EOC), there is a critical unmet need to develop therapeutic interventions for EOC treatment. EOC metastasis is unique. Initial dissemination is not primarily hematogenous, yet is facilitated through shedding of primary tumor cells into the peritoneal fluid and accumulating ascites. Increasingly, isolated patient spheroids point to a clinical role for spheroids in EOC metastasis. EOC spheroids are highly invasive structures that disseminate upon peritoneal mesothelium, and visceral tissues including liver and omentum. Selection for this subset of chemoresistant EOC cells could influence disease progression and/or recurrence. Thus, targeting spheroid integrity/structure may improve the chemotherapeutic responsiveness of EOC. We discovered a critical role for mammalian Diaphanous (mDia)-related formin-2 in maintaining EOC spheroid structure. Both mDia2 and the related mDia1 regulate F-actin networks critical to maintain cell-cell contacts and the integrity of multi-cellular epithelial sheets. We investigated if mDia2 functional inhibition via a small molecule inhibitor SMIFH2 combined with chemotherapeutics, such as taxol and cisplatin, inhibits the viability of EOC monolayers and clinically relevant spheroids. SMIFH2-mediated mDia formin inhibition significantly reduced both ES2 and Skov3 EOC monolayer viability while spheroid viability was minimally impacted only at the highest concentrations. Combining either cisplatin or taxol with SMIFH2 did not significantly enhance the effects of either drug alone in ES2 monolayers, while Skov3 monolayers treated with taxol or cisplatin and SMIFH2 showed significant additive inhibition of viability. ES2 spheroids were highly responsive with clear additive anti-viability effects with dual taxol or cisplatin when combined with SMIFH2 treatments. While combined taxol with SMIFH2 in spheroids showed an additive effect relative to single

Analysis of Theoretical Relationships between Learning Styles of Students and Their Preferences for Learning Activities.

ERIC Educational Resources Information Center

Rollins, Timothy J.

1990-01-01

A study of 10,603 students enrolled in 262 secondary agricultural programs examined learning styles and individual preferences and tested the Myers-Briggs theory that certain learning activities are associated with learning styles. Confirmed the Myers-Briggs finding that 70 percent prefer the sensing learning style. (JOW)

Kernel Ada Programming Support Environment (KAPSE) Interface Team. Public Report. Volume 3.

DTIC Science & Technology

1983-10-25

NWC MYERS, Gil NOSC MYERS, Philip NAVELEX NELSON, Eldred TRW OBERNDORF, Tricia NOSC P E, Shirley FCDSSA 2A-10 PURRIER, Lee FCDSSA OTB ROBERTSON...Sciences Corp. GRIESHEIMER, Eric McDonnel Douglas Astronautics JOHNSON, Ron Boeing Aerospace Co. KERNER, Judy Norden Systems KOTLER , Reed Lockheed Missiles

Risk factors for road traffic accidents in cats up to age 12 months that were registered between 2010 and 2013 with the UK pet cat cohort ('Bristol Cats').

PubMed

Wilson, J L; Gruffydd-Jones, T J; Murray, J K

2017-02-25

Road traffic accidents (RTAs) are a common cause of death and injury in domestic cats, and a concern to many owners. This study assessed potential risk factors for RTAs in cats up to 12 months of age within a UK cat cohort known as 'The Bristol Cats study'. Data were obtained from three questionnaires, completed by cat owners when their cats were approximately 8-16 weeks old, 6 months old and 12 months old. Information was gathered regarding environmental conditions, cat characteristics and owner management factors. Univariable and multivariable logistic regression models were used to assess associations between these factors and RTAs. Of 1264 eligible study cats, 49 (3.9 per cent) had been involved in an RTA, of which 71.4 per cent (35/49) were known to result in fatal injuries. Rural locations were associated with a higher odds of RTAs than towns, cities or suburban locations. An increased odds of an RTA was also associated with cats that were reported by their owners to hunt at the roadside, as well as cats whose owners classified the road by their house as being a 'long straight section of road'. No significant associations were found between coat colour, breed, sex or neuter status and the odds of an RTA. British Veterinary Association.

MCAK and Stathmin Upregulation in Breast Cancer Cells: Etiology and Response to Pharmacologic Reagents

DTIC Science & Technology

2004-07-01

and the affinity for MTs are cells (Maney et al., 2001). Finally, the neck domain is not molecular refinements that adapt motile kinesins for specific...1,500 nM taxol-stabilized MTs in 80 p.I of BRB80 (80 mM molecular motor. Nature. 389:93-96. Pipes, pH 6.8, 1 mM EGTA, and 1 mM MgCI2), 12.5 p.M taxol, 1...summarizes the biological functions and examines the possible molecular the r egio immeiatel iete mt core mechanisms of Kin C and Kin I unconventional

Honey Do Franchising Group, Inc. Information Sheet

EPA Pesticide Factsheets

Honey Do Franchising Group, Inc., a/k/a The Honey Do Service, Inc. (the Company) is located in Bristol, Virginia. The settlement involves renovation activities conducted at properties constructed prior to 1978, located in Bristol, Virginia.

Differences among Community College Students on Dimensions of Wellness as Measured by the 5F-WEL-A

ERIC Educational Resources Information Center

McNeely, Abigail Rankin

2010-01-01

The study herein compares students in a metropolitan community college on dimensions of wellness based on age, sex/gender, ethnicity, and socioeconomic status. The Five Factor Wellness Evaluation of Lifestyle-Adult Version (Myers & Sweeney, 2005), which is based on the Indivisible Self model (Myers & Sweeney, 2005), along with the Barratt…

Psychometric Properties of Scores on a New Measure of Psychological Type.

ERIC Educational Resources Information Center

Vacha-Haase, Tammi; Thompson, Bruce

Instruments measuring Carl Jung's (1921/1971) theory of psychological types have been widely used in various counseling contexts. The most popular measure of types has been the Myers-Briggs Type Indicator (K. Briggs and I. Myers). This measure has been criticized for dichotomous scoring, forced-choice response formats, and differential gender…

Personality Type and Temperament in Industrial Education Students: A Descriptive Study.

ERIC Educational Resources Information Center

Edmunds, Neil; Schultz, Andrew

1989-01-01

Using Myers-Briggs Type Inventory, authors studied 213 industrial education students in 22 secondary schools in Nebraska to ascertain whether the inventory placed students proportionately into same categories as Myers-Briggs normative group--defined by Keirsey. Large numbers of Sensory Thinker (ST) type found in 60 percent of classes. STs aimed…

On Discrete-Time Pursuit-Evasion Games with Sensing Limitations

DTIC Science & Technology

2008-01-01

observations in the biology literature by Caraco and Wolf [24] that have reported higher group size in foraging lions during the wet season (prey...H. Myers, and S. L. Myers, Probability and Statistics for Engineers and Scientists, 6th ed. New Jersey, USA: Prentice Hall, 1998. [24] T. Caraco and

An Assessment of Potential Mining Impacts on Salmon ...

EPA Pesticide Factsheets

The Bristol Bay watershed in southwestern Alaska supports the largest sockeye salmon fishery in the world, is home to 25 federally recognized tribal governments, and contains large mineral resources. The potential for large-scale mining activities in the watershed has raised concerns about the impact of mining on the sustainability of Bristol Bay’s world-class commercial, recreational and subsistence fisheries and the future of Alaska Native tribes in the watershed who have maintained a salmon-based culture and subsistence-based way of life for at least 4,000 years. The purpose of this assessment is to provide a characterization of the biological and mineral resources of the Bristol Bay watershed, increase understanding of the potential impacts of large-scale mining on the region’s fish resources, and inform future government decisions related to protecting and maintaining the chemical, physical, and biological integrity of the watershed. It will also serve as a technical resource for the public, tribes, and governments who must consider how best to address the challenges of mining and ecological protection in the Bristol Bay watershed. The purpose of this assessment is to understand how future large-scale mining may affect water quality and the Bristol Bay salmon fisheries, which includes the largest wild sockeye salmon fishery in the world. Bristol Bay, Alaska, is home to a salmon fishery that is of significant economic and subsistence value to the peopl

Molecular cloning and characterization of a cytochrome P450 taxoid 9á-hydroxylase in Ginkgo biloba cells.

PubMed

Zhang, Nan; Han, Zhentai; Sun, Guiling; Hoffman, Angela; Wilson, Iain W; Yang, Yanfang; Gao, Qian; Wu, Jianqiang; Xie, Dan; Dai, Jungui; Qiu, Deyou

2014-01-17

Taxol is a well-known effective anticancer compound. Due to the inability to synthesize sufficient quantities of taxol to satisfy commercial demand, a biotechnological approach for a large-scale cell or cell-free system for its production is highly desirable. Several important genes in taxol biosynthesis are currently still unknown and have been shown to be difficult to isolate directly from Taxus, including the gene encoding taxoid 9α-hydroxylase. Ginkgo biloba suspension cells exhibit taxoid hydroxylation activity and provides an alternate means of identifying genes encoding enzymes with taxoid 9α-hydroxylation activity. Through analysis of high throughput RNA sequencing data from G. biloba, we identified two candidate genes with high similarity to Taxus CYP450s. Using in vitro cell-free protein synthesis assays and LC-MS analysis, we show that one candidate that belongs to the CYP716B, a subfamily whose biochemical functions have not been previously studied, possessed 9α-hydroxylation activity. This work will aid future identification of the taxoid 9α-hydroxylase gene from Taxus sp. Copyright © 2013 Elsevier Inc. All rights reserved.

Elevating the frequency of chromosome mis-segregation as a strategy to kill tumor cells

PubMed Central

Janssen, Aniek; Kops, Geert J. P. L.; Medema, René H.

2009-01-01

The mitotic checkpoint has evolved to prevent chromosome mis-segregations by delaying mitosis when unattached chromosomes are present. Inducing severe chromosome segregation errors by ablating the mitotic checkpoint causes cell death. Here we have analyzed the consequences of gradual increases in chromosome segregation errors on the viability of tumor cells and normal human fibroblasts. Partial reduction of essential mitotic checkpoint components in four tumor cell lines caused mild chromosome mis-segregations, but no lethality. These cells were, however, remarkably more sensitive to low doses of taxol, which enhanced the amount and severity of chromosome segregation errors. Sensitization to taxol was achieved by reducing levels of Mps1 or BubR1, proteins having dual roles in checkpoint activation and chromosome alignment, but not by reducing Mad2, functioning solely in the mitotic checkpoint. Moreover, we find that untransformed human fibroblasts with reduced Mps1 levels could not be sensitized to sublethal doses of taxol. Thus, targeting the mitotic checkpoint and chromosome alignment simultaneously may selectively kill tumor cells by enhancing chromosome mis-segregations. PMID:19855003

Design and synthesis of new hybrids from 2-cyano-3,12-dioxooleana- 9-dien-28-oic acid and O2-(2,4-dinitrophenyl) diazeniumdiolate for intervention of drug-resistant lung cancer.

PubMed

Kang, Fenghua; Ai, Yong; Zhang, Yihua; Huang, Zhangjian

2018-04-10

To search for new drugs for intervention of drug-resistant lung cancer, a series of hybrids 4-15 from 2-cyano-3,12-dioxooleana-9-dien-28-oic acid (CDDO) and O 2 -(2,4-dinitrophenyl) diazeniumdiolate were designed, synthesized and biologically evaluated. The most active compound 7 produced relatively high levels of nitric oxide (NO) and reactive oxygen species (ROS) in drug-resistant lung cancer A549/Taxol cells which over-express glutathione S-transferase π (GSTπ), and significantly inhibited the cells' proliferation (IC 50  = 0.349 ± 0.051 μM), superior to the positive controls CDDO-Me, JS-K and Taxol. The inhibitory activity of 7 could be attenuated by an NO scavenger, ROS scavenger or GSTπ inhibitor. In addition, 7 suppressed the Lon protease expression as well as induced cell apoptosis and cycle arrest in A549/Taxol cells more strongly than CDDO-Me or JS-K. Together, our findings suggest that 7 may be worth studying further for intervention of drug-resistant lung cancer. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Prevention effect of rare ginsenosides against stress-hormone induced MTOC amplification

PubMed Central

Lee, Jee-Hyun; Cheong, Kyu Jin; Jung, Youn-Sang; Woo, Tae-Gyun; Yoon, Min-Ho; Oh, Ah-Young; Kang, So-Mi; Lee, Chunghui; Sun, Hokeun; Hwang, Jihwan; Song, Gyu-Yong; Park, Bum-Joon

2016-01-01

Stress has been suggested as one of important cause of human cancer without molecular biological evidence. Thus, we test the effect of stress-related hormones on cell viability and mitotic fidelity. Similarly to estrogen, stress hormone cortisol and its relative cortisone increase microtubule organizing center (MTOC) number through elevated expression of γ-tubulin and provide the Taxol resistance to human cancer cell lines. However, these effects are achieved by glucocorticoid hormone receptor (GR) but not by estrogen receptor (ER). Since ginsenosides possess steroid-like structure, we hypothesized that it would block the stress or estrogen-induced MTOC amplification and Taxol resistance. Among tested chemicals, rare ginsenoside, CSH1 (Rg6) shows obvious effect on inhibition of MTOC amplification, γ-tubulin induction and Taxol resistance. Comparing to Fulvestant (FST), ER-α specific inhibitor, this chemical can block the cortisol/cortisone-induced MTOC deregulation as well as ER-α signaling. Our results suggest that stress hormone induced tumorigenesis would be achieved by MTOC amplification, and CSH1 would be useful for prevention of stress-hormone or steroid hormone-induced chromosomal instability. PMID:27147573

Comments on "Another Look at the New York City Voucher Experiment."

ERIC Educational Resources Information Center

Myers, David E.; Mayer, Daniel P.

This brief paper is a response to a reanalysis (Krueger & Zhu, 2003) of a report (Mayer, Peterson, Myers, Tuttle, & Howell, 2002). The response is offered by two of the authors (Myers & Mayer) of the original report. The original report presented an evaluation of the impact of vouchers on students' reading and mathematics achievement…

The role of microtubules in contractile ring function.

PubMed

Conrad, A H; Paulsen, A Q; Conrad, G W

1992-05-01

During cytokinesis, a cortical contractile ring forms around a cell, constricts to a stable tight neck and terminates in separation of the daughter cells. At first cleavage, Ilyanassa obsoleta embryos form two contractile rings simultaneously. The cleavage furrow (CF), in the animal hemisphere between the spindle poles, constricts to a stable tight neck and separates the daughter cells. The third polar lobe constriction (PLC-3), in the vegetal hemisphere below the spindle, constricts to a transient tight neck, but then relaxes, allowing the polar lobe cytoplasm to merge with one daughter cell. Eggs exposed to taxol, a drug that stabilizes microtubules, before the CF or the PLC-3 develop, fail to form CFs, but form stabilized tight PLCs. Eggs exposed to taxol at the time of PLC-3 formation develop varied numbers of constriction rings in their animal hemispheres and one PLC in their vegetal hemisphere, none of which relax. Eggs exposed to taxol after PLC-3 initiation form stabilized tight CFs and PLCs. At maximum constriction, control embryos display immunolocalization of nonextractable alpha-tubulin in their CFs, but not in their PLCs, and reveal, via electron microscopy, many microtubules extending through their CFs, but not through their PLCs. Embryos which form stabilized tightly constricted CFs and PLCs in the presence of taxol display immunolocalization of nonextractable alpha-tubulin in both constrictions and show many polymerized microtubules extending through both CFs and PLCs. These results suggest that the extension of microtubules through a tight contractile ring may be important for stabilizing that constriction and facilitating subsequent cytokinesis.

The role of microtubules in contractile ring function

NASA Technical Reports Server (NTRS)

Conrad, A. H.; Paulsen, A. Q.; Conrad, G. W.; Spooner, B. S. (Principal Investigator)

1992-01-01

During cytokinesis, a cortical contractile ring forms around a cell, constricts to a stable tight neck and terminates in separation of the daughter cells. At first cleavage, Ilyanassa obsoleta embryos form two contractile rings simultaneously. The cleavage furrow (CF), in the animal hemisphere between the spindle poles, constricts to a stable tight neck and separates the daughter cells. The third polar lobe constriction (PLC-3), in the vegetal hemisphere below the spindle, constricts to a transient tight neck, but then relaxes, allowing the polar lobe cytoplasm to merge with one daughter cell. Eggs exposed to taxol, a drug that stabilizes microtubules, before the CF or the PLC-3 develop, fail to form CFs, but form stabilized tight PLCs. Eggs exposed to taxol at the time of PLC-3 formation develop varied numbers of constriction rings in their animal hemispheres and one PLC in their vegetal hemisphere, none of which relax. Eggs exposed to taxol after PLC-3 initiation form stabilized tight CFs and PLCs. At maximum constriction, control embryos display immunolocalization of nonextractable alpha-tubulin in their CFs, but not in their PLCs, and reveal, via electron microscopy, many microtubules extending through their CFs, but not through their PLCs. Embryos which form stabilized tightly constricted CFs and PLCs in the presence of taxol display immunolocalization of nonextractable alpha-tubulin in both constrictions and show many polymerized microtubules extending through both CFs and PLCs. These results suggest that the extension of microtubules through a tight contractile ring may be important for stabilizing that constriction and facilitating subsequent cytokinesis.

Trial of Cisplatin Plus Radiation Followed by Carbo and Taxol Vs. Sandwich Therapy of Carbo and Taxol Followed Radiation Then Further Carbo and Taxol

ClinicalTrials.gov

2017-10-30

Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer

U.S. Department of Defense Official Website

Science.gov Websites

updated and may no longer be applicable as a result of changes in law, regulation and/or administration changes to the U.S. military's global posture. Rumsfeld and Joint Chiefs Chairman Air Force Gen. Richard B . Myers discussed the changes. Air Force Gen. Richard B. Myers, chairman, Joint Chiefs of Staff, answers

Examination of Psychological Type and Preferred Negotiation Tactics and Strategies of Contract Negotiators

DTIC Science & Technology

1992-09-01

Auxiliary Process .................. 23 iii Page The Myers-Briggs Type Indicator ....................... 24 The Relationship of Personality Type and...negotiation tactics and/or strategies. Major Charan Johnstone (1986) studied the relationship of psychological type as measured by the Myers-Briggs Type...1986:118). Determining psychological type for both government and industry negotiators, and the relationship to negotiation tactics and strategies may

The Elephants Teach: Creative Writing since 1880

ERIC Educational Resources Information Center

Myers, David Gershom

2006-01-01

When Vladimir Nabokov was up for a chair in literature at Harvard, the linguist Roman Jakobson protested: "What's next? Shall we appoint elephants to teach zoology?" That anecdote, with which D. G. Myers begins "The Elephants Teach", perfectly frames the issues this book tackles. Myers explores more than a century of debate over how writing should…

Family Matters: Father and Son Follow Same Career Path; Succeed

ERIC Educational Resources Information Center

Cooper, Kenneth J.

2012-01-01

Together, Samuel L. Myers Sr. and Jr. prove that the apple tree, when properly nurtured in the rich intellectual orchards of academia, will bear prime fruit that lands close to its roots. The Doctors Myers both earned bachelor's degrees from Morgan State University and then ventured to Boston for their Ph.D.s in economics. Though their specialties…

Physicians, formula companies, and advertising. A historical perspective.

PubMed

Greer, F R; Apple, R D

1991-03-01

The recent advent of new advertising campaigns for infant formulas aimed at the general public via television commercials, newspapers, free formula coupons, and lay periodicals has disrupted a comfortable symbiotic relationship between infant food manufacturers and the medical profession that has endured for more than 50 years. In the late 19th century, physicians were concerned about the advertising claims of these products and generally felt that indications and directions for their use should be the province of the physician. Between 1929 and 1932, the American Medical Association, through its Committee on Foods and "Seal of Acceptance," essentially required the entire formula industry to advertise only to the medical profession. Since 1932, the US formula industry has developed into a $1.6 billion market. In 1988, Nestlé (absent from the US infant formula industry since the 1940s) acquired the Carnation Company and launched an advertising campaign to the general public for its formula products. Bristol Myers/Mead Johnson, in cooperation with Gerber Products Company, quickly followed suit. These actions threaten to once again remove the realm of infant feeding from the exclusive supervision of the medical profession. The new multimedia public advertising campaigns may increase the cost of infant formula to the general public and have a negative impact on the incidence of breast-feeding. In addition, formula advertising campaigns will likely increase the danger of advertising hyperbole and affect the level of financial support by formula companies for scientific meetings, medical research, education, and social events at medical meetings.

77 FR 52232 - Approval and Promulgation of Implementation Plans and Designations of Areas for Air Quality...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-29

...: Bristol; Determination of Attaining Data for the 2008 Lead Standards AGENCY: Environmental Protection... nonattainment area (hereafter also referred to as the ``Bristol Area'' or ``Area'') has attained the 2008 lead... 2008 lead national ambient air quality standards (NAAQS or standard) has attained the 2008 lead NAAQS...

50 CFR 600.1104 - Bering Sea and Aleutian Islands (BSAI) crab species fee payment and collection system.

Code of Federal Regulations, 2010 CFR

2010-10-01

... endorsement for Norton Sound red king. More specifically, the reduction endorsement fisheries, and the crab... endorsement fisheries, are: (1) Bristol Bay red king (the corresponding crab rationalization fishery is Bristol Bay red king crab), (2) Bering Sea and Aleutian Islands Area C. opilio and C. bairdi (the...

50 CFR 600.1104 - Bering Sea and Aleutian Islands (BSAI) crab species fee payment and collection system.

Code of Federal Regulations, 2011 CFR

2011-10-01

... endorsement for Norton Sound red king. More specifically, the reduction endorsement fisheries, and the crab... endorsement fisheries, are: (1) Bristol Bay red king (the corresponding crab rationalization fishery is Bristol Bay red king crab), (2) Bering Sea and Aleutian Islands Area C. opilio and C. bairdi (the...

33 CFR 100.736 - Annual Fort Myers Beach air show; Fort Myers Beach, FL.

Code of Federal Regulations, 2010 CFR

2010-07-01

...°59′15″ W. All coordinates referenced use datum: NAD 83. (2) Air Box Area. The air box area is... coordinates referenced use datum: NAD 83. (b) Special local regulations. (1) Vessels and persons are... referenced use datum: NAD 83. (c) Dates. This section will be enforced annually on the second consecutive...

Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial.

PubMed

Pol, Tymon; Held, Claes; Westerbergh, Johan; Lindbäck, Johan; Alexander, John H; Alings, Marco; Erol, Cetin; Goto, Shinya; Halvorsen, Sigrun; Huber, Kurt; Hanna, Michael; Lopes, Renato D; Ruzyllo, Witold; Granger, Christopher B; Hijazi, Ziad

2018-02-01

Authors and Bristol‐Myers Squibb. Published on behalf of the American Heart Association, Inc., by Wiley.

The Relationship of Stated Learning Preferences, Personality Type, and Career Background to Academic and Leadership Performance at the United States Air Command and Staff College

DTIC Science & Technology

1999-12-11

Kolb envisioned experiential 26 Table 2 Subscales on the NASSP Learning Styles Profile Cognitive Styles Perceptual Responses Analytic Skill...Research Type Theory and Learning Preferences Jung and the Theory of Psychological Types Isabel Briggs Myers’ Contribution to Jung’s Work The Myers...Implications Recommendations for Further Study Summary of Specific Conclusions Discussion Grounded Curriculum Learning Preferences Type Theory Student

Mcl-1 dynamics influence mitotic slippage and death in mitosis.

PubMed

Sloss, Olivia; Topham, Caroline; Diez, Maria; Taylor, Stephen

2016-02-02

Microtubule-binding drugs such as taxol are frontline treatments for a variety of cancers but exactly how they yield patient benefit is unclear. In cell culture, inhibiting microtubule dynamics prevents spindle assembly, leading to mitotic arrest followed by either apoptosis in mitosis or slippage, whereby a cell returns to interphase without dividing. Myeloid cell leukaemia-1 (Mcl-1), a pro-survival member of the Bcl-2 family central to the intrinsic apoptosis pathway, is degraded during a prolonged mitotic arrest and may therefore act as a mitotic death timer. Consistently, we show that blocking proteasome-mediated degradation inhibits taxol-induced mitotic apoptosis in a Mcl-1-dependent manner. However, this degradation does not require the activity of either APC/C-Cdc20, FBW7 or MULE, three separate E3 ubiquitin ligases implicated in targeting Mcl-1 for degradation. This therefore challenges the notion that Mcl-1 undergoes regulated degradation during mitosis. We also show that Mcl-1 is continuously synthesized during mitosis and that blocking protein synthesis accelerates taxol induced death-in-mitosis. Modulating Mcl-1 levels also influences slippage; overexpressing Mcl-1 extends the time from mitotic entry to mitotic exit in the presence of taxol, while inhibiting Mcl-1 accelerates it. We suggest that Mcl-1 competes with Cyclin B1 for binding to components of the proteolysis machinery, thereby slowing down the slow degradation of Cyclin B1 responsible for slippage. Thus, modulating Mcl-1 dynamics influences both death-in-mitosis and slippage. However, because mitotic degradation of Mcl-1 appears not to be under the control of an E3 ligase, we suggest that the notion of network crosstalk is used with caution.

Blockade of epidermal growth factor receptor signaling in tumor cells and tumor-associated endothelial cells for therapy of androgen-independent human prostate cancer growing in the bone of nude mice.

PubMed

Kim, Sun-Jin; Uehara, Hisanori; Karashima, Takashi; Shepherd, David L; Killion, Jerald J; Fidler, Isaiah J

2003-03-01

We determined whether blockade of the epidermal growth factor receptor (EGF-R) signaling pathway by oral administration of the EGF-R tyrosine kinase inhibitor (PKI 166) alone or in combination with injectable Taxol inhibits the growth of PC-3MM2 human prostate cancer cells in the bone of nude mice. Male nude mice implanted with PC-3MM2 cells in the tibia were treated with oral administrations of PKI 166 or PKI 166 plus injectable Taxol beginning 3 days after implantation. The incidence and size of bone tumors and destruction of bone were determined by digitalized radiography. Expression of epidermal growth factor (EGF), EGF-R, and activated EGF-R in tumor cells and tumor-associated endothelial cells was determined by immunohistochemistry. Oral administration of PKI 166 or PKI 166 plus injectable Taxol reduced the incidence and size of bone tumors and destruction of bone. Immunohistochemical analysis revealed that PC-3MM2 cells growing adjacent to the bone expressed high levels of EGF and activated EGF-R, whereas tumor cells in the adjacent musculature did not. Moreover, endothelial cells within the bone tumor lesions, but not in uninvolved bone or tumors in the muscle, expressed high levels of activated EGF-R. Treatment with PKI 166 and more so with PKI 166 plus Taxol significantly inhibited phosphorylation of EGF-R on tumor and endothelial cells and induced significant apoptosis and endothelial cells within tumor lesions. These data indicate that endothelial cells exposed to EGF produced by tumor cells express activated EGF-R and that targeting EGF-R can produce significant therapeutic effects against prostate cancer bone metastasis.

[Rhinobasale mucormycosis (author's transl)].

PubMed

Behbehani, A A; Theopold, H M

1981-05-01

A case of mucormycosis in a 82-year old woman is reported. In spite of an early diagnosis, a surgical intervention and the antimycotic treatment with Miconazol-Sodium (Daktar [R]) and Amphothericin B "Squibb" (R) could only prolonge the bad prognosis of this infection. The pathogenesis, the typical, in most cases letal fungal infection and its therapy is discussed.

Insights into the Distinct Mechanisms of Action of Taxane and Non-Taxane Microtubule Stabilizers from Cryo-EM Structures.

PubMed

Kellogg, Elizabeth H; Hejab, Nisreen M A; Howes, Stuart; Northcote, Peter; Miller, John H; Díaz, J Fernando; Downing, Kenneth H; Nogales, Eva

2017-03-10

A number of microtubule (MT)-stabilizing agents (MSAs) have demonstrated or predicted potential as anticancer agents, but a detailed structural basis for their mechanism of action is still lacking. We have obtained high-resolution (3.9-4.2Å) cryo-electron microscopy (cryo-EM) reconstructions of MTs stabilized by the taxane-site binders Taxol and zampanolide, and by peloruside, which targets a distinct, non-taxoid pocket on β-tubulin. We find that each molecule has unique distinct structural effects on the MT lattice structure. Peloruside acts primarily at lateral contacts and has an effect on the "seam" of heterologous interactions, enforcing a conformation more similar to that of homologous (i.e., non-seam) contacts by which it regularizes the MT lattice. In contrast, binding of either Taxol or zampanolide induces MT heterogeneity. In doubly bound MTs, peloruside overrides the heterogeneity induced by Taxol binding. Our structural analysis illustrates distinct mechanisms of these drugs for stabilizing the MT lattice and is of relevance to the possible use of combinations of MSAs to regulate MT activity and improve therapeutic potential. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Insights into the Distinct Mechanisms of Action of Taxane and Non-Taxane Microtubule Stabilizers from Cryo-EM Structures

DOE PAGES

Kellogg, Elizabeth H.; Hejab, Nisreen M. A.; Howes, Stuart; ...

2017-01-17

A number of microtubule (MT)-stabilizing agents (MSAs) have demonstrated or predicted potential as anticancer agents, but a detailed structural basis for their mechanism of action is still lacking. We have obtained high-resolution (3.9–4.2 Å) cryo-electron microscopy (cryo-EM) reconstructions of MTs stabilized by the taxane-site binders Taxol and zampanolide, and by peloruside, which targets a distinct, non-taxoid pocket on β-tubulin. We find that each molecule has unique distinct structural effects on the MT lattice structure. Peloruside acts primarily at lateral contacts and has an effect on the “seam” of heterologous interactions, enforcing a conformation more similar to that of homologous (i.e., non-seam)more » contacts by which it regularizes the MT lattice. In contrast, binding of either Taxol or zampanolide induces MT heterogeneity. In doubly bound MTs, peloruside overrides the heterogeneity induced by Taxol binding. Our structural analysis illustrates distinct mechanisms of these drugs for stabilizing the MT lattice and is of relevance to the possible use of combinations of MSAs to regulate MT activity and improve therapeutic potential.« less

The battle of "nano" paclitaxel.

PubMed

Sofias, Alexandros Marios; Dunne, Michael; Storm, Gert; Allen, Christine

2017-12-01

Paclitaxel (PTX) is one of the three most widely used chemotherapeutic agents, together with doxorubicin and cisplatin, and is first or second line treatment for several types of cancers. In 2000, Taxol, the conventional formulation of PTX, became the best-selling cancer drug of all time with annual sales of 1.6 billion. In 2005, the introduction of the albumin-based formulation of PTX, known as Abraxane, ended Taxol's monopoly of the PTX market. Abraxane's ability to push the Taxol innovator and generic formulations aside attracted fierce competition amongst competitors worldwide to develop their own unique, new and improved formulation of PTX. At this time there are at least 18 companies focused on pre-clinical and/or clinical development of nano-formulations of PTX. These pharmaceutical companies are investing substantial capital to capture a share of the lucrative global PTX market. It is hoped that any formulation that dominates the market will result in tangible benefits to patients in terms of both survival and quality of life. Given all of this activity, here we address the question: Who is going to win the battle of "nano" paclitaxel? Copyright © 2017 Elsevier B.V. All rights reserved.

Insights into the Distinct Mechanisms of Action of Taxane and Non-Taxane Microtubule Stabilizers from Cryo-EM Structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kellogg, Elizabeth H.; Hejab, Nisreen M. A.; Howes, Stuart

A number of microtubule (MT)-stabilizing agents (MSAs) have demonstrated or predicted potential as anticancer agents, but a detailed structural basis for their mechanism of action is still lacking. We have obtained high-resolution (3.9–4.2 Å) cryo-electron microscopy (cryo-EM) reconstructions of MTs stabilized by the taxane-site binders Taxol and zampanolide, and by peloruside, which targets a distinct, non-taxoid pocket on β-tubulin. We find that each molecule has unique distinct structural effects on the MT lattice structure. Peloruside acts primarily at lateral contacts and has an effect on the “seam” of heterologous interactions, enforcing a conformation more similar to that of homologous (i.e., non-seam)more » contacts by which it regularizes the MT lattice. In contrast, binding of either Taxol or zampanolide induces MT heterogeneity. In doubly bound MTs, peloruside overrides the heterogeneity induced by Taxol binding. Our structural analysis illustrates distinct mechanisms of these drugs for stabilizing the MT lattice and is of relevance to the possible use of combinations of MSAs to regulate MT activity and improve therapeutic potential.« less

The Chemical Synthesis of Discodermolide

NASA Astrophysics Data System (ADS)

Paterson, I.; Florence, G. J.

The marine sponge-derived polyketide discodermolide is a potent antimitotic agent that represents a promising natural product lead structure in the treatment of cancer. Discodermolide shares the same microtubule-stabilising mechanism of action as Taxol®, inhibits the growth of solid tumours in animal models and shows synergy with Taxol. The pronounced cytotoxicity of discodermolide, which is maintained against cancer cell lines that display resistance to Taxol and other drugs, combined with its scarce availability from its natural source, has fuelled significant academic and industrial interest in devising a practical total synthesis as a means of ensuring a sustainable supply for drug development. This chapter surveys the various total syntheses of discodermolide that have been completed over the period 1993-2007, focusing on the strategies employed for introduction of the multiple stereocentres and achieving control over the alkene geometry, along with the various methods used for realising the pivotal fragment couplings to assemble progressively the full carbon skeleton. This dedicated synthetic effort has triumphed in removing the supply problem for discodermolide, providing sufficient material for extensive biological studies and enabling its early stage clinical development, as well as facilitating SAR studies for lead optimisation.

Materials Research Society (MRS) 2014 Fall Meeting, Boston, MA on November 30 December 5, 2014

DTIC Science & Technology

2015-12-18

10.1557/opl.2015.216, Published online by Cambridge University Press 03 Mar 2015 Lithium - ion Diffusion in Solid Electrolyte Interface (SEI) Predicted by...challenges; Innovation and Inclusion: What It Takes to Move Diversity Forward, Vern Myers, Esq., principal of Vern Myers Consulting Group, LLC, engaged...bacteriophage to synthesize radically novel electronic and battery devices at protein and semiconductor interfaces. Ashutosh Chilkoti (Duke Univ

Shared Displays: An Overview of Perceptual and Cognitive Issues

DTIC Science & Technology

2007-06-01

workload (Emery, L ., Catchpole, K., Macklin, C., Dudfield, H., & Myers, E., 2001) during a simulated C2 exercise at the Joint Force Air Component...individual workstations, shared displays, and C2 personnel. REFERENCES Aleva, D. L ., & Meyer, F. M. (2004). AFRL battlespace visualization branch...education. Emery, L ., Catchpole, K., Macklin, C., Dudfield, H., & Myers, E. (2001). Big is better? Empirical results of an assessment of command teams

Ecosystem Services Connect Environmental Change to Human Health Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bayles, Brett R.; Brauman, Kate A.; Adkins, Joshua N.

Global environmental change, driven in large part by human activities, profoundly impacts the structure and functioning of Earth’s ecosystems (Millennium Ecosystem Assessment 2005). We are beginning to push beyond planetary boundaries (Steffan et al. 2015), and the consequences for human health remain largely unknown (Myers et al. 2013). Growing evidence suggests that ecological transformations can dramatically affect human health in ways that are both obvious and obscure (Myers and Patz 2009; Myers et al. 2013). The framework of ecosystem services, designed to evaluate the benefits that people derive from ecosystem products and processes, provides a compelling framework for integrating themore » many factors that influence the human health response to global change, as well as for integrating health impacts into broader analyses of the impacts of this change« less

Biomarker Discovery Using New Metabolomics Software for Automated Processing of High Resolution LC-MS Data

PubMed Central

Hnatyshyn, S.; Reily, M.; Shipkova, P.; McClure, T.; Sanders, M.; Peake, D.

2011-01-01

Robust biomarkers of target engagement and efficacy are required in different stages of drug discovery. Liquid chromatography coupled to high resolution mass spectrometry provides sensitivity, accuracy and wide dynamic range required for identification of endogenous metabolites in biological matrices. LCMS is widely-used tool for biomarker identification and validation. Typical high resolution LCMS profiles from biological samples may contain greater than a million mass spectral peaks corresponding to several thousand endogenous metabolites. Reduction of the total number of peaks, component identification and statistical comparison across sample groups remains to be a difficult and time consuming challenge. Blood samples from four groups of rats (male vs. female, fully satiated and food deprived) were analyzed using high resolution accurate mass (HRAM) LCMS. All samples were separated using a 15 minute reversed-phase C18 LC gradient and analyzed in both positive and negative ion modes. Data was acquired using 15K resolution and 5ppm mass measurement accuracy. The entire data set was analyzed using software developed in collaboration between Bristol Meyers Squibb and Thermo Fisher Scientific to determine the metabolic effects of food deprivation on rats. Metabolomic LC-MS data files are extraordinarily complex and appropriate reduction of the number of spectral peaks via identification of related peaks and background removal is essential. A single component such as hippuric acid generates more than 20 related peaks including isotopic clusters, adducts and dimers. Plasma and urine may contain 500-1500 unique quantifiable metabolites. Noise filtering approaches including blank subtraction were used to reduce the number of irrelevant peaks. By grouping related signals such as isotopic peaks and alkali adducts, data processing was greatly simplified by reducing the total number of components by 10-fold. The software processes 48 samples in under 60minutes. Principle

Adding Value to Large Multimedia Collections through Annotation Technologies and Tools: Serving Communities of Interest.

ERIC Educational Resources Information Center

Shabajee, Paul; Miller, Libby; Dingley, Andy

A group of research projects based at HP-Labs Bristol, the University of Bristol (England) and ARKive (a new large multimedia database project focused on the worlds biodiversity based in the United Kingdom) are working to develop a flexible model for the indexing of multimedia collections that allows users to annotate content utilizing extensible…

Psychological Type and Preferences in the Academic Environment

DTIC Science & Technology

1994-09-01

INTJ Perceiving ISTP ISFP INFP INTP EXTRA VERSION Perceiving ESTP ESFP ENFP ENTP Judging ESTJ ESFJ ENFJ ENTJ (Kroeger and Thuesen, 1992: 44) (Note: In...significant relationships between the components of an individual’s psychological type and cognitive style, as measured by the Myers-Briggs Type Indicator...nature and addressed the following question: What are the relationships between the preferences as measured by the Myers-Briggs Type Indicator (MBTI) and

On Risk: Risk and Decision Making in Military Combat and Training Environments

DTIC Science & Technology

2012-12-01

DECISION MAKING IN MILITARY COMBAT AND TRAINING ENVIRONMENTS by Matthew R. Myer Jason R. Lojka December 2012 Thesis Advisor...SUBTITLE ON RISK: RISK AND DECISION MAKING IN MILITARY COMBAT AND TRAINING ENVIRONMENTS 5. FUNDING NUMBERS 6. AUTHOR(S) Matthew R. Myer and Jason R...of the nation that has sent them abroad. It is paramount, therefore, that we utilize a decision process to reveal how emotions can affect our

Using a Tracking System to Improve Prostate Cancer Screening and Follow-up in a Small Urban Community

DTIC Science & Technology

2001-05-01

clinical practice, attention is directed toward informing the general public about them. In the late 1980 ’s, the Prostate Cancer Education Council...impact of abnormal mammograms on psychosocial outcomes and subsequent screening. PsychoOncology, 9, 402-410. Myers, R.E., Hyslop T., Jennings-Dozier, K...impact of abnormal mammograms on psychosocial outcomes and subsequent screening. PsychoOncology, 9, 402- 410. Myers, R.E., Hyslop T., Jennings-Dozier, K

Military Police Brigade, Operational Art, and the Army Operating Concept 2016-2028

DTIC Science & Technology

2011-05-19

The Military Police Brigade, Operational Art , and the Army Operating Concept 2016-2028 A Monograph by Major Jon P. Myers United States...Brigade, Operational Art , and the Army Operating Concept 2016-2028 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS MAJ Jon P. Myers 6. AUTHOR(S...to, operational art by military police brigades and demonstrate their viability as a bridging mechanism to the operating concepts of wide area

Kernel ADA Programming Support Environment (KAPSE) Interface Team Public Report. Volume 4.

DTIC Science & Technology

1984-04-30

the document until further discussion has taken place among the group metbers. RACWG announced their editor, Reed Kotler . The RACWG plans to narrow...KRUTAR, Rudy NRL *LAPLANT, Bill HQ USAF LOPER, Warren NOSC *MAGLIERI, Lucas Canadian National Defense HQ MILLER, Jo NWC MYERS, Gil NOSC *MYERS, Philip ...HUMPHREY, Dianna Control Data Corp. JOHNSON, Ron Boeing Aerospace Co. KERNER, Judy Norden Systems KOTLER , Reed Lockheed Missiles & Space LAMB, J. Eli

Activation of maternal centrosomes in unfertilized sea urchin eggs

NASA Technical Reports Server (NTRS)

Schatten, H.; Walter, M.; Biessmann, H.; Schatten, G.

1992-01-01

Centrosomes are undetectable in unfertilized sea urchin eggs, and normally the sperm introduces the cell's microtubule-organizing center (MTOC) at fertilization. However, artificial activation or parthenogenesis triggers microtubule assembly in the unfertilized egg, and this study explores the reappearance and behavior of the maternal centrosome. During activation with A23187 or ammonia, microtubules appear first at the cortex; centrosomal antigen is detected diffusely throughout the entire cytoplasm. Later, the centrosome becomes more distinct and organizes a radial microtubule shell, and eventually a compact centrosome at the egg center organizes a monaster. In these activated eggs, centrosomes undergo cycles of compaction and decompaction in synchrony with the chromatin, which also undergoes cycles of condensation and decondensation. Parthenogenetic activation with heavy water (50% D2O) or the microtubule-stabilizing drug taxol (10 microM) induces numerous centrosomal foci in the unfertilized sea urchin egg. Within 15 min after incubation in D2O, numerous fine centrosomal foci are detected, and they organize a connected network of numerous asters which fill the entire egg. Taxol induces over 100 centrosomal foci by 15 min after treatment, which organize a corresponding number of asters. The centrosomal material in either D2O- or taxol-treated eggs aggregates with time to form fewer but denser foci, resulting in fewer and larger asters. Fertilization of eggs pretreated with either D2O or taxol shows that the paternal centrosome is dominant over the maternal centrosome. The centrosomal material gradually becomes associated with the enlarged sperm aster. These experiments demonstrate that maternal centrosomal material is present in the unfertilized egg, likely as dispersed undetectable material, which can be activated without paternal contributions. At fertilization, paternal centrosomes become dominant over the maternal centrosomal material.

Synthesis and Turnover of Embryonic Sea Urchin Ciliary Proteins during Selective Inhibition of Tubulin Synthesis and Assembly

PubMed Central

Stephens, Raymond E.

1997-01-01

When ciliogenesis first occurs in sea urchin embryos, the major building block proteins, tubulin and dynein, exist in substantial pools, but most 9+2 architectural proteins must be synthesized de novo. Pulse-chase labeling with [3H]leucine demonstrates that these proteins are coordinately up-regulated in response to deciliation so that regeneration ensues and the tubulin and dynein pools are replenished. Protein labeling and incorporation into already-assembled cilia is high, indicating constitutive ciliary gene expression and steady-state turnover. To determine whether either the synthesis of tubulin or the size of its available pool is coupled to the synthesis or turnover of the other 9+2 proteins in some feedback manner, fully-ciliated mid- or late-gastrula stage Strongylocentrotus droebachiensis embryos were pulse labeled in the presence of colchicine or taxol at concentrations that block ciliary growth. As a consequence of tubulin autoregulation mediated by increased free tubulin, no labeling of ciliary tubulin occurred in colchicine-treated embryos. However, most other proteins were labeled and incorporated into steady-state cilia at near-control levels in the presence of colchicine or taxol. With taxol, tubulin was labeled as well. An axoneme-associated 78 kDa cognate of the molecular chaperone HSP70 correlated with length during regeneration; neither colchicine nor taxol influenced the association of this protein in steady-state cilia. These data indicate that 1) ciliary protein synthesis and turnover is independent of tubulin synthesis or tubulin pool size; 2) steady-state incorporation of labeled proteins cannot be due to formation or elongation of cilia; 3) substantial tubulin exchange takes place in fully-motile cilia; and 4) chaperone presence and association in steady-state cilia is independent of background ciliogenesis, tubulin synthesis, and tubulin assembly state. PMID:9362062

Factors Influencing Teachers in Engaging with University Outreach: Is It Just Cost?

ERIC Educational Resources Information Center

Glover, S. R.; Harrison, T. G.; Shallcross, D. E.

2016-01-01

A chemistry outreach day event was offered, free-of-charge, to schools in the south west of England who do not normally engage with Bristol ChemLabS outreach events delivered at the University of Bristol. The participating teachers were interviewed to find out their expectations of the day in terms of helping their students or in helping the…

50 CFR Table 9 to Part 680 - Initial Issuance of Crab PQS by Crab QS Fishery

Code of Federal Regulations, 2011 CFR

2011-10-01

... fisheries for any... Bristol Bay red king crab (BBR) 3 years of the 3-year QS base period beginning on: (1... Bristol Bay red king crab fishery during the qualifying years established for that fishery. Pribilof Islands red and blue king crab (PIK) 3 years of the 3-year period beginning on: (1) September 15-26, 1996...

50 CFR Table 9 to Part 680 - Initial Issuance of Crab PQS by Crab QS Fishery

Code of Federal Regulations, 2010 CFR

2010-10-01

... fisheries for any... Bristol Bay red king crab (BBR) 3 years of the 3-year QS base period beginning on: (1... Bristol Bay red king crab fishery during the qualifying years established for that fishery. Pribilof Islands red and blue king crab (PIK) 3 years of the 3-year period beginning on: (1) September 15-26, 1996...

Opening a window of opportunity through technology and coordination: a multisite case study.

PubMed

Cherry, Julie Cheitlin; Dryden, Kirsten; Kobb, Rita; Hilsen, Patricia; Nedd, Nicole

2003-01-01

The Community Care Coordination Service (CCCS) program was implemented in April, 2000, at the Veterans Integrated Service Network (VISN 8). The goals of the CCCS were to improve the coordination of care for clinically complex patients, referred to as veterans, and to increase their access to care while reducing complications, hospital admissions, and emergency room (ER) visits. This program used a coordinated care approach, a process whereby veterans were followed throughout the continuum of care. The information presented in this case study is specific to three medical centers that implemented the CCCS: Ft. Myers, Lake City, and Miami. Analysis of utilization and clinical impact were conducted after 18 months. Inpatient admissions were reduced by 46% at Ft. Myers, 68% at Lake City, and 13% at Miami. ER encounters were reduced by 19% at Ft. Myers, 70% at Lake City, and 15% at Miami. Reductions in bed days were demonstrated at Ft. Myers (29%) and Lake City (71%). In Miami, there was a 13% increase in the number of bed days of care for the patients after 1 year in the program. In addition to these changes in health-care utilization, quality of life was significantly improved as evidenced by increases in the four of the eight components scores of the Medical Outcomes Study 36-item Short Form health survey for veterans (SF36V) at Lake City and Ft. Myers. In the CCCS model of care using home telehealth technology, the Care Coordinators bridged the gap between office visits by providing a daily connection between the coordinators and the patients. This daily communication made it possible for problems to be identified early and interventions implemented before problems escalated.

Bio-production of Baccatin III, an Important Precursor of Paclitaxel by a Cost-Effective Approach.

PubMed

Lin, Shu-Ling; Wei, Tao; Lin, Jun-Fang; Guo, Li-Qiong; Wu, Guang-Pei; Wei, Jun-Bin; Huang, Jia-Jun; Ouyang, Ping-Lan

2018-07-01

Natural production of anti-cancer drug taxol from Taxus has proved to be environmentally unsustainable and economically unfeasible. Currently, bioengineering the biosynthetic pathway of taxol is an attractive alternative production approach. 10-deacetylbaccatin III-10-O-acetyl transferase (DBAT) was previously characterized as an acyltransferase, using 10-deacetylbaccatin III (10-DAB) and acetyl CoA as natural substrates, to form baccatin III in the taxol biosynthesis. Here, we report that other than the natural acetyl CoA (Ac-CoA) substrate, DBAT can also utilize vinyl acetate (VA), which is commercially available at very low cost, acylate quickly and irreversibly, as acetyl donor in the acyl transfer reaction to produce baccatin III. Furthermore, mutants were prepared via a semi-rational design in this work. A double mutant, I43S/D390R was constructed to combine the positive effects of the different single mutations on catalytic activity, and its catalytic efficiency towards 10-DAB and VA was successfully improved by 3.30-fold, compared to that of wild-type DBAT, while 2.99-fold higher than the catalytic efficiency of WT DBAT towards 10-DAB and Ac-CoA. These findings can provide a promising economically and environmentally friendly method for exploring novel acyl donors to engineer natural product pathways.

FAA Aviation Forecasts

DTIC Science & Technology

1992-02-01

MKK) Daytona Beach, FL (DAB) Boise, ID (BOI) Fort Lauderdale, FL (FLL) Idaho Falls Fanning Field, ID (IDA) Fort Lauderdale Executive, FL (FXE... Lewiston , ID (LWS) Fort Myers Page Field, FL (FMY) Pocatello, ID (PIH) Fort Myers Regional, FL (RSW) Twin Falls, ID (TWF) Fort Pierce, FL (FPR) Alton St... Idaho (SUN) 6. Marion Williamson County, Illinois (MWA) 7. Waukegan, Illinois (UGN) 8. Topeka-Phillip Ballard, Kansas (TOP) 9. Owensboro-Daviees County

Army Communicator. Volume 35, Number 2

DTIC Science & Technology

2010-01-01

official U.S. Army position and does not change or supersede any information in other official U.S. Army publications. Use of news items constitutes...familiar with the Bain electrochemical telegraph system. Myer used this experience to devise A New Sign Language for Deaf Mutes, the subject of his...Signal officer on 27 June thus becoming the first Signal officer in the U.S. Army. Myer tested his wigwag system during operations in New

28. VIEW OF WHITE SAGE PRIOR TO BEING PAINTED COAST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

28. VIEW OF WHITE SAGE PRIOR TO BEING PAINTED COAST GUARD COLORS OF BLACK AND WHITE. NOTE ALSO THE PHOTOGRAPH WAS TAKEN PRIOR TO THE INSTALLATION OF A-FRAME MAST AND BOOM AND TO THE CONSTRUCTION OF TURTLE DECK. - U.S. Coast Guard Cutter WHITE SAGE, U.S. Coast Guard 1st District Base, 1 Thames Street, Bristol, Bristol County, RI

50 CFR Table 7 to Part 680 - Initial Issuance of Crab QS by Crab QS Fishery

Code of Federal Regulations, 2011 CFR

2011-10-01

... used to calculate QS for each QS fishery is: 1. Bristol Bay red king crab (BBR) 4 years of the 5-year..., Western Aleutian Island golden (brown) king crab, Bering Sea snow crab, or Bristol Bay red king crab fisheries. 4 years 5. Pribilof red king and blue king crab (PIK) 4 years of the 5-year period beginning on...

Types of Weapon Programs and Their Implications for NATO Standardization or Interoperability

DTIC Science & Technology

1978-07-01

mines , etc.). 3. Enemy Counter-measures. Lack of standardisation or Interoperability complicates Warsaw Pact problem by forcing them to counter...Licensed Production U.K. Sikorsky S-5F helicopter (U.S.) (Westland, "Hessex") Canada Canadair CC-106 transport (derivative of the Bristol Britannia ...U.K.) Canadair CP-107 Argus maritime reconnaissance aircraft (modification of the Bristol Britannia , U.K.) Federal Republic of Germany Air-Fouga

Toward Development of an Integrated Aerospace Power Doctrine.

DTIC Science & Technology

1999-03-01

W. Ashy, Howell M. Estes III, and Richard B. Myers. 33 Air Force in 2025," Grant Hammond claims, "Space Command is to the US Air Force today as the...special program, like special operations"(1 32). General Richard Myers (USAF), current USCINCSPACE, thinks the questioning of the Air Force’s leadership of...be unavailable"(33:42-3). Air Force Historian Richard Hallion has implied functions by describing doctrine as being "the binder, the adhesive

Inhibition of the MUC1-C oncoprotein is synergistic with cytotoxic agents in the treatment of breast cancer cells

PubMed Central

Uchida, Yasumitsu; Raina, Deepak; Kharbanda, Surender; Kufe, Donald

2013-01-01

Mucin 1 (MUC1) is a heterodimeric glycoprotein that is aberrantly overexpressed in most human breast cancers. The oncogenic MUC1-C subunit promotes survival and blocks the apoptotic response to genotoxic anticancer agents. In the present studies, human MCF-7 and ZR-75-1 breast cancer cells were treated with the MUC1-C inhibitor, GO-203, a cell-penetrating peptide that blocks MUC1-C homodimerization and thereby its oncogenic function. Treatment with GO-203 was found to promote the apoptotic response of MCF-7 and ZR-75-1 cells to the therapeutic drugs taxol and doxorubicin (DOX). This effect was (1) attenuated by a pan-caspase inhibitor, and (2) mediated, at least in part, by activation of the effector caspase-7 and cleavage of the downstream substrate PARP. Further analysis of the interaction between GO-203 and taxol using isobolograms, which evaluate the nature of the interaction of two drugs, demonstrated that the combination is highly synergistic. These results were supported by combination index (CI) analysis with values of less than 1. GO-203 was also highly synergistic with DOX in studies of both MCF-7 and ZR-75-1 breast cancer cells. These findings indicate that blocking MUC1-C function could be effective in combination with taxol and DOX for the treatment of breast cancer. PMID:23114713

The in vitro sub-cellular localization and in vivo efficacy of novel chitosan/GMO nanostructures containing paclitaxel.

PubMed

Trickler, W J; Nagvekar, A A; Dash, A K

2009-08-01

To determine the in vitro sub-cellular localization and in vivo efficacy of chitosan/GMO nanostructures containing paclitaxel (PTX) compared to a conventional PTX treatment (Taxol). The sub-cellular localization of coumarin-6 labeled chitosan/GMO nanostructures was determined by confocal microscopy in MDA-MB-231 cells. The antitumor efficacy was evaluated in two separate studies using FOX-Chase (CB17) SCID Female-Mice MDA-MB-231 xenograph model. Treatments consisted of intravenous Taxol or chitosan/GMO nanostructures with or without PTX, local intra-tumor bolus of Taxol or chitosan/GMO nanostructures with or without PTX. The tumor diameter and animal weight was monitored at various intervals. Histopathological changes were evaluated in end-point tumors. The tumor diameter increased at a constant rate for all the groups between days 7-14. After a single intratumoral bolus dose of chitosan/GMO containing PTX showed significant reduction in tumor diameter on day 15 when compared to control, placebo and intravenous PTX administration. The tumor diameter reached a maximal decrease (4-fold) by day 18, and the difference was reduced to approximately 2-fold by day 21. Qualitatively similar results were observed in a separate study containing PTX when administered intravenously. Chitosan/GMO nanostructures containing PTX are safe and effective administered locally or intravenously. Partially supported by DOD Award BC045664.

Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial.

PubMed

Lalezari, Jacob P; Latiff, Gulam H; Brinson, Cynthia; Echevarría, Juan; Treviño-Pérez, Sandra; Bogner, Johannes R; Thompson, Melanie; Fourie, Jan; Sussmann Pena, Otto A; Mendo Urbina, Fernando C; Martins, Marcelo; Diaconescu, Iulian G; Stock, David A; Joshi, Samit R; Hanna, George J; Lataillade, Max

2015-10-01

received at least one dose of ritonavir-boosted atazanavir. At week 24, 40 (80%) of 50 patients in the BMS-663068 400 mg twice daily group, 34 (69%) of 49 patients in the 800 mg twice daily group, 39 (76%) of 51 patients in the 600 mg once daily group, and 36 (72%) of 50 patients in the 1200 mg once daily group had an HIV-1 RNA viral load less than 50 copies per mL, compared with 38 (75%) of 51 patients in the ritonavir-boosted atazanavir group. Serious adverse events were noted in 13 (7%) of 200 patients in the BMS-663068 groups and five (10%) of the 51 patients in the ritonavir-boosted atazanavir group. Four (2%) of the 200 patients in the BMS-663068 groups and two (4%) of the 51 patients in the ritonavir-boosted atazanavir group discontinued because of adverse events. No serious adverse events or adverse events leading to discontinuation were BMS-663068-related. Grade 2-4 adverse events related to study drug(s) occurred in 17 (9%) of 200 patients across the BMS-663068 groups and 14 (27%) of 51 patients in the ritonavir-boosted atazanavir group. For the BMS-663068 groups these events were mostly single instances with no dose relation and for the ritonavir-boosted atazanavir group these were mostly gastrointestinal or hepatobiliary disorders associated with hyperbilirubinaemia. In a comparison with ritonavir-boosted atazanavir, efficacy and safety of BMS-663068 up to the week 24 analysis support continued development of BMS-663068, which is being assessed in a phase 3 trial in heavily treatment-experienced individuals. Bristol-Myers Squibb. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial.

PubMed

Del Mastro, Lucia; De Placido, Sabino; Bruzzi, Paolo; De Laurentiis, Michele; Boni, Corrado; Cavazzini, Giovanna; Durando, Antonio; Turletti, Anna; Nisticò, Cecilia; Valle, Enrichetta; Garrone, Ornella; Puglisi, Fabio; Montemurro, Filippo; Barni, Sandro; Ardizzoni, Andrea; Gamucci, Teresa; Colantuoni, Giuseppe; Giuliano, Mario; Gravina, Adriano; Papaldo, Paola; Bighin, Claudia; Bisagni, Giancarlo; Forestieri, Valeria; Cognetti, Francesco

2015-05-09

chemotherapy-type comparison, disease-free survival at 5 years was 78% (75-81) in the FEC-P groups and 79% (76-82) in the EC-P groups (HR 1·06, 0·89-1·25; p=0·561); overall survival rates at 5 years were 91% (89-93) and 92% (90-94; 1·16, 0·91-1·46; p=0·234). Compared with 3 week dosing, chemotherapy every 2 weeks was associated with increased rate of grade 3-4 of anaemia (14 [1·4%] of 988 patients vs two [0·2%] of 984 patients; p=0·002); transaminitis (19 [1·9%] vs four [0·4%]; p=0·001), and myalgias (31 [3·1%] vs 16 [1·6%]; p=0·019), and decreased rates of grade 3-4 neutropenia (147 [14·9%] vs 433 [44·0%]; p<0·0001). Addition of fluorouracil led to increased rates of grade 3-4 neutropenia (354 [34·5%] of 1025 patients on FEC-P vs 250 [24·2%] of 1032 patients on EC-P; p<0·0001), fever (nine [0·9%] vs two [0·2%]), nausea (47 [4·6%] vs 28 [2·7%]), and vomiting (32 [3·1%] vs 15 [1·4%]). In patients with node-positive early breast cancer, dose-dense adjuvant chemotherapy improved disease-free survival compared with standard interval chemotherapy. Addition of fluorouracil to a sequential EC-P regimen was not associated with an improved disease-free survival outcome. Bristol-Myers Squibb, Pharmacia, and Dompè Biotec. Copyright © 2015 Elsevier Ltd. All rights reserved.

Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis.

PubMed

Sterne, Jonathan Ac; Bodalia, Pritesh N; Bryden, Peter A; Davies, Philippa A; López-López, Jose A; Okoli, George N; Thom, Howard Hz; Caldwell, Deborah M; Dias, Sofia; Eaton, Diane; Higgins, Julian Pt; Hollingworth, Will; Salisbury, Chris; Savović, Jelena; Sofat, Reecha; Stephens-Boal, Annya; Welton, Nicky J; Hingorani, Aroon D

2017-03-01

15 September 2014, and covered the period 2010 to September 2014. The search for the three reviews in VTE was run on the 19 March 2014, updated on 15 September 2014, and covered the period 2008 to September 2014. Two reviewers screened search results, extracted and checked data, and assessed risk of bias. For each outcome we conducted standard meta-analysis and NMA. We evaluated cost-effectiveness using discrete-time Markov models. Apixaban (Eliquis ® , Bristol-Myers Squibb, USA; Pfizer, USA) [5 mg bd (twice daily)] was ranked as among the best interventions for stroke prevention in AF, and had the highest expected net benefit. Edoxaban (Lixiana ® , Daiichi Sankyo, Japan) [60 mg od (once daily)] was ranked second for major bleeding and all-cause mortality. Neither the clinical effectiveness analysis nor the CEA provided strong evidence that NOACs should replace postoperative LMWH in primary prevention of VTE. For acute treatment and secondary prevention of VTE, we found little evidence that NOACs offer an efficacy advantage over warfarin, but the risk of bleeding complications was lower for some NOACs than for warfarin. For a willingness-to-pay threshold of > £5000, apixaban (5 mg bd) had the highest expected net benefit for acute treatment of VTE. Aspirin or no pharmacotherapy were likely to be the most cost-effective interventions for secondary prevention of VTE: our results suggest that it is not cost-effective to prescribe NOACs or warfarin for this indication. NOACs have advantages over warfarin in patients with AF, but we found no strong evidence that they should replace warfarin or LMWH in primary prevention, treatment or secondary prevention of VTE. These relate mainly to shortfalls in the primary data: in particular, there were no head-to-head comparisons between different NOAC drugs. Calculating the expected value of sample information to clarify whether or not it would be justifiable to fund one or more head-to-head trials. This study is

Synchronously Pumped Optical Parametric Oscillator with Intracavity Difference Frequency Mixing

DTIC Science & Technology

1998-06-29

Phys. B, vol. 63, no. 5, pp. 437-441, 1996. [11] T. Töpfer, K. P. Petrov, Y. Mine, L. E. Myers, and R. W. Wallace , "Room- temperature midinfrared...generation in diazo-dye-substitured polymer channel waveguides," IEEE J. of Quant. Electron., vol. 33, no. 3, pp. 349-357, 1997. [56] A. Szilagyi ...periodically poled lithium- niobate," Opt. Lett, vol. 23, no. 9, pp. 664-666, 1998. [119] W. R. Bosenberg, J. I. Alexander, L. E. Myers, and R. W. Wallace

The Electra KRF Laser System

DTIC Science & Technology

2007-06-01

the Naval Research Laboratory used to advance the technology towards a KrF laser driver for inertial fusion energy [1-7]. Electra consists of two e...krypton fluoride lasers for fusion energy ," Proc. IEEE, vol. 92, pp. 1043-1056, July 2004. [2] M. C. Myers, J. D. Sethian, J. L. Giuliani, R. Lehmberg...KrF lasers for inertial fusion energy ," Nucl. Fusion, vol. 44, pp. S247-S253, Nov. 2004. [3] J. D. Sethian, M. Friedman, R. H. Lehmberg, M. Myers

Prevention of chemotherapy-induced alopecia in rodent models

PubMed Central

Jimenez, Joaquin J.; Roberts, Stephen M.; Mejia, Jessica; Mauro, Lucia M.; Munson, John W.; Elgart, George W.; Connelly, Elizabeth Alvarez; Chen, Qingbin; Zou, Jiangying; Goldenberg, Carlos

2008-01-01

Alopecia (hair loss) is experienced by thousands of cancer patients every year. Substantial-to-severe alopecia is induced by anthracyclines (e.g., adriamycin), taxanes (e.g., taxol), alkylating compounds (e.g., cyclophosphamide), and the topisomerase inhibitor etoposide, agents that are widely used in the treatment of leukemias and breast, lung, ovarian, and bladder cancers. Currently, no treatment appears to be generally effective in reliably preventing this secondary effect of chemotherapy. We observed in experiments using different rodent models that localized administration of heat or subcutaneous/intradermal injection of geldanamycin or 17-(allylamino)-17-demethoxygeldanamycin induced a stress protein response in hair follicles and effectively prevented alopecia from adriamycin, cyclophosphamide, taxol, and etoposide. Model tumor therapy experiments support the presumption that such localized hair-saving treatment does not negatively affect chemotherapy efficacy. PMID:18347939

Political non-speak. Gadfly: Norman Myers.

PubMed

Myers, N

1992-01-01

Election years in Britain, the USA, France, and Italy have not granted the environment a high place on the political agenda even in the year of the UN Conference on Environment and Development (UNCED). The erosion of the natural resources base is not included as natural resource accounting in the computation of gross national product (GNP). In countries such as Germany, Australia, Indonesia, and Costa Rica, 50% of GNP growth annually is cancelled out by soil erosion, pollution, excessive logging, and other environmental degradation. The economic health of the country including recovery from recessions is related to environmental protection. The economic practices involve ecological deficit accounting. It has been suggested by Lester Brown of the Worldwatch Institute that an economical deflator is needed to gage economic progress. The ecological illiteracy of politicians prevents the American people from realizing the actual cost of ignoring the problems. Politicians fight against raising taxes on gasoline and ignore the cost of carbon dioxide emissions and destabilization of climate. Americans pay a 1/4 the price Europeans pay for gasoline. Energy conservation must be expanded from current levels. Improvements have been made since the first OPEC price hike in 1973; the economy saved $100 billion a year and improved efficiency and production. American conservation in line with European conservation would save $200 billion a year; matching Japanese conservation would generate a savings of $300 billion. This sum exceeds the Federal deficit or the Pentagon budget. It is enough to save 8 million children who die from preventable causes or provide $4.5 billion/year annually to the year 2000 for foreign aid for UN family planning programs. The savings compares favorable with the UNCED estimates of $125 billion/year for environmental protection in the South. The question is whether politicians really would be committing political suicide by listening less to oil and car lobbyists and listening more to those promoting long term interests and security.

Earth observations taken during the STS-77 mission

NASA Image and Video Library

1996-05-26

STS077-744-046 (19-29 May 1996) --- This view shows ship wakes off the coast of Fort Myers, Florida. The Sun glint reflecting off the ocean surfaces allowed man-made features to be seen and photographed by the astronaut crew members. When a ship or boat goes through the water it disturbs the surface of the water which causes the Sun?s rays to reflect back differently than the surrounding waters. Photographed on a weekend, this image illustrates how popular recreational boating is around the Fort Myers area.

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis

PubMed Central

Chmielowski, Bartosz; Lao, Christopher D.; Hodi, F. Stephen; Sharfman, William; Weber, Jeffrey; Suijkerbuijk, Karijn P. M.; Azevedo, Sergio; Li, Hewei; Reshef, Daniel; Avila, Alexandre; Reardon, David A.

2017-01-01

Abstract Background. Despite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune‐related adverse events (irAEs), including neurologic events ranging from mild headache to potentially life‐threatening encephalitis. Here, we summarize neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment, present cases of treatment‐related encephalitis, and provide practical guidance on diagnosis and management. Methods. We searched a Global Pharmacovigilance and Epidemiology database for neurologic irAEs reported over an 8‐year period in patients with advanced melanoma receiving nivolumab with or without ipilimumab from 12 studies sponsored by Bristol‐Myers Squibb. Serious neurologic irAEs were reviewed, and relationship to nivolumab or ipilimumab was assigned. Results. In our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious neurologic irAEs, including neuropathy (n = 22), noninfective meningitis (n = 5), encephalitis (n = 6), neuromuscular disorders (n = 3), and nonspecific adverse events (n = 7). Study drug was discontinued (n = 20), interrupted (n = 8), or unchanged (n = 7). Most neurologic irAEs resolved (26/35 patients; 75%). Overall, median time to onset was 45 days (range 1–170) and to resolution was 32 days (2–809+). Median time to onset of encephalitis was 55.5 days (range 18–297); four cases resolved and one was fatal. Conclusion. Both oncologists and neurologists need to be aware of signs and symptoms of serious but uncommon neurologic irAEs associated with checkpoint inhibitors. Prompt diagnosis and management using an established algorithm are critical to minimize serious complications from these neurologic irAEs. Implications for Practice. With increasing use of checkpoint inhibitors in cancer, practicing oncologists need to be aware of the potential risk of neurologic immune�

Bibliography on Cold Regions Science and Technology. Volume 34, Part 1 and Part 2

DTIC Science & Technology

1980-12-01

Remote sensing ol the terrestrial environ- ment, edited by R F, Peel ct al. Symposium of the Colston Research Society, 28th. Lniversily of Bristol...edited by R,F, Peel et al. Symposium of the Colston Research Society. 28th. University of Bristol. Apr, 5th to 9th. 1976, Proceedings. London. Butter...be effective in decrepsing the friction factor when it remains intact: when it peels off. it appears to make conditions worse than plain paint. An

Linkages between Alaskan sockeye salmon abundance, growth at sea, and climate, 1955-2002

USGS Publications Warehouse

Ruggerone, G.T.; Nielsen, J.L.; Bumgarner, J.

2007-01-01

We tested the hypothesis that increased growth of salmon during early marine life contributed to greater survival and abundance of salmon following the 1976/1977 climate regime shift and that this, in turn, led to density-dependent reductions in growth during late marine stages. Annual measurements of Bristol Bay (Bering Sea) and Chignik (Gulf of Alaska) sockeye salmon scale growth from 1955 to 2002 were used as indices of body growth. During the first and second years at sea, growth of both stocks tended to be higher after the 1976-1977 climate shift, whereas growth during the third year and homeward migration was often below average. Multiple regression models indicated that return per spawner of Bristol Bay sockeye salmon and adult abundance of western and central Alaska sockeye salmon were positively correlated with growth during the first 2 years at sea and negatively correlated with growth during later life stages. After accounting for competition between Bristol Bay sockeye and Asian pink salmon, age-specific adult length of Bristol Bay salmon increased after the 1976-1977 regime shift, then decreased after the 1989 climate shift. Late marine growth and age-specific adult length of Bristol Bay salmon was exceptionally low after 1989, possibly reducing their reproductive potential. These findings support the hypothesis that greater marine growth during the first 2 years at sea contributed to greater salmon survival and abundance, which in turn led to density-dependent growth during later life stages when size-related mortality was likely lower. Our findings provide new evidence supporting the importance of bottom-up control in marine ecosystems and highlight the complex dynamics of species interactions that continually change as salmon grow and mature in the ocean. ?? 2007 Elsevier Ltd. All rights reserved.

Is it intelligent to intercalate? A two centre cross-sectional study exploring the value of intercalated degrees, and the possible effects of the recent tuition fee rise in England.

PubMed

Stubbs, Timothy Alan; Lightman, Elewys G; Mathieson, Peter

2013-01-24

To explore the value of intercalated degrees, including student perceptions and academic sequelae. To gauge the likely effect of the recent tuition fee rise and to identify any differences in intercalated degrees between Bristol and Sheffield universities. Cross-sectional study using questionnaires. Bristol and Sheffield Medical Schools, UK. 1484 medical students in their clinical years were e-mailed the questionnaire. 578 students responded: 291 from Bristol and 287 from Sheffield (n=578; mean age=22.41; SD 1.944; 38.9% male; 61.1% female). The response rate from previous intercalators was 52.5% from Bristol and 58.7% from Sheffield, while for non-intercalators it was 27.7% and 34.6%, respectively. (1) Student preconceptions, opinions, results and academic sequelae from intercalated degrees at both centres. (2) Students' attitudes concerning the effect of the increase in tuition fees. Those with clinical academic supervisors gained significantly more posters (p=0.0002) and publications (p<0.0001), and also showed a trend to gain more first class honours (p=0.055). Students at Sheffield had a significantly greater proportion of clinical academic supervisors than students at Bristol (p<0.0001). 89.2% said that an intercalated degree was the right decision for them; however, only 27.4% stated they would have intercalated if fees had been £9000 per annum. Students clearly value intercalated degrees, feel they gained a substantial advantage over their peers as well as skills helpful for their future careers. The rise in tuition fees is likely to reduce the number of medical students opting to undertake an intercalated degree, and could result in a further reduction in numbers following an academic path. Sheffield University have more intercalating students supervised by clinical academics. Clinical academics appear more effective as supervisors for medical students undertaking an intercalated degree in terms of results and additional academic sequelae.

Red Maca (Lepidium meyenii) did not affect cell viability despite increased androgen receptor and prostate-specific antigen gene expression in the human prostate cancer cell line LNCaP.

PubMed

Díaz, P; Cardenas, H; Orihuela, P A

2016-10-01

We examined whether aqueous extract of Lepidium meyenii (red Maca) could inhibit growth, potentiate apoptotic activity of two anticancer drugs Taxol and 2-methoxyestradiol (2ME) or change mRNA expression for the androgen target genes, androgen receptor (Ar) and prostate-specific antigen (Psa) in the human prostate cancer cell line LNCaP. Red Maca aqueous extract at 0, 10, 20, 40 or 80 μg/ml was added to LNCaP cells, and viability was evaluated by the MTS assay at 24 or 48 hr after treatment. Furthermore, LNCaP cells were treated with 80 μg/ml of red Maca plus Taxol or 2ME 5 μM and viability was assessed 48 hr later. Finally, LNCaP cells were treated with red Maca 0, 20, 40 or 80 μg/ml, and 12 hr later, mRNA level for Ar or Psa was assessed by real-time PCR. Treatment with red Maca did not affect viability of LNCaP cells. Apoptotic activity induced by Taxol and 2ME in LNCaP cells was not altered with red Maca treatment. Relative expression of the mRNA for Ar and Psa increased with red Maca 20 and 40 μg/ml, but not at 80 μg/ml. We conclude that red Maca aqueous extract does not have toxic effects, but stimulates androgen signalling in LNCaP cells. © 2016 Blackwell Verlag GmbH.

Paclitaxel Nano-Delivery Systems: A Comprehensive Review

PubMed Central

Ma, Ping; Mumper, Russell J.

2013-01-01

Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles. PMID:24163786

Preclinical Pharmacology and Structure-Activity Studies of Epothilones

NASA Astrophysics Data System (ADS)

Altmann, Karl-Heinz

Microtubule inhibitors are an important class of anticancer agents (1), with clinical applications in the treatment of a variety of cancer types, either as single agents or as part of different combination regimens (2, 3). Microtubule-interacting agents can be grouped into two distinct functional classes, namely, compounds that inhibit the assembly of tubulin heterodimers into microtubule polymers (“tubulin polymerization inhibitors”) and those that stabilize microtubules under normally destabilizing conditions (“microtubule stabilizers”) (4). The latter will also promote the assembly of tubulin heterodimers into microtubule polymers and, as will be discussed later, the induction of tubulin polymerization is often used as a biochemical readout for a quantitative assessment of the interaction of microtubule-stabilizing agents with tubulin. Tubulin polymerization inhibitors such as vincristine and vinblastine have been employed in cancer therapy for more than 40 years (vincristine and vinblastine received FDA approval in 1963 and 1965, respectively). In contrast, the clinical history of microtubule-stabilizing agents is significantly shorter and its beginning dates back no more than 15 years. The first microtubule stabilizer to be introduced into clinical practice was the natural product taxol (paclitaxel; Taxol®) in 1993 (Fig. 1), with FDA approval for the semi-synthetic taxol analog docetaxel (Taxotere®) following three years later. Both compounds rapidly became an important part of today’s armamentarium in the battle against cancer,which marks the emergence of microtubule-stabilizing anti-cancer drugs as an important milestone in the development of modern cancer chemotherapy (5).

A novel paclitaxel-loaded poly(d,l-lactide-co-glycolide)-Tween 80 copolymer nanoparticle overcoming multidrug resistance for lung cancer treatment

PubMed Central

Yuan, Xun; Ji, Wenxiang; Chen, Si; Bao, Yuling; Tan, Songwei; Lu, Shun; Wu, Kongming; Chu, Qian

2016-01-01

Drug resistance has become a main obstacle for the effective treatment of lung cancer. To address this problem, a novel biocompatible nanoscale package, poly(d,l-lactide-co-glycolide)-Tween 80, was designed and synthesized to overcome paclitaxel (PTX) resistance in a PTX-resistant human lung cancer cell line. The poly(d,l-lactide-co-glycolide) (PLGA)-Tween 80 nanoparticles (NPs) could efficiently load PTX and release the drug gradually. There was an increased level of uptake of PLGA-Tween 80 in PTX-resistant lung cancer cell line A549/T, which achieved a significantly higher level of cytotoxicity than both PLGA NP formulation and Taxol®. The in vivo antitumor efficacy also showed that PLGA-Tween 80 NP was more effective than Taxol®, indicating that PLGA-Tween 80 copolymer was a promising carrier for PTX in resistant lung cancer. PMID:27307727

STREPTOMYCES NODOSUS SP. N., THE AMPHOTERICIN-PRODUCING ORGANISM

PubMed Central

Trejo, William H.; Bennett, R. E.

1963-01-01

Trejo, William (Squibb Institute for Medical Research, New Brunswick, N.J.) and Ralph E. Bennett. Streptomyces nodosus sp. n., the amphotericin-producing organism. J. Bacteriol. 85:436–439. 1963.—Streptomyces nodosus, the amphotericin-producing organism, is described as a new species in conformity with the rules of nomenclature as applied to streptomycetes. The relationship between S. nodosus and S. rutgersensis is discussed, and the basis for separation of the species is presented. Images PMID:13994057

New Agents for Taxol-Resistant Breast Adenocarcinoma

DTIC Science & Technology

2004-07-01

mg/ mi2 (14) using 3 hr infusion schedules failed to demonstrate marked improvement in disease response or survival, despite incurring severe sensory...analyzed immediately by flow cytometry. Immunoblotting The anti-human HER-2/neu mouse monoclonal antibody , clone 3B5, isotype IgGI, was obtained from...carboxyl domain of the human c-neu gene product. An affinity-purified sheep anti-mouse IgG whole antibody preparation conjugated to horseradish peroxidase

Preparation and characterization of paclitaxel nanosuspension using novel emulsification method by combining high speed homogenizer and high pressure homogenization.

PubMed

Li, Yong; Zhao, Xiuhua; Zu, Yuangang; Zhang, Yin

2015-07-25

The aim of this study was to develop an alternative, more bio-available, better tolerated paclitaxel nanosuspension (PTXNS) for intravenous injection in comparison with commercially available Taxol(®) formulation. In this study, PTXNS was prepared by emulsification method through combination of high speed homogenizer and high pressure homogenization, followed by lyophilization process for intravenous administration. The main production parameters including volume ratio of organic phase in water and organic phase (Vo:Vw+o), concentration of PTX, content of PTX and emulsification time (Et), homogenization pressure (HP) and passes (Ps) for high pressure homogenization were optimized and their effects on mean particle size (MPS) and particle size distribution (PSD) of PTXNS were investigated. The characteristics of PTXNS, such as, surface morphology, physical status of paclitaxel (PTX) in PTXNS, redispersibility of PTXNS in purified water, in vitro dissolution study and bioavailability in vivo were all investigated. The PTXNS obtained under optimum conditions had an MPS of 186.8 nm and a zeta potential (ZP) of -6.87 mV. The PTX content in PTXNS was approximately 3.42%. Moreover, the residual amount of chloroform was lower than the International Conference on Harmonization limit (60 ppm) for solvents. The dissolution study indicated PTXNS had merits including effect to fast at the side of raw PTX and sustained-dissolution character compared with Taxol(®) formulation. Moreover, the bioavailability of PTXNS increased 14.38 and 3.51 times respectively compared with raw PTX and Taxol(®) formulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of Wall Boundary Conditions for Impedance Eduction Using a Dual-Source Method

NASA Technical Reports Server (NTRS)

Watson, W. R.; Jones, M. G.

2012-01-01

The accuracy of the Ingard-Myers boundary condition and a recently proposed modified Ingard-Myers boundary condition is evaluated for use in impedance eduction under the assumption of uniform mean flow. The evaluation is performed at three centerline Mach numbers, using data acquired in a grazing flow impedance tube, using both upstream and downstream propagating sound sources, and on a database of test liners for which the expected behavior of the impedance spectra is known. The test liners are a hard-wall insert consisting of 12.6 mm thick aluminum, a linear liner without a facesheet consisting of a number of small diameter but long cylindrical channels embedded in a ceramic material, and two conventional nonlinear liners consisting of a perforated facesheet bonded to a honeycomb core. The study is restricted to a frequency range for which only plane waves are cut on in the hard-wall sections of the flow impedance tube. The metrics used to evaluate each boundary condition are 1) how well it educes the same impedance for upstream and downstream propagating sources, and 2) how well it predicts the expected behavior of the impedance spectra over the Mach number range. The primary conclusions of the study are that the same impedance is educed for upstream and downstream propagating sources except at the highest Mach number, that an effective impedance based on both the upstream and downstream measurements is more accurate than an impedance based on the upstream or downstream data alone, and that the Ingard-Myers boundary condition with an effective impedance produces results similar to that achieved with the modified Ingard-Myers boundary condition.

Is it intelligent to intercalate? A two centre cross-sectional study exploring the value of intercalated degrees, and the possible effects of the recent tuition fee rise in England

PubMed Central

Stubbs, Timothy Alan; Lightman, Elewys G; Mathieson, Peter

2013-01-01

Aims and objectives To explore the value of intercalated degrees, including student perceptions and academic sequelae. To gauge the likely effect of the recent tuition fee rise and to identify any differences in intercalated degrees between Bristol and Sheffield universities. Design Cross-sectional study using questionnaires. Setting Bristol and Sheffield Medical Schools, UK. Participants 1484 medical students in their clinical years were e-mailed the questionnaire. 578 students responded: 291 from Bristol and 287 from Sheffield (n=578; mean age=22.41; SD 1.944; 38.9% male; 61.1% female). The response rate from previous intercalators was 52.5% from Bristol and 58.7% from Sheffield, while for non-intercalators it was 27.7% and 34.6%, respectively. Main outcome measures (1) Student preconceptions, opinions, results and academic sequelae from intercalated degrees at both centres. (2) Students’ attitudes concerning the effect of the increase in tuition fees. Results Those with clinical academic supervisors gained significantly more posters (p=0.0002) and publications (p<0.0001), and also showed a trend to gain more first class honours (p=0.055). Students at Sheffield had a significantly greater proportion of clinical academic supervisors than students at Bristol (p<0.0001). 89.2% said that an intercalated degree was the right decision for them; however, only 27.4% stated they would have intercalated if fees had been £9000 per annum. Conclusions Students clearly value intercalated degrees, feel they gained a substantial advantage over their peers as well as skills helpful for their future careers. The rise in tuition fees is likely to reduce the number of medical students opting to undertake an intercalated degree, and could result in a further reduction in numbers following an academic path. Sheffield University have more intercalating students supervised by clinical academics. Clinical academics appear more effective as supervisors for medical students undertaking

4-Nitroquinoline-1-oxide effects human lung adenocarcinoma A549 cells by regulating the expression of POLD4

PubMed Central

HUANG, QIN-MIAO; ZENG, YI-MING; ZHANG, HUA-PING; LV, LIANG-CHAO; YANG, DONG-YONG; LIN, HUI-HUANG

2016-01-01

The aim of the present study was to explore the expression of POLD4 in human lung adenocarcinoma A549 cells under 4-nitroquinoline-1-oxide (4NQO) stimulation to investigate the role of POLD4 in smoking-induced lung cancer. The lung cancer A549 cell line was treated with 4NQO, with or without MG132 (an inhibitor of proteasome activity), and subsequently the POLD4 level was determined by western blot analysis. Secondly, the cell sensitivity to 4NQO and Taxol was determined when the POLD4 expression level was downregulated by siRNA. The POLD4 protein levels in the A549 cells decreased following treatment with 4NQO; however, MG132 could reverse this phenotype. Downregulation of the POLD4 expression by siRNA enhanced A549 cell sensitivity to 4NQO, but not to Taxol. In conclusion, 4NQO affects human lung adenocarcinoma A549 cells by regulating the expression of POLD4. PMID:26998273

Slick Nanoparticles and Other Gleanings from Nature

NASA Astrophysics Data System (ADS)

Heinhorst, Sabine; Cannon, Gordon C.

1997-09-01

The total synthesis of a new class of compounds that promise to be cancer chemotherapeutic agents at least as effective as taxol was presented in the May 15 issue (Vol. 387, pp 238-239) as a "News and Views" article. Although structurally unrelated, epothilones, like taxol, target the microtubules of the cytoskeleton and inhibit cancer cell growth by polymerizing these subcellular structures. Future research will have to determine which derivatives of natural epothilones are effective and which functional groups hold the key to the compounds' biological activity. An article by Deshpande and Danishefsky (May 8 issue of Vol. 387, pp 164-166) details the successful chemical synthesis of an oligosaccharide that is frequently found on the surface of colon adenocarcinomas. While the small quantities of this cancer antigen that can be purified from natural sources preclude its usefulness as an immunological tool, the synthetic compound and an analog that can be linked to a carrier molecule for biological delivery have potential as vaccines for several human cancers.

Effect and cost of an after-school dance programme on the physical activity of 11-12 year old girls: The Bristol Girls Dance Project, a school-based cluster randomised controlled trial.

PubMed

Jago, Russell; Edwards, Mark J; Sebire, Simon J; Tomkinson, Keeley; Bird, Emma L; Banfield, Kathryn; May, Thomas; Kesten, Joanna M; Cooper, Ashley R; Powell, Jane E; Blair, Peter S

2015-10-06

The aim of this study was to examine the effectiveness and cost of an after-school dance intervention at increasing the physical activity levels of Year 7 girls (age 11-12). A cluster randomised controlled trial was conducted in 18 secondary schools. Participants were Year 7 girls attending a study school. The Bristol Girls Dance Project (BGDP) intervention consisted of up to forty, 75-minute dance sessions delivered in the period immediately after school by experienced dance instructors over 20-weeks. The pre-specified primary outcome was accelerometer assessed mean minutes of weekday moderate to vigorous physical activity (MVPA) at time 2 (52 weeks are T0 baseline assessments). Secondary outcomes included accelerometer assessed mean minutes of weekday MVPA at time 1 (while the intervention was still running) and psychosocial outcomes. Intervention costs were assessed. 571 girls participated. Valid accelerometer data were collected from 549 girls at baseline with 508 girls providing valid accelerometer data at baseline and time 2. There were no differences between the intervention and control group for accelerometer assessed physical activity at either time 1 or time 2. Only one third of the girls in the intervention arm met the pre-set adherence criteria of attending two thirds of the dance sessions that were available to them. Instrumental variable regression analyses using complier average causal effects provided no evidence of a difference between girls who attended the sessions and the control group. The average cost of the intervention was £73 per girl, which was reduced to £63 when dance instructor travel expenses were excluded. This trial showed no evidence that an after-school dance programme can increase the physical activity of Year 7 girls. The trial highlighted the difficulty encountered in maintaining attendance in physical activity programmes delivered in secondary schools. There is a need to find new ways to help adolescent girls to be

The role of microtubules in the regulation of proteoglycan synthesis in chondrocytes under hydrostatic pressure.

PubMed

Jortikka, M O; Parkkinen, J J; Inkinen, R I; Kärner, J; Järveläinen, H T; Nelimarkka, L O; Tammi, M I; Lammi, M J

2000-02-15

Chondrocytes of the articular cartilage sense mechanical factors associated with joint loading, such as hydrostatic pressure, and maintain the homeostasis of the extracellular matrix by regulating the metabolism of proteoglycans (PGs) and collagens. Intermittent hydrostatic pressure stimulates, while continuous high hydrostatic pressure inhibits, the biosynthesis of PGs. High continuous hydrostatic pressure also changes the structure of cytoskeleton and Golgi complex in cultured chondrocytes. Using microtubule (MT)-affecting drugs nocodazole and taxol as tools we examined whether MTs are involved in the regulation of PG synthesis in pressurized primary chondrocyte monolayer cultures. Disruption of the microtubular array by nocodazole inhibited [(35)S]sulfate incorporation by 39-48%, while MT stabilization by taxol caused maximally a 17% inhibition. Continuous hydrostatic pressure further decreased the synthesis by 34-42% in nocodazole-treated cultures. This suggests that high pressure exerts its inhibitory effect through mechanisms independent of MTs. On the other hand, nocodazole and taxol both prevented the stimulation of PG synthesis by cyclic 0. 5 Hz, 5 MPa hydrostatic pressure. The drugs did not affect the structural and functional properties of the PGs, and none of the treatments significantly affected cell viability, as indicated by the high level of PG synthesis 24-48 h after the release of drugs and/or high hydrostatic pressure. Our data on two-dimensional chondrocyte cultures indicate that inhibition of PG synthesis by continuous high hydrostatic pressure does not interfere with the MT-dependent vesicle traffic, while the stimulation of synthesis by cyclic pressure does not occur if the dynamic nature of MTs is disturbed by nocodazole. Similar phenomena may operate in cartilage matrix embedded chondrocytes. Copyright 2000 Academic Press.

Synthesis of Taxol-Like Prostate Cancer Chemotherapeutic Agents

DTIC Science & Technology

2007-11-01

in Scheme 5, conventional condition utilizing n- BuLi as a base was not successful in the preparation of the desired Diels-Alder substrate 19 as only...unsuccessful. The only product obtained was n- BuLi addition to aldehyde 21. Thus, deprotonation conditions of terminal alkyne 17 or 20 are now being

"Real World" Connections Through Videoconferences

NASA Astrophysics Data System (ADS)

Kolecki, Joseph; Petersen, Ruth

2001-11-01

During the week of July 23, 2001, a workshop called 'Japan 2001 Science, Creativity and the Young Mind' took place at Bristol University in Bristol, England. Coordinated under the direction of Dr. Eric Albone, Clifton Scientific Trust, it brought together 60 British and Japanese students and provided them with a forum for learning and interacting. We at the NASA Glenn Research Center (GRC) in Cleveland, Ohio, had the good fortune to participate with six of those students and their team leaders in a Space Science Workshop. The Space Science Team was led by two Bristol University people from the Earth Sciences Department - Carsten Riedel and Stuart Stansfield - under the direction of Professor Steve Sparks, FRS. The Team was assisted by Lawrence Williams, Director of Studies, Holy Cross School, UK. Funding was provided by the Daiwa Anglo-Japanese Foundation, the Great Britain Sasakawa Foundation, and Japan 2001. This report is a compilation of correspondence via e-mail that took place before, during, and immediately after the workshop. A final report from the students on their findings is now in production and will be made available from Clifton Scientific Trust.

"Real World" Connections Through Videoconferences

NASA Technical Reports Server (NTRS)

Kolecki, Joseph; Petersen, Ruth

2001-01-01

During the week of July 23, 2001, a workshop called 'Japan 2001 Science, Creativity and the Young Mind' took place at Bristol University in Bristol, England. Coordinated under the direction of Dr. Eric Albone, Clifton Scientific Trust, it brought together 60 British and Japanese students and provided them with a forum for learning and interacting. We at the NASA Glenn Research Center (GRC) in Cleveland, Ohio, had the good fortune to participate with six of those students and their team leaders in a Space Science Workshop. The Space Science Team was led by two Bristol University people from the Earth Sciences Department - Carsten Riedel and Stuart Stansfield - under the direction of Professor Steve Sparks, FRS. The Team was assisted by Lawrence Williams, Director of Studies, Holy Cross School, UK. Funding was provided by the Daiwa Anglo-Japanese Foundation, the Great Britain Sasakawa Foundation, and Japan 2001. This report is a compilation of correspondence via e-mail that took place before, during, and immediately after the workshop. A final report from the students on their findings is now in production and will be made available from Clifton Scientific Trust.

PREFACE: The 16th International Conference on Positron Annihilation (ICPA-16)

NASA Astrophysics Data System (ADS)

Alam, Ashraf; Coleman, Paul; Dugdale, Stephen; Roussenova, Mina

2013-06-01

The 16th International Conference on Positron Annihilation (ICPA-16) was held at the University of Bristol, United Kingdom during 19-24 August, 2012. This triennial conference is the foremost gathering of the Positron Annihilation Physics community and it was hosted in the UK for the first time since the series of meetings first started back in 1965. The University of Bristol, the Alma Mater of Paul Dirac, is situated at the heart of the city, and it has established a worldwide reputation in research and teaching. Many of the topics which were discussed during ICPA-16 form an integral part of the research themes in the schools of Physics, Chemistry and Engineering of this University. ICPA-16 attracted a diverse audience, both from academic and industrial institutions, with over 200 participants from 29 countries. It continued the long held tradition of showcasing novel research in the field of positron annihilation and a total of 170 papers were presented as talks and posters. The papers reported studies of metallic and semi-conducting solids, polymers and soft matter, porous materials, surfaces and interfaces, as well as advances in experimental, analytical and biomedical applications. The high quality of the presented work, coupled with the enthusiastic exchange of ideas, provided an invaluable forum, especially for younger researchers and postgraduate students. The excellence of student presentations was acknowledged by the award of prizes for the best student posters, which were received by David Billington (University of Bristol, UK), Moussa Sidibe (CEMHTI, France) and Hongxia Xu (Tohoku University, Japan). All papers published in the Conference Proceedings were reviewed by ICPA-16 participants. We are indebted to all reviewers who contributed their time and intellectual resources, allowing the refereeing and editing process to move smoothly toward the compilation of the Proceedings. Our sincere thanks and gratitude go to everyone who contributed to the

Low-dose naltrexone suppresses ovarian cancer and exhibits enhanced inhibition in combination with cisplatin.

PubMed

Donahue, Renee N; McLaughlin, Patricia J; Zagon, Ian S

2011-07-01

Ovarian cancer is the leading cause of death from gynecological malignancies. Although initial therapeutic modalities are successful, 65% of these women relapse with only palliative treatments available thereafter. Endogenous opioids repress the proliferation of human ovarian cancer cells in vitro, and do so in a receptor-mediated manner. The present study examined whether modulation of opioid systems by the opioid antagonist naltrexone (NTX), alone or in combination with standard of care therapies (taxol/paclitaxel, cisplatin), alters human ovarian cancer cell proliferation in tissue culture and tumor progression in mice. Administration of NTX for six hours every two days, but not continuously, reduced DNA synthesis and cell replication from vehicle-treated controls in tissue culture. Moreover, brief exposure to NTX in combination with taxol or cisplatin had an enhanced anticancer action. Mice with established ovarian tumors and treated with a low dosage of NTX (LDN), which invokes a short period of opioid receptor blockade, repressed tumor progression in a non-toxic fashion by reducing DNA synthesis and angiogenesis but not altering cell survival. The combination of LDN with cisplatin, but not taxol, resulted in an additive inhibitory effect on tumorigenesis with enhanced depression of DNA synthesis and angiogenesis. LDN combined with cisplatin alleviated the toxicity (e.g. weight loss) associated with cisplatin. LDN treatment upregulated the expression of the opioid growth factor (OGF, chemical term ([Met(5)]-enkephalin) and its receptor, OGFr. Previous tissue culture studies have reported that OGF is the only opioid peptide with antiproliferative activity on ovarian cancer cells, with OGF action mediated by OGFr. Thus, the common denominator of intermittent opioid receptor blockade by short-term NTX or LDN on ovarian cancer proliferation and tumorigenesis recorded herein appears to be related to the OGF-OGFr axis. These preclinical data may offer a non

Cytokinetic study of MCF-7 cells treated with commercial and recombinant bromelain.

PubMed

Fouz, Nour; Amid, Azura; Hashim, Yumi Zuhanis Has-Yun

2014-01-01

Breast cancer is a leading cause of death in women. The available chemotherapy drugs have been associated with many side effects. Bromelain has novel medicinal qualities including anti-inflammatory, anti-thrombotic, fibrinolytic and anti-cancer functions. Commercially available bromelain is obtained through tedious methods; therefore, recombinant bromelain may provide a cheaper and simpler choice with similar quality. This study aimed to assess the effects of commercial and recombinant bromelain on the cytokinetic behavior of MCF-7 breast cancer cells and their potential as therapeutic alternatives in cancer treatment. Cytotoxic activities of commercial and recombinant bromelain were determined using (sulforhodamine) SRB assay. Next, cell viability assays were conducted to determine effects of commercial and recombinant bromelain on MCF-7 cell cytokinetic behavior. Finally, the established growth kinetic data were used to modify a model that predicts the effects of commercial and recombinant bromelain on MCF-7 cells. Commercial and recombinant bromelain exerted strong effects towards decreasing the cell viability of MCF-7 cells with IC50 values of 5.13 μg/mL and 6.25 μg/mL, respectively, compared to taxol with an IC50 value of 0.063 μg/mL. The present results indicate that commercial and recombinant bromelain both have anti-proliferative activity, reduced the number of cell generations from 3.92 to 2.81 for commercial bromelain and to 2.86 for recombinant bromelain, while with taxol reduction was to 3.12. Microscopic observation of bromelain-treated MCF-7 cells demonstrated detachment. Inhibition activity was verified with growth rates decreased dynamically from 0.009 h-1 to 0.0059 h-1 for commercial bromelain and to 0.0063 h-1 for recombinant bromelain. Commercial and recombinant bromelain both affect cytokinetics of MCF-7 cells by decreasing cell viability, demonstrating similar strength to taxol.

Evaluation of Interacavitary Chemotherapy Delivery for Treatment of Mammary Carcinoma

DTIC Science & Technology

2005-04-01

Celltiter 96 Aqueous one solution cell proliferation assay - Promega) in 96 well plates were used, each well received 100 ul of cell culture medium and...treatments: a) polotax (200 ul of 22% poloxamer/5.4mg/ml taxol suspension) in wound, b) 200 ul polotax remote (between 2 scapulae ), c) 200 ul 22% poloxamer in

Pregnant and breastfeeding women: A priority population for HIV viral load monitoring.

PubMed

Myer, Landon; Essajee, Shaffiq; Broyles, Laura N; Watts, D Heather; Lesosky, Maia; El-Sadr, Wafaa M; Abrams, Elaine J

2017-08-01

Landon Myer and colleagues discuss viral load monitoring for pregnant HIV-positive women and those breastfeeding; ART treatments can suppress viral load and are key to preventing transmission to the child.

Effect of rottlerin, a PKC-{delta} inhibitor, on TLR-4-dependent activation of murine microglia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Dong-Chan; Division of Research and Development, Neuronex, Inc., San31, Hyoja-dong, Nam-gu, Pohang 790-784; Kim, Sun-Hee

2005-11-11

In microglia, Toll-like receptors have been shown to recognize pathogen-associated molecular patterns and initiate innate immune responses upon interaction with infectious agents. The effect of rottlerin, a PKC-{delta} specific inhibitor, on TLR-4-mediated signaling was investigated in murine microglia stimulated with lipopolysaccharide and taxol. Pretreatment of microglia cells with rottlerin decreased LPS- and taxol-induced nitric oxide production in a concentration-dependent manner (IC{sub 50} = 99.1 {+-} 1.5 nM). Through MTT and FACS analysis, we found that the inhibition effect of rottlerin was not due to microglial cell death. Rottlerin pretreatment also attenuated LPS-induced phosphorylation of I{kappa}B-{alpha}, nuclear translocation of NF-{kappa}B, andmore » expression of type II nitric oxide synthase. In addition, microglial phagocytosis in response to TLR-4 activation was diminished in which rottlerin was pretreated. Together, these data raise the possibility that certain PKC-{delta} specific inhibitors can modulate TLR-4-derived signaling and inflammatory target gene expression, and can alter susceptibility to microbial infection and chronic inflammatory diseases in central nervous system.« less

Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement

PubMed Central

Bui, Loan; Hendricks, Alissa; Wright, Jamie; Chuong, Cheng-Jen; Davé, Digant; Bachoo, Robert; Kim, Young-tae

2016-01-01

Brain tumor cells remain highly resistant to radiation and chemotherapy, particularly malignant and secondary cancers. In this study, we utilized microchannel devices to examine the effect of a confined environment on the viability and drug resistance of the following brain cancer cell lines: primary cancers (glioblastoma multiforme and neuroblastoma), human brain cancer cell lines (D54 and D54-EGFRvIII), and genetically modified mouse astrocytes (wild type, p53−/−, p53−/− PTEN−/−, p53−/− Braf, and p53−/− PTEN−/− Braf). We found that loss of PTEN combined with Braf activation resulted in higher viability in narrow microchannels. In addition, Braf conferred increased resistance to the microtubule-stabilizing drug Taxol in narrow confinement. Similarly, survival of D54-EGFRvIII cells was unaffected following treatment with Taxol, whereas the viability of D54 cells was reduced by 75% under these conditions. Taken together, our data suggests key targets for anticancer drugs based on cellular genotypes and their specific survival phenotypes during confined migration. PMID:27184621

Direct writing of bio-functional coatings for cardiovascular applications.

PubMed

Perkins, Jessica; Hong, Yi; Ye, Sang-Ho; Wagner, William R; Desai, Salil

2014-12-01

The surface modification of metallic biomaterials is of critical importance to enhance the biocompatibility of surgical implant materials and devices. This article investigates the use of a direct-write inkjet technique for multilayer coatings of a biodegradable polymer (polyester urethane urea (PEUU)) embedded with an anti-proliferation drug paclitaxel (Taxol). The direct-write inkjet technique provides selective patterning capability for depositing multimaterial coatings on three-dimensional implant devices such as pins, screws, and stents for orthopedic and vascular applications. Drug release profiles were studied to observe the influence of drug loading and coating thickness for obtaining tunable release kinetics. Platelet deposition studies were conducted following ovine blood contact and significant reduction in platelet deposition was observed on the Taxol loaded PEUU substrate compared with the unloaded control. Rat smooth muscle cells were used for cell proliferation studies. Significant reduction in cell growth was observed following the release of anti-proliferative drug from the biopolymer thin film. This research provides a basis for developing anti-proliferative biocompatible coatings for different biomedical device applications. © 2014 Wiley Periodicals, Inc.

78 FR 27414 - Massachusetts; Major Disaster and Related Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-10

..., Berkshire, Bristol, Dukes, Essex, Franklin, Hampden, Hampshire, Middlesex, Nantucket, Norfolk, Plymouth..., Hampshire, Middlesex, Norfolk, Suffolk, and Worcester Counties for snow assistance under the Public...

Effect of an intensified multifactorial intervention on cardiovascular outcomes and mortality in type 2 diabetes (J-DOIT3): an open-label, randomised controlled trial.

PubMed

Ueki, Kohjiro; Sasako, Takayoshi; Okazaki, Yukiko; Kato, Masayuki; Okahata, Sumie; Katsuyama, Hisayuki; Haraguchi, Mikiko; Morita, Ai; Ohashi, Ken; Hara, Kazuo; Morise, Atsushi; Izumi, Kazuo; Ishizuka, Naoki; Ohashi, Yasuo; Noda, Mitsuhiko; Kadowaki, Takashi

2017-12-01

were excluded from the analyses. During the intervention period, mean HbA 1c , systolic blood pressure, diastolic blood pressure, and LDL cholesterol concentrations were significantly lower in the intensive therapy group than in the conventional therapy group (6·8% [51·0 mmol/mol] vs 7·2% [55·2 mmol/mol]; 123 mm Hg vs 129 mm Hg; 71 mm Hg vs 74 mm Hg; and 85 mg/dL vs 104 mg/dL, respectively; all p<0·0001). The primary outcome occurred in 109 patients in the intensive therapy group and in 133 patients in the conventional therapy group (hazard ratio [HR] 0·81, 95% CI 0·63-1·04; p=0·094). In a post-hoc breakdown of the composite outcome, frequencies of all-cause mortality (HR 1·01, 95% CI 0·68-1·51; p=0·95) and coronary events (myocardial infarction, coronary artery bypass surgery, and percutaneous transluminal coronary angioplasty; HR 0·86, 0·58-1·27; p=0·44) did not differ between groups, but cerebrovascular events (stroke, carotid endarterectomy, percutaneous transluminal cerebral angioplasty, and carotid artery stenting) were significantly less frequent in the intensive therapy group (HR 0·42, 0·24-0·74; p=0·002). Apart from non-severe hypoglycaemia (521 [41%] patients in the intensive therapy group vs 283 [22%] in the conventional therapy group, p<0·0001) and oedema (193 [15%] vs 129 [10%], p=0·0001), the frequencies of major adverse events did not differ between groups. Our results do not fully support the efficacy of further intensified multifactorial intervention compared with current standard care for the prevention of a composite of coronary events, cerebrovascular events, and all-cause mortality. Nevertheless, our findings suggest a potential benefit of an intensified intervention for the prevention of cerebrovascular events in patients with type 2 diabetes. Ministry of Health, Labour and Welfare of Japan, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Glaxo

Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model.

PubMed

Jones-Hughes, Tracey; Snowsill, Tristan; Haasova, Marcela; Coelho, Helen; Crathorne, Louise; Cooper, Chris; Mujica-Mota, Ruben; Peters, Jaime; Varley-Campbell, Jo; Huxley, Nicola; Moore, Jason; Allwood, Matt; Lowe, Jenny; Hyde, Chris; Hoyle, Martin; Bond, Mary; Anderson, Rob

2016-08-01

End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations

Predicting Adherence and Persistence with Oral Bisphosphonate Therapy in an Integrated Health Care Delivery System.

PubMed

Hui, Rita L; Adams, Annette L; Niu, Fang; Ettinger, Bruce; Yi, David K; Chandra, Malini; Lo, Joan C

2017-04-01

excess of the 60-day allowable gap between prescription/refills (median cumulative nonpersistence = 0.65, IQR = 0.30-1.25 years). Women with mPDC ≥ 75% during the first year had a 12-fold and 6-fold increased odds of mPDC ≥ 75% during year 2 and year 3, respectively. BP discontinuation rates are highest for women during the first year. Among those continuing treatment in subsequent years, adherence rates were relatively stable. Persistence and adherence varied slightly by age and was somewhat higher in Asians, contributing to differences in cumulative BP exposure. We also found evidence that optimal adherence in the first year was highly predictive of optimal adherence in the subsequent 1-2 years. Hence, subgroups of patients receiving oral BP drugs may require different levels of support and monitoring to maximize treatment benefit, especially based on early patterns of use. This study was supported by grants from the Kaiser Permanente Northern California Community Benefit Program and the National Institutes of Health, 1R01AG047230-01A1. The opinions expressed in this publication are solely the responsibility of the authors and do not represent the official views of Kaiser Permanente or the National Institutes of Health. Hui, Yi, and Chandra have received past research funding from Amgen not related to the current study. Adams has received research funding from Amgen, Merck, and Otsuka not related to the current study. Niu has received research funding from Bristol-Myers Squibb not related to the current study. Ettinger has received past legal fees in litigation involving Fosamax. Lo has received past research funding from Amgen and current research funding from Sanofi not related to the current study. The data from this study were presented at the Academy of Managed Care Pharmacy Annual Meeting; April 19-22, 2016; San Francisco, California. Study concept and design were contributed primarily by Hui and Lo, along with Adams, Niu, Yi, and Ettinger. Hui took the lead

Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model.

PubMed Central

Jones-Hughes, Tracey; Snowsill, Tristan; Haasova, Marcela; Coelho, Helen; Crathorne, Louise; Cooper, Chris; Mujica-Mota, Ruben; Peters, Jaime; Varley-Campbell, Jo; Huxley, Nicola; Moore, Jason; Allwood, Matt; Lowe, Jenny; Hyde, Chris; Hoyle, Martin; Bond, Mary; Anderson, Rob

2016-01-01

BACKGROUND End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. METHODS Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI

Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation.

PubMed Central

Haasova, Marcela; Snowsill, Tristan; Jones-Hughes, Tracey; Crathorne, Louise; Cooper, Chris; Varley-Campbell, Jo; Mujica-Mota, Ruben; Coelho, Helen; Huxley, Nicola; Lowe, Jenny; Dudley, Jan; Marks, Stephen; Hyde, Chris; Bond, Mary; Anderson, Rob

2016-01-01

BACKGROUND End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation. DATA SOURCES Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE

Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation.

PubMed

Haasova, Marcela; Snowsill, Tristan; Jones-Hughes, Tracey; Crathorne, Louise; Cooper, Chris; Varley-Campbell, Jo; Mujica-Mota, Ruben; Coelho, Helen; Huxley, Nicola; Lowe, Jenny; Dudley, Jan; Marks, Stephen; Hyde, Chris; Bond, Mary; Anderson, Rob

2016-08-01

End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival. To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation. Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS

Daclatasvir for the Treatment of Chronic Hepatitis C: A Critique of the Clinical and Economic Evidence.

PubMed

Llewellyn, Alexis; Faria, Rita; Woods, Beth; Simmonds, Mark; Lomas, James; Woolacott, Nerys; Griffin, Susan

2016-10-01

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of daclatasvir (Bristol-Myers Squibb) to submit clinical and cost-effectiveness evidence for daclatasvir in combination with other medicinal products within its licensed indication for the treatment of chronic hepatitis C, as part of the Institute's single technology appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article presents the ERG's critical review of the evidence presented in the company submission in the context of a description of the company submission, and the resulting NICE guidance. The main clinical effectiveness data for daclatasvir in combination with sofosbuvir (daclatasvir + sofosbuvir) were derived from two uncontrolled open-label trials. Among patients with genotype 1 infection, 98-100 % of patients had a sustained virologic response at week 12 (SVR12), overall. Among genotype 3 patients, between 85 and 100 % had SVR12 across patient populations and regimens. The main evidence for daclatasvir + pegylated interferon-α and ribavirin (PR) came from one randomised controlled trial comparing daclatasvir + PR with PR in patients with genotype 4. This found an SVR12 rate of 82 % in previously untreated patients. Serious adverse event rates associated with daclatasvir were low. The lack of comparative trial evidence for daclatasvir + sofosbuvir and many of the comparators defined in the NICE scope meant that established methods for comparing interventions either directly via head-to-head trial comparisons or via adjusted indirect comparisons were not feasible. Comparisons of SVR rates were therefore largely based on unadjusted estimates drawn from individual trial arms and subgroups of individual trial arms. The ERG concluded that, despite limited evidence, daclatasvir in combination with other treatments

AMCP Partnership Forum: Enabling the Exchange of Clinical and Economic Information Pre-FDA Approval.

PubMed

2017-01-01

, since PIE is a novel category of information. New legislation could provide a safe harbor and clarity that PIE does not violate preapproval promotion and the Federal Food, Drug, and Cosmetic Act and its regulations. The AMCP Partnership Forum on Enabling the Exchange of Clinical and Economic Data Pre-FDA Approval and the development of this proceedings document were supported by AbbVie, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Celgene, Intarcia Therapeutics, Eli Lilly and Company, GlaxoSmithKline, Merck, National Pharmaceutical Council, Novo Nordisk, Pfizer, Pharmaceutical Research and Manufacturers of America, Precision for Value, Sanofi, Takeda Pharmaceuticals, U.S.A., and Xcenda. All sponsors participated in the forum and in revising and approving the manuscript.

Metformin extended release: metformin gastric retention, metformin GR, metformin XR.

PubMed

2005-01-01

Therapeutic Products Directorate in Canada issued a Notice of Compliance for metformin extended release (Glumetza) 500mg and 1000mg for the treatment of type 2 diabetes. Biovail Pharmaceuticals Canada plans to launch the product in the fourth quarter of 2005. Biovail has submitted an application for metformin extended release with the Therapeutic Products Directorate in Canada. and received notification of acceptance for review in August 2004. Bristol-Myers Squibb is marketing a proprietary, once-daily extended-release formulation of metformin (Glucophage XR). Several companies are developing controlled-release and extended-release formulations of metformin.

Stump sprouting of Pacific yew.

Treesearch

Don Minore; Howard G. Weatherly

1996-01-01

Large numbers of Pacific yew (Taxus brevifolia Nutt.) trees have been cut to supply bark for taxol production, and replacement of those trees may depend on their ability to sprout from the stump. Stump characteristics were related to the initiation and survival of epicormic branches (sprouts) on 100 yew stumps in each of 11 recently harvested...

Regio- and stereoselectivities in plant cell biotransformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamada, H.

1995-12-01

The ability of plant cultured cells to convert foreign substrates into more useful substances is of considerable interest. Therefore I have studied biotransformation of foreign substrate by plant cell suspension cultures. In this presentation, I report regio- and stereoselectivities in biotransformation of steroids and indole alkaloids and taxol by plant (tobacco, periwinkle, moss, orchid) cell suspension cultures.

Steve Rummel | NREL

Science.gov Websites

Module Intercomparison," Proc. Solar Energies Technologies Review Meeting Nov. 7-10, 2005, NREL tech . Rummel, D.R. Myers, T.L. Stoffel, and D. Waddington, "A Comparison of Photovoltaic Calibration

The Capital Budgeting Policies of the U. S. Shipbuilding Industry: An Analysis of Defense Industry Behavior

DTIC Science & Technology

1979-10-01

Johns - Manville ) and one whose net worth was comparable in 1976 (Cluett Peabody). • One company whose asset base was comparable to Lockheed’s in 1967...AVERAGE2 30.2 ’ KODAK ARMCO SFERRY RAND JOHNS - MANVILLE CLCETt PEABODY AMER.CYANAMID SINGER-1’ N.A. N.A. N.A. N.A. N.A. M.A. N.A. 9 11 10 22 4 13 N.A. 10...JIM WALTER 8 23 CUMMINS 58 8 MARTIN MARIETTA 9 90 SQUIBB 851 KOPPERS 708 UNION CAMP 624 INT’L MINING 68 2 JOHNS MANVILLE 814 EMERSON ELEC

Cluttering

MedlinePlus

... to plan and evaluate treatment.) Myers, F. L. & St. Louis, K. O. (1992). Cluttering: A clinical perspective . ... on the nature, diagnosis, and treatment of cluttering.) St. Louis, K. O. (Ed.) (1996). Research and opinion ...

Myers-Briggs Type Indicator Applied to Executive Leadership

DTIC Science & Technology

1987-01-01

preferences. fftl Z.) ISTJ ISFJ INFJ INTJ ISTP ISFP INFP INTP ESTP ESFP ENFP ENTP ESTJ ESFJ ENFJ ENTJ Table 6: Sixteen Types David Keirsey and...personality types are generated by combinations of preferences and are listed in Table 2 (1:7-8). ISTJ ISFJ INFJ INTJ ISTP ISFP INFP INTP ESTP ESFP...ENFP • ENTP ESTJ E3FJ ENFJ ENTJ Table 2: Sixteen Types David Keirsey and Marilyn Bates, the authors of Please Understand Me, Character and

NASA Participated in the Japan 2001 Science, Creativity and the Young Mind Workshop

NASA Technical Reports Server (NTRS)

Kolecki, Joseph C.; Petersen, Ruth A.

2002-01-01

During the week of July 23, 2001, a workshop called the Japan 2001 Science, Creativity and the Young Mind took place at Bristol University in Bristol, England. Coordinated by the Clifton Scientific Trust, it brought together 60 British and Japanese students and provided them with a forum for learning and interacting. All the students were chosen from geographical areas of social deprivation, where university education is not seen as a natural progression for students. One of the aims of the workshop was to give the combined group a new view of themselves as potential scientists and an ambition to succeed at the highest level. Members of the Glenn Research Center's Learning Technologies Project participated with six of the students and their team leaders as a Space Science Team. Four interactive videoconferencing sessions were held between the NASA Glenn Research Center and Bristol University on four consecutive days. During the sessions, students raised questions concerning various theories about the probable formation of volcanoes on Mars. Of specific interest was if the great Tharsis volcanoes might be the result of an ancient collision of planetary proportions, or if plate tectonic movement, evidence for which was recently discovered by NASA's Mars Global Surveyor Spacecraft, might account for them.

75 FR 54297 - Tri-County Advisory Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-07

.... ADDRESSES: The meeting will be held at the USDA building located 1002 Hollenback Road, Deer Lodge, Montana.... Dated: August 24, 2010. David R. Myers, Designated Federal Official. [FR Doc. 2010-22113 Filed 9-3-10; 8...

76 FR 75942 - Qualification of Drivers; Exemption Applications; Vision

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-05

... renewable two-year period. They are: Anthony Brandano (MA) William R. Braun (NM) Stanley E. Elliott (UT.... Mallory (OK) Eldon Miles (IN) Norman V. Myers (WA) Jack E. Potts, Jr. (PA) Neal A. Richard (LA) John E...

ONR National Defense Science and Engineering Graduate Fellowship Program

DTIC Science & Technology

2000-05-05

Annau, Thomas Barnard, Thomas Beauchamp, Nathaniel Berger, Adam Black, Charles Boutin , Debra Bouwhuis, Mary Boyan, Justin Brandes, Jay...David Houser, Dorian Jacobs, Robert Jayne, Steven Keeton, Charles Marsh, Elizabeth Myers, David Nerney, Jacqueline Pierre, Darren Reed, Eric

Self-consolidating concrete (SCC) and high-volume fly ash concrete (HVFAC) for infrastructure elements: implementation.

DOT National Transportation Integrated Search

2016-06-01

Myers, John J.: http://orcid.org/0000-0001-5269-8218 : Because of its unique nature, self-consolidating concrete (SCC) has the potential to significantly reduce costs associated with transportation-related infrastructure, benefiting both MoDOT and th...

Level II scour analysis for Bridge 20 (BRISTH00270020) on Town Highway 27, crossing Little Notch Brook, Bristol, Vermont

USGS Publications Warehouse

Boehmler, Erick M.

1997-01-01

This report provides the results of a detailed Level II analysis of scour potential at structure BRISTH00270020 on Town Highway 27 crossing Little Notch Brook, Bristol, Vermont (figures 1–8). A Level II study is a basic engineering analysis of the site, including a quantitative analysis of stream stability and scour (U.S. Department of Transportation, 1993). Results of a Level I scour investigation also are included in Appendix E of this report. A Level I investigation provides a qualitative geomorphic characterization of the study site. Information on the bridge, gleaned from Vermont Agency of Transportation (VTAOT) files, was compiled prior to conducting Level I and Level II analyses and is found in Appendix D. The site is in the Green Mountain section of the New England physiographic province in west-central Vermont. The 8.43-mi2 drainage area is in a predominantly rural and forested basin. In the vicinity of the study site, the surface cover consists of pasture with trees, shrubs, and brush along the road embankments and the stream banks, except for the downstream left overbank area. Surface cover on the downstream left overbank is forest with dense undergrowth consisting of vines, shrubs, and brush. In the study area, Little Notch Brook has a sinuous channel with a slope of approximately 0.006 ft/ft, an average channel top width of 47 feet and an average bank height of 3 feet. The predominant channel bed materials are gravel and cobbles with a median grain size (D50) of 66.0 mm (0.216 ft). The geomorphic assessment at the time of the Level I and Level II site visit on June 19, 1995, indicated that the reach was stable. The Town Highway 27 crossing of Little Notch Brook is a 48-ft-long, one-lane bridge consisting of one 45-foot steel pony-truss span (Vermont Agency of Transportation, written communication, November 30, 1995). The opening length of the structure parallel to the bridge face is 42.8 feet. The bridge is supported by vertical, concrete abutments

Novobiocin and additional inhibitors of the Hsp90 C-terminal nucleotide-binding pocket.

PubMed

Donnelly, Alison; Blagg, Brian S J

2008-01-01

The 90 kDa heat shock proteins (Hsp90), which are integrally involved in cell signaling, proliferation, and survival, are ubiquitously expressed in cells. Many proteins in tumor cells are dependent upon the Hsp90 protein folding machinery for their stability, refolding, and maturation. Inhibition of Hsp90 uniquely targets client proteins associated with all six hallmarks of cancer. Thus, Hsp90 has emerged as a promising target for the treatment of cancer. Hsp90 exists as a homodimer, which contains three domains. The N-terminal domain contains an ATP-binding site that binds the natural products geldanamycin and radicicol. The middle domain is highly charged and has high affinity for co-chaperones and client proteins. Initial studies by Csermely and co-workers suggested a second ATP-binding site in the C-terminus of Hsp90. This C-terminal nucleotide binding pocket has been shown to not only bind ATP, but cisplatin, novobiocin, epilgallocatechin-3-gallate (EGCG) and taxol. The coumarin antibiotics novobiocin, clorobiocin, and coumermycin A1 were isolated from several streptomyces strains and exhibit potent activity against Gram-positive bacteria. These compounds bind type II topoisomerases, including DNA gyrase, and inhibit the enzyme-catalyzed hydrolysis of ATP. As a result, novobiocin analogues have garnered the attention of numerous researchers as an attractive agent for the treatment of bacterial infection. Novobiocin was reported to bind weakly to the newly discovered Hsp90 C-terminal ATP binding site ( approximately 700 M in SkBr3 cells) and induce degradation of Hsp90 client proteins. Structural modification of this compound has led to an increase of 1000-fold in activity in anti-proliferative assays. Recent studies of structure-activity relationship (SAR) by Renoir and co-workers highlighted the crucial role of the C-4 and/or C-7 positions of the coumarin and removal of the noviose moiety, which appeared to be essential for degradation of Hsp90 client

Nocturia Think Tank: focus on nocturnal polyuria: ICI-RS 2011.

PubMed

Weiss, Jeffrey P; Bosch, J L H Ruud; Drake, Marcus; Dmochowski, Roger R; Hashim, Hashim; Hijaz, Adonis; Johnson, Theodore M; Juul, Kristian Vinter; Nørgaard, Jens Peter; Norton, Peggy; Robinson, Dudley; Tikkinen, Kari A O; Van Kerrebroeck, Philip E V; Wein, Alan J

2012-03-01

The following is a report of the proceedings of the Nocturia Think Tank sessions of the annual International Consultation on Incontinence-Research Society, which took place June 13-15, 2011 in Bristol, UK. The report is organized into sections pertaining to the main topics of discussions having occurred at that meeting, centering on the relationship of nocturnal polyuria (NP) and nocturia but also synthesizing more current evidence advancing our knowledge of the diagnosis and management of nocturia. This article is not meant to be a comprehensive review on the subject of nocturia, a number of which are available in the recent literature. All authors were physically present during, or in a preliminary session just prior to, the meeting in Bristol. Copyright © 2012 Wiley Periodicals, Inc.

78 FR 67452 - Qualification of Drivers; Exemption Applications; Vision

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

... exemption for a renewable two-year period. They are: Anthony Brandano (MA) Stanley E. Elliott (UT) Elmer E...) Raymond P. Madron (MD) Ronald S. Mallory (OK) Eldon Miles (IN) Norman V. Myers (WA) Jack E. Potts, Jr. (PA...

78 FR 56941 - Aerospace Safety Advisory Panel; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-16

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice: 13-114] Aerospace Safety Advisory Panel... Aeronautics and Space Administration announces a forthcoming meeting of the Aerospace Safety Advisory Panel.... Harmony Myers, Aerospace Safety Advisory Panel Executive Director, National Aeronautics and Space...

77 FR 58413 - Aerospace Safety Advisory Panel; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-20

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice 12-074] Aerospace Safety Advisory Panel... Aeronautics and Space Administration announces a forthcoming meeting of the Aerospace Safety Advisory Panel.... Harmony Myers, Aerospace Safety Advisory Panel Executive Director, National Aeronautics and Space...

77 FR 38090 - Aerospace Safety Advisory Panel; Meeting.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-26

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION [Notice 12-044] Aerospace Safety Advisory Panel... Aeronautics and Space Administration announces a forthcoming meeting of the Aerospace Safety Advisory Panel.... Harmony Myers, Aerospace Safety Advisory Panel Executive Director, National Aeronautics and Space...

76 FR 3077 - Notice of Decision To Revise a Heat Treatment Schedule for Emerald Ash Borer

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-19

... faster than in any of the other experiments. The heating rates in all of the Myers et al. (2009... core temperature reading to be at least 160 [deg]F for 75 minutes on the largest pieces of firewood...

50 CFR 100.22 - Subsistence resource regions.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Bristol Bay Region; (5) Yukon-Kuskokwim Delta Region; (6) Western Interior Region; (7) Seward Peninsula Region; (8) Northwest Arctic Region; (9) Eastern Interior Region; (10) North Slope Region. (b) You may...

The Antitumor Effect of Single-domain Antibodies Directed Towards Membrane-associated Catalase and Superoxide Dismutase.

PubMed

Bauer, Georg; Motz, Manfred

2016-11-01

Neutralizing single-domain antibodies directed towards catalase or superoxide dismutase (SOD) caused efficient reactivation of intercellular reactive oxygen species/reactive nitrogen species (ROS/RNS)-dependent apoptosis-inducing signaling specifically in human tumor cells. Single-domain antibodies targeted tumor cell-specific membrane-associated SOD and catalase, but not the corresponding intracellular enzymes. They were shown to be about 200-fold more effective than corresponding classical recombinant antigen-binding fragments and more than four log steps more efficient than monoclonal antibodies. Combined addition of single-domain antibodies against catalase and SOD caused a remarkable synergistic effect. Proof-of-concept experiments in immunocompromised mice using human tumor xenografts and single-domain antibodies directed towards SOD showed an inhibition of tumor growth. Neutralizing single-domain antibodies directed to catalase and SOD also caused a very strong synergistic effect with the established chemotherapeutic agent taxol, indicating an overlap of signaling pathways. This effect might also be useful in order to avoid unwanted side-effects and to drastically lower the costs for taxol-based therapy. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Paclitaxel loaded folic acid targeted nanoparticles of mixed lipid-shell and polymer-core: in vitro and in vivo evaluation.

PubMed

Zhao, Peiqi; Wang, Hanjie; Yu, Man; Liao, Zhenyu; Wang, Xianhuo; Zhang, Fei; Ji, Wei; Wu, Bing; Han, Jinghua; Zhang, Haichang; Wang, Huaqing; Chang, Jin; Niu, Ruifang

2012-06-01

A functional drug carrier comprised of folic acid modified lipid-shell and polymer-core nanoparticles (FLPNPs) including poly(D,L-lactide-co-glycolide) (PLGA) core, PEGylated octadecyl-quaternized lysine modified chitosan (PEG-OQLCS) as lipid-shell, folic acid as targeting ligand and cholesterol was prepared and evaluated for targeted delivery of paclitaxel (PTX). Confocal microscopy analysis confirmed the coating of the lipid-shell on the polymer-core. Physicochemical characterizations of FLPNPs, such as particle size, zeta potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. The internalization efficiency and targeting ability of FLPNPs were demonstrated by flow cytometry and confocal microscopy. PTX loaded FLPNPs showed a significantly higher cytotoxicity than the commercial PTX formulation (Taxol®). The intravenous administration of PTX encapsulated FLPNPs led to tumor regression and improvement of animal survival in a murine model, compared with that observed with Taxol® and biodistribution study showed that PTX concentration in tumor for PTX encapsulated FLPNPs was higher than other PTX formulations. Our data indicate that PTX loaded FLPNPs are a promising nano-sized drug formulation for cancer therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Surface modification of paclitaxel-loaded tri-block copolymer PLGA- b-PEG- b-PLGA nanoparticles with protamine for liver cancer therapy

NASA Astrophysics Data System (ADS)

Gao, Nansha; Chen, Zhihong; Xiao, Xiaojun; Ruan, Changshun; Mei, Lin; Liu, Zhigang; Zeng, Xiaowei

2015-08-01

In order to enhance the therapeutic effect of chemotherapy on liver cancer, a biodegradable formulation of protamine-modified paclitaxel-loaded poly(lactide- co-glycolide)- b-poly(ethylene glycol)- b-poly(lactide- co-glycolide) (PLGA- b-PEG- b-PLGA) nanoparticles (PTX-loaded/protamine NPs) was prepared. Tri-block copolymer PLGA- b-PEG- b-PLGA was synthesized by ring-opening polymerization and characterized by 1H NMR spectroscopy and gel permeation chromatography. PTX-loaded and PTX-loaded/protamine NPs were characterized in terms of size, size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release. Confocal laser scanning microscopy showed that coumarin 6-loaded/protamine NPs were internalized by hepatocellular carcinoma cell line HepG2. The cellular uptake efficiency of NPs was obviously elevated after protamine modification. With commercial formulation Taxol® as the reference, HepG2 cells were also used to study the cytotoxicity of the NPs. PTX-loaded/protamine NPs exhibited significantly higher cytotoxicity than PTX-loaded NPs and Taxol® did. All the results suggested that surface modification of PTX-loaded PLGA- b-PEG- b-PLGA NPs with protamine boosted the therapeutic efficacy on liver cancer.

TAK228 With Carbo and Taxol in Advanced Malignancies

ClinicalTrials.gov

2018-03-12

Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic

Codeswitching Worldwide II. Trends in Linguistics: Studies and Monographs 126.

ERIC Educational Resources Information Center

Jacobson, Rodolfo, Ed.

This edited volume includes the following chapters: "The Matrix Language Frame Model: Development and Responses" (Carol Myers-Scotton); "Language Alternation: The Third Kind of Codeswitching Mechanism" (Rodolfo Jacobson); "Contrastive Sociolinguistics: Borrowed and Codeswitched Past Participles in Romance-Germanic Language…