Phenotypic Characterization of the Komeda Miniature Rat Ishikawa, an Animal Model of Dwarfism Caused by a Mutation in Prkg2

PubMed Central

Tsuchida, Atsuko; Yokoi, Norihide; Namae, Misako; Fuse, Masanori; Masuyama, Taku; Sasaki, Masashi; Kawazu, Shoji; Komeda, Kajuro

2008-01-01

The Komeda miniature rat Ishikawa (KMI) is a spontaneous animal model of dwarfism caused by a mutation in Prkg2, which encodes cGMP-dependent protein kinase type II (cGKII). This strain has been maintained as a segregating inbred strain for the mutated allele mri. In this study, we characterized the phenotype of the KMI strain, particularly growth traits, craniofacial measurements, and organ weights. The homozygous mutant (mri/mri) animals were approximately 70% to 80% of the size of normal, heterozygous (mri/+) animals in regard to body length, weight, and naso-occipital length of the calvarium, and the retroperitoneal fat of mri/mri rats was reduced greatly. In addition, among progeny of the (BN×KMI-mri/mri)F1×KMI-mri/mri backcross, animals with the KMI phenotype (mri/mri) were easily distinguished from those showing the wild-type phenotype (mri/+) by using growth traits such as body length and weight. Genetic analysis revealed that all of the backcrossed progeny exhibiting the KMI phenotype were homozygous for the KMI allele in the 1.2-cM region between D14Rat5 and D14Rat80 on chromosome 14, suggesting strongly that mri acts in a completely recessive manner. The KMI strain is the first and only rat model with a confirmed mutation in Prkg2 and is a valuable model for studying dwarfism and longitudinal growth traits in humans and for functional studies of cGKII. PMID:19149413

Street Gangs: A Modeling Approach to Evaluating At Risk Youth

DTIC Science & Technology

2008-03-01

Kaoru Ishikawa (Ryan, 2000; Herrmann, 2001). Ishikawa diagrams stem from the area of quality control but have been used in many other areas such as...Overview................................................................................................................43 Ishikawa Diagram...Figure 1. Example Ishikawa “Fishbone” Diagram.......................................................31 Figure 2. Example Value Hierarchy

Research Institute for the Education of Exceptional Children. Research Report 43.

ERIC Educational Resources Information Center

Tokyo Gakugei Univ. (Japan). Research Inst. for the Education of Exceptional Children.

This Japanese research report, with English abstracts, presents the following papers: "The Deterioration of the Intelligence with Age in Mental Retardation" (Atsushi Kanno and Souichi Hasimoto); "Development of Janken Skills in Autistic Children--Additional Data on Janken Echolalia in Normal Children" (Tohsuke Nomura);…

JPRS Report, Science & Technology, Japan, 1989 S&T Agency Annual 33

DTIC Science & Technology

1991-01-10

enter- prises are being put into operation. 46 JPRS-JST-91-001 10 January 1991 Shizuoka Prefecture, the Toyama Prefecture and Ishikawa Prefecture...Technology Agency, Ishikawa Prefecture "Topics in 21st-Century-Oriented Science and Technology Promotion in Ishikawa Prefecture" 200 people (From...Shiga Atomic Energy Ooi3 Ikata3 Genkai Atomic Energy 3 Shizuoka Prefecture, Oryu District, Hamaoka Town Ishikawa Prefecture, Hanesa District

[Effect of GPER on the activation of PI3K/Akt induced by 17β-estradiol in endometrial carcinoma cells].

PubMed

Zhang, Yan-Cai; Guo, Rui-Xia; Ge, Xin; Qiao, Yu-Huan

2012-04-01

To investigate the expression of G protein-coupled ER (GPER) and ER in the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) induced by 17β-estradiol (17β-E(2))in endometrial carcinoma cells, Ishikawa and HEC-1A. Expressions of GPER, ERα and ERβ protein in Ishikawa and HEC-1A cells were detected by immunohistochemical SP method. Levels of GPER, ERα and ERβ were examined by western blot in Ishikawa and HEC-1A cells after treated with 1×10(-6) mol/L 17β-E(2) at different time (0, 15, 30, 60, 120 minutes). GPER was positive expressed in Ishikawa and HEC-1A cells. ERα and ERβ were both positive expressed in Ishikawa cells. While, ERα was weakly expressed and ERβ was almost negatively expressed in HEC-1A cells. Western blot analysis showed that 1×10(-6) mol/L 17β-E(2) treatment, the Ishikawa and HEC-1A cells GPER protein level for 15 minutes markedly increased (P < 0.05), which Ishikawa 30 minutes, when cells reached the highest level (0.192 ± 0.004), HEC-1A cells for 15 minutes and reached the highest level (0.184 ± 0.006); Ishikawa and HEC-1A cells, Akt, activation of 15 minutes from the treatment start was significantly increased (P < 0.05), which Ishikawa cells for 30 minutes and reached the highest level (0.666 ± 0.021), HEC-1A cells for 15 minutes and reached maximum (0.788 ± 0.035); Ishikawa and HEC-1A cells, ERα and ERβ protein expression did not change significantly (P > 0.05). GPER likely involved in non-nuclear activation of PI3K/Akt signaling pathways in endometrial carcinoma cells, Ishikawa and HEC-1A.

An Analysis of the State of Total Quality In Academia

DTIC Science & Technology

1991-12-01

sense, quality is anything that can be improved." [Imai, 1986] 3. Joseph M. Juran "Quality is fitness for use." [Juran, 19891 4. Kaoru Ishikawa ...121 v L m 1111 X. INTRODUCTION "Quality Control begins with education and ends with education" Karou Ishikawa [ Ishikawa , 1985...revolution, the magnitude of which has been compared to that of the industrial revolution. [ Ishikawa , 1985, Deming, 1982] Dramatic changes are

Investigating the Role of Identity in L2 Writing Using Electronic Bulletin Boards

ERIC Educational Resources Information Center

Spiliotopoulos, Valia; Carey, Steven

2005-01-01

Recent research has focused on the relationship between language and identity (Ivanic, 1998; Kanno & Norton, 2003). International students who come to Canada to learn English as a second language realize that to succeed in the academic community, they must be particularly adept at writing in English for academic purposes. This article…

Total Quality Management: Implications for Nursing Information Systems

DTIC Science & Technology

1992-01-01

the Defense Department’s TQM model (see Appendix M) and TQM master plan (see Appendix N) (Hunt, 1992). Ishikawa . Kaoru Ishikawa was the best known of...the subject -- Deming, Juran, Crosby, Feigenbaum, Ishikawa , etc. (see Chapter 2). One of the most concise definitions on TQM was given in a speech by...with the contributions of key quality authors, including Deming, Juran, Crosby, Costello, and Ishikawa . The use of TQM in business and in healthcare

Total Quality Management Analysis of LAMPS MK 1 Aviation Maintenance Data

DTIC Science & Technology

1992-06-05

Qualit Control? The Japanese Way by Dr. Kaoru Ishikawa translated by David J. Lu offers the Japanese version of Total Quality Management. Dr...causes to an effect or problem. It is called the Ishikawa Diagram after its inventor Kaoru Ishikawa , a pioneer in quality control. The name fishbone...pathways involved. 2) Cause and Effect Diagram (also known as an Ishikawa Diagram or a Fishbone Diagram). This diagram used to identify the causes, and

Statistics of Mass Production

DTIC Science & Technology

1993-05-01

smaller ones, and the second after Kaoru Ishikawa who developed it in 1943. 22 UCL LCL Sample number Sample numbe CYCLES ON A CONTROL CHART A SHIFT IN...include Phillip Crosby, W. Edwards Deming, Armand Feigenbaum, Kaoru Ishikawa , and Joseph Juran. As an example of the ideas, the well-known 14 points of...tool for analyzing process dispersion. It is also referred to as the Ishikawa diagram, because Kaoru Ishikawa developed it, and the fishbone diagram

Determination of Heavy Metal Concentrations in Normal and Pathological Human Endometrial Biopsies and In Vitro Regulation of Gene Expression by Metals in the Ishikawa and Hec-1b Endometrial Cell Line

PubMed Central

Tomkiewicz, Céline; Leblanc, Alix; Pierre, Stéphane; El Balkhi, Souleiman; Le Frère-Belda, Marie-Aude; Lecuru, Fabrice; Poupon, Joël; Barouki, Robert; Aggerbeck, Martine; Coumoul, Xavier

2015-01-01

It is well known that several metals, such as lead, mercury, cadmium, and vanadium, can mimic the effects of estrogens (metallo-estrogens). Nevertheless, there are only a few studies that have assessed the effects of toxic metals on the female genital tract and, in particular, endometrial tissue. In this context, we measured the concentrations of several trace elements in human endometrial tissue samples from individuals with hyperplasia or adenocarcinoma and in normal tissues. Hyperplasic endometrial tissue has a 4-fold higher concentration of mercury than normal tissue. Mercury can affect both the AhR and ROS signaling pathways. Thus, we investigated the possible toxic effects of mercury by in vitro studies. We found that mercury increases oxidative stress (increased HO1 and NQO1 mRNA levels) and alters the cytoskeleton in the human endometrial Ishikawa cell line and to a lesser extent, in the “less-differentiated” human endometrial Hec-1b cells. The results might help to explain a potential link between this metal and the occurrence of endometrial hyperplasia. PMID:26600472

The Navy’s Quality Journey: Operational Implementation of TQL

DTIC Science & Technology

1993-04-01

training. Dr. Kaoru Ishikawa "Guide to Ouality Control" "QC begins with education and ends with education. To implement TQC, we need to carry out...York: McGraw-Hill, 1986. 20. Ishikawa , Kaoru . What is Total Qualit Control? Englewood Cliffs, NJ: Prentice-Hall, Inc., 1985. 21. Ishikawa , Kaoru

Black cohosh inhibits 17β-estradiol-induced cell proliferation of endometrial adenocarcinoma cells.

PubMed

Park, So Yun; Kim, Hee Ja; Lee, Sa Ra; Choi, Youn-Hee; Jeong, Kyungah; Chung, Hyewon

2016-10-01

This study was conducted to investigate the effect of black cohosh (BC) extract on the proliferation and apoptosis of Ishikawa cells. Ishikawa human endometrial adenocarcinoma cells were treated with or without BC (1, 5, 10 and 25 μM) and cell proliferation and cytotoxicity were measured by CCK-8 assays and flow cytometry analysis. Additionally, Ishikawa cells were treated with 17β-estradiol (E2), E2 + progesterone and E2 + BC (5 and 10 μM) and the effect of BC and progesterone on E2-induced cell proliferation was analyzed. BC decreased the proliferation of Ishikawa cells at a dose-dependent rate compared with the control group (p < 0.05). The proliferation of Ishikawa cells increased in the presence of E2, whereas the subsequent addition of progesterone or BC decreased proliferation to the level of the control group (p < 0.05). The inhibitory effect of BC on E2-induced cell proliferation was greater than the inhibitory effect of progesterone. In conclusion, BC induces apoptosis in Ishikawa cells and suppresses E2-induced cell proliferation in Ishikawa cells. BC could be considered a candidate co-treatment agent of estrogen-dependent tumors, especially those involving endometrial cells.

Imagined Identities and Investment in L2 Learning

ERIC Educational Resources Information Center

Wu, Hao-yu

2017-01-01

Imagined identity, referring to the ideal self that L2 learners aspire to become in the future (Norton & Toohey, 2011), has been identified as a critical factor that could guide learners to make a learning investment that they believe would in turn reward them with the social capital for which they yearn (Kanno & Norton, 2003). This…

Discovering Aspects of Teacher Identity through Volunteering in the Noncredit ESL Classroom

ERIC Educational Resources Information Center

Jurkunas, Lina

2015-01-01

As many scholars in the field of TESOL (Danielewicz, 2001; Harlow & Cobb, 2014; Kanno & Stuart, 2011) point out, the development of teacher identity is an ongoing, multifaceted process. Thus, quite frequently, novice teachers feel as though they take on a role when they are in the classroom, as opposed to fully embodying an identity of a…

Contributions of the Study of Japanese as a Second language to our General Understanding of Second Language Acquisition and the Definition of Second Language Acquisition Research.

ERIC Educational Resources Information Center

Wakabayashi, Shigenori

2003-01-01

Reviews three books on the acquisition of Japanese as a second language: "Second Language Acquisition Process in the Classroom" by A.S. Ohta;"The Acquisition of Grammar by Learners of Japanese" (English translation of title), by H. Noda, K. Sakoda, K. Shibuya, and N. Kobayashi; and "The Acquisition of Japanese as a Second Language," B. K. Kanno,…

Fishbone Diagrams: Organize Reading Content with a "Bare Bones" Strategy

ERIC Educational Resources Information Center

Clary, Renee; Wandersee, James

2010-01-01

Fishbone diagrams, also known as Ishikawa diagrams or cause-and-effect diagrams, are one of the many problem-solving tools created by Dr. Kaoru Ishikawa, a University of Tokyo professor. Part of the brilliance of Ishikawa's idea resides in the simplicity and practicality of the diagram's basic model--a fish's skeleton. This article describes how…

Total Quality Management in the United States Army Corps of Engineers

DTIC Science & Technology

1993-05-01

Office. Telephone interview with author, 20 November 1992. Ishikawa , Kaoru (1985). What is Total Quality Control? The Japanese Way. Prentice-Hall, Inc...Organizations ..... 55 Table 13. Ishikawa PDCA Cycle .......................................................... 68 Table 14. TQM Training M atrix...Standards 1008 ( Ishikawa 1985). The Japanese were aware of both the American and British work with standards. The standards were studied by

Quality in the Operational Air Force: A Case of Misplaced Emphasis

DTIC Science & Technology

1994-05-01

other quality advocates of the era. These men included Joseph Juran, Armand Feigenbaum, Kaoru Ishikawa , and Genichi Taguchi. Juran contributed disciplined...planning theories, while Feigenbaum felt that producing quality could actually reduce production costs. In addition, Ishikawa and Taguchi lent...statistically based problem solving techniques, but the more modem approaches of Ishikawa , Taguchi and others. The operative concept of TQM is ’continuous

A Methodology for Performing Effects-Based Assessments

DTIC Science & Technology

2006-03-01

can then be used to make assessments (Smith, 2002:384). 2.8 Cause-and-Effect Diagrams Developed by Dr. Kaoru Ishikawa in the field of Quality Control...John Wiley & Sons, Inc., 2004. Ishikawa , Kaoru . Guide to Quality Control. White Plains NY: Asian Productivity Organization, 1989...various causes affecting product quality by sorting out and relating the causes. Cause-and-effect diagrams are sometimes called Ishikawa diagrams, or

Total Quality Management Guide. Volume 2. A Guide to Implementation

DTIC Science & Technology

1990-02-15

Kaoru . Guide to Quality Control. Asian Productivity Organization. 1984. Ishikawa , Kaoru . What is Total Quality Control? The Japanese Way. Englewood...of the new Systems Age. The theories of Deming, Juran, Ishikawa , and other management methods that still predominate are pioneers of Systems Age...Feigenbaum, Armand V. Total Quality Control. New York: McGraw-Hill Book Company. 1983. bnai, Masaaki. Kaizen. New York: Random House. 1986. Ishikawa

Total Quality Management (TQM) Awareness Seminar. Revision 8

DTIC Science & Technology

1990-04-18

in the United States and abroad, including Dr. W. Edwards Deming, Dr. Joseph Juran, Philip Crosby, Genichi Taguchi, Kaoru Ishikawa , and Armand...Hall, Inc., Englewood Cliffs, NJ 07022. 1985 Ishikawa , Kaoru , Guide to Quality Control, Tokyo; Asian Productivity Organization, 1976 (Available from...Random House Business Division, 201 East 50th Street, New York, NY 10022. � Ishikawa , Karou, What is Total Quality Control?: The Japanese Way, Prentice

Defense Manufacturing Management Guide for Program Managers, Third Edition

DTIC Science & Technology

1989-04-01

Crosby (Quality goals of quality, cost, schedule, mission need, College), Genechi Taguchi (Experimental 5-1 Design), Dr. Kaoru Ishikawa (Cause/Effect...the remaining problems were resolved. 5-7 6. Ishikawa Diagram 7. Control Charts This technique was developed by Dr. In the minds of some quality Kaoru ... Ishikawa , one of the foremost professionals and nonprofesslonals alike, the authorities on quality control in Japan. The control chart is synonymous

An Analysis of Measures Used to Evaluate the Air Force Critical Item Program

DTIC Science & Technology

1991-09-01

example of a histogram. Cause & Effect Diagram. The cause and effect diagram was introduced in 1953 by Dr. Kaoru Ishikawa in summarizing the opinions of...Personal Interview. Air Force Institute of Technology, School of Engineering, Wright-Patterson AFB OH, 24 April 1991. 31. Ishikawa , Dr. Kaoru . Guide to...collected. How the data are collected will determine which measurement techniques are appropriate. Ishikawa classifies data collection into five categories

Readings on Managing Organizational Quality

DTIC Science & Technology

1990-05-01

Produc- tivify Review, Autumn, 1985. VI. Acknow ledg- Ishikawa , Kaoru . Guide to Quality Control. Tokyo: Asian Productivity Organization.m ents 1976. We are...indebted to many people for the develop- Ishikawa , Kaoru What is Total Quality Con- ment of the ideas expressed in this paper. Chief trol?: The...Developed by Kaoru Ishikawa , this di- Yes agram breaks the causes into general categories like methods. .............. materials, machines, and man, and

Total Quality Management: A Guide to Implementation

DTIC Science & Technology

1989-08-01

Kaizen. New York: Random House. 1986. Ishikawa , Kaoru . Guide to Quality Control. Asian Productivity Organization. 1984. Ishikawa , Kaoru . What is Total...with the problems and the new management principles are based on the complexities of the new Systems Age. The theories of Deming, Juran, Ishikawa , and...Progress. Jun 1985. Miller, Jeffery G. and Thomas E. Vollmann. "The Hidden Factory." Harvard Business Review. Sep-Oct 1985. Shimoyamada, Kaoru . "The

The Subject Matter of Process Improvement: A Topic and Reference Source for Software Engineering Educators and Trainers.

DTIC Science & Technology

1995-05-01

Random House Business Division, 1986. Ishikawa , Kaoru . What is Total Quality Control?: The Japanese Way. En- glewood Cliffs, NJ: Prentice-Hall...by drawing attention to the vital few truly important problems. Cause-and-effect diagrams. Also called fishbone and Ishikawa diagrams due to their...February 1994. 5.2 The Seeds [Aguayo 91] [Crosby 79] [Crosby 92] [Deming 86] [Fellers 92] [Gitlow 87] [Gluckman 93] [Imai 86] [ Ishikawa 85] [Juran

A Revision of the Adult and Larval Mosquitoes of Japan (Including the Ryukyu Archipelago and the Ogasawara Islands) and Korea (Diptera: Culicidae)

DTIC Science & Technology

1979-01-01

Ryukyu Archipelago Ogasawara and Volcano islands Prefectures of Japan (large bold numerals) 13. Hyogo 14. Ibaraki 15. Ishikawa 16. Iwate 17...Kishimoto, 1969: 33, Haneji and Ishikawa , Okinawa Is. ; &omi and Sonae, Iriomote Is. ; Ryukyu Archipelago. Descriptions based on specimens from Taiwan...d, 9, P, L). Type-locality: Mt. Hakusan, Ishikawa Pref., Japan. FEMALE (Fig. 216). Wing length 5.1-5.4 mm. Head. Eyes narrowly narrowly separated

Practical Software Measurement: Measuring for Process Management and Improvement,

DTIC Science & Technology

1997-04-01

Ishikawa , Kaoru . Guide to Quality Control, Second Revised Edition. White Plains, N.Y.: UNIPUB-Kraus International Publications, 1986. CMU/SEI-97...begin, you may want to assemble a group of people who work within the process to brainstorm possible reasons for the unusual behavior. Ishikawa charts...control limits and center line. • Cause-and-effect diagrams (also know as Ishikawa charts) allow you to probe for, map, and prioritize a set of factors

USAF Summer Research Program - 1995 Summer Faculty Research Program Final Reports, Volume 5A, Wright Laboratory

DTIC Science & Technology

1995-12-01

Certification. Oliver Wight Publications, Inc. Essex Junction. 1993. Ishikawa , Kaoru . (Translation by David J. Lu) What is Total Quality Control? The Japanese...approximation to the eight-harness satin weave (8H SW) is made, following the mosaic model ( Ishikawa and Chou, 1983) which treats woven composites as cross...K. W. and Bailey, J. E. (1978) Journal of Material Science, Vol. 13, pp. 195. Ishikawa , T. and Chou, T. W. (1983) One-dimensional micromechanical

Quality Control in construction.

DTIC Science & Technology

1984-01-01

behavioral scientists. In 1962, Dr. Kaoru Ishikawa gave shape to the form of training which featured intradepartmental groups of ten or so workers seated...and Japanese circles bears closer scrutiny. 4.3.1 Japanese Ingredients of Quality The founder of quality circles, Dr. Kaoru Ishikawa , gives six...around 51 a table; hence the name Quality Control Circle. 4 Dr. 0 Ishikawa was an engineering professor at Tokyo University, and the circles were

Ship Production Symposium Held in Arlington, Virginia on September 13-15, 1989 (The National Shipbuilding Research Program)

DTIC Science & Technology

1989-09-01

1986. 4. Kaoru Ishikawa , What is Total quality control? The Japanese way, Prentice-Hall, Englewood Cliffs, New Jersey, 1985. 22-1o No. 23 C o m b i n...Y. Ichinose presented a paper which disclosed how standards, including flexible standards, were organized and employed by Ishikawa - jima-Harima Heavy...result by sorting out and relating the causes. The cause-and- effect diagram, sometimes called an “ Ishikawa diagram” after the Japanese professor that

Examination of Various Methods Used in Support of Concurrent Engineering

DTIC Science & Technology

1990-03-01

1989. F.Y.I. Drawing a2Ther Productivity. Industrial Engineering 21: 80. Ishi82 Ishikawa , Kaoru . 1982. Guide to Quality Control. White Plains, NY: Kraus...observe it in practice have an easier time identifying the different methods or tech- niques (such as the Ishikawa tools) used than understanding the...simple histogram to show what prob- lems should be attacked first. Cause and Effect Diagrams Sometimes called the fishbone or Ishikawa diagrams-a kind

Quality Circles: Determination of Significant Factors for Success an a General Model for Implementing a Quality Circle Process.

DTIC Science & Technology

1981-06-01

receive for contributions to quality and productivity /4:Apdx-47. The initiative for the Quality Circle concept came from Dr Kaoru Ishikawa , a...eloquently summarized by the "Father of Quality Circles", Dr Kaoru Ishikawa . He sees that, although Japan started with the worst quality reputation among...Perceptions of Influence, Academy of Management Journal. December 1974, pp 649-bz. 49. Ishikawa , Kaoru . S.C. Circle Activities. Union of Japanese Scientists and

Lessons Learned from the Implementation of Total Quality Management at the Naval Aviation Depot, North Island, California

DTIC Science & Technology

1988-12-01

Kaoru Ishikawa recognized the potential of statistical process control during one of Dr. Deming’s many instructional visits to Japan. He wrote the Guide...to Quality Control which has been utilized for both self-study and classroom training. In the Guide to Quality Control, Dr. Ishikawa describes...job data are essential for making a proper evaluation.( Ishikawa , p. 14) The gathering of data and its subsequent analysis are the foundation of

TQM - Total Quality Management (Bibliography)

DTIC Science & Technology

1990-05-01

ISBN: 0-941893-00-6 Price: $27.00 NAVSWC Library Call No: TS156 S358 GUIDE TO OUALITY CONTROL Author: Ishikawa , Kaoru Publisher: Asian Productivity...teachings of Juran, Deming, Feigenbaum, Crosby, Taguchi, Shewhart, Ishikawa , and others. 19 OUT OF BEDLAM: MANAGEMENT BY QUALITY LEADERSHIP Author...Price: $60.00 WHAT IS TOTAL QUALITY CONTROL? THE JAPANESE WAY Author. Ishikawa , K oru Publisher: Prentice Hall Date: 1985 Pagination: 215pp ISBN: 0-13

Implementation of the Total Quality Leadership Process in U.S. Marine Corps Field Contracting Offices

DTIC Science & Technology

1993-06-01

8 b. Dr. Joseph M. Juran ... .......... 11 c. Dr. Kaoru Ishikawa .... .......... .. 13 2. TQM in the Department of Defense ..... ... 15 3. TQL in the...qualification, etc. [Ref. 8] 12 c. Dr. Kaoru Ishikawa Japan is often lauded as the world’s leader in the quality movement. To understand how the Japanese view the...34The Real Message of the Quality Movement: Building Learning Organizations", Journal for Quality and Participation, March 1992. 10. Ishikawa , Kaoru

Quality Circles: An Innovative Program to Improve Military Hospitals

DTIC Science & Technology

1982-08-01

quality control. However, Dr. Kaoru Ishikawa is credited with starting the first "Quality Control Circles" and registering them with the Japanese Union of...McGregor and Abraham Maslow into a unique style of management. In 1962 Dr. Ishikawa , a professor at Tokyo University, developed the QC concept based on...RECOMMENDATIONS Conclusions The QC concept has come a long way since Dr. Ishikawa gave it birth in 1962. It has left an enviable record of success along its

On-Site Construction Productivity Improvement Through Total Quality Management

DTIC Science & Technology

1991-12-01

morale of the work force. i Kaoru Ishikawa , Guide to Ouality Control, (2d ed; New York: Asian Productivity Organization, 1982), p. 45. ’"Ibid. 34...Curve Kaoru Ishikawa , Guide to Quality Control, (2d ed; New York: Asian Productivity Organization, 1982), p. 62. 54 For any normal distribution, 99.73...KAIZEN The Key to Japan’s Comoetitive Success. New York: Random House Business Division, 1986. Ishikawa , Kaoru , Guide to Ouality Control. 2d ed; New

Total Quality Management Implementation: Selected Readings

DTIC Science & Technology

1989-04-01

October 1986; Kaoru Ishikawa , Watj is Total Quality Control? The Japanese Way (Englewood Cliffs, NJ.r Prentice Hall, Inc. 1985), pp. 59-71 and chapter 7...and teachings of Dr. Kaoru Ishikawa and Prcfess:- Yoshikazu Tsuda. In their presentations I find ideas which conflict with current belie’s in t- s cou...responsible for S. Kaoru Ishikawa . 147iat is Total Quahn Control’ Th, Japar,,I the safety of all passengers and their belongings. w. (Englewood Hills. NJ

Total Quality Management: A Selected Bibliography

DTIC Science & Technology

1993-03-01

Business One Irwin, 1992. 3 0 8 pp. Pp. 47-88: "Different Drummers." (HD62.15 H86 1992) Ishikawa , Kaoru . INTRODUCTION TO QUALITY CONTROL. Tokyo: 3A...Corporation, 1990. 435pp. (TS156 183 1990) Ishikawa , Kaoru . WHAT IS TOTAL QUALITY CONTROL? THE JAPANESE WAY. Englewocd Cliffs, NJ: Prentice-Hall, 1985...Using Measurement Data." (TS156 M34 1987) Ishikawa , Kaoru . INTRODUCTION TO QUALITY CONTROL. Tokyo: 3A Corporation, 1990. 435pp. (TS156 183 1990) Juran

Evaluating the potential bioactivity of a novel compound ER1626.

PubMed

Wang, Lijun; Zeng, Yanyan; Wang, Tianling; Liu, Hongyi; Xiao, Hong; Xiang, Hua

2014-01-01

ER1626, a novel compound, is a derivate of indeno-isoquinoline ketone. This study was designed to evaluate the biological activity and potential anti-tumor mechanism of ER1626. MTT assay, scratch assay and flow cytometry were used to determine cell proliferation, cell migration and cell cycle distribution as well as cell apoptosis on human breast cancer MCF-7 cells and endometrial cancer Ishikawa cells. We also explored the antiangiogenic effect of ER1626 on HUVEC cells and chicken embryos. The expression of estrogen receptor protein was investigated with western-blot analysis. ER1626 down-regulated the expression of estrogen receptor α protein and up-regulated β protein in MCF-7 and Ishikawa cells. The value of IC50 of ER1626 on MCF-7 and Ishikawa cells were respectively 8.52 and 3.08 µmol/L. Meanwhile, ER1626 decreased VEGF secretion of MCF-7 and Ishikawa cells, disturbed the formation of VEGF-stimulated tubular structure in HUVEC cells, and inhibited the angiogenesis on the chicken chorioallantoic membrane. Scratch assay revealed that ER1626 suppressed the migration of MCF-7, Ishikawa and HUVEC cells. In addition to induction tumor cell apoptosis, ER1626 arrested cell cycle in G1/G0 phase in MCF-7 cells and G2/M phase in Ishikawa cells. In conclusion, our results demonstrated that ER1626 has favorable bioactivities to be a potential candidate against breast cancer and angiogenesis.

Substance P Promotes the Progression of Endometrial Adenocarcinoma.

PubMed

Ma, Jing; Yuan, Shifa; Cheng, Jianxin; Kang, Shan; Zhao, Wenhong; Zhang, Jie

2016-06-01

It has been demonstrated that substance P (SP) promotes while neurokinin-1 receptor (NK-1R) antagonist inhibits the proliferation of several human cancer cells. Currently, it is still unknown whether such actions exist in human endometrial carcinoma. This study aimed to explore the role of SP/NK-1R signaling in the progression of endometrial adenocarcinoma. The expression levels of SP and NK-1R in endometrial adenocarcinoma tissues and Ishikawa cell line were detected by real-time quantitative PCR and Western blot analysis. The effects of SP on Ishikawa cells proliferation and invasion were analyzed using MTT assay and transwell matrigel invasion assay, respectively. The expression levels of matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor C (VEGF-C) in Ishikawa cells after administration of SP were detected by real-time quantitative RCR and Western blot analysis. The expression levels of SP and NK-1R were significantly higher in endometrial adenocarcinoma tissues and Ishikawa cells than in normal endometrium. Substance P significantly enhanced the proliferation and invasion of Ishikawa cells. In addition, SP induced the expression of MMP-9 and VEGF-C in Ishikawa cells, whereas NK-1R antagonist inhibited these effects. Substance P plays an important role in the development of endometrial carcinoma by inducing the expression of MMP-9 and VEGF-C and promoting cancer cell proliferation and metastasis, which can be blocked by NK-1R antagonist.

Proceedings of the 1997 IEEE International Symposium on Compound Semiconductors (1997) Held in San Diego, California, on 8-11 September 1997

DTIC Science & Technology

1998-05-01

Lett. 54 2458 [6] Sasaki M., Kawakya Y., Ishikawa H. and Mashita M. 1989 Appl. Surface Sei. 41/42 342 [7] McCaulley J.A., McCrary V.R. and Donnelly...Dev. Lett. 14, 25 (1993). [2] M Ishikawa , Y. Ohba, H. Sugawara, M. Yamamoto and T. Nakanisi Appl. Phys. Lett. 48, 207 (1986). [3] J M Olson, S. R...H 1996 Appl. Phys. Lett. 69 955. [3] Lopez M, Tanaka N, Matsuyama I and Ishikawa T 1996 Appl. Phys. Lett. 68 658. [4] Finnie P, Buchanan M, Lacelle

Total Quality Management Implementation Strategy: Directorate of Quality Assurance

DTIC Science & Technology

1989-05-01

Total Quality Control Harrington, H. James The Improvement Process Imai, Masaaki Kaizen Ishikawa , Kaoru What is Total Quality Control Ishikawa ... Kaoru Statistical Quality Control Juran, J. M. Managerial Breakthrough Juran, J. M. Quality Control Handbook Mizuno, Ed Managing for Quality Improvements

Self-Ratings of Eight Factors of Quality Management at Naval Avionics Center

DTIC Science & Technology

1991-12-01

revised edition, North Rivers Press, Inc., 1986. Ishikawa , Kaoru , What is Total Quality Control? the Japanese Way, Prentice-Hall, Inc., 1985. Jaeger...including such authors as Deming, Juran, Ishikawa , and Crosby. The questionnaire was validated using a sample from private sector organizations in

The National Shipbuilding Research Program, Analytical Quality Circles

DTIC Science & Technology

1986-09-01

standard tools for quality control, in English, see “Guide to Quality Control” by Dr. Kaoru Ishikawa , Asian Productivity Organization, Aoyama Dai-ichi...factors affect work evaluation is shown schemati- cally by Characteristic-Factor Diagrams (also called Fishbone or Ishikawa Diagrams), see Figure 2-5

CrossTalk. The Journal of Defense Software Engineering. Volume 25, Number 1, Jan/Feb 2012

DTIC Science & Technology

2012-01-01

Considerations in Airborne Systems and Equipment Certification – RTCA/DO-178B,” Washington, D.C., 1992. 5. Ishikawa , Kaoru (Translator: J. H...significant, repeated issue, a formal root cause analysis process is performed. This method uses fishbone or Ishikawa diagrams [5], where possible

Terms of Productivity, Including the Relationship Between Productivity, Effectiveness and Efficiency.

DTIC Science & Technology

1989-04-01

for Awareness Juran on Planning for Quality, 1988, J.M. Juran What is Total Quality Control? The Japanese Way, 1985, Kaoru Ishikawa Guide to Quality...Control, 1982, Kaoru Ishikawa Andrews, M. (1985). Statistical Process Control: Mandatory Management Tool. Production April 1985. Bushe, G. (1988

Proceedings of the Acquisition Research Symposium: Imagnination, Innovation, and Implementation, 1991. Volume 1.

DTIC Science & Technology

1991-01-01

Construction Industry Institute, Austin, Texas, April 1990. 6. Ishikawa , Kaoru , What is Total Quality Control? The Japanese Way, Prentice-Hall, N.J., 1985. 7...customer. Ishikawa , a leading Japanese management and line personnel, and where authority on quality management, claims that appropriate, the customer

The National Shipbuilding Research Program. Design for Production Manual 2nd Edition

DTIC Science & Technology

1999-07-01

New York, 1979 Montgomery, Douglas C., Introduction to Statistical Quality Control, 3rd Edition, John Wiley & Sons, New York, 1997 Ishikawa , Kaoru ...references: Feigenbaum, A.V., Total Quality Control: Engineering and Management, 3rd edition, New York McGraw Hill, 1983. Ishikawa , Kaouro., Guide to

The Ninth U.S. - Japan Seminar on Dielectric and Piezoelectric Ceramics. Program and Evaluations

DTIC Science & Technology

1999-11-05

Yamamoto DeptElectrical Eng. National Defense Academy 1-10-20 Hashirimizu, Yokosuka, 239-8686 Japan Phone: 81-468-41-3810 (ext.2585) Fax: 81-468...Takashi Yamamoto , National Defense Academy 9:00-10:00 Plenary Lectures page PI-1 MLCs Technologies of Today and Future, Yukin Sakahp...of PbTi03 Single Crystals by Kelvin Force Microscope, 19 Takashi Yamamoto , Shinobu Omika, Junichi Sakamoto and Eiji Matsuzaki National Defense

CrossTalk: The Journal of Defense Software Engineering. Volume 25, Number 1, January/February 2012

DTIC Science & Technology

2012-02-01

Equipment Certification – RTCA/DO-178B,” Washington, D.C., 1992. 5. Ishikawa , Kaoru (Translator: J. H. Loftus), Introduction to Quality Control, Tokyo...cause analysis process is performed. This method uses fishbone or Ishikawa diagrams [5], where possible causes for the outliers are listed, followed by

Program Manager: Journal of the Defense Systems Management College, Volume 22, Number 5, September-October 1993

DTIC Science & Technology

1993-10-01

Edwards Deming, Joseph M. Juran, Process Kaoru Ishikawa and Philip B. Crosby Activities stress the importance of work-force employee involvement to...contracts. The Ishikawa - An atmosphere of mutual work-force employee involvement ac- DOD executives have lectured at con- trust and respect is neces- tions

Global Governance: The Role of States and International Organizations

DTIC Science & Technology

2003-10-01

1752002) Ishikawa , Kaoru . Nation Building and Development Assistance in Africa: Different but Egual. New York: St. Martin’s, 1999. (HC 800 .184 1999...C242454 2001) Irwin, Douglas A. Free Trade under Fire. Princeton: Princeton UP, 2002. (HF 1756 .1682002) Ishikawa , Kaoru . Nation Building and

Quality Management: Survey of Federal Organizations

DTIC Science & Technology

1992-10-01

Deming, Armand Feigenbaum, Kaoru Ishikawa , and J. M. Juran. For purposes of our survey, quality improvement efforts which have the same basic goals and...Feigenbaum, Kaoru Ishikawa , and J.M. Juran. Even though this approach may have different names, it most often includes the following five concepts

Selected Works: 1990-1994

DTIC Science & Technology

1995-08-01

soldiers: 43 tanks: 37 Isaacs, Betty: 336 Isherwood, Mike: 336 Ishikawa , Kaoru : 263 Isolationism: 137 Israel: 29, 229, 335 383 Israeli Air Force: 335...Deming, Juran, Ishikawa , and others—have long been practiced by the Air Force. We’ve used these principles from our beginnings as an institution—long

Investigation and Root Cause Analysis Guideline for Undetected Cracking Incidents in Safety-of-Flight Aircraft Structure

DTIC Science & Technology

2007-01-01

diagram” because it was invented by Kaoru Ishikawa , or a “Fishbone Diagram” because of the way it looks. This diagram should incorporate the resulting...the relationships between a given outcome and all the factors that influence the outcome. This type of diagram is sometimes called an “ Ishikawa

Variations in Cognitive Maps: Understanding Individual Differences in Navigation

ERIC Educational Resources Information Center

Weisberg, Steven M.; Schinazi, Victor R.; Newcombe, Nora S.; Shipley, Thomas F.; Epstein, Russell A.

2014-01-01

There are marked individual differences in the formation of cognitive maps both in the real world and in virtual environments (VE; e.g., Blajenkova, Motes, & Kozhevnikov, 2005; Chai & Jacobs, 2010; Ishikawa & Montello, 2006; Wen, Ishikawa, & Sato, 2011). These differences, however, are poorly understood and can be difficult to…

The Establishment of a Quality Circles Program and Its Effect on Employee Attitudes, Morale, and Performance at an Army Medical Treatment Facility.

DTIC Science & Technology

1984-08-01

more times. Dr. Kaoru Ishikawa , a professor at the University of Tokyo and a board member of JUSE, used the efforts of Dr. Juran as the background for...his later work with quality circles. Dr. Ishikawa and the JUSE are generally credited with formalizing the modern Japanese quality circle technique in

Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells.

PubMed

Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui

2016-04-19

The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17β-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17β-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17β-estradiol-induced cell proliferation and reversed 17β-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of βKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of βKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of βKlotho in Ishikawa cells abolished 17β-estradiol-induced EMT via inhibiting ERK1/2 signaling. βKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKα signaling inhibitor. In conclusion, metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin.

Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells

PubMed Central

Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui

2016-01-01

The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17β-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17β-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17β-estradiol-induced cell proliferation and reversed 17β-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of βKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of βKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of βKlotho in Ishikawa cells abolished 17β-estradiol-induced EMT via inhibiting ERK1/2 signaling. βKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKα signaling inhibitor. In conclusion, metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin. PMID:26824324

Lost in Translation: The Importance of Retaining Army Sociocultural Capabilities in an Era of Persistent Conflict

DTIC Science & Technology

2014-05-22

Operations Those who cannot remember the past are condemned to repeat it. ― George Santayana, The Life of Reason History provides more than enough...York: Dodd, Mead , 1980), 13. 79Takamae Eiji, Inside GHQ: The Allied Occupation of Japan and Its Legacy (New York: Continuum International, 2002), 93...response to the need to assess and unify the operations of the opinion agencies in Japan. 100 According to POSRs first director, Dr. Herbert Passin

DCASR (Defense Contract Administration Services Region) Dallas Total Quality Management Implementation Plan

DTIC Science & Technology

1989-07-01

Competitive Success e. What is Total Quality Kaoru Ishikawa Control? The Japanese Way f. Managerial Break Through J. M. Juran g. The Deming Route to...Berger and Thomas H. Hart p. Juran’s Quality Control J. M. Juran Handbook, Fourth Edition q. Guide to Quality Control Kaoru Ishikawa r. Quality Assurance

Introduction to Financial Management for Foreign Military Staff Officers

DTIC Science & Technology

1991-06-01

House: New York, 1986. 5. Ishikawa , Kaoru . What is Total Quality Control? The Japanese Way. Prentice-Hall: Englewood Cliffs, NJ., 1985. 6. Juran, J. M...the key to process improvement is the infinite human potential of an organization’s people." 5 [ Ishikawa , 85) 6. Processes, not people, are the root

Applying Total Quality Leadership to an Aviation Squadron

DTIC Science & Technology

1991-12-01

was developed in 1950 by Professor Kaoru Ishikawa . (Juran,1988,pp.22.37) It was developed to show the relationship between some fail point or desired...AND-EFmECT DIAGRAM 1. Description of Cause-and-Effect Diagram The cause-and-effect diagram (also known as the Ishikawa diagram or the fishbone diagram

The effects of estradiol and selective estrogen receptor modulators on gene expression and messenger RNA stability in immortalized sheep endometrial stromal cells and human endometrial adenocarcinoma cells.

PubMed

Farnell, Yuhua Z; Ing, Nancy H

2003-03-01

The purpose of this study was to identify an endometrial cell line that maintained the E2 up-regulation of estrogen receptor (ER) mRNA by enhanced message stability and to assess its dependence on ER protein. Estradiol (E2) effects on gene expression were measured in three cell lines: one immortalized from sheep endometrial stroma (ST) and two from human endometrial adenocarcinomas (Ishikawa and ECC-1). E2 up-regulated ER mRNA levels in ST and Ishikawa cells, but down-regulated ER mRNA levels in ECC-1 cells. E2 up-regulated progesterone receptor (PR), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and transforming growth factor-alpha (TGF-alpha) in both Ishikawa and ECC-1 cells. The selective estrogen receptor modulator ICI 182,780 antagonized the E2-induced up-regulation of ER and/or PR mRNA levels in all three cells, while another, GW 5638, antagonized the up-regulation of PR mRNA in Ishikawa and ECC-1 cells. In mechanistic studies, E2 had no effect on ER mRNA stability in ST cells and it destabilized ER mRNA in ECC-1 cells. Thus, Ishikawa cells appear to be the most physiologically relevant cell line in which to study the up-regulation of ER mRNA levels by enhanced mRNA stability. Its antagonism by ICI 182,780 reveals that ER protein is involved in this E2 response.

Aromatase inhibitor regulates let-7 expression and let-7f induced cell migration in endometrial cells from women with endometriosis

PubMed Central

Cho, SiHyun; Mutlu, Levent; Zhou, Yuping; Taylor, Hugh S.

2018-01-01

Objectives To evaluate associations between aromatase inhibitor (AI) treatment and let-7 family microRNA expression in endometriosis. Design In vitro study using Ishikawa cells and human endometrial stromal cells (HESC) obtained from patients with endometriosis Setting University research center. Patients Women undergoing laparoscopic surgery for endometriosis Interventions HESCs and Ishikawa cells treated with various letrozol concentrations and transfected with a mimic of let-7 subtypes of interest Main Outcome Measures microRNAs let7a-f and aromatase expression were evaluated. Migration potential after transfection with a let-7f mimic were analyzed. Results After letrozole treatment for 48 hours, all let-7 subtypes showed a trend toward increased expression in a dose dependent manner in Ishikawa cells, and significant differences were found in let-7b and let-7f between controls and the 20 μmol/L treated groups. Further, let-7f showed significant differences between control and 1.0 μmol/L treatment group, a typical therapeutic level, in HESCs. Transfection of a let-7f mimic decreased aromatase expression in both Ishikawa cells and HESC, and led to a significant decrease in number of migrating cells in both cell types. Conclusions AI treatment significantly increased expression of let-7f in Ishikawa cells and HESCs from patient with endometriosis; increased lef-7f expression effectively reduced the migration of endometrial cells. Modulation of miRNAs involved in the pathogenesis of endometriosis may have therapeutic potential for endometriosis. PMID:27320036

Studies Using an in Vitro Model Show Evidence of Involvement of Epithelial-Mesenchymal Transition of Human Endometrial Epithelial Cells in Human Embryo Implantation*

PubMed Central

Uchida, Hiroshi; Maruyama, Tetsuo; Nishikawa-Uchida, Sayaka; Oda, Hideyuki; Miyazaki, Kaoru; Yamasaki, Akiko; Yoshimura, Yasunori

2012-01-01

Human embryo implantation is a critical multistep process consisting of embryo apposition/adhesion, followed by penetration and invasion. Through embryo penetration, the endometrial epithelial cell barrier is disrupted and remodeled by an unknown mechanism. We have previously developed an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial adenocarcinoma cell line Ishikawa. Using this model we have shown that stimulation with ovarian steroid hormones (17β-estradiol and progesterone, E2P4) and suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, enhances the attachment and adhesion of JAR spheroids to Ishikawa. In the present study we showed that the attachment and adhesion of JAR spheroids and treatment with E2P4 or SAHA individually induce the epithelial-mesenchymal transition (EMT) in Ishikawa cells. This was evident by up-regulation of N-cadherin and vimentin, a mesenchymal cell marker, and concomitant down-regulation of E-cadherin in Ishikawa cells. Stimulation with E2P4 or SAHA accelerated Ishikawa cell motility, increased JAR spheroid outgrowth, and enhanced the unique redistribution of N-cadherin, which was most prominent in proximity to the adhered spheroids. Moreover, an N-cadherin functional blocking antibody attenuated all events but not JAR spheroid adhesion. These results collectively provide evidence suggesting that E2P4- and implanting embryo-induced EMT of endometrial epithelial cells may play a pivotal role in the subsequent processes of human embryo implantation with functional control of N-cadherin. PMID:22174415

The γ-aminobutyric acid-producing ability under low pH conditions of lactic acid bacteria isolated from traditional fermented foods of Ishikawa Prefecture, Japan, with a strong ability to produce ACE-inhibitory peptides.

PubMed

Barla, Florin; Koyanagi, Takashi; Tokuda, Naoko; Matsui, Hiroshi; Katayama, Takane; Kumagai, Hidehiko; Michihata, Toshihide; Sasaki, Tetsuya; Tsuji, Atsushi; Enomoto, Toshiki

2016-06-01

Many traditional fermented products are onsumed in Ishikawa Prefecture, Japan, such as kaburazushi , narezushi , konkazuke , and ishiru. Various kinds of lactic acid bacteria (LAB) are associated with their fermentation, however, characterization of LAB has not yet been elucidated in detail. In this study, we evaluated 53 isolates of LAB from various traditional fermented foods by taxonomic classification at the species level by analyzing the 16S ribosomal RNA gene (rDNA) sequences and carbohydrate assimilation abilities. We screened isolates that exhibited high angiotensin-converting enzyme (ACE) inhibitory activities in skim milk or soy protein media and produced high γ-aminobutyric acid (GABA) concentrations in culture supernatants when grown in de Man Rogosa Sharpe broth in the presence of 1% (w/v) glutamic acid. The results revealed that 10 isolates, i.e., Lactobacillus buchneri (2 isolates), Lactobacillus brevis (6 isolates), and Weissella hellenica (2 isolates) had a high GABA-producing ability of >500 mg/100 ml after 72 h of incubation at 35 °C. The ACE inhibitory activity of the whey cultured with milk protein by using L. brevis (3 isolates), L. buchneri (2 isolates), and W. hellenica (2 isolates) was stronger than that of all whey cultured with soy protein media, and these IC 50 were < 1 mg protein/ml. Three of 10 isolates had high GABA-producing activities at pH 3, suggesting that they could be powerful candidates for use in the fermentation of food materials having low pH.

An Annotated Reading List for Concurrent Engineering

DTIC Science & Technology

1989-07-01

The seven tools are sometimes referred to as the seven old tools.) -9- Ishikawa , Kaoru , What is Total Quality Control? The Japanese Way, Prentice-Hall...some solutions. * Ishikawa (1982) presents a practical guide (with easy to use tools) for implementing qual- ity control at the working level...study of, :-, ieering for the last two years. Is..ikawa, Kaoru , Guide to Quality Control, Kraus International Publications, White Plains, NY, 1982. The

Total Quality Management in Construction

DTIC Science & Technology

1993-08-01

1989. I Ishikawa , Kaoru . Guide to Quality Control. White Plains, New York: Asian Productivity Organization, 1982. 5 Kelso, Frank B. II, Admiral...category are explored to determine the most significant causes which produce the effect. Figure 24 shows a typical cause-and effect diagram. Kaoru ... Ishikawa describes cause-and-effect diagrams as I an effective tool "to clearly illustrate the various causes I affecting quality by sorting out and relating

New Frontier Process using Bio Technology

DTIC Science & Technology

2013-02-05

p.58-59,2012. (2) H.Yamazaki, M.Fujii, Y.Ueoka, Y.ishikawa, M.Fujiwara, E.Takahashi, Y.Uraoka, “Highly Reliable a-InGaZnO Thin Film Transistors ...Electron Traps in SiO2/ IGZO Interface by Cyclic Capacitance–Voltage Method”, IEEE/ 2012 International Meeting for Future of Electron Devices, Kansai...Horita, Yasuaki Ishikawa, Yukiharu Uraoka, and Shinji Koh, “Characterizatio of Graphene Based Field Effect Transistors Using Nano Probing Microscopy

The New Partnership for Africa’s Development (NEPAD) -- Will It Succeed or Fail?

DTIC Science & Technology

2005-03-18

elites.” Global Information Network . (30 May 2003):1. Database on-line. Available from ProQuest. Accessed 21 October 2004. Ishikawa , Kaoru . Nation...Threat to Regional Integration?” TWN Africa, available from http://twnafrica.org/news_detail.asp?twnID=541; Internet: accessed 21 October 2004. 41 Kaoru ... Ishikawa , Nation Building and Development Assistance in Africa , (New York, N.Y.: St. Martin’s Press, 1999), 79-80. 42 “African Women Respond: Summary

High Glucose-Mediated STAT3 Activation in Endometrial Cancer Is Inhibited by Metformin: Therapeutic Implications for Endometrial Cancer

PubMed Central

Wallbillich, John J.; Josyula, Srirama; Saini, Uksha; Zingarelli, Roman A.; Dorayappan, Kalpana Deepa Priya; Riley, Maria K.; Wanner, Ross A.; Cohn, David E.; Selvendiran, Karuppaiyah

2017-01-01

Objectives STAT3 is over-expressed in endometrial cancer, and diabetes is a risk factor for the development of type 1 endometrial cancer. We therefore investigated whether glucose concentrations influence STAT3 expression in type 1 endometrial cancer, and whether such STAT3 expression might be inhibited by metformin. Methods In Ishikawa (grade 1) endometrial cancer cells subjected to media with low, normal, or high concentrations of glucose, expression of STAT3 and its target proteins was evaluated by real-time quantitative PCR (qPCR). Ishikawa cells were treated with metformin and assessed with cell proliferation, survival, migration, and ubiquitin assays, as well as Western blot and qPCR. Expression of apoptosis proteins was evaluated with Western blot in Ishikawa cells transfected with a STAT3 overexpression plasmid and treated with metformin. A xenograft tumor model was used for studying the in vivo efficacy of metformin. Results Expression of STAT3 and its target proteins was increased in Ishikawa cells cultured in high glucose media. In vitro, metformin inhibited cell proliferation, survival and migration but induced apoptosis. Metformin reduced expression levels of pSTAT3 ser727, total STAT3, and its associated cell survival and anti-apoptotic proteins. Additionally, metformin treatment was associated with increased degradation of pSTAT3 ser727. No change in apoptotic protein expression was noticed with STAT3 overexpression in Ishikawa cells. In vivo, metformin treatment led to a decrease in tumor weight as well as reductions of STAT3, pSTAT3 ser727, its target proteins. Conclusions These results suggest that STAT3 expression in type 1 endometrial cancer is stimulated by a high glucose environment and inhibited by metformin. PMID:28114390

Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste-berry).

PubMed

Liu, J; Burdette, J E; Sun, Y; Deng, S; Schlecht, S M; Zheng, W; Nikolic, D; Mahady, G; van Breemen, R B; Fong, H H S; Pezzuto, J M; Bolton, J L; Farnsworth, N R

2004-01-01

A methanol extract of chaste-tree berry (Vitex agnus-castus L.) was tested for its ability to displace radiolabeled estradiol from the binding site of estrogen receptors alpha (ERalpha) and beta (ERbeta). The extract at 46 +/- 3 microg/ml displaced 50% of estradiol from ERalpha and 64 +/- 4 microg/ml from ERbeta. Treatment of the ER+ hormone-dependent T47D:A18 breast cancer cell line with the extract induced up-regulation of ERbeta mRNA. Progesterone receptor (PR) mRNA was upregulated in the Ishikawa endometrial cancer cell line. However, chaste-tree berry extract did not induce estrogen-dependent alkaline phosphatase (AP) activity in Ishikawa cells. Bioassay-guided isolation, utilizing ER binding as a monitor, resulted in the isolation of linoleic acid as one possible estrogenic component of the extract. The use of pulsed ultrafiltration liquid chromatography-mass spectrometry, which is an affinity-based screening technique, also identified linoleic acid as an ER ligand based on its selective affinity, molecular weight, and retention time. Linoleic acid also stimulated mRNA ERbeta expression in T47D:A18 cells, PR expression in Ishikawa cells, but not AP activity in Ishikawa cells. These data suggest that linoleic acid from the fruits of Vitex agnus-castus can bind to estrogen receptors and induce certain estrogen inducible genes.

Effect of mTOR Inhibitors in Nude Mice with Endometrial Carcinoma and Variable PTEN Expression Status

PubMed Central

Fong, Pedro; Meng, Li-rong

2014-01-01

Background The aim of this study was to investigate the sensitivity to rapamycin of endometrial cancer cells with different phosphatase and tensin homologue (PTEN) expression to understand the mechanism of resistance to mammalian target of rapamycin (mTOR) inhibitors in the treatment of endometrial cancer. Material/Methods Twenty specific pathogen-free female BALB/c mice received transplants of either HEC-1A (PTEN-positive) or Ishikawa (PTEN-negative) cells. Mice in the treatment group were injected intraperitoneally once a week for 4 consecutive weeks. The control group was injected weekly with phosphate buffer saline (PBS) for 4 consecutive weeks. Tumor volume, tumor mass, growth curves, and inhibition rate were measured, after which the mice were killed. Results Both tumor growth rate and size were slower in the treatment group than in the control group for all mice that received transplants of either HEC-1A or Ishikawa cells. The tumor inhibition rates in the treatment group were 48.1% and 67.1% in mice transplanted with HEC-1A and Ishikawa cells, respectively. Conclusions The inhibitory effects of rapamycin were enhanced in PTEN-negative Ishikawa tumor cells compared with PTEN-positive HEC-1A cells, which could explain the reduced effect of rapalogues in some endometrial cancer patients and help to understand the mechanism of resistance to this drug. PMID:25266877

Paeonia lactiflora Enhances the Adhesion of Trophoblast to the Endometrium via Induction of Leukemia Inhibitory Factor Expression

PubMed Central

Park, Mi-Ju; Lee, Kyu Sup; Yoon, Youngjin; Kim, Hyung Sik; Lee, Jun Hee; Kwon, Sang-Mo; Lee, Syng-Ook; Kim, Keuk-Jun; Baek, Jin-Ho; Ha, Ki-Tae

2016-01-01

In the present study, we investigated the role of Paeonia lactiflora Pall. extract on embryo implantation in vitro and in vivo. A polysaccharides depleted-water extract of P. lactiflora (PL-PP) increased LIF expression in human endometrial Ishikawa cells at non-cytotoxic doses. PL-PP significantly increased the adhesion of the human trophectoderm-derived JAr spheroids to endometrial Ishikawa cells. PL-PP-induced LIF expression was decreased in the presence of a p38 kinase inhibitor SB203580 and an MEK/ERK inhibitor U0126. Furthermore, endometrial LIF knockdown by shRNA reduced the expression of integrins β3 and β5 and adhesion of JAr spheroids to Ishikawa cells. In vivo administration of PL-PP restored the implantation of mouse blastocysts in a mifepristone-induced implantation failure mice model. Our results demonstrate that PL-PP increases LIF expression via the p38 and MEK/ERK pathways and favors trophoblast adhesion to endometrial cells. PMID:26839969

Record of Operations Against Soviet Russia on Northern and Western Fronts of Manchuria, and in Northern Korea (August 1945)

DTIC Science & Technology

1954-09-01

Col Masao Segawa Col Kaoru Okano Col Shigeru Imada - Maj Akizo Yokoyama Capt Toyonobu Kondo Maj Toru Mi tano - Lt Col Sen Nagai - 1st Lt Ichiro...nchurians, and its commander, 1st Lieutenant Ishikawa , was killed. The only unit of the division to engage in action--the 5th Company of the 24lst...Lieutenant: 161 Irie, Major: 43 Ishikawa , 1st Lt: 160 Itung River: 15, 37, 42-43 Iwai, Lt Gen, Torajiro (Cmdr lOath Div): 143, 147-48, 154 Japanese

Seasonal variation of red clover (Trifolium pratense L., Fabaceae) isoflavones and estrogenic activity

PubMed Central

Booth, Nancy L.; Overk, Cassia R.; Yao, Ping; Totura, Steve; Deng, Yunfan; Hedayat, A. S.; Bolton, Judy L.; Pauli, Guido F.; Farnsworth, Norman R.

2007-01-01

Red clover (Trifolium pratense L., Fabaceae) dietary supplements are currently used to treat menopausal symptoms because of their high content of the mildly estrogenic isoflavones daidzein, genistein, formononetin and biochanin A. These compounds are estrogenic in vitro and in vivo, but little information exists on the best time to harvest red clover fields to maximize content of the isoflavones and thus make an optimal product. Samples of cultivated red clover aboveground parts and flower heads were collected in parallel over one growing season in northeastern Illinois. Generally, autohydrolytic extracts of aboveground parts contained more isoflavones and had more estrogenic activity in Ishikawa endometrial cells, compared with extracts of flower heads. Daidzein and genistein content peaked around June to July, while formononetin and biochanin A content peaked in early September. Flower head and total aboveground parts extracts exhibited differential estrogenic activity in an Ishikawa (endometrial) cell-based alkaline phosphatase (AP) induction assay, whereas nondifferential activity was observed for most extracts tested in an MCF-7 (breast) cell proliferation assay when tested at the same final concentrations. Ishikawa assay results could be mapped onto the extracts’ content of individual isoflavones, but MCF-7 results did not show such a pattern. These results suggest that significant metabolism of isoflavones may occur in MCF-7 cells, but not in Ishikawa cells, and therefore caution is advised in the choice of bioassay used for the biological standardization of botanical dietary supplements. PMID:16478248

An Exploratory Survey of Methods Used to Develop Measures of Performance

DTIC Science & Technology

1993-09-01

E3 Genichi Taguchi O3 Robert C. Camp 0 Kaoru Ishikawa 0 Dorsey J. Talley o Philip B. Crosby 0 J.M. Juran 0 Arthur R. Tenner 0 W. Edwards Deming 0...authored books or papers on the subject of quality? (Mark all that apply) o Nancy Brady 0 H. James Harrington 03 Genichi Taguchi o Robert C. Camp 0 Kaoru ... Ishikawa 03 Dorsey J. Talley 0 Philip B. Crosby 0 J.M. Juran 0 Arthur R. Tenner o W. Edwards Deming 0 Dennis Kinlaw 03 Hans J. Thamhain 0 Irving J

Impact of ER520, a candidate of selective estrogen receptor modulators, on in vitro cell growth, migration, invasion, angiogenesis and in vivo tumor xenograft of human breast cancer cells.

PubMed

Wang, Lijun; Wang, Ying; Du, Huaqing; Jiang, Yao; Tang, Zhichao; Liu, Hongyi; Xiang, Hua; Xiao, Hong

2015-12-01

ER520, a derivative of indenoisoquinoline, is a patented compound. This study was designed to screen its biological properties and to evaluate its antineoplastic and antiangiogenic effect. Western blot was employed to monitor the ERα and ERβ protein expression in human breast cancer MCF-7 cells and endometrial carcinoma Ishikawa cells. MTT assay was employed to determine cell proliferation. Cell adhesion, scratch and Transwell assay were utilized to estimate the ability of cellular adhesion, migration and invasion. ELISA kit was applied to detect the VEGF products in culture medium. In addition, the inhibitory effect of ER520 on the vessel-like construction of HUVEC cells and the angiogenesis of chicken embryos was investigated. The efficiency of ER520 on tumor growth in nude mice was also assessed. ER520 inhibited the expression of ERα in MCF-7 and Ishikawa cells, while it increased ERβ protein level. ER520 also suppressed the proliferation of MCF-7 and Ishikawa cells. Due to its remarkably negative role in cell adhesion, migration and invasion, ER520 showed a potential ability of inhibiting tumor metastasis. Meanwhile, ER520 reduced the VEGF secretion of MCF-7 and Ishikawa cells, prevented the formation of VEGF-stimulated tubular structure and the cell migration of HUVEC cells, and inhibited the angiogenesis of chicken chorioallantoic membrane. Animal experiment also demonstrated that ER520 could frustrate the in vivo tumor growth and the inhibitory ratio was 48.5 % compared with control group. Our findings indicate that ER520 possesses the competence to be a candidate against breast cancer and angiogenesis.

EphA2 Targeted Chemotherapy Using an Antibody Drug Conjugate in Endometrial Carcinoma

PubMed Central

Lee, Jeong-Won; Stone, Rebecca L.; Lee, Sun Joo; Nam, Eun Ji; Roh, Ju-Won; Nick, Alpa M.; Han, Hee-Dong; Shahzad, Mian M.K.; Kim, Hye-Sun; Mangala, Lingegowda S.; Jennings, Nicholas B.; Mao, Shenlan; Gooya, John; Jackson, Dowdy; Coleman, Robert L.; Sood, Anil K.

2013-01-01

Purpose EphA2 overexpression is frequently observed in endometrial cancers, and is predictive of poor clinical outcome. Here, we utilize an antibody drug conjugate (MEDI-547) composed of a fully human monoclonal antibody against both human and murine EphA2 (1C1) and the tubulin polymerization inhibitor, monomethylauristatin F (MMAF). Experimental design EphA2 expression was examined in endometrial cancer cell lines by Western Blot. Specificity of MEDI-547 was examined by antibody degradation and internalization assays. Viability and apoptosis were investigated in endometrial cancer cell lines and orthotopic tumor models. Results EphA2 was expressed in the Hec-1A and Ishikawa cells, but was absent in the SPEC-2 cells. Antibody degradation and internalization assays showed that the antibody drug conjugate decreased EphA2 protein levels and was internalized in EphA2 positive cells (Hec-1A and Ishikawa). Moreover, in vitro cytotoxicity and apoptosis assays demonstrated that the antibody drug conjugate decreased viability and increased apoptosis of Hec-1A and Ishikawa cells. In vivo therapy experiments in mouse orthotopic models with this antibody drug conjugate resulted in 86 to 88% growth inhibition (P < 0.001) in the orthotopic Hec-1A and Ishikawa models compared to controls. Moreover, the mice treated with this antibody drug conjugate had a lower incidence of distant metastasis compared with controls. The anti-tumor effects of the therapy were related to decreased proliferation and increased apoptosis of tumor and associated endothelial cells. Conclusions The preclinical data for endometrial cancer treatment using MEDI-547 demonstrate substantial anti-tumor activity. PMID:20388851

The impact of 27-hydroxycholesterol on endometrial cancer proliferation.

PubMed

Gibson, Douglas A; Collins, Frances; Cousins, Fiona L; Esnal Zufiaurre, Arantza; Saunders, Philippa T K

2018-04-01

Endometrial cancer (EC) is the most common gynaecological malignancy. Obesity is a major risk factor for EC and is associated with elevated cholesterol. 27-hydroxycholesterol (27HC) is a cholesterol metabolite that functions as an endogenous agonist for Liver X receptor (LXR) and a selective oestrogen receptor modulator (SERM). Exposure to oestrogenic ligands increases risk of developing EC; however, the impact of 27HC on EC is unknown. Samples of stage 1 EC ( n  = 126) were collected from postmenopausal women undergoing hysterectomy. Expression of LXRs ( NR1H3 , LXRα; NR1H2 , LXRβ) and enzymes required for the synthesis ( CYP27A1 ) or breakdown ( CYP7B1 ) of 27HC were detected in all grades of EC. Cell lines originating from well-, moderate- and poorly-differentiated ECs (Ishikawa, RL95, MFE 280 respectively) were used to assess the impact of 27HC or the LXR agonist GW3965 on proliferation or expression of a luciferase reporter gene under the control of LXR- or ER-dependent promoters (LXRE, ERE). Incubation with 27HC or GW3965 increased transcription via LXRE in Ishikawa, RL95 and MFE 280 cells ( P  < 0.01). 27HC selectively activated ER-dependent transcription ( P  < 0.001) in Ishikawa cells and promoted proliferation of both Ishikawa and RL95 cells ( P  < 0.001). In MFE 280 cells, 27HC did not alter proliferation but selective targeting of LXR with GW3965 significantly reduced cell proliferation ( P  < 0.0001). These novel results suggest that 27HC can contribute to risk of EC by promoting proliferation of endometrial cancer epithelial cells and highlight LXR as a potential therapeutic target in the treatment of advanced disease. © 2018 The authors.

How to apply clinical cases and medical literature in the framework of a modified "failure mode and effects analysis" as a clinical reasoning tool--an illustration using the human biliary system.

PubMed

Wong, Kam Cheong

2016-04-06

Clinicians use various clinical reasoning tools such as Ishikawa diagram to enhance their clinical experience and reasoning skills. Failure mode and effects analysis, which is an engineering methodology in origin, can be modified and applied to provide inputs into an Ishikawa diagram. The human biliary system is used to illustrate a modified failure mode and effects analysis. The anatomical and physiological processes of the biliary system are reviewed. Failure is defined as an abnormality caused by infective, inflammatory, obstructive, malignancy, autoimmune and other pathological processes. The potential failures, their effect(s), main clinical features, and investigation that can help a clinician to diagnose at each anatomical part and physiological process are reviewed and documented in a modified failure mode and effects analysis table. Relevant medical and surgical cases are retrieved from the medical literature and weaved into the table. A total of 80 clinical cases which are relevant to the modified failure mode and effects analysis for the human biliary system have been reviewed and weaved into a designated table. The table is the backbone and framework for further expansion. Reviewing and updating the table is an iterative and continual process. The relevant clinical features in the modified failure mode and effects analysis are then extracted and included in the relevant Ishikawa diagram. This article illustrates an application of engineering methodology in medicine, and it sows the seeds of potential cross-pollination between engineering and medicine. Establishing a modified failure mode and effects analysis can be a teamwork project or self-directed learning process, or a mix of both. Modified failure mode and effects analysis can be deployed to obtain inputs for an Ishikawa diagram which in turn can be used to enhance clinical experiences and clinical reasoning skills for clinicians, medical educators, and students.

Qualification of computerized monitoring systems in a cell therapy facility compliant with the good manufacturing practices.

PubMed

Del Mazo-Barbara, Anna; Mirabel, Clémentine; Nieto, Valentín; Reyes, Blanca; García-López, Joan; Oliver-Vila, Irene; Vives, Joaquim

2016-09-01

Computerized systems (CS) are essential in the development and manufacture of cell-based medicines and must comply with good manufacturing practice, thus pushing academic developers to implement methods that are typically found within pharmaceutical industry environments. Qualitative and quantitative risk analyses were performed by Ishikawa and Failure Mode and Effects Analysis, respectively. A process for qualification of a CS that keeps track of environmental conditions was designed and executed. The simplicity of the Ishikawa analysis permitted to identify critical parameters that were subsequently quantified by Failure Mode Effects Analysis, resulting in a list of test included in the qualification protocols. The approach presented here contributes to simplify and streamline the qualification of CS in compliance with pharmaceutical quality standards.

An update on minding the gap in cancer.

PubMed

Mesnil, Marc; Aasen, Trond; Boucher, Jonathan; Chépied, Amandine; Cronier, Laurent; Defamie, Norah; Kameritsch, Petra; Laird, Dale W; Lampe, Paul D; Lathia, Justin D; Leithe, Edward; Mehta, Parmender P; Monvoisin, Arnaud; Pogoda, Kristin; Sin, Wun-Chey; Tabernero, Arantxa; Yamasaki, Hiroshi; Yeh, Elizabeth S; Dagli, Maria Lucia Zaidan; Naus, Christian C

2018-01-01

This article is a report of the "International Colloquium on Gap junctions: 50Years of Impact on Cancer" that was held 8-9 September 2016, at the Amphitheater "Pôle Biologie Santé" of the University of Poitiers (Poitiers, France). The colloquium was organized by M Mesnil (Université de Poitiers, Poitiers, France) and C Naus (University of British Columbia, Vancouver, Canada) to celebrate the 50th anniversary of the seminal work published in 1966 by Loewenstein and Kanno [Intercellular communication and the control of tissue growth: lack of communication between cancer cells, Nature, 116 (1966) 1248-1249] which initiated studies on the involvement of gap junctions in carcinogenesis. During the colloquium, 15 participants presented reviews or research updates in the field which are summarized below. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of GAB1 Expression Over the Menstrual Cycle in Women With and Without Polycystic Ovarian Syndrome Provides a New Insight Into Its Pathophysiology

PubMed Central

Roemer, K. L.; Young, S. L.

2014-01-01

Context: In a previous microarray analysis, GRB2-associated binding protein 1 (GAB1), a docking protein closely related to the insulin receptor substrate, was down-regulated in endometrium of women with polycystic ovary syndrome (PCOS). Objective: The objective of the study was to characterize the cyclic expression of endometrial GAB1 in vivo in normal women and those with PCOS as well as investigate the possible mechanisms of endometrial regulation of GAB1 expression and action in vitro. Design: This was an experimental and case-control study. Setting: The study was conducted at a tertiary university hospital. Patients: Normal proven fertile women (controls; n = 31) and women with PCOS (cases; n = 26) participated in the study. Interventions: Interventions included timed endometrial biopsies at different phases of the menstrual cycle. Ishikawa cells were cultured with β-estradiol (E2), medroxyprogesterone acetate, and E2 + medroxyprogesterone acetate. Transfection of small interfering RNA for GAB1 in Ishikawa cells incubated with or without insulin. Main Outcome Measures: GAB1 mRNA expression in Ishikawa cells and in endometrium of cases and controls was measured. Protein expression of phosphorylated MAPK by Western blot was also measured. Immunohistochemical localization and expression of phosphorylated GAB1 in endometrium was also measured, using a digital histological score. Results: In endometrial tissue, GAB1 mRNA was reduced in the proliferative phase of PCOS women, compared with controls (P = .003; ANOVA). When all the phases of the menstrual cycle were grouped, GAB1 protein expression was reduced in endometrium of PCOS women (P < .0001; Student t test). E2 increases GAB1 mRNA expression in Ishikawa cells (P = .001; ANOVA). Phosphorylated MAPK is reduced in cells transfected with small interfering RNA for GAB1 (P = .008; ANOVA) and incubated with insulin. Conclusions: GAB1 mRNA expression is positively modulated by E2. Endometrial GAB1 protein and m

[Influence of pertussis toxin on GPER-mediated activation of phosphatidylinositol 3-kinase/protein kinase B signaling induced by 17β-estradiol in endometrial carcinoma cells].

PubMed

Guo, Rui-xia; Lei, Jia; Wang, Xin-yan; Ge, Xin; Hu, Dong-mei; Ma, Xiu-ying; Li, Liu-xia; Qiao, Yu-huan

2013-02-01

To investigate the influence of pertussis toxin (PTX) on G protein-coupled estrogen receptor (GPER)-mediated activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling activated by 17β-estradiol (17β-E2) in endometrial carcinoma cells. Expressions of GPER protein were detected by immunohistochemical SP method in Ishikawa and HEC-1A cells. Changes of levels of GPER, ERα and ERβ protein and the activation of Akt protein were observed by western blot in the two cells after they were treated by PTX for 30 minutes at different concentrations (0, 0.1, 0.5, 1.0 µg/ml), and then co-stimulated with with 1×10(-6) mol/L 17β-E2 respectively at different time (Ishikawa 30 minutes, HEC-1A 15 minutes). (1) Immunohistochemical SP method showed that GPER was positive stained in cell cytoplasm of Ishikawa and HEC-1A cell. (2) After co-treated with PTX at different concentrations (0, 0.1, 0.5, 1.0 µg/ml) and 10(-6) mol/L 17β-E2, in Ishikawa cell, the ratio of p-Akt/Akt was 0.74 ± 0.54, 0.34 ± 0.06, 0.18 ± 0.03, 0.07 ± 0.15, the gray values of GPER was 0.872 ± 0.490, 0.395 ± 0.054, 0.145 ± 0.014, 0.034 ± 0.008, and with increasing concentration of PTX, the ratio of p-Akt/Akt and the expression of GPER decreased gradually (P < 0.05), which was most obviously when the concentration was 1.0 µg/ml (F = 63.729, P = 0.0001; F = 160.284, P = 0.0001); ERα and ERβ protein had no significant change among different groups (P > 0.05). In HEC-1A cell, the ratio of p-Akt/Akt was 0.73 ± 0.09, 0.26 ± 0.14, 0.11 ± 0.03, 0, the Gray values of GPER is 0.927 ± 0.134, 0.485 ± 0.022, 0.194 ± 0.004, 0, and with increasing concentration of PTX, the ratio of p-Akt/Akt and the expression of GPER decreased gradually (P < 0.05), which were also completely inhibited when the concentration was 1 µg/ml (F = 1039.321, P = 0.0001; F = 109.646, P = 0.0001), ERα protein had no significant differences (P > 0.05) among different groups. ERβ was negatively expressed

Expression of adhesion and extracellular matrix genes in human blastocysts upon attachment in a 2D co-culture system.

PubMed

Aberkane, A; Essahib, W; Spits, C; De Paepe, C; Sermon, K; Adriaenssens, T; Mackens, S; Tournaye, H; Brosens, J J; Van de, Velde H

2018-05-26

What are the changes in human embryos, in terms of morphology and gene expression, upon attachment to endometrial epithelial cells? Apposition and adhesion of human blastocysts to endometrial epithelial cells are predominantly initiated at the embryonic pole and these steps are associated with changes in expression of adhesion and extracellular matrix (ECM) genes in the embryo. Both human and murine embryos have been co-cultured with Ishikawa cells, although embryonic gene expression associated with attachment has not yet been investigated in an in-vitro implantation model. Vitrified human blastocysts were warmed and co-cultured for up to 48 h with Ishikawa cells, a model cell line for receptive endometrial epithelium. Six-days post fertilisation (6dpf) human embryos were co-cultured with Ishikawa cells for 12 h, 24 h (7dpf) or 48 h (8dpf) and attachment rate and morphological development investigated. Expression of 84 adhesion and ECM genes was analysed by quantitative PCR. Immunofluorescence microscopy was used to assess the expression of three informative genes at the protein level. Data are reported on 115 human embryos. Mann-Whitney U was used for statistical analysis between two groups, with P < 0.05 considered significant. The majority of embryos attached to Ishikawa cells at the level of the polar trophectoderm; 41% of co-cultured embryos were loosely attached after 12 h and 86% firmly attached after 24 h. Outgrowth of hCG-positive embryonic cells at 8dpf indicated differentiation of trophectoderm into invasive syncytiotrophoblast. Gene expression analysis was performed on loosely attached and unattached embryos co-cultured with Ishikawa cells for 12 h. In contrast to unattached embryos, loosely attached embryos expressed THBS1, TNC, COL12A1, CTNND2, ITGA3, ITGAV, and LAMA3 and had significantly higher CD44 and TIMP1 transcript levels (P = 0.014 and P = 0.029, respectively). LAMA3, THBS1 and TNC expression was validated at the protein

Curcumin exhibits anti-tumor effect and attenuates cellular migration via Slit-2 mediated down-regulation of SDF-1 and CXCR4 in endometrial adenocarcinoma cells.

PubMed

Sirohi, Vijay Kumar; Popli, Pooja; Sankhwar, Pushplata; Kaushal, Jyoti Bala; Gupta, Kanchan; Manohar, Murli; Dwivedi, Anila

2017-06-01

Although curcumin shows anti-proliferative and anti-inflammatory activities in various cancers, the effect of curcumin on cellular migration in endometrial adenocarcinoma cells remains to be understood. The current investigation was aimed to explore the anti-proliferative and anti-migratory effects of curcumin and its mechanism of action in endometrial cancer cells. Our in-vitro and in-vivo experimental studies showed that curcumin inhibited the proliferation of endometrial cancer cells and suppressed the tumor growth in Ishikawa xenograft mouse model. Curcumin induced ROS-mediated apoptosis in endometrial cancer cells. Curcumin suppressed the migration rate of Ishikawa and Hec-1B cells as analyzed by scratch wound assay. In transwell migration studies, knock down of Slit-2 reversed the anti-migratory effect of curcumin in these cell lines. Curcumin significantly up-regulated the expression of Slit-2 in Ishikawa, Hec-1B and primary endometrial cancer cells while it down-regulated the expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 which in turn, suppressed the expression of matrix metallopeptidases (MMP) 2 and 9, thus attenuating the migration of endometrial cancer cells. In summary, we have demonstrated that curcumin has inhibitory effect on cellular migration via Slit-2 mediated down-regulation of CXCR4, SDF-1, and MMP2/MMP9 in endometrial carcinoma cells. These findings helped explore the role of Slit-2 in endometrial cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

The Quality Revolution in Education.

ERIC Educational Resources Information Center

Bonstingl, John Jay

1992-01-01

Whether viewed through Deming's 14 points, Juran's Trilogy, or Kaoru Ishikawa's Thought Revolution, Total Quality Management embodies 4 fundamental tenets: primary focus on customers and suppliers, universal commitment to continuous improvement, a systems approach, and top management responsibility. Educational organizations are recreating their…

Environmental Investigations and Analyses for Los Angeles-Long Beach Harbors, Los Angeles, California, 1973-1976.

DTIC Science & Technology

1976-12-01

Christine Yonai Fred Piltz Ichthyology Jay Carroll Karl Lyde John Helle Scott Ralston S. Ishikawa Steve Subber Catherine Kusick Catherine Terry...Charles Greaves Catherine Link Susan Harrison Julie Thompson Kaoru 0. Kendis Ismay Stanley Randall Kendis Marine Technicians Bruce Adams Gene Mummert

Protein Kinase C alpha (PKCα) dependent signaling mediates endometrial cancer cell growth and tumorigenesis

PubMed Central

Haughian, James M.; Reno, Elaine M.; Thorne, Alicia M.; Bradford, Andrew P.

2009-01-01

Endometrial cancer is the most common invasive gynecologic malignancy, yet molecular mechanisms and signaling pathways underlying its etiology and pathophysiology remain poorly characterized. We sought to define a functional role for the protein kinase C (PKC) isoform, PKCα, in an established cell model of endometrial adenocarcinoma. Ishikawa cells depleted of PKCα protein grew slower, formed fewer colonies in anchorage-independent growth assays and exhibited impaired xenograft tumor formation in nude mice. Consistent with impaired growth, PKCα knockdown increased levels of the cyclin dependent kinase (CDK) inhibitors p21Cip1/WAF1 (p21) and p27Kip1 (p27). Despite the absence of functional phosphatase and tensin homologue (PTEN) protein in Ishikawa cells, PKCα knockdown reduced Akt phosphorylation at serine 473 and concomitantly inhibited phosphorylation of the Akt target, glycogen synthase kinase-3β (GSK-3β). PKCα knockdown also resulted in decreased basal ERK phosphorylation and attenuated ERK activation following EGF stimulation. p21 and p27 expression was not increased by treatment of Ishikawa cells with ERK and Akt inhibitors, suggesting PKCα regulates CDK expression independently of Akt and ERK. Immunohistochemical analysis of grade 1 endometrioid adenocarcinoma revealed aberrant PKCα expression, with foci of elevated PKCα staining, not observed in normal endometrium. These studies demonstrate a critical role for PKCα signaling in endometrial tumorigenesis by regulating expression of CDK inhibitors p21 and p27 and activation of Akt and ERK dependent proliferative pathways. Thus, targeting PKCα may provide novel therapeutic options in endometrial tumors. PMID:19672862

Expression of HOXA10 in endometrial hyperplasia and adenocarcinoma and regulation by sex hormones in vitro.

PubMed

Zhong, Gang; Wang, Yan; Liu, Xuemei

2011-07-01

The objective of the study was to determine the expression of HOXA10 in human endometrial tissue in endometrial hyperplasia and carcinomas, and regulation by sex steroids in Ishikawa cells. Endometrial tissue was obtained from 133 subjects with normal endometria, endometrial hyperplasia, or endometrial adenocarcinoma. Among 133 specimens, 20 were normal endometria, 19 were simple hyperplasias without atypia, 20 were complex hyperplasias without atypia, 33 were atypical hyperplasias, and 41 were endometrial adenocarcinomas. The expression of HOXA10 was analyzed by immunohistochemistry. Ishikawa cell lines were incubated with 17β estradiol (10⁻⁸ mol/L) alone, medroxyprogesterone acetate (10⁻⁶ mol/L) alone, or the combination of estrogen and progesterone for 48 hours, respectively. In certain experiments, the antiprogestin antagonist, RU486 (10⁻⁵ mol/L), was also added to Ishikawa cells along with estradiol and medroxyprogesterone acetate for 48 hours. The expression of HOXA10 gene was detected by reverse transcriptase-polymerase chain reaction and Western blotting. HOXA10 was expressed in both normal and neoplastic endometria. No significant difference in HOXA10 expression was found between normal and hyperplastic endometrial tissues. The expression of HOXA10 was decreased in endometrial adenocarcinomas compared with normal endometria. Estrogen alone, progestin alone, or progestin combined with estrogen could significantly increase the expression of HOXA10 gene (P<0.05). RU486 could inhibit the effect of up-regulation of HOXA10 expression by progestin. The expression of HOXA10 was deregulated in endometrial carcinomas and up-regulated by sex hormones.

Editor's Highlight: Development of an In vitro Assay Measuring Uterine-Specific Estrogenic Responses for Use in Chemical Safety Assessment.

PubMed

Miller, Michelle M; Alyea, Rebecca A; LeSommer, Caroline; Doheny, Daniel L; Rowley, Sean M; Childs, Kristin M; Balbuena, Pergentino; Ross, Susan M; Dong, Jian; Sun, Bin; Andersen, Melvin A; Clewell, Rebecca A

2016-11-01

A toxicity pathway approach was taken to develop an in vitro assay using human uterine epithelial adenocarcinoma (Ishikawa) cells as a replacement for measuring an in vivo uterotrophic response to estrogens. The Ishikawa cell was determined to be fit for the purpose of recapitulating in vivo uterine response by verifying fidelity of the biological pathway components and the dose-response predictions to women of child-bearing age. Expression of the suite of estrogen receptors that control uterine proliferation (ERα66, ERα46, ERα36, ERβ, G-protein coupled estrogen receptor (GPER)) were confirmed across passages and treatment conditions. Phenotypic responses to ethinyl estradiol (EE) from transcriptional activation of ER-mediated genes, to ALP enzyme induction and cellular proliferation occurred at concentrations consistent with estrogenic activity in adult women (low picomolar). To confirm utility of this model to predict concentration-response for uterine proliferation with xenobiotics, we tested the concentration-response for compounds with known uterine estrogenic activity in humans and compared the results to assays from the ToxCast and Tox21 suite of estrogen assays. The Ishikawa proliferation assay was consistent with in vivo responses and was a more sensitive measure of uterine response. Because this assay was constructed by first mapping the key molecular events for cellular response, and then ensuring that the assay incorporated these events, the resulting cellular assay should be a reliable tool for identifying estrogenic compounds and may provide improved quantitation of chemical concentration response for in vitro-based safety assessments. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

[Mifepristone inhibites the migration of endometrial cancer cells through regulating H19 methylation].

PubMed

Lu, Z Z; Yan, L; Zhang, H; Li, M J; Zhang, X H; Zhao, X X

2016-06-23

To investigate the effect and mechanism of mifepristone on the migration of human endometrial carcinoma cells. A human endometrial carcinoma cell line, Ishikawa cells, was cultured in vitro and treated with mifepristone at different concentrations. Wound healing assay was applied to detect the migration of Ishikawa cells. RT-PCR and methylation-specific PCR (MSP) were used to detect the levels of H19 mRNA and its DNA methylation. Western-blot was used to detect the expressions of HMGA2 and epithelial to mesenchymal transition (EMT) related proteins. When treated with different concentrations of mifepristone for 48 hours, the width of scratch of the the control group, the 5 mg/L and the 10 mg/L mifepristone treatment groups were (4.18±0.07)mm, (4.68±0.07)mm, and(4.99±0.07)mm, respectively (P<0.05 for all) and treated with mifepristone for 72 hours, those were(3.46±0.07)mm, (4.29±0.07)mm, and(4.78±0.04)mm, respectively (P<0.05 for all). In the Ishikawa cells, mifepristone suppressed the transcriptional level of H19 through enhancing its promoter methylation, which resulted in inhibited expressions of HMGA2 and vimentin and increased expression of E-cadherin in a time- and concentration-dependent manner. Mifepristone inhibits the migration of endometrial carcinoma cells partially through methylation-induced of transcriptional inhibition of H19, which results in the down-regulation of HMGA2 and vimentin and upregulation of E-cadherin.

Androgen-induced alterations in endometrial proteins crucial in recurrent miscarriages.

PubMed

Rahman, Tanzil Ur; Ullah, Kamran; Guo, Meng-Xi; Pan, Hai-Tao; Liu, Juan; Ren, Jun; Jin, Lu-Yang; Zhou, Yu-Zhong; Cheng, Yi; Sheng, Jian-Zhong; Huang, He-Feng

2018-05-15

High androgen level impairs endometrial receptivity in women experiences the recurrent miscarriage. The mechanism of androgen actions on endometrium is still uncertain. We hypothesized that androgen has a direct effect on the endometrium in women with recurrent miscarriage. In the present study, we assess the impact of androgen (A 2 ) at high concentration (10 -7 M) on Ishikawa cells compared with the physiological concentration of androgen (10 -9 M). To go into deeper analysis, we use global stable isotopes labeled profiling tactic using iTRAQ reagents, followed by 2D LC-MS/MS. We determine 175 non-redundant proteins, and 18 of these were quantified. The analysis of differentially expressed proteins (DEPs) identified 8 up-regulated proteins and 10 down-regulated in the high androgen group. These DEPs were examined by ingenuity pathway (IPA) analysis and established that these proteins might play vital roles in recurrent miscarriage and endometrium receptivity. In addition, proteins cyclin-dependent kinase inhibitor 2a (CDKN2a), endothelial protein C receptor (EPCR), armadillo repeat for velocardiofacial (ARVCF) were independently confirmed using western blot. Knockdown of CDKN2a significantly decreased the expression level of CDKN2a protein in ishikawa cells, and decreased migration ( p < 0.01), invasion ( p < 0.05), proliferation ( p < 0.05), and the rate of Jar spheroid attachment ( p < 0.05) to Ishikawa cell monolayer. The present results suggest that androgen at high concentration could alter the expression levels of proteins related to endometrium development and embryo implantation, which might be a cause of the impaired endometrial receptivity and miscarriage.

The BCL2 antagonist of cell death pathway influences endometrial cancer cell sensitivity to cisplatin.

PubMed

Chon, Hye Sook; Marchion, Douglas C; Xiong, Yin; Chen, Ning; Bicaku, Elona; Stickles, Xiaomang Ba; Bou Zgheib, Nadim; Judson, Patricia L; Hakam, Ardeshir; Gonzalez-Bosquet, Jesus; Wenham, Robert M; Apte, Sachin M; Lancaster, Johnathan M

2012-01-01

To identify pathways that influence endometrial cancer (EC) cell sensitivity to cisplatin and to characterize the BCL2 antagonist of cell death (BAD) pathway as a therapeutic target to increase cisplatin sensitivity. Eight EC cell lines (Ishikawa, MFE296, RL 95-2, AN3CA, KLE, MFE280, MFE319, HEC-1-A) were subjected to Affymetrix Human U133A GeneChip expression analysis of approximately 22,000 probe sets. In parallel, endometrial cell line sensitivity to cisplatin was quantified by MTS assay, and IC(50) values were calculated. Pearson's correlation test was used to identify genes associated with response to cisplatin. Genes associated with cisplatin responsiveness were subjected to pathway analysis. The BAD pathway was identified and subjected to targeted modulation, and the effect on cisplatin sensitivity was evaluated. Pearson's correlation analysis identified 1443 genes associated with cisplatin resistance (P<0.05), which included representation of the BAD-apoptosis pathway. Small interfering RNA (siRNA) knockdown of BAD pathway protein phosphatase PP2C expression was associated with increased phosphorylated BAD (serine-155) levels and a parallel increase in cisplatin resistance in Ishikawa (P=0.004) and HEC-1-A (P=0.02) cell lines. In contrast, siRNA knockdown of protein kinase A expression increased cisplatin sensitivity in the Ishikawa (P=0.02) cell line. The BAD pathway influences EC cell sensitivity to cisplatin, likely via modulation of the phosphorylation status of the BAD protein. The BAD pathway represents an appealing therapeutic target to increase EC cell sensitivity to cisplatin. Copyright © 2011 Elsevier Inc. All rights reserved.

Conference Proceedings of the Productivity Program Implementation Conference Held in Jacksonville, Florida on 20-22 May 1981.

DTIC Science & Technology

1981-05-01

first Quality Circle was registered with the Japanese Union of Scientists and Engineers (JUSE) in 1962. The concept was conceived by Dr. Kaoru ... Ishikawa , a professor of engineering at Tokyo University, and developed under the sponsorship of . JUSE. Quality Circles fuse the quality sciences

The HPT Value Proposition in the Larger Improvement Arena.

ERIC Educational Resources Information Center

Wallace, Guy W.

2003-01-01

Discussion of human performance technology (HPT) emphasizes the key variable, which is the human variable. Highlights include the Ishikawa Diagram; human performance as one variable of process performance; collaborating with other improvement approaches; value propositions; and benefits to stakeholders, including real return on investments. (LRW)

Spherical Hecke algebra in the Nekrasov-Shatashvili limit

NASA Astrophysics Data System (ADS)

Bourgine, Jean-Emile

2015-01-01

The Spherical Hecke central (SHc) algebra has been shown to act on the Nekrasov instanton partition functions of gauge theories. Its presence accounts for both integrability and AGT correspondence. On the other hand, a specific limit of the Omega background, introduced by Nekrasov and Shatashvili (NS), leads to the appearance of TBA and Bethe like equations. To unify these two points of view, we study the NS limit of the SHc algebra. We provide an expression of the instanton partition function in terms of Bethe roots, and define a set of operators that generates infinitesimal variations of the roots. These operators obey the commutation relations defining the SHc algebra at first order in the equivariant parameter ɛ 2. Furthermore, their action on the bifundamental contributions reproduces the Kanno-Matsuo-Zhang transformation. We also discuss the connections with the Mayer cluster expansion approach that leads to TBA-like equations.

JPRS Report, Science & Technology, Japan, Structure, Properties of Al Amorphous Alloys

DTIC Science & Technology

1990-12-04

present report, and to the members of the staff, particularly Masaji Nomura, Tetsuya Ishikawa , and Atsushi Koyama, of the High Energy Physics Laboratory...Aichi Educational University, and the research on Al-based quasicrystals was with Shin Takeuchi, and Kaoru Kimura, both of Tokyo University, and Takeshi

Graphic Organizers: Outlets for Your Thoughts.

ERIC Educational Resources Information Center

Ekhaml, Leticia

1998-01-01

Graphs, bars, charts, and diagrams have been used by designers, writers, and scientists to communicate. Now, research suggests that graphic organizers benefit teaching and learning. This article describes graphic organizers: sequential, conceptual, hierarchical, cyclical, Venn, fishbone or Ishikawa, squeeze and stretch, why-why, t-chart, KWL…

Dynamic fluctuation of proteins watched in real time

PubMed Central

Ormos, Pál

2008-01-01

The dynamic nature of protein function is a fundamental concept in the physics of proteins. Although the basic general ideas are well accepted most experimental evidence has an indirect nature. The detailed characterization of the dynamics is necessary for the understanding in detail. The dynamic fluctuations thought crucial for the function span an extremely broad time, starting from the picosecond regime. Recently, a few new experimental techniques emerged that permit the observation of dynamical phenomena directly. Notably, pulsed infrared (IR) spectroscopy has been applied with great success to observe structural changes with picosecond time resolution. Using two-dimensional-IR vibrational echo chemical exchange spectroscopy Ishikawa and co-workers [Ishikawa et al. (2008), Proc. Natl. Acad. Sci. U.S.A. 101, 14402–14407] managed to observe the transition between well defined conformational substrates of carbonmonoxy myoglobin directly. This is an important step in improving our insight into the details of protein function. PMID:19436491

Genetics Home Reference: inclusion body myopathy 2

MedlinePlus

... Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from http://www.ncbi.nlm.nih.gov/books/NBK1262/ Citation on PubMed Tomimitsu H, Shimizu J, Ishikawa K, Ohkoshi N, Kanazawa I, ...

Nuclear PTEN localization contributes to DNA damage repair in Endometrial cancer and could have a diagnostic benefit for therapeutic management of the disease.

PubMed

Mukherjee, Ananda; Patterson, Amanda L; George, Jitu W; Carpenter, Tyler J; Madaj, Zachary B; Hostetter, Galen; Risinger, John I; Teixeira, Jose M

2018-06-13

Endometrial adenocarcinoma (EndoCA) is the most common gynecological cancer type in the US, and its incidence is increasing. The majority of patients are disease-free after surgical resection of stage I tumors, which is often followed by radiation therapy, but most patients with advanced disease recur and have a poor prognosis, largely because the tumors become refractory to cytotoxic chemotherapies. PTEN, a commonly mutated tumor suppressor in EndoCAs, is well known for its ability to inhibit the AKT/mTOR signaling pathway. Nuclear functions for PTEN have been proposed as well, but whether those affect EndoCA development, progression, or outcomes is not well understood. Using immunohistochemistry, nuclear PTEN expression was observed in approximately half of EndoCA patient tumors, independent of grade and cytoplasmic PTEN expression. Higher levels of the DNA damage response (DDR) marker, yH2AX, were observed by immunohistochemistry and immunofluorescence in human EndoCA tumor sections that were PTEN-negative, in murine EndoCA tissues that were genetically modified to be PTEN-null, and in Ishikawa EndoCA cells, which do not express endogenous PTEN. Over-expression of exogenous PTEN-WT or PTEN-NLS, a modified PTEN with an added nuclear localization signal, significantly improved both DDR and G2/M transition in Ishikawa cells treated with a DNA damaging agent. Whereas PARP inhibition with Olaparib was not as effective in Ishikawa cells expressing native or PTEN-NLS, inhibition with Talazoparib was not affected by PTEN overexpression. These results suggest that nuclear PTEN subcellular localization in human EndoCA could be diagnostic when considering DDR therapeutic intervention. Copyright ©2018, American Association for Cancer Research.

The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol.

PubMed

Naciff, Jorge M; Khambatta, Zubin S; Thomason, Ryan G; Carr, Gregory J; Tiesman, Jay P; Singleton, David W; Khan, Sohaib A; Daston, George P

2009-01-01

We have determined the gene expression profile induced by 17 alpha-ethynyl estradiol (EE) in Ishikawa cells, a human uterine-derived estrogen-sensitive cell line, at various doses (1 pM, 100 pM, 10 nM, and 1 microM) and time points (8, 24, and 48 h). The transcript profiles were compared between treatment groups and controls (vehicle-treated) using high-density oligonucleotide arrays to determine the expression level of approximately 38,500 human genes. By trend analysis, we determined that the expression of 2560 genes was modified by exposure to EE in a dose- and time-dependent manner (p Ishikawa cells showed that 71 genes are regulated in a similar manner in vivo as well as in vitro. Further, some of the genes that show a robust response to estrogen exposure in Ishikawa cells are well known to be estrogen responsive, in various in vivo studies, such as PGR, MMP7, IGFBP3, IGFBP5, SOX4, MYC, EGR1, FOS, CKB, and CCND2, among others. These results indicate that transcript profiling can serve as a viable tool to select reliable in vitro systems to evaluate potential estrogenic activities of target chemicals and to identify genes that are relevant for the estrogen response.

Nestin suppression attenuates invasive potential of endometrial cancer cells by downregulating TGF-β signaling pathway.

PubMed

Bokhari, Amber A; Baker, Tabari M; Dorjbal, Batsukh; Waheed, Sana; Zahn, Christopher M; Hamilton, Chad A; Maxwell, G Larry; Syed, Viqar

2016-10-25

Nestin, an intermediate filament protein and a stem cell marker is expressed in several tumors. Until recently, little was known about the expression levels and the role of Nestin in endometrial cancer. Compared to the immortalized endometrial epithelial cell line EM-E6/E7-TERT, endometrial cancer cell lines express high to moderate levels of Nestin. Furthermore, endometrial tumors and tumor cell lines have a cancer stem-like cell subpopulation expressing CD133. Among the cancer lines, AN3CA and KLE cells exhibited both a significantly higher number of CD133+ cells and expressed Nestin at higher levels than Ishikawa cells. Knockdown of Nestin in AN3CA and KLE increased cells in G0/G1 phase of the cell cycle, whereas overexpression in Ishikawa decreased cells in G0/G1 phase and increased cells in S-phase. Nestin knockdown cells showed increased p21, p27, and PNCA levels and decreased expression of cyclin-D1 and D3. In contrast, Nestin overexpression revealed an inverse expression pattern of cell cycle regulatory proteins. Nestin knockdown inhibited cancer cell growth and invasive potential by downregulating TGF-β signaling components, MMP-2, MMP-9, vimentin, SNAIL, SLUG, Twist, N-cadherin, and upregulating the epithelial cell marker E-cadherin whereas the opposite was observed with Nestin overexpressing Ishikawa cells. Nestin knockdown also inhibited, while overexpression promoted invadopodia formation and pFAK expression. Knockdown of Nestin significantly reduced tumor volume in vivo. Finally, progesterone inhibited Nestin expression in endometrial cancer cells. These results suggest that Nestin can be a therapeutic target for cancer treatment.

Nestin suppression attenuates invasive potential of endometrial cancer cells by downregulating TGF-β signaling pathway

PubMed Central

Bokhari, Amber A.; Baker, Tabari M.; Dorjbal, Batsukh; Waheed, Sana; Zahn, Christopher M.; Hamilton, Chad A.; Maxwell, G. Larry; Syed, Viqar

2016-01-01

Nestin, an intermediate filament protein and a stem cell marker is expressed in several tumors. Until recently, little was known about the expression levels and the role of Nestin in endometrial cancer. Compared to the immortalized endometrial epithelial cell line EM-E6/E7-TERT, endometrial cancer cell lines express high to moderate levels of Nestin. Furthermore, endometrial tumors and tumor cell lines have a cancer stem-like cell subpopulation expressing CD133. Among the cancer lines, AN3CA and KLE cells exhibited both a significantly higher number of CD133+ cells and expressed Nestin at higher levels than Ishikawa cells. Knockdown of Nestin in AN3CA and KLE increased cells in G0/G1 phase of the cell cycle, whereas overexpression in Ishikawa decreased cells in G0/G1 phase and increased cells in S-phase. Nestin knockdown cells showed increased p21, p27, and PNCA levels and decreased expression of cyclin-D1 and D3. In contrast, Nestin overexpression revealed an inverse expression pattern of cell cycle regulatory proteins. Nestin knockdown inhibited cancer cell growth and invasive potential by downregulating TGF-β signaling components, MMP-2, MMP-9, vimentin, SNAIL, SLUG, Twist, N-cadherin, and upregulating the epithelial cell marker E-cadherin whereas the opposite was observed with Nestin overexpressing Ishikawa cells. Nestin knockdown also inhibited, while overexpression promoted invadopodia formation and pFAK expression. Knockdown of Nestin significantly reduced tumor volume in vivo. Finally, progesterone inhibited Nestin expression in endometrial cancer cells. These results suggest that Nestin can be a therapeutic target for cancer treatment. PMID:27626172

Total Quality Management: Empirical, Conceptual, and Practical Issues.

ERIC Educational Resources Information Center

Hackman, J. Richard; Wageman, Ruth

1995-01-01

Total quality management (TQM) has become a U.S. social movement. This commentary analyzes the writings of W. Edwards Deming, Joseph Juran, and Kaoru Ishikawa to assess TQM's coherence, distinctiveness, and likely perseverance. Rhetoric is winning over substance, unrelated interventions are being herded under the TQM banner, and research is not…

Japanese Encephalitis Virus in Meningitis Patients, Japan

PubMed Central

Ito, Mikako; Takao, Shinichi; Shimazu, Yukie; Fukuda, Shinji; Miyazaki, Kazuo; Kurane, Ichiro; Takasaki, Tomohiko

2005-01-01

Cerebrospinal fluid specimens from 57 patients diagnosed with meningitis were tested for Japanese encephalitis virus. Total RNA was extracted from the specimens and amplified. Two products had highest homology with Nakayama strain and 2 with Ishikawa strain. Results suggest that Japanese encephalitis virus causes some aseptic meningitis in Japan. PMID:15757569

The Role of Online Academic Coaching on Levels of Self-Determination of College Students with Learning Disabilities

ERIC Educational Resources Information Center

Bomar, Ruth Angulo

2017-01-01

The numbers show that more students with LD/ADHD are gaining college admission (Madaus & Shaw, 2010; Pryor, Hurtado, DeAngelo, Blake, & Trane, 2010). Even so ever-increasing issues face colleges and universities in the retention and graduation rate of these students (Anctil, Ishikawa, & Tao Scott, 2008; Getzel & Thoma, 2008).…

A Paradigm Shift for Educational Administrators: The Total Quality Movement.

ERIC Educational Resources Information Center

Hough, M. J.

This paper reviews the major ideas of the seminal total quality management theorists, such as Deming, Crosby, Juran, Ishikawa, and Imai, to illustrate how total quality management is applicable to education. It is argued that there is a need for a paradigm shift in educational administration. The first part reviews current Australian societal…

Japanese Ground Forces Order of Battle Bulletins (7 April - 2 June 1945) Part 1

DTIC Science & Technology

1945-01-01

Narumi (49) ISHII Mas’ayoshi (121) . ( ISHII Shiro (99) ISHIKAWA Megumu (—). 10/41 8/59 INAMURA Toyojiro (60) 12/40 INOUE Fumio (100) 8/48 8/41...MGHITA Ncrimasa (~) ,• MORXTAMA Tokuaitsu (131) MQTOlzttel Kaoru {116) MOTOYOSHI* KeisiSr6iilbb)3 a’ MUKAI Xinjiro (95)-^\\s) :- HURAJI Toshio 144

Expression of two isoforms of CD44 in human endometrium.

PubMed

Behzad, F; Seif, M W; Campbell, S; Aplin, J D

1994-10-01

The distribution of the cell-surface adhesion glycoprotein CD44 in human endometrium was examined by immunofluorescence using six monoclonal antibodies to epitopes common to all forms of the molecule, and by reverse transcription-polymerase chain reaction (RT-PCR). Immunoreactivity was observed throughout the menstrual cycle in stroma, vessels, glandular, and luminal epithelium. Variations in staining intensity were observed, especially in the epithelial compartment. CD44 was also expressed strongly by decidualized stromal cells of first-trimester pregnancy. No systematic variation of immunoreactivity was observed with stages of the normal cycle, but a fraction (25%) of the specimens lacked reactivity in the epithelium. To determine the molecular size of the epithelial isoform, an immunoprecipitation technique was developed using surface-radioiodinated, detergent-extracted glands. This indicated the presence at the cell surface of a single dominant CD44E species with an approximate molecular mass of 130 kDa. RT-PCR was used to investigate the isoforms present in whole endometrial tissue, isolated gland fragments, and Ishikawa endometrial carcinoma cells. Complementary DNA produced from total endometrial mRNA was PCR-amplified across the splice junction between exons 5 and 15. Transcripts corresponding to the hyaluronate receptor CD44H as well as a larger isoform were identified. CD44H was absent, or very scarce, in cDNA from purified gland epithelium. In contrast, Ishikawa cells expressed this form abundantly. The glands and Ishikawa cells also expressed CD44E containing sequences encoded by exons 12, 13, and 14. These data demonstrate the presence of CD44 in human endometrium and decidua, and show that different isoforms of CD44 are associated with tissue compartments in which different functional roles can be anticipated.

Posttranscriptional Control of PD-L1 Expression by 17β-Estradiol via PI3K/Akt Signaling Pathway in ERα-Positive Cancer Cell Lines.

PubMed

Yang, Lingyun; Huang, Feng; Mei, Jiandong; Wang, Xun; Zhang, Qiuyang; Wang, Hongjing; Xi, Mingrong; You, Zongbing

2017-02-01

Estrogen is a well-known oncogenic driver in endometrial (ECs) and breast cancers (BCs). Programmed cell death protein 1 (PD-1) and its ligands PD-1 Ligand 1 (PD-L1) and PD-L2 have been shown to mediate immune evasion of the tumor cells. The purpose of the present study was to assess the effects of estrogen on PD-L1 and PD-L2 expression in EC and BC cell lines. 17β-Estradiol (E2)-induced expression of PD-L1 and PD-L2 and possible signaling pathway were investigated in EC and BC cells. Coculture of T cells and cancer cells with E2 stimulation was performed to assess the functions of T cells. We found that E2 increased expression of PD-L1, but not PD-L2, protein via activation of phosphoinositide 3-kinase (PI3K)/Akt pathway in Ishikawa and Michigan Cancer Foundation-7 (MCF-7) cells. Phosphoinositide 3-kinase and Akt inhibitors could block E2's effects. 17β-Estradiol did not increase PD-L1 mRNA transcription, but stabilized PD-L1 mRNA. 17β-Estradiol's effects were only observed in estrogen receptor α (ERα)-positive Ishikawa and MCF-7 cells, but not in ERα-negative MDA-MB-231 cells. Coculture of Ishikawa or MCF-7 cells with T cells inhibited expression of interferon-γ and interleukin-2 and increased BCL-2-interacting mediator of cell death expression in the presence of E2. This study provides the first evidence that estrogen upregulates PD-L1 protein expression in ERα-positive EC and BC cells to suppress immune functions of T cells in the tumor microenvironment, demonstrating a new mechanism of how estrogen drives cancer progression.

Post-transcriptional control of PD-L1 expression by 17β-estradiol via PI3K/Akt signaling pathway in ERα-positive cancer cell lines

PubMed Central

Yang, Lingyun; Huang, Feng; Mei, Jiandong; Wang, Xun; Zhang, Qiuyang; Wang, Hongjing; Xi, Mingrong; You, Zongbing

2016-01-01

Objective Estrogen is a well-known oncogenic driver in endometrial and breast cancers. Programmed cell death protein 1 (PD-1) and its ligands PD-L1 and PD-L2 have been shown to mediate immune evasion of the tumor cells. The purpose of the present study was to assess the effects of estrogen on PD-L1 and PD-L2 expression in endometrial and breast cancer cell lines. Methods 17β-estradiol (E2) -induced expression of PD-L1 and PD-L2 and possible signaling pathway were investigated in endometrial and breast cancer cells. Co-culture of T cells and cancer cells with E2 stimulation was performed to assess the functions of T cells. Results We found that 17β-estradiol (E2) increased expression of PD-L1, but not PD-L2 protein via activation of phosphoinositide 3-kinase (PI3K)/Akt pathway in Ishikawa and MCF-7 cells. PI3K and Akt inhibitors could block E2's effects. E2 did not increase PD-L1 mRNA transcription, but stabilized PD-L1 mRNA. E2's effects were only observed in estrogen receptor α (ERα) -positive Ishikawa and MCF-7 cells, but not in ERα-negative MDA-MB-231 cells. Co-culture of Ishikawa or MCF-7 cells with T cells inhibited expression of interferon-γ and interleukin-2 and increased Bim expression in the presence of E2. Conclusion This study provides the first evidence that estrogen up-regulates PD-L1 protein expression in ERα-positive endometrial and breast cancer cells to suppress immune functions of T cells in the tumor microenvironment, demonstrating a new mechanism of how estrogen drives cancer progression. PMID:27870715

How Six Sigma Methodology Improved Doctors' Performance

ERIC Educational Resources Information Center

Zafiropoulos, George

2015-01-01

Six Sigma methodology was used in a District General Hospital to assess the effect of the introduction of an educational programme to limit unnecessary admissions. The performance of the doctors involved in the programme was assessed. Ishikawa Fishbone and 5 S's were initially used and Pareto analysis of their findings was performed. The results…

JPRS Report - Science & Technology Japan: New Functional Materials.

DTIC Science & Technology

1989-12-27

Using Modified and Controlled High Pressure Environments [Masao Wakatsuki, Kaoru J. Takano] 21 Molecular Design, Synthesis, and Evaluation of High...Crystals [ Shigetoshi Takahashi ] 51 Synthesis of New Organosilicon Polymers and Their Functionalities [Mitsuo Ishikawa , Joji Ohshita] 52...Analysis of The Formation Mechanisms Using Modified and Controlled High Pressure Environments Masao Wakatsuki and Kaoru J. Takano Institute of

Classroom Conditions for Effective Learning: Hearing the Voice of Key Stage 3 Pupils

ERIC Educational Resources Information Center

Hopkins, Elizabeth

2010-01-01

This article argues that accessing and taking note of the voice of pupils is critical in working towards removing barriers to effective learning. Pupil voice was accessed using an innovative form of group interview incorporating an Ishikawa or fishbone tool and card sorting exercise. The data were collected from 132 pupils, from Years 7 to 9 (aged…

JPRS Report, Science & Technology, Japan, 27th Aircraft Symposium, Part 3

DTIC Science & Technology

1991-02-14

Kaoru Wakairo, et al.] Aircraft-Mounted Optical Data Bus (3): Bus Control Software, Performance Evaluation Test [Mitsumi Mayanägi, Minoru...Article by Hiroyasu Kawahara, Kaoru Wakairo, and Akira Watanabe, National Aerospace Laboratory; Tomoyuli Udagawa, Kengo Takeda, and Noboru Shobayashi...89 pp 518-521 [Article by Tadao Uchida, Mitsumi Mayanagi, Minoru Takizawa, Toshiharu Inagaki, Koki Hozumi, and Kazutoshi Ishikawa , National

G Protein-Coupled Estrogen Receptor (GPER) Expression in Normal and Abnormal Endometrium

PubMed Central

Lessey, Bruce A.; Taylor, Robert N.; Wang, Wei; Bagchi, Milan K.; Yuan, Lingwen; Scotchie, Jessica; Fritz, Marc A.; Young, Steven L.

2012-01-01

Rapid estrogen effects are mediated by membrane receptors, and evidence suggests a role for both a membrane-associated form of estrogen receptor alpha (ESR1; ERα) and G-protein coupled receptor 30 (GPER; GPR30). Considering estrogen’s importance in endometrial physiology and endometriosis pathophysiology, we hypothesized that GPER could be involved in both cyclic changes in endometrial estrogen action and that aberrant expression might be seen in the eutopic endometrium of women with endometriosis. Using real-time reverse transcriptase–polymerase chain reaction (RT-PCR) and immunohistochemical analysis of normal endometrium, endometrial samples demonstrated cycle-regulated expression of GPER, with maximal expression in the proliferative phase. Eutopic and ectopic endometrium from women with endometriosis overexpressed GPER as compared to eutopic endometrium of normal participants. Ishikawa cells, an adenocarcinoma cell line, expressed GPER, with increased expression upon treatment with estrogen or an ESR1 agonist, but not with a GPER-specific agonist. Decreased expression was seen in Ishikawa cells stably transfected with progesterone receptor A. Together, these data suggest that normal endometrial GPER expression is cyclic and regulated by nuclear estrogen and progesterone receptors, while expression is dysregulated in endometriosis. PMID:22378861

Insulin-like growth factor-I regulates GPER expression and function in cancer cells.

PubMed

De Marco, P; Bartella, V; Vivacqua, A; Lappano, R; Santolla, M F; Morcavallo, A; Pezzi, V; Belfiore, A; Maggiolini, M

2013-02-07

Functional cross talk between insulin-like growth factor-I (IGF-I) system and estrogen signaling has been largely reported, although the underlying molecular mechanisms remain to be fully elucidated. As GPR30/GPER mediates rapid cell responses to estrogens, we evaluated the potential of IGF-I to regulate GPER expression and function in estrogen receptor (ER)α-positive breast (MCF-7) and endometrial (Ishikawa) cancer cells. We found that IGF-I transactivates the GPER promoter sequence and upregulates GPER mRNA and protein levels in both cells types. Similar data were found, at least in part, in carcinoma-associated fibroblasts. The upregulation of GPER expression by IGF-I involved the IGF-IR/PKCδ/ERK/c-fos/AP1 transduction pathway and required ERα, as ascertained by specific pharmacological inhibitors and gene-silencing. In both MCF-7 and Ishikawa cancer cells, the IGF-I-dependent cell migration required GPER and its main target gene CTGF, whereas the IGF-I-induced proliferation required both GPER and cyclin D1. Our data demonstrate that the IGF-I system regulates GPER expression and function, triggering the activation of a signaling network that leads to the migration and proliferation of cancer cells.

Experimental and in silico analysis of cordycepin and its derivatives as endometrial cancer treatment.

PubMed

Fong, Pedro; Ao, Cheng N; Tou, Kai I; Huang, Ka M; Cheong, Chi C; Meng, Li R

2018-04-19

The aim of this study was to investigate the inhibition effects of cordycepin and its derivatives on endometrial cancercell growth. Cytotoxicity MTT assays, clonogenic assays and flow cytometry were used to observe the effects on apoptosis and regulation of the cell cycle of Ishikawa cells under various concentrations of cordycepin, cisplatin and combinations of the two. Validated in silico docking simulations were performed on 31 cordycepin derivatives against adenosine deaminase (ADA) to predict their binding affinities and hence their potential tendency to be metabolized by ADA. Cordycepin has a significant dose-dependent inhibitory effect on cell proliferation. The combination of cordycepin and cisplatin produced greater inhibition effects than did cordycepin alone. Apoptosis investigations confirmed the ability of cordycepin to induce the apoptosis of Ishikawa cells. The in silico results indicate that compound MRS5698 is least metabolized by ADA and has acceptable drug-likeness and safety profiles. This is the first study to confirm the cytotoxic effects of cordycepin on endometrial cancer cells. This study also identified cordycepin derivatives with promising pharmacological and pharmacokinetic properties for further investigation in the development of new treatments for endometrial cancer.

G protein-coupled estrogen receptor (GPER) expression in normal and abnormal endometrium.

PubMed

Plante, Beth J; Lessey, Bruce A; Taylor, Robert N; Wang, Wei; Bagchi, Milan K; Yuan, Lingwen; Scotchie, Jessica; Fritz, Marc A; Young, Steven L

2012-07-01

Rapid estrogen effects are mediated by membrane receptors, and evidence suggests a role for both a membrane-associated form of estrogen receptor alpha (ESR1; ERα) and G-protein coupled receptor 30 (GPER; GPR30). Considering estrogen's importance in endometrial physiology and endometriosis pathophysiology, we hypothesized that GPER could be involved in both cyclic changes in endometrial estrogen action and that aberrant expression might be seen in the eutopic endometrium of women with endometriosis. Using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical analysis of normal endometrium, endometrial samples demonstrated cycle-regulated expression of GPER, with maximal expression in the proliferative phase. Eutopic and ectopic endometrium from women with endometriosis overexpressed GPER as compared to eutopic endometrium of normal participants. Ishikawa cells, an adenocarcinoma cell line, expressed GPER, with increased expression upon treatment with estrogen or an ESR1 agonist, but not with a GPER-specific agonist. Decreased expression was seen in Ishikawa cells stably transfected with progesterone receptor A. Together, these data suggest that normal endometrial GPER expression is cyclic and regulated by nuclear estrogen and progesterone receptors, while expression is dysregulated in endometriosis.

Cell dimensions and antiferromagnetism of lunar and terrestrial ilmenite single crystals

USGS Publications Warehouse

Thorpe, A.N.; Minkin, J.A.; Senftle, F.E.; Alexander, Corrine; Briggs, Charles; Evans, H.T.; Nord, G.L.

1977-01-01

X-Ray diffraction and anisotropic magnetic measurements have been made on single crystals of lunar ilmenite and on terrestrial ilmenite from Bancroft, Ontario, Canada and the Ilmen Mountains, U.S.S.R. The elongated c-axis of lunar ilmenite, previously reported, is confirmed by new measurements. The shorter c-axis found in terrestrial specimens is ascribed to Fe3+ substitution for Ti4+ in the titanium layer. Magnetic measurements on the same specimens show that, in agreement with the Ishikawa-Shirane et al. model, the initial shortening of the c-axis by the above substitution of small amounts of Fe3+ (<8%) causes an increase in Fe2+-Fe2+ exchange coupling through Fe3+ in the titanium layer that lowers the Ne??el transition temperature. The Weiss temperatures and other magnetic parameters confirm this model proposed by Ishikawa and Shirane et al. Additional transitions found in one of the terrestrial specimens (Bancroft) have been ascribed to a small amount of an exsolved spinel phase, possibly a solid solution phase of magnetite-u??lvospinel. The spinel phase is localized in hematite-rich blebs which exsolved from the host ilmenite-rich phase. ?? 1977.

In vivo RNAi Library Screen to Identify Mediators of Disease Progression and Drug Resistance in CML

DTIC Science & Technology

2006-09-01

O. N., Ozawa, K., Ishikawa, T., Yazaki, Y., and Hirai, H. Development of acute lymphoblastic leukemia and myeloproliferative disorder in...of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow. Blood 1998;92:3780-92. 7...Consistent with previous reports (27), these animals developed a CML-like myeloproliferative disease and, occasionally, an acute leukemia. Although p53

Bibliography on Cold Regions Science and Technology. Volume 41. Part 2

DTIC Science & Technology

1987-12-01

Aletschgletscher [1984, p.9-25, eng, 41-622 Aleksandrov, B.M. Multivariate regression analysis of the process of frozen peat dehydration [1986. p.15-19...freezing of high- way bridge decks [1977. 5p., eng] 41-4604 Britton, K.B. Low temperature effects on sorption. hydrolysis ...snowy season in 1986 at Sapporo [1986. p.17-23. jpn) 41-3503 Ishikawa, S. Experimental decomposition of

Application of ISO22000 and Failure Mode and Effect Analysis (fmea) for Industrial Processing of Poultry Products

NASA Astrophysics Data System (ADS)

Varzakas, Theodoros H.; Arvanitoyannis, Ioannis S.

Failure Mode and Effect Analysis (FMEA) model has been applied for the risk assessment of poultry slaughtering and manufacturing. In this work comparison of ISO22000 analysis with HACCP is carried out over poultry slaughtering, processing and packaging. Critical Control points and Prerequisite programs (PrPs) have been identified and implemented in the cause and effect diagram (also known as Ishikawa, tree diagram and fishbone diagram).

Improving the accuracy of total quality management instruments.

PubMed

Bechtel, G A; Wood, D

1996-03-01

Total quality management (TQM) instruments are essential tools in defining concepts identified in an Ishikawa or ¿cause-and-effect¿ diagram. Collecting meaningful and accurate data using TQM instruments is imperative if productivity and quality of care are to be enhanced. This article provides managers with techniques and guidelines that will enhance the reliability and validity of TQM instruments, thereby promoting organization efficiency and customer satisfaction.

Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

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

Fischer, L.; Deppert, W.R.; Pfeifer, D.

Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As workingmore » basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

Diacylglycerol, phosphatidic acid, and their metabolic enzymes in synaptic vesicle recycling.

PubMed

Tu-Sekine, Becky; Goldschmidt, Hana; Raben, Daniel M

2015-01-01

exocytosis: sphingosine (Camoletto et al., 2009; Chan et al., 2012; Chan and Sieburth, 2012; Darios et al., 2009; Kanno et al., 2010; Rohrbough et al., 2004) and sphingosine-1-phosphate (Chan, Hu, 2012; Chan and Sieburth, 2012; Kanno et al., 2010). Finally a number of reports have focused on the somewhat less well studies roles of sphingolipids and cholesterol in SV cycling. In this report, we review the recent understanding of the roles PLDs, DGKs, and DAG lipases, as well as sphingolipids and cholesterol play in synaptic vesicle cycling. Copyright © 2014. Published by Elsevier Ltd.

The Role of Concurrent Engineering in Weapons System Acquisition

DTIC Science & Technology

1988-12-01

checx sheets, Pareto diagrams, graphs, control charts, and scatter diagrams. Kaoru Iskilkawa, Guide to Qualiy Conmi, Asian Productivity Organization...Dewing [3 !,Juran [141, and Ishikawa [l𔃿). Managers in the United States and Japan have used techniques of statistics to measure performance and they have...New York (1962). 15. Kaoru Ishkawa, Guide to Quall’y Control, KRAUS International Publications, White Plains, NY (1-982). 16. Robert H. Hayc,%. St

JPRS Report. Science & Technology: Japan

DTIC Science & Technology

1987-07-29

for NBR, CR, and EPDM which have been in use, the adoption of fluoric rubber , acrylic rubber , and hydrin rubber attracts attention. Adhesives have... Propeller Analysis, by Shigeru Saito 56 Null-Collision Technique, by Katsuhisa Koura 59 Laminated Carbon Fiber Composite, by Ryuji Ishikawa 60 Flutter...tendency will last in the future. On the contrary, there is a slight decrease in the amount of paint and rubber . The application of ceramics for not

A separate universe view of the asymmetric sky

NASA Astrophysics Data System (ADS)

Kobayashi, Takeshi; Cortês, Marina; Liddle, Andrew R.

2015-05-01

We provide a unified description of the hemispherical asymmetry in the cosmic microwave background generated by the mechanism proposed by Erickcek, Kamionkowski, and Carroll, using a δ Script N formalism that consistently accounts for the asymmetry-generating mode throughout. We derive a general form for the power spectrum which explicitly exhibits the broken translational invariance. This can be directly compared to cosmic microwave background observables, including the observed quadrupole and fNL values, automatically incorporating the Grishchuk-Zel'dovich effect. Our calculation unifies and extends previous calculations in the literature, in particular giving the full dependence of observables on the phase of our location in the super-horizon mode that generates the asymmetry. We demonstrate how the apparently different results obtained by previous authors arise as different limiting cases. We confirm the existence of non-linear contributions to the microwave background quadrupole from the super-horizon mode identified by Erickcek et al. and further explored by Kanno et al., and show that those contributions are always significant in parameter regimes capable of explaining the observed asymmetry. We indicate example parameter values capable of explaining the observed power asymmetry without violating other observational bounds.

Important roles of the AKR1C2 and SRD5A1 enzymes in progesterone metabolism in endometrial cancer model cell lines.

PubMed

Sinreih, Maša; Anko, Maja; Zukunft, Sven; Adamski, Jerzy; Rižner, Tea Lanišnik

2015-06-05

Endometrial cancer is the most frequently diagnosed gynecological malignancy. It is associated with prolonged exposure to estrogens that is unopposed by progesterone, whereby enhanced metabolism of progesterone may decrease its protective effects, as it can deprive progesterone receptors of their active ligand. Furthermore, the 5α-pregnane metabolites formed can stimulate proliferation and may thus contribute to carcinogenesis. The aims of our study were to: (1) identify and quantify progesterone metabolites formed in the HEC-1A and Ishikawa model cell lines of endometrial cancer; and (2) pinpoint the enzymes involved in progesterone metabolism, and delineate their roles. Progesterone metabolism studies combined with liquid chromatography-tandem mass spectrometry enabled identification and quantification of the metabolites formed in these cells. Further quantitative PCR analysis and small-interfering-RNA-mediated gene silencing identified individual progesterone metabolizing enzymes and their relevant roles. In Ishikawa and HEC-1A cells, progesterone was metabolized mainly to 20α-hydroxy-pregn-4-ene-3-one, 20α-hydroxy-5α-pregnane-3-one, and 5α-pregnane-3α/β,20α-diol. The major difference between these cell lines was rate of progesterone metabolism, which was faster in HEC-1A cells. In the Ishikawa and HEC-1A cells, expression of AKR1C2 was 110-fold and 6800-fold greater, respectively, than expression of AKR1C1, which suggests that 20-ketosteroid reduction of 5α-pregnanes and 4-pregnenes is catalyzed mainly by AKR1C2. AKR1C1/AKR1C2 gene silencing showed decreased progesterone metabolism in both cell lines, thus further supporting the significant role of AKR1C2. SRD5A1 was also expressed in these cells, and its silencing confirmed that 5α-reduction is catalyzed by 5α-reductase type 1. Silencing of SRD5A1 also had the most pronounced effects, with decreased rate of progesterone metabolism, and consequently higher concentrations of unmetabolized progesterone

Molecular Modeling of Estrogen Receptor Alpha Mutated Breast Cancer to Guide New Therapeutic Strategies

DTIC Science & Technology

2017-10-01

We first started this project using the standard CRISPR /Cas9 approach: design and clone guide RNAs that target near the desired mutation, construct...R01HG008974, R21CA196455, R01DE023414 Zannel Blanchard Grad. student ZBLANCHARD 12 Responsible for the molecular biology, CRISPR /Cas9...knowledge, we have utilized a CRISPR -mediated epitope tagging strategy to create an isogenic model of the D538G ER LBD mutation in Ishikawa cells, where the

Emodin enhances the chemosensitivity of endometrial cancer by inhibiting ROS-mediated Cisplatin-resistance.

PubMed

Ding, Ning; Zhang, Hong; Su, Shan; Ding, Yumei; Yu, Xiaohui; Tang, Yujie; Wang, Qingfang; Liu, Peishu

2017-12-18

Background Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure. Objective Emodin is commonly used clinically to increase the sensitivity of chemotherapeutic agents, yet whether Emodin promotes the role of Cisplatin in the treatment of endometrial cancer has not been studied. Method CCK-8 kit was utilized to determine the growth of two endometrial cancer cell lines, Ishikawa and HEC-IB. The apoptosis level of Ishikawa and HEC-IB cells was detected by Annexin V / propidium iodide double-staining assay. ROS level was detected by DCFH-DA and NADPH oxidase expression. Expressions of drug-resistant genes were examined by real-time PCR and Western blotting. Results Emodin combined with Cisplatin reduced cell growth and increased the apoptosis of endometrial cancer cells. Co-treatment of Emodin and Cisplatin increased chemosensitivity by inhibiting the expression of drug-resistant genes through reducing the ROS levels in endometrial cancer cells. In an endometrial cancer xenograft murine model, the tumor size was reduced and animal survival time was increased by co-treatment of Emodin and Cisplatin. Conclusion This study demonstrates that Emodin enhances the chemosensitivity of Cisplatin on endometrial cancer by inhibiting ROS-mediated expression of drug-resistance genes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Chromophores from photolyzed ammonia reacting with acetylene: Application to Jupiter's Great Red Spot

NASA Astrophysics Data System (ADS)

Carlson, R. W.; Baines, K. H.; Anderson, M. S.; Filacchione, G.; Simon, A. A.

2016-08-01

The high altitude of Jupiter's Great Red Spot (GRS) may enhance the upward flux of gaseous ammonia (NH3) into the high troposphere, where NH3 molecules can be photodissociated and initiate a chain of chemical reactions with downwelling acetylene molecules (C2H2). These reactions, experimentally studied earlier by (Ferris and Ishikawa [1987] Nature 326, 777-778) and (Ferris and Ishikawa [1988] J. Amer. Chem. Soc. 110, 4306-4312), produce chromophores that absorb in the visible and ultraviolet regions. In this work we photolyzed mixtures of NH3 and C2H2 using ultraviolet radiation with a wavelength of 214 nm and measured the spectral transmission of the deposited films in the visible region (400-740 nm). From these transmission data we estimated the imaginary indices of refraction. Assuming that ammonia grains at the top of the GRS clouds are coated with this material, we performed layered sphere and radiative transfer calculations to predict GRS reflection spectra. Comparison of those results with observed and previously unreported Cassini visible spectra and with true-color images of the GRS show that the unknown GRS chromophore is spectrally consistent with the coupled NH3-C2H2 photochemical products produced in our laboratory experiments. Using high-resolution mass spectrometry and infrared spectroscopy we infer that the chromophore-containing residue is composed of aliphatic azine, azo, and diazo compounds.

Population structure and landscape genetics of two endangered frog species of genus Odorrana: different scenarios on two islands

PubMed Central

Igawa, T; Oumi, S; Katsuren, S; Sumida, M

2013-01-01

Isolation by distance and landscape connectivity are fundamental factors underlying speciation and evolution. To understand how landscapes affect gene flow and shape population structures, island species provide intrinsic study objects. We investigated the effects of landscapes on the population structure of the endangered frog species, Odorrana ishikawae and O. splendida, which each inhabit an island in southwest Japan. This was done by examining population structure, gene flow and demographic history of each species by analyzing 12 microsatellite loci and exploring causal environmental factors through ecological niche modeling (ENM) and the cost-distance approach. Our results revealed that the limited gene flow and multiple-population structure in O. splendida and the single-population structure in O. ishikawae were maintained after divergence of the species through ancient vicariance between islands. We found that genetic distance correlated with geographic distance between populations of both species. Our landscape genetic analysis revealed that the connectivity of suitable habitats influences gene flow and leads to the formation of specific population structures. In particular, different degrees of topographical complexity between islands are the major determining factor for shaping contrasting population structures of two species. In conclusion, our results illustrate the diversification mechanism of organisms through the interaction with space and environment. Our results also present an ENM approach for identifying the key factors affecting demographic history and population structures of target species, especially endangered species. PMID:22990312

Clusters and holes: Exchange networks in hematite-ilmenite solid solutions

NASA Astrophysics Data System (ADS)

Fabian, K.; McEnroe, S. A.; Robinson, P.

2009-04-01

Holes and clusters of exchange networks dominate the low-temperature, metastable phase diagram of the system (1 - x)Fe2O3 xF eTiO3 (Ilmx ). By our measurements we have probed and extended the phase diagram of Ishikawa et al. (1985) in the light of magnetic influences of the random exchange links, which originate either by replacing random pairs of Fe2+ and Ti4+ ions in the ordered ilmenite lattice by two Fe3+ions (ordered Ilmx phase), or by randomly replacing two Fe3+ ions in the hematite lattice by a pair of Fe2+ and Ti4+ ions (disordered Ilmx phase). Now a large dataset is available from these measurements, and we propose several new ideas to interpret the sometimes unexpected results. By refining a method of Ishikawa (1967), we analyze the PM' region of the phase diagram in terms of a mean field theory of interacting clusters. This allows to determine cluster sizes and interaction field distribution by inverting hysteresis measurements of Ilm92 and Ilm97. To understand the relation between ordered and disordered phases we design a mean field theory to determine Neel and Curie temperatures of both. An especially interesting finding is that the experimentally observed intersection of PM-PM' crossover with the AF phase boundary close to Ilm97 can be explained by analyzing average exchange interaction strengths.

Phytoestrogenic activity of blackcurrant (Ribes nigrum) anthocyanins is mediated through estrogen receptor alpha.

PubMed

Nanashima, Naoki; Horie, Kayo; Tomisawa, Toshiko; Chiba, Mitsuru; Nakano, Manabu; Fujita, Toshifumi; Maeda, Hayato; Kitajima, Maiko; Takamagi, Shizuka; Uchiyama, Daishi; Watanabe, Jun; Nakamura, Toshiya; Kato, Yoji

2015-12-01

Blackcurrants (Ribes nigrum L., Grossulariaceae) contain high amounts of anthocyanin polyphenols, which have antioxidant and anti-carcinogenic health benefits. This study analyzed the potential phytoestrogenic effects of blackcurrant extract (BCE) in breast cancer (MCF-7) and human endometrial cancer (Ishikawa) cell lines that over-express estrogen receptor alpha (ERα), as well as in immature female rats. Microarray analysis and Ingenuity® Pathway Analysis showed that BCE activated the ERα pathway, whereas quantitative-PCR confirmed that BCE and four types of anthocyanins up-regulated genes downstream of ERα. BCE (0.1-1.0 μg/mL) and anthocyanins (0.1-10 μM) induced MCF-7 cell proliferation; however, this effect was blocked by ER antagonist fulvestrant. Flow cytometry showed that anthocyanins reduced and increased the number of MCF-7 cells in the G0/G1 and G2/M phases, respectively. Anthocyanins stimulated ERα transcriptional activity in human ERα reporter assays and induced alkaline phosphatase activity in Ishikawa cells. Competition assays and in silico analysis indicated that anthocyanins bind to ERα. Finally, BCE focally induced stratification of columnar epithelial cells in the rat uterus and increased cytoplasmic mucin levels in these cells. These results suggest that blackcurrant anthocyanins act as phytoestrogens in vitro and in vivo. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chromophores from photolyzed ammonia reacting with acetylene: Application to Jupiters Great Red Spot

NASA Technical Reports Server (NTRS)

Carlson, Robert W.; Baines, Kevin H.; Anderson, M. S.; Filacchione, G.; Simon, A. A.

2016-01-01

The high altitude of Jupiter's Great Red Spot (GRS) may enhance the upward flux of gaseous ammonia (NH3 ) into the high troposphere, where NH3 molecules can be photodissociated and initiate a chain of chemical reactions with downwelling acetylene molecules (C2H2 ). These reactions, experimentally studied earlier by (Ferris and Ishikawa [1987] Nature 326, 777-778) and (Ferris and Ishikawa [1988] J. Amer. Chem. Soc. 110, 4306-4312), produce chromophores that absorb in the visible and ultraviolet regions. In this work we photolyzed mixtures of NH3 and C2H2 using ultraviolet radiation with a wavelength of 214 nm and measured the spectral transmission of the deposited films in the visible region (400-740 nm). From these transmission data we estimated the imaginary indices of refraction. Assuming that ammonia grains at the top of the GRS clouds are coated with this material, we performed layered sphere and radiative transfer calculations to predict GRS reflection spectra. Comparison of those results with observed and previously unreported Cassini visible spectra and with true-color images of the GRS show that the unknown GRS chromophore is spectrally consistent with the coupled NH3-C2H2 photochemical products produced in our laboratory experiments. Using high-resolution mass spectrometry and infrared spectroscopy we infer that the chromophore-containing residue is composed of aliphatic azine, azo, and diazo compounds.

Mössbauer study on a two-dimensional random mixture with competing spin anisotropies K2Ni1- x Fe x F4

NASA Astrophysics Data System (ADS)

Ito, A.; Anma, T.

1987-03-01

Mössbauer measurements have been made on a two-dimensional (2D) random mixture K2Ni1- x Fe x F4 with competing spin anisotropies. The concentration versus temperature phase diagram predicted by Oguchi and Ishikawa for mixed systems with competition between orthorhombic anisotropies has been shown to exist in K2Ni1- x Fe x F4. The coexistence of two kinds of Mössbauer spectra is seen in the transition regions, and is believed to be an intrinsic property of this system.

The estimation of the measurement results with using statistical methods

NASA Astrophysics Data System (ADS)

Velychko, O.; Gordiyenko, T.

2015-02-01

The row of international standards and guides describe various statistical methods that apply for a management, control and improvement of processes with the purpose of realization of analysis of the technical measurement results. The analysis of international standards and guides on statistical methods estimation of the measurement results recommendations for those applications in laboratories is described. For realization of analysis of standards and guides the cause-and-effect Ishikawa diagrams concerting to application of statistical methods for estimation of the measurement results are constructed.

Nucleobindin 2 (NUCB2) in human endometrial carcinoma: a potent prognostic factor associated with cell proliferation and migration.

PubMed

Takagi, Kiyoshi; Miki, Yasuhiro; Tanaka, Sota; Hashimoto, Chiaki; Watanabe, Mika; Sasano, Hironobu; Ito, Kiyoshi; Suzuki, Takashi

2016-01-01

Nucleobindin 2 (NUCB2) is a multifunctional protein containing several functional domains, and associated with wide variety of biological process such as food intake and energy homeostasis. Recently, NUCB2 has been implicated in not only normal human tissues but also some kinds of human malignancies. However, its clinical and/or biological significance has largely remained unknown in endometrial carcinomas. We therefore immunolocalized NUCB2 protein in 87 endometrial carcinoma tissues and examined its clinical significance. NUCB2 immunoreactivity was detected in 19 out of 87 (22%) of endometrial carcinoma cases examined, and positively correlated with Ki67 labeling index, while there was no significant correlation between NUCB2 and stage, histological grade, and progesterone receptor status. Furthermore, NUCB2 immunoreactivity was significantly correlated with increased risk of recurrence and worse clinical outcome regardless of stage or histological grade. Subsequent multivariate analyses did reveal that NUCB2 immunoreactivity was an independent prognostic factor for both disease-free survival and endometrial cancer specific survival. In vitro experiments demonstrated that knockdown of NUCB2 using specific siRNA for NUCB2 significantly impaired cell proliferation and migration of the endometrial carcinoma cell lines, Ishikawa and Sawano cells, and that nesfatin-1 treatment significantly promoted cell proliferation and migration in Ishikawa cells. These findings possibly suggested that NUCB2 and/or nesfatin-1 had pivotal roles in the progression of endometrial carcinomas. Immunohistochemical NUCB2 status may therefore serve as a potent biomarker for endometrial carcinomas.

Review of high pressure phases of calcium by first-principles calculations

NASA Astrophysics Data System (ADS)

Ishikawa, T.; Nagara, H.; Suzuki, N.; Tsuchiya, J.; Tsuchiya, T.

2010-03-01

We review high pressure phases of calcium which have obtained by recent experimental and first-principles studies. In this study, we investigated the face-centered cubic (fcc) structure, the body-centered cubic (bcc) structure, the simple cubic (sc) structure, a tetragonal P43212 [Ishikawa T et al. 2008 Phys. Rev. B 77 020101(R)], an orthorhombic Cmca [Ishikawa T et al. 2008 Phys. Rev. B 77 020101(R)], an orthorhombic Cmcm [Teweldeberhan A M and Bonev S A 2008 Phys. Rev. B 78 140101(R)], an orthorhombic Pnma [Yao Y et al. 2008 Phys. Rev. B 78 054506] and a tetragonal I4/mcm(00) [Arapan S et al. 2008 Proc. Natl. Acad. Sci. USA 105 20627]. We compared the enthalpies among the structures up to 200 GPa and theoretically determined the phase diagram of calcium. The sequence of the structural transitions is fcc (0- 3.5 GPa) → bcc (3.5 - 35.7 GPa) → Cmcm (35.7- 52GPa) → P43212 (52-109 GPa) → Cmca (109-117.4GPa) → Pnma (117.4-134.6GPa) → I4/mcm(00) (134.6 GPa -). The sc phase is experimentally observed in the pressure range from 32 to 113 GPa but, in our calculation, there is no pressure region where the sc phase is the most stable. In addition, we found that the enthalpy of the hexagonal close-packed (hcp) structure is lower than that of I4/mcm(00) above 495 GPa.

Application of Failure Mode and Effect Analysis (FMEA) and cause and effect analysis in conjunction with ISO 22000 to a snails (Helix aspersa) processing plant; A case study.

PubMed

Arvanitoyannis, Ioannis S; Varzakas, Theodoros H

2009-08-01

Failure Mode and Effect Analysis (FMEA) has been applied for the risk assessment of snails manufacturing. A tentative approach of FMEA application to the snails industry was attempted in conjunction with ISO 22000. Preliminary Hazard Analysis was used to analyze and predict the occurring failure modes in a food chain system (snails processing plant), based on the functions, characteristics, and/or interactions of the ingredients or the processes, upon which the system depends. Critical Control points have been identified and implemented in the cause and effect diagram (also known as Ishikawa, tree diagram, and fishbone diagram). In this work a comparison of ISO22000 analysis with HACCP is carried out over snails processing and packaging. However, the main emphasis was put on the quantification of risk assessment by determining the RPN per identified processing hazard. Sterilization of tins, bioaccumulation of heavy metals, packaging of shells and poisonous mushrooms, were the processes identified as the ones with the highest RPN (280, 240, 147, 144, respectively) and corrective actions were undertaken. Following the application of corrective actions, a second calculation of RPN values was carried out leading to considerably lower values (below the upper acceptable limit of 130). It is noteworthy that the application of Ishikawa (Cause and Effect or Tree diagram) led to converging results thus corroborating the validity of conclusions derived from risk assessment and FMEA. Therefore, the incorporation of FMEA analysis within the ISO22000 system of a snails processing industry is considered imperative.

A selective estrogen receptor modulator for the treatment of hot flushes.

PubMed

Wallace, Owen B; Lauwers, Kenneth S; Dodge, Jeffrey A; May, Scott A; Calvin, Joel R; Hinklin, Ronald; Bryant, Henry U; Shetler, Pamela K; Adrian, Mary D; Geiser, Andrew G; Sato, Masahiko; Burris, Thomas P

2006-02-09

A selective estrogen receptor modulator (SERM) for the potential treatment of hot flushes is described. (R)-(+)-7,9-difluoro-5-[4-(2-piperidin-1-ylethoxy)phenyl]-5H-6-oxachrysen-2-ol, LSN2120310, potently binds ERalpha and ERbeta and is an antagonist in MCF-7 breast adenocarcinoma and Ishikawa uterine cancer cell lines. The compound is a potent estrogen antagonist in the rat uterus. In ovariectomized rats, the compound lowers cholesterol, maintains bone mineral density, and is efficacious in a morphine dependent rat model of hot flush efficacy.

Qualifying Examination Intended to Promote Students‧ Interest in Basic Engineering Course

NASA Astrophysics Data System (ADS)

Yamada, Kenji

In order to develop self-affirmation and confidence, all the third year students in the Department of Electronics and Information Engineering at Ishikawa National College of Technology have been assigned to take a qualifying examination : the Digital Technology Certificate Examination, which is supported by the Ministry of Education, Culture, Sports, Science and Technology. The students who have passed it have gained self-assurance, while the unsuccessful candidates need close attention. This paper discusses the effects of the examination, which was introduced as an incentive for the students to have interest in the specialized course.

Precision VUV Spectro-Polarimetry for Solar Chromospheric Magnetic Field Measurements

NASA Astrophysics Data System (ADS)

Ishikawa, R.; Bando, T.; Hara, H.; Ishikawa, S.; Kano, R.; Kubo, M.; Katsukawa, Y.; Kobiki, T.; Narukage, N.; Suematsu, Y.; Tsuneta, S.; Aoki, K.; Miyagawa, K.; Ichimoto, K.; Kobayashi, K.; Auchère, F.; Clasp Team

2014-10-01

The Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) is a VUV spectro-polarimeter optimized for measuring the linear polarization of the Lyman-α line (121.6 nm) to be launched in 2015 with NASA's sounding rocket (Ishikawa et al. 2011; Narukage et al. 2011; Kano et al. 2012; Kobayashi et al. 2012). With this experiment, we aim to (1) observe the scattering polarization in the Lyman-α line, (2) detect the Hanle effect, and (3) assess the magnetic fields in the upper chromosphere and transition region for the first time. The polarization measurement error consists of scale error δ a (error in amplitude of linear polarization), azimuth error Δφ (error in the direction of linear polarization), and spurious polarization ɛ (false linear polarization signals). The error ɛ should be suppressed below 0.1% in the Lyman-α core (121.567 nm ±0.02 nm), and 0.5% in the Lyman-α wing (121.567 nm ±0.05 nm), based on our scientific requirements shown in Table 2 of Kubo et al. (2014). From scientific justification, we adopt Δ φ<2° and δ a<10% as the instrument requirements. The spectro-polarimeter features a continuously rotating MgF2 waveplate (Ishikawa et al. 2013), a dual-beam spectrograph with a spherical grating working also as a beam splitter, and two polarization analyzers (Bridou et al. 2011), which are mounted at 90 degree from each other to measure two orthogonal polarization simultaneously. For the optical layout of the CLASP instrument, see Figure 3 in Kubo et al. (2014). Considering the continuous rotation of the half-waveplate, the modulation efficiency is 0.64 both for Stokes Q and U. All the raw data are returned and demodulation (successive addition or subtraction of images) is done on the ground. We control the CLASP polarization performance in the following three steps. First, we evaluate the throughput and polarization properties of each optical component in the Lyman-α line, using the Ultraviolet Synchrotron ORbital Radiation Facility (UVSOR

Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation.

PubMed

Lin, Benjamin C; Suzawa, Miyuki; Blind, Raymond D; Tobias, Sandra C; Bulun, Serdar E; Scanlan, Thomas S; Ingraham, Holly A

2009-07-01

Estrogens and selective estrogen receptor (ER) modulators such as tamoxifen are known to increase uterine cell proliferation. Mounting evidence suggests that estrogen signaling is mediated not only by ERalpha and ERbeta nuclear receptors, but also by GPR30 (GPER), a seven transmembrane (7TM) receptor. Here, we report that primary human endometriotic H-38 cells express high levels of GPR30 with no detectable ERalpha or ERbeta. Using a novel tamoxifen analogue, STX, which activates GPR30 but not ERs, significant stimulation of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways was observed in H-38 cells and in Ishikawa endometrial cancer cells expressing GPR30; a similar effect was observed in JEG3 choriocarcinoma cells. STX treatment also increased cellular pools of phosphatidylinositol (3,4,5) triphosphate, a proposed ligand for the nuclear hormone receptor SF-1 (NR5A1). Consistent with these findings, STX, tamoxifen, and the phytoestrogen genistein were able to increase SF-1 transcription, promote Ishikawa cell proliferation, and induce the SF-1 target gene aromatase in a GPR30-dependent manner. Our findings suggest a novel signaling paradigm that is initiated by estrogen activation of the 7TM receptor GPR30, with signal transduction cascades (PI3K and MAPK) converging on nuclear hormone receptors (SF-1/LRH-1) to modulate their transcriptional output. We propose that this novel GPR30/SF-1 pathway increases local concentrations of estrogen, and together with classic ER signaling, mediate the proliferative effects of synthetic estrogens such as tamoxifen, in promoting endometriosis and endometrial cancers.

Application of ISO22000, failure mode, and effect analysis (FMEA) cause and effect diagrams and pareto in conjunction with HACCP and risk assessment for processing of pastry products.

PubMed

Varzakas, Theodoros H

2011-09-01

The Failure Mode and Effect Analysis (FMEA) model has been applied for the risk assessment of pastry processing. A tentative approach of FMEA application to the pastry industry was attempted in conjunction with ISO22000. Preliminary Hazard Analysis was used to analyze and predict the occurring failure modes in a food chain system (pastry processing plant), based on the functions, characteristics, and/or interactions of the ingredients or the processes, upon which the system depends. Critical Control points have been identified and implemented in the cause and effect diagram (also known as Ishikawa, tree diagram, and fishbone diagram). In this work a comparison of ISO22000 analysis with HACCP is carried out over pastry processing and packaging. However, the main emphasis was put on the quantification of risk assessment by determining the Risk Priority Number (RPN) per identified processing hazard. Storage of raw materials and storage of final products at -18°C followed by freezing were the processes identified as the ones with the highest RPN (225, 225, and 144 respectively) and corrective actions were undertaken. Following the application of corrective actions, a second calculation of RPN values was carried out leading to considerably lower values (below the upper acceptable limit of 130). It is noteworthy that the application of Ishikawa (Cause and Effect or Tree diagram) led to converging results thus corroborating the validity of conclusions derived from risk assessment and FMEA. Therefore, the incorporation of FMEA analysis within the ISO22000 system of a pastry processing industry is considered imperative.

Prokineticin-1 (PROK1) modulates interleukin (IL)-11 expression via prokineticin receptor 1 (PROKR1) and the calcineurin/NFAT signalling pathway.

PubMed

Cook, Ian H; Evans, Jemma; Maldonado-Pérez, David; Critchley, Hilary O; Sales, Kurt J; Jabbour, Henry N

2010-03-01

Prokineticin-1 (PROK1) is a multifunctional secreted protein which signals via the G-protein coupled receptor, PROKR1. Previous data from our laboratory using a human genome survey microarray showed that PROK1-prokineticin receptor 1 (PROKR1) signalling regulates numerous genes important for establishment of early pregnancy, including the cytokine interleukin (IL)-11. Here, we have shown that PROK1-PROKR1 induces the expression of IL-11 in PROKR1 Ishikawa cells and first trimester decidua via the calcium-calcineurin signalling pathway in a guanine nucleotide-binding protein (G(q/11)), extracellular signal-regulated kinases, Ca(2+) and calcineurin-nuclear factor of activated T cells dependent manner. Conversely, treatment of human decidua with a lentiviral miRNA to abolish endogenous PROK1 expression results in a significant reduction in IL-11 expression and secretion. Importantly, we have also shown a regulatory role for the regulator of calcineurin 1 isoform 4 (RCAN1-4). Overexpression of RCAN1-4 in PROKR1 Ishikawa cells using an adenovirus leads to a reduction in PROK1 induced IL-11 indicating that RCAN1-4 is a negative regulator in the calcineurin-mediated signalling to IL-11. Finally, we have shown the potential for both autocrine and paracrine signalling in the human endometrium by co-localizing IL-11, IL-11Ralpha and PROKR1 within the stromal and glandular epithelial cells of non-pregnant endometrium and first trimester decidua. Overall we have identified and characterized the signalling components of a novel PROK1-PROKR1 signalling pathway regulating IL-11.

Prokineticin-1 (PROK1) modulates interleukin (IL)-11 expression via prokineticin receptor 1 (PROKR1) and the calcineurin/NFAT signalling pathway

PubMed Central

Cook, Ian H.; Evans, Jemma; Maldonado-Pérez, David; Critchley, Hilary O.; Sales, Kurt J.; Jabbour, Henry N.

2010-01-01

Prokineticin-1 (PROK1) is a multifunctional secreted protein which signals via the G-protein coupled receptor, PROKR1. Previous data from our laboratory using a human genome survey microarray showed that PROK1–prokineticin receptor 1 (PROKR1) signalling regulates numerous genes important for establishment of early pregnancy, including the cytokine interleukin (IL)-11. Here, we have shown that PROK1–PROKR1 induces the expression of IL-11 in PROKR1 Ishikawa cells and first trimester decidua via the calcium–calcineurin signalling pathway in a guanine nucleotide-binding protein (Gq/11), extracellular signal-regulated kinases, Ca2+ and calcineurin–nuclear factor of activated T cells dependent manner. Conversely, treatment of human decidua with a lentiviral miRNA to abolish endogenous PROK1 expression results in a significant reduction in IL-11 expression and secretion. Importantly, we have also shown a regulatory role for the regulator of calcineurin 1 isoform 4 (RCAN1-4). Overexpression of RCAN1-4 in PROKR1 Ishikawa cells using an adenovirus leads to a reduction in PROK1 induced IL-11 indicating that RCAN1-4 is a negative regulator in the calcineurin-mediated signalling to IL-11. Finally, we have shown the potential for both autocrine and paracrine signalling in the human endometrium by co-localizing IL-11, IL-11Rα and PROKR1 within the stromal and glandular epithelial cells of non-pregnant endometrium and first trimester decidua. Overall we have identified and characterized the signalling components of a novel PROK1–PROKR1 signalling pathway regulating IL-11. PMID:19801577

Hypoxia and prostaglandin E receptor 4 signalling pathways synergise to promote endometrial adenocarcinoma cell proliferation and tumour growth.

PubMed

Catalano, Rob D; Wilson, Martin R; Boddy, Sheila C; McKinlay, Andrew T M; Sales, Kurt J; Jabbour, Henry N

2011-05-12

The prostaglandin endoperoxide synthase (PTGS) pathway is a potent driver of tumour development in humans by enhancing the biosynthesis and signalling of prostaglandin (PG) E(2). PTGS2 expression and PGE(2) biosynthesis is elevated in endometrial adenocarcinoma, however the mechanism whereby PTGS and PGE(2) regulate endometrial tumour growth is unknown. Here we investigated (a) the expression profile of the PGE synthase enzymes (PTGES, PTGES-2, PTGES-3) and PGE receptors (PTGER1-4) in endometrial adenocarcinomas compared with normal endometrium and (b) the role of PTGER4 in endometrial tumorigenesis in vivo. We found elevated expression of PTGES2 and PTGER4 and suppression of PTGER1 and PTGER3 in endometrial adenocarcinomas compared with normal endometrium. Using WT Ishikawa endometrial adenocarcinoma cells and Ishikawa cells stably transfected with the full length PTGER4 cDNA (PTGER4 cells) xenografted in the dorsal flanks of nude mice, we show that PTGER4 rapidly and significantly enhances tumour growth rate. Coincident with enhanced PTGER4-mediated tumour growth we found elevated expression of PTGS2 in PTGER4 xenografts compared with WT xenografts. Furthermore we found that the augmented growth rate of the PTGER4 xenografts was not due to enhanced angiogenesis, but regulated by an increased proliferation index and hypoxia. In vitro, we found that PGE(2) and hypoxia independently induce expression of PTGER4 indicating two independent pathways regulating prostanoid receptor expression. Finally we have shown that PGE(2) and hypoxia synergise to promote cellular proliferation of endometrial adenocarcinoma cells.

Hypoxia and Prostaglandin E Receptor 4 Signalling Pathways Synergise to Promote Endometrial Adenocarcinoma Cell Proliferation and Tumour Growth

PubMed Central

Catalano, Rob D.; Wilson, Martin R.; Boddy, Sheila C.; McKinlay, Andrew T. M.; Sales, Kurt J.; Jabbour, Henry N.

2011-01-01

The prostaglandin endoperoxide synthase (PTGS) pathway is a potent driver of tumour development in humans by enhancing the biosynthesis and signalling of prostaglandin (PG) E2. PTGS2 expression and PGE2 biosynthesis is elevated in endometrial adenocarcinoma, however the mechanism whereby PTGS and PGE2 regulate endometrial tumour growth is unknown. Here we investigated (a) the expression profile of the PGE synthase enzymes (PTGES, PTGES-2, PTGES-3) and PGE receptors (PTGER1–4) in endometrial adenocarcinomas compared with normal endometrium and (b) the role of PTGER4 in endometrial tumorigenesis in vivo. We found elevated expression of PTGES2 and PTGER4 and suppression of PTGER1 and PTGER3 in endometrial adenocarcinomas compared with normal endometrium. Using WT Ishikawa endometrial adenocarcinoma cells and Ishikawa cells stably transfected with the full length PTGER4 cDNA (PTGER4 cells) xenografted in the dorsal flanks of nude mice, we show that PTGER4 rapidly and significantly enhances tumour growth rate. Coincident with enhanced PTGER4-mediated tumour growth we found elevated expression of PTGS2 in PTGER4 xenografts compared with WT xenografts. Furthermore we found that the augmented growth rate of the PTGER4 xenografts was not due to enhanced angiogenesis, but regulated by an increased proliferation index and hypoxia. In vitro, we found that PGE2 and hypoxia independently induce expression of PTGER4 indicating two independent pathways regulating prostanoid receptor expression. Finally we have shown that PGE2 and hypoxia synergise to promote cellular proliferation of endometrial adenocarcinoma cells. PMID:21589857

GPER mediates the Egr-1 expression induced by 17β-estradiol and 4-hydroxitamoxifen in breast and endometrial cancer cells.

PubMed

Vivacqua, Adele; Romeo, Enrica; De Marco, Paola; De Francesco, Ernestina Marianna; Abonante, Sergio; Maggiolini, Marcello

2012-06-01

Early growth response-1 (Egr-1) is an immediate early gene involved in relevant biological events including the proliferation of diverse types of cell tumors. In a microarray analysis performed in breast cancer cells, 17β-estradiol (E2) and the estrogen receptor antagonist 4-hydroxitamoxifen (OHT) up-regulated Egr-1 through the G protein-coupled receptor named GPR30/GPER. Hence, in this study, we aimed to provide evidence regarding the ability of E2, OHT and the selective GPER ligand G-1 to regulate Egr-1 expression and function through the GPER/EGFR/ERK transduction pathway in both Ishikawa (endometrial) and SkBr3 (breast) cancer cells. Interestingly, we demonstrate that Egr-1 is involved in the transcription of genes regulating cell proliferation like CTGF and cyclin D1 and required for the proliferative effects induced by E2, OHT, and G-1 in both Ishikawa and SkBr3 cells. In addition, we show that GPER mediates the expression of Egr-1 also in carcinoma-associated fibroblasts (CAFs). Our data suggest that Egr-1 may represent an important mediator of the biological effects induced by E2 and OHT through GPER/EGFR/ERK signaling in breast and endometrial cancer cells. The results obtained in CAFs provide further evidence regarding the potential role exerted by the GPER-dependent Egr-1 up-regulation in tumor development and progression. Therefore, Egr-1 may be included among the bio-markers of estrogen and antiestrogen actions and may be considered as a further therapeutic target in both breast and endometrial tumors.

Centchroman induces redox-dependent apoptosis and cell-cycle arrest in human endometrial cancer cells.

PubMed

Shyam, Hari; Singh, Neetu; Kaushik, Shweta; Sharma, Ramesh; Balapure, Anil K

2017-04-01

Centchroman (CC) or Ormeloxifene has been shown to induce apoptosis and cell cycle arrest in various types of cancer cells. This has, however, not been addressed for endometrial cancer cells where its (CC) mechanism of action remains unclear. This study focuses on the basis of antineoplasticity of CC by blocking the targets involved in the cell cycle, survival and apoptosis in endometrial cancer cells. Ishikawa Human Endometrial Cancer Cells were cultured under estrogen deprived medium, exposed to CC and analyzed for proliferation and apoptosis. Additionally, we also analyzed oxidative stress induced by CC. Cell viability studies confirmed the IC 50 of CC in Ishikawa cells to be 20 µM after 48 h treatment. CC arrests the cells in G0/G1 phase through cyclin D1 and cyclin E mediated pathways. Phosphatidylserine externalization, nuclear morphology changes, DNA fragmentation, PARP cleavage, and alteration of Bcl-2 family protein expression clearly suggest ongoing apoptosis in the CC treated cells. Activation of caspase 3 & 9, up-regulation of AIF and inhibition of apoptosis by z-VAD-fmk clearly explains the participation of the intrinsic pathway of programmed cell death. Further, the increase of ROS, loss of MMP, inhibition of antioxidant (MnSOD, Cu/Zn-SOD and GST) and inhibition of apoptosis with L-NAC suggests CC induced oxidative stress leading to apoptosis via mitochondria mediated pathway. Therefore, CC could be a potential therapeutic agent for the treatment of Endometrial Cancer adjunct to its utility as a contraceptive and an anti-breast cancer agent.

Application of ISO 22000 and Failure Mode and Effect Analysis (FMEA) for industrial processing of salmon: a case study.

PubMed

Arvanitoyannis, Ioannis S; Varzakas, Theodoros H

2008-05-01

The Failure Mode and Effect Analysis (FMEA) model was applied for risk assessment of salmon manufacturing. A tentative approach of FMEA application to the salmon industry was attempted in conjunction with ISO 22000. Preliminary Hazard Analysis was used to analyze and predict the occurring failure modes in a food chain system (salmon processing plant), based on the functions, characteristics, and/or interactions of the ingredients or the processes, upon which the system depends. Critical Control points were identified and implemented in the cause and effect diagram (also known as Ishikawa, tree diagram and fishbone diagram). In this work, a comparison of ISO 22000 analysis with HACCP is carried out over salmon processing and packaging. However, the main emphasis was put on the quantification of risk assessment by determining the RPN per identified processing hazard. Fish receiving, casing/marking, blood removal, evisceration, filet-making cooling/freezing, and distribution were the processes identified as the ones with the highest RPN (252, 240, 210, 210, 210, 210, 200 respectively) and corrective actions were undertaken. After the application of corrective actions, a second calculation of RPN values was carried out resulting in substantially lower values (below the upper acceptable limit of 130). It is noteworthy that the application of Ishikawa (Cause and Effect or Tree diagram) led to converging results thus corroborating the validity of conclusions derived from risk assessment and FMEA. Therefore, the incorporation of FMEA analysis within the ISO 22000 system of a salmon processing industry is anticipated to prove advantageous to industrialists, state food inspectors, and consumers.

Collaborative problem solving with a total quality model.

PubMed

Volden, C M; Monnig, R

1993-01-01

A collaborative problem-solving system committed to the interests of those involved complies with the teachings of the total quality management movement in health care. Deming espoused that any quality system must become an integral part of routine activities. A process that is used consistently in dealing with problems, issues, or conflicts provides a mechanism for accomplishing total quality improvement. The collaborative problem-solving process described here results in quality decision-making. This model incorporates Ishikawa's cause-and-effect (fishbone) diagram, Moore's key causes of conflict, and the steps of the University of North Dakota Conflict Resolution Center's collaborative problem solving model.

Breakdown Cause and Effect Analysis. Case Study

NASA Astrophysics Data System (ADS)

Biały, Witold; Ružbarský, Juraj

2018-06-01

Every company must ensure that the production process proceeds without interferences. Within this article, the author uses the term "interferences" in reference to unplanned stoppages caused by breakdowns. Unfortunately, usually due to machine operators' mistakes, machines break, which causes stoppages thus generating additional costs for the company. This article shows a cause and effect analysis of a breakdown in a production process. The FMEA as well as quality management tools: the Ishikawa diagram and Pareto chart were used for the analysis. Correction measures were presented which allowed for a significant reduction in the number of stoppages caused by breakdowns.

Quality and Efficiency Improvement Tools for Every Radiologist.

PubMed

Kudla, Alexei U; Brook, Olga R

2018-06-01

In an era of value-based medicine, data-driven quality improvement is more important than ever to ensure safe and efficient imaging services. Familiarity with high-value tools enables all radiologists to successfully engage in quality and efficiency improvement. In this article, we review the model for improvement, strategies for measurement, and common practical tools with real-life examples that include Run chart, Control chart (Shewhart chart), Fishbone (Cause-and-Effect or Ishikawa) diagram, Pareto chart, 5 Whys, and Root Cause Analysis. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Estrogenic activity of isoflavonoids from the stem bark of the tropical tree Amphimas pterocarpoides, a source of traditional medicines.

PubMed

Tchoumtchoua, Job; Makropoulou, Maria; Ateba, Sylvain Benjamin; Boulaka, Athina; Halabalaki, Maria; Lambrinidis, George; Meligova, Aggeliki K; Mbanya, Jean Claude; Mikros, Emmanuel; Skaltsounis, Alexios-Leandros; Mitsiou, Dimitra J; Njamen, Dieudonne; Alexis, Michael N

2016-04-01

Various preparations of the African tree Amphimas pterocarpoides Harms are traditionally used to treat endocrine- related adverse health conditions. In the ovariectomized rat, the enriched in phenolics fraction of the methanol extract of stem bark of A. pterocarpoides acted as vaginotrophic agent of considerably weaker uterotrophic activity compared to estradiol. Evaluation of the fraction and 11 isoflavonoids isolated therefrom using Ishikawa cells and estrogen receptor (ER) isotype-specific reporter cells suggested that the estrogenic activity of the fraction could be attributed primarily to daidzein and dihydroglycitein and secondarily to glycitein. The potency-based selectivity of daidzein, dihydroglycitein and glycitein for gene expression through ERβ versus ERα, expressed relative to estradiol, was 37, 27 and 20, respectively. However, the rank order of relative-to-estradiol potencies of induction of alkaline phosphatase in Ishikawa cells, a reliable marker of estrogenic activity, was daidzein>dihydroglycitein>glycitein. The considerably higher estrogenic activity of dihydroglycitein compared to glycitein could be attributed to the partial agonist/antagonist activity of dihydroglycitein through ERβ. Calculation of theoretical free energies of binding predicted the partial agonism/antagonism of dihydroglycitein through ERβ. The fraction and the isolated isoflavonoids promoted lactogenic differentiation of HC11 mammary epithelial cells at least as effectively as premenopausal levels of estradiol. This data suggests that the estrogenic activity of the fraction likely depends on the metabolism of glycitein to dihydroglycitein; that the fraction could exert vaginotrophic activity likely without challenging endocrine cancer risk more than estrogen-alone supplementation; and that the fraction's safety for the reproductive track warrants a more detailed evaluation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quality of basic life support education and automated external defibrillator setting in schools in Ishikawa, Japan.

PubMed

Takamura, Akiteru; Ito, Sayori; Maruyama, Kaori; Ryo, Yusuke; Saito, Manami; Fujimura, Shuhei; Ishiura, Yuna; Hori, Ariyuki

2017-03-01

Automated external defibrillators (AED) have been installed in schools in Japan since 2004, and the government strongly recommends teaching basic life support (BLS). We therefore examined the quality of BLS education and AED installation in schools. We conducted a prefecture-wide questionnaire survey of all primary and junior high schools in 2016, to assess BLS education and AED installation against the recommendations of the Japan Circulation Society. The results were analyzed using descriptive statistics and chi-squared test. In total, 195 schools out of 315 (62%) responded, of which 38% have introduced BLS education for children. BLS training was held in a smaller proportion of primary schools (18%) than junior high schools (86%). More than 90% of primary school staff had undergone BLS training in the previous 2 years. The most common locations of AED were the gymnasium (32%) followed by entrance hall (28%), staffroom (25%), and infirmary (12%). The reasons given for location were that it was obvious (34%), convenient for staff (32%), could be used out of hours (17%), and the most likely location for a heart attack (15%). Approximately 18% of schools reported that it takes >5 min to reach the AED from the furthest point. BLS training, AED location, and understanding of both are not sufficient to save children's lives efficiently. Authorities should make recommendations about the correct number of AED, and their location, and provide more information to improve the quality of BLS training in schools. © 2016 Japan Pediatric Society.

DNA profiling analysis of endometrial and ovarian cell lines reveals misidentification, redundancy and contamination.

PubMed

Korch, Christopher; Spillman, Monique A; Jackson, Twila A; Jacobsen, Britta M; Murphy, Susan K; Lessey, Bruce A; Jordan, V Craig; Bradford, Andrew P

2012-10-01

Cell lines derived from human ovarian and endometrial cancers, and their immortalized non-malignant counterparts, are critical tools to investigate and characterize molecular mechanisms underlying gynecologic tumorigenesis, and facilitate development of novel therapeutics. To determine the extent of misidentification, contamination and redundancy, with evident consequences for the validity of research based upon these models, we undertook a systematic analysis and cataloging of endometrial and ovarian cell lines. Profiling of cell lines by analysis of DNA microsatellite short tandem repeats (STR), p53 nucleotide polymorphisms and microsatellite instability was performed. Fifty-one ovarian cancer lines were profiled with ten found to be redundant and five (A2008, OV2008, C13, SK-OV-4 and SK-OV-6) identified as cervical cancer cells. Ten endometrial cell lines were analyzed, with RL-92, HEC-1A, HEC-1B, HEC-50, KLE, and AN3CA all exhibiting unique, uncontaminated STR profiles. Multiple variants of Ishikawa and ECC-1 endometrial cancer cell lines were genotyped and analyzed by sequencing of mutations in the p53 gene. The profile of ECC-1 cells did not match the EnCa-101 tumor, from which it was reportedly derived, and all ECC-1 isolates were genotyped as Ishikawa cells, MCF-7 breast cancer cells, or a combination thereof. Two normal, immortalized endometrial epithelial cell lines, HES cells and the hTERT-EEC line, were identified as HeLa cervical carcinoma and MCF-7 breast cancer cells, respectively. Results demonstrate significant misidentification, duplication, and loss of integrity of endometrial and ovarian cancer cell lines. Authentication by STR DNA profiling is a simple and economical method to verify and validate studies undertaken with these models. Copyright © 2012 Elsevier Inc. All rights reserved.

Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis.

PubMed

Fonseca, B M; Correia-da-Silva, G; Teixeira, N A

2018-05-01

Among a variety of phytocannabinoids, Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most promising therapeutic compounds. Besides the well-known palliative effects in cancer patients, cannabinoids have been shown to inhibit in vitro growth of tumor cells. Likewise, the major endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), induce tumor cell death. The purpose of the present study was to characterize cannabinoid elements and evaluate the effect of cannabinoids in endometrial cancer cell viability. The presence of cannabinoid receptors, transient receptor potential vanilloid 1 (TRPV1), and endocannabinoid-metabolizing enzymes were determined by qRT-PCR and Western blot. We also examined the effects and the underlying mechanisms induced by eCBs and phytocannabinoids in endometrial cancer cell viability. Besides TRPV1, both EC cell lines express all the constituents of the endocannabinoid system. We observed that at concentrations higher than 5 μM, eCBs and CBD induced a significant reduction in cell viability in both Ishikawa and Hec50co cells, whereas THC did not cause any effect. In Ishikawa cells, contrary to Hec50co, treatment with AEA and CBD resulted in an increase in the levels of activated caspase -3/-7, in cleaved PARP, and in reactive oxygen species generation, confirming that the reduction in cell viability observed in the MTT assay was caused by the activation of the apoptotic pathway. Finally, these effects were dependent on TRPV1 activation and intracellular calcium levels. These data indicate that cannabinoids modulate endometrial cancer cell death. Selective targeting of TPRV1 by AEA, CBD, or other stable analogues may be an attractive research area for the treatment of estrogen-dependent endometrial carcinoma. Our data further support the evaluation of CBD and CBD-rich extracts for the potential treatment of endometrial cancer, particularly, that has become non-responsive to common therapies.

CHEMICAL MODIFICATION MODULATES ESTROGENIC ACTIVITY, OXIDATIVE REACTIVITY, & METABOLIC STABILITY IN 4′F-DMA, A NEW BENZOTHIOPHENE SELECTIVE ESTROGEN RECEPTOR MODULATOR

PubMed Central

Liu, Hong; Bolton, Judy L.; Thatcher, Gregory R. J.

2008-01-01

The benzothiophene SERMs raloxifene and arzoxifene, in the clinic or clinical trials for treatment of breast cancer and postmenopausal symptoms, are highly susceptible to oxidative metabolism and formation of electrophilic metabolites. 4′F-DMA, fluoro-substituted desmethyl arzoxifene (DMA), showed attenuated oxidation to quinoids in incubation with rat hepatocytes as well as in rat and human liver microsomes. Incubations of 4′F-DMA with hepatocytes yielded only one glucuronide conjugate and no GSH conjugates; whereas DMA underwent greater metabolism giving two glucuronide conjugates, one sulfate conjugate, and two GSH conjugates. Phase I and phase II metabolism was further evaluated in human small intestine microsomes and in human intestinal Caco-2 cells. In comparison to DMA, 4′F-DMA formed significantly less glucuronide and sulfate conjugates. The formation of quinoids was futher explored in hepatocytes in which DMA was observed to give concentration and time dependent depletion of GSH accompanied by damage to DNA which showed inverse dependence on GSH; in contrast, GSH depletion and DNA damage were almost completely abrogated in incubations with 4′F-DMA. 4′F-DMA shows ligand binding affinity to ERα and ERβ with similarity to both raloxifene and to DMA. ER-mediated biological activity was measured with the ERE-luciferase reporter system in transfected MCF-7 cells and Ishikawa cells, and in MCF-7 cells proliferation was measured. In all systems, 4′F-DMA exhibited anitestrogenic acitivty of comparable potency to raloxifene, but did not manifest estrogenic properties, mirroring previous results on inhibition of estradiol-mediated induction of alkaline phosphatase activity in Ishikawa cells. These results suggest that 4′F-DMA might be an improved benzothiophene SERM with similar antiestrogenic activity to raloxifene, but improved metabolic stability and attenuated toxicity; showing that simple chemical modification can abrogate oxidative bioactivation

Anti-tumorigenic action of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran: evidence for involvement of GPR30/EGFR signaling pathway.

PubMed

Chandra, V; Fatima, I; Saxena, R; Hussain, M K; Hajela, K; Sankhwar, P; Roy, B G; Chandna, S; Dwivedi, A

2013-05-01

The aim of the present study was to investigate the effect of non-steroidal, pure antiestrogenic benzopyran derivative i.e., 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) on the growth of human endometrial cancer cells in vivo and in vitro and to elucidate its mechanism of action. Cell proliferation was assayed by measuring the incorporation of 5'-bromo-2'-deoxyuridine in Ishikawa and primary endometrial cancer cells. The expression of proliferation and apoptotic markers was analyzed by immunoblotting. The effect of K-1 on GPR30-regulated proteins was analyzed by ELISA and by immunoblotting. Nude mice bearing subcutaneous implanted-Ishikawa tumors, were treated for 14days with K-1 (200μg/kg body weight/day/orally). The proliferation markers, GPR30-regulated proteins and apoptotic markers were analyzed by immunoblotting in tumor xenograft. The apoptotic effect of compound K-1 was determined by TUNEL assay. Compound K-1 inhibited proliferation of endometrial adenocarcinoma cells and decreased the expression of proliferation markers. It caused apoptosis by increasing the expression of apoptotic markers (NOXA, PUMAα) and reducing the expression of p-CREB and BclxL. Compound interfered with GPR30-regulated-EGFR activation, decreased p-ERK, p-c-jun, c-fos, cyclinD1 and c-myc expression. Treatment of tumor-bearing mice with K-1 resulted in a significant decrease in tumor volume and weight. Decreased expression of p-ERK and its downstream molecules and increased expression of apoptotic markers were observed in tumor in K-1 treated animals. Findings suggest the potent inhibitory effect of compound K-1 on endometrial cancer cellular growth (in-vitro) and on tumor size (in-vivo) which is mediated at least, in part, by interference with GPR30-signaling. Copyright © 2013 Elsevier Inc. All rights reserved.

Endocannabinoids modulate apoptosis in endometriosis and adenomyosis.

PubMed

Bilgic, Elif; Guzel, Elif; Kose, Sevil; Aydin, Makbule Cisel; Karaismailoglu, Eda; Akar, Irem; Usubutun, Alp; Korkusuz, Petek

2017-06-01

Adenomyosis that is a form of endometriosis is the growth of ectopic endometrial tissue within the muscular wall of the uterus (myometrium), which may cause dysmenorrhea and infertility. Endocannabinoid mediated apoptotic mechanisms of endometriosis and adenomyosis are not known. We hypothesized that the down regulation of endocannabinoid receptors and/or alteration in their regulatory enzymes may have a direct role in the pathogenesis of endometriosis and adenomyosis through apoptosis. Endocannabinoid receptors CB1 and CB2, their synthesizing and catabolizing enzymes (FAAH, NAPE-PLD, DAGL, MAGL) and the apoptotic indexes were immunohistochemically assessed in endometriotic and adenomyotic tissues. Findings were compared to normal endometrium and myometrium. Endometrial adenocarcinoma (Ishikawa) and ovarian endometriosis cyst wall stromal (CRL-7566) cell lines were furthermore cultured with or without cannabinoid receptor agonists. The IC50 value for CB1 and CB2 receptor agonists was quantified. Cannabinoid agonists on cell death were investigated by Annexin-V/Propidium iodide labeling with flow cytometry. CB1 and CB2 receptor levels decreased in endometriotic and adenomyotic tissues compared to the control group (p=0,001 and p=0,001). FAAH, NAPE-PLD, MAGL and DAGL enzyme levels decreased in endometriotic and adenomyotic tissues compared to control (p=0,001, p=0,001, p=0,001 and p=0,002 respectively). Apoptotic cell indexes both in endometriotic and adenomyotic tissues also decreased significantly, compared to the control group (p=0,001 and p=0,001). CB1 and CB2 receptor agonist mediated dose dependent fast anti-proliferative and pro-apoptotic effects were detected in Ishikawa and ovarian endometriosis cyst wall stromal cell lines (CRL-7566). Endocannabinoids are suggested to increase apoptosis mechanisms in endometriosis and adenomyosis. CB1 and CB2 antagonists can be considered as potential medical therapeutic agents for endometriosis and adenomyosis. Copyright �

[AntiEGFRnano inhibites proliferation and migration of estrogen-dependent Ishikawa cells of human endometrial cancer cell line].

PubMed

Diao, Zhen-yu; Lu, Wu-guang; Cao, Peng; Hu, Yun-long; Zhou, Xing; Xue, Ping-ping; Shen, Li; Sun, Hai-xiang

2012-10-01

Nanobody is a kind of antibody from camel, which misses light chain. Nanobody has the same antigen binding specificity and affinity as mAb. Moreover, because of its small molecular weight, high stability and easy preparation, nanobody has great value of biomedical applications. In this study, we successfully prepared highly pure antiEGFR nanobody in E.coli using genetic engineering techniques. Cell proliferation assay (CCK-8 assay) and migration experiments (cell scratch test and Transwell assay) indicated that the recombinant antiEGFRnano can significantly inhibit the proliferation and migration of endometrial cancer cells. These results provide a new way of thinking and methods for EGFR-targeted therapy of endometrial cancer.

New Recombinant Mycobacterium bovis BCG Expression Vectors: Improving Genetic Control over Mycobacterial Promoters.

PubMed

Kanno, Alex I; Goulart, Cibelly; Rofatto, Henrique K; Oliveira, Sergio C; Leite, Luciana C C; McFadden, Johnjoe

2016-04-01

The expression of many antigens, stimulatory molecules, or even metabolic pathways in mycobacteria such as Mycobacterium bovis BCG or M. smegmatis was made possible through the development of shuttle vectors, and several recombinant vaccines have been constructed. However, gene expression in any of these systems relied mostly on the selection of natural promoters expected to provide the required level of expression by trial and error. To establish a systematic selection of promoters with a range of strengths, we generated a library of mutagenized promoters through error-prone PCR of the strong PL5 promoter, originally from mycobacteriophage L5. These promoters were cloned upstream of the enhanced green fluorescent protein reporter gene, and recombinant M. smegmatis bacteria exhibiting a wide range of fluorescence levels were identified. A set of promoters was selected and identified as having high (pJK-F8), intermediate (pJK-B7, pJK-E6, pJK-D6), or low (pJK-C1) promoter strengths in both M. smegmatis and M. bovisBCG. The sequencing of the promoter region demonstrated that it was extensively modified (6 to 11%) in all of the plasmids selected. To test the functionality of the system, two different expression vectors were demonstrated to allow corresponding expression levels of the Schistosoma mansoni antigen Sm29 in BCG. The approach used here can be used to adjust expression levels for synthetic and/or systems biology studies or for vaccine development to maximize the immune response. Copyright © 2016 Kanno et al.

Phase change alloy viscosities down to T{sub g} using Adam-Gibbs-equation fittings to excess entropy data: A fragile-to-strong transition

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

Wei, Shuai, E-mail: shuai.wei@asu.edu; Department of Materials Science and Engineering, University of Arizona, Tucson, Arizona 85712; Lucas, Pierre

2015-07-21

A striking anomaly in the viscosity of Te{sub 85}Ge{sub 15} alloys noted by Greer and coworkers from the work of Neumann et al. is reminiscent of the equally striking comparison of liquid tellurium and water anomalies documented long ago by Kanno et al. In view of the power laws that are used to fit the data on water, we analyze the data on Te{sub 85}Ge{sub 15} using the Speedy-Angell power-law form, and find a good account with a singularity T{sub s} only 25 K below the eutectic temperature. However, the heat capacity data in this case are not diverging, but insteadmore » exhibit a sharp maximum like that observed in fast cooling in the Molinero-Moore model of water. Applying the Adam-Gibbs viscosity equation to these calorimetric data, we find that there must be a fragile-to-strong liquid transition at the heat capacity peak temperature, and then predict the 'strong' liquid course of the viscosity down to T{sub g} at 406 K (403.6 K at 20 K min{sup −1} in this study). Since crystallization can be avoided by moderately fast cooling in this case, we can check the validity of the extrapolation by making a direct measurement of fragility at T{sub g}, using differential scanning calorimetric techniques, and then comparing with the value from the extrapolated viscosity at T{sub g}. The agreement is encouraging, and prompts discussion of relations between water and phase change alloy anomalies.« less

Heterogeneous nuclear ribonucleoprotein C1 may control miR-30d levels in endometrial exosomes affecting early embryo implantation.

PubMed

Balaguer, N; Moreno, I; Herrero, M; González, M; Simón, C; Vilella, F

2018-05-29

Is there a specific mechanism to load the microRNA, hsa-miR-30d, into exosomes to facilitate maternal communication with pre-implantation embryos? The heterogeneous nuclear ribonucleoprotein C1 (hnRNPC1) is involved in the internalization of endometrial miR-30d into exosomes to prepare for its subsequent incorporation into trophectoderm cells. Our group previously described a novel cell-to-cell communication mechanism involving the delivery of endometrial microRNAs (miRNAs) from the maternal endometrium to the trophectoderm cells of preimplantation embryos. Specifically, human endometrial miR-30d is taken up by murine blastocysts causing the overexpression of certain genes involved in embryonic adhesion (Itb3, Itga7 and Cdh5) increasing embryo adhesion rates. Transfer of maternal miR-30d to preimplantation embryos was confirmed by co-culture of Wild-type (WT) and miR-30d knockout (KO) murine embryos with primary cultures of human endometrial epithelial cells (hEECs) in which mir-30d was labelled with specific Molecular Beacon or SmartFlare probes. Potential molecules responsible for the miR-30d loading into exosomes were purified by pull-down analysis with a biotinylated form of miR-30d on protein lysates from human endometrial exosomes, identified using mass spectrometry and assessed by flow cytometry, western blotting and co-localization studies. The role of hnRNPC1 in the miR-30d loading and transportation was interrogated by quantification of this miRNA in exosomes isolated from endometrial cells in which hnRNPC1 was transiently silenced using small interference RNA. Finally, the transfer of miR-30d to WT and KO embryos was assessed upon co-culture with sihnRNPC1 transfected cells. Murine embryos from miR-30d WT and KO mice, (strain MirC26tm1Mtm/Mmjax), were obtained by oviduct flushing of superovulated females. Endometrial Exosomes were purified by ultracentrifugation of supernatants from primary cultures of hEECs or Ishikawa cells. Molecular beacon and

Stability of iterative procedures with errors for approximating common fixed points of a couple of q-contractive-like mappings in Banach spaces

NASA Astrophysics Data System (ADS)

Zeng, Lu-Chuan; Yao, Jen-Chih

2006-09-01

Recently, Agarwal, Cho, Li and Huang [R.P. Agarwal, Y.J. Cho, J. Li, N.J. Huang, Stability of iterative procedures with errors approximating common fixed points for a couple of quasi-contractive mappings in q-uniformly smooth Banach spaces, J. Math. Anal. Appl. 272 (2002) 435-447] introduced the new iterative procedures with errors for approximating the common fixed point of a couple of quasi-contractive mappings and showed the stability of these iterative procedures with errors in Banach spaces. In this paper, we introduce a new concept of a couple of q-contractive-like mappings (q>1) in a Banach space and apply these iterative procedures with errors for approximating the common fixed point of the couple of q-contractive-like mappings. The results established in this paper improve, extend and unify the corresponding ones of Agarwal, Cho, Li and Huang [R.P. Agarwal, Y.J. Cho, J. Li, N.J. Huang, Stability of iterative procedures with errors approximating common fixed points for a couple of quasi-contractive mappings in q-uniformly smooth Banach spaces, J. Math. Anal. Appl. 272 (2002) 435-447], Chidume [C.E. Chidume, Approximation of fixed points of quasi-contractive mappings in Lp spaces, Indian J. Pure Appl. Math. 22 (1991) 273-386], Chidume and Osilike [C.E. Chidume, M.O. Osilike, Fixed points iterations for quasi-contractive maps in uniformly smooth Banach spaces, Bull. Korean Math. Soc. 30 (1993) 201-212], Liu [Q.H. Liu, On Naimpally and Singh's open questions, J. Math. Anal. Appl. 124 (1987) 157-164; Q.H. Liu, A convergence theorem of the sequence of Ishikawa iterates for quasi-contractive mappings, J. Math. Anal. Appl. 146 (1990) 301-305], Osilike [M.O. Osilike, A stable iteration procedure for quasi-contractive maps, Indian J. Pure Appl. Math. 27 (1996) 25-34; M.O. Osilike, Stability of the Ishikawa iteration method for quasi-contractive maps, Indian J. Pure Appl. Math. 28 (1997) 1251-1265] and many others in the literature.

Enhancement of high-order harmonic generation by a two-color field: Influence of propagation effects

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

Schiessl, K.; Persson, E.; Burgdoerfer, J.

2006-11-15

Recent calculations of the response of a single atom subjected to a two-color laser pulse with the higher frequency being resonant with an excitation of the target atom revealed a significant enhancement of photoionization as well as high-order harmonic generation [K. Ishikawa, Phy. Rev. Lett. 91, 043002 (2003)]. We investigate the problem in the framework a fully quantum-mechanical pulse propagation algorithm and perform calculations for rare gases in the single-active-electron approximation. The enhancement of harmonic output compared to the corresponding one-color pulse remains intact for short propagation lengths, promising the feasibility of experimental realization. We also study weak second colorsmore » resonant via a two-photon transition where significant enhancements in harmonic yields can be observed as well.« less

Optimisation of shock absorber process parameters using failure mode and effect analysis and genetic algorithm

NASA Astrophysics Data System (ADS)

Mariajayaprakash, Arokiasamy; Senthilvelan, Thiyagarajan; Vivekananthan, Krishnapillai Ponnambal

2013-07-01

The various process parameters affecting the quality characteristics of the shock absorber during the process were identified using the Ishikawa diagram and by failure mode and effect analysis. The identified process parameters are welding process parameters (squeeze, heat control, wheel speed, and air pressure), damper sealing process parameters (load, hydraulic pressure, air pressure, and fixture height), washing process parameters (total alkalinity, temperature, pH value of rinsing water, and timing), and painting process parameters (flowability, coating thickness, pointage, and temperature). In this paper, the process parameters, namely, painting and washing process parameters, are optimized by Taguchi method. Though the defects are reasonably minimized by Taguchi method, in order to achieve zero defects during the processes, genetic algorithm technique is applied on the optimized parameters obtained by Taguchi method.

Psychophysiological profiles of batterers: autonomic emotional reactivity as it predicts the antisocial spectrum of behavior among intimate partner abusers.

PubMed

Babcock, Julia C; Green, Charles E; Webb, Sarah A; Yerington, Timothy P

2005-08-01

On the basis of studies finding heart rate deceleration among severely violent (SV) batterers (J. M. Gottman et al., 1995) and unsuccessful psychopaths (S. S. Ishikawa, A. Raine, T. Lencz, S. Bihrle, & L. Lacasse, 2001), this study compares the physiological reactivity of SV batterers (n=35) with low-level violent (LLV) batterers (n=37) and nonviolent men (n=21) during 2 laboratory tasks. Men's heart rate and skin conductance level were recorded during baseline, a conflict discussion, and a standardized anger induction. Results suggest that autonomic hyporeactivity is a risk marker for antisocial features among SV men, whereas autonomic hyperreactivity is a risk marker among LLV men. Psychophysiological responding appears to be a stronger correlate of general antisocial behavior than of intimate partner abuse. Copyright (c) 2005 APA, all rights reserved.

An overview of Quality Management System implementation in a research laboratory

NASA Astrophysics Data System (ADS)

Molinéro-Demilly, Valérie; Charki, Abdérafi; Jeoffrion, Christine; Lyonnet, Barbara; O'Brien, Steve; Martin, Luc

2018-02-01

The aim of this paper is to show the advantages of implementing a Quality Management System (QMS) in a research laboratory in order to improve the management of risks specific to research programmes and to increase the reliability of results. This paper also presents experience gained from feedback following the implementation of the Quality process in a research laboratory at INRA, the French National Institute for Agronomic Research and details the various challenges encountered and solutions proposed to help achieve smoother adoption of a QMS process. The 7Ms (Management, Measurement, Manpower, Methods, Materials, Machinery, Mother-nature) methodology based on the Ishikawa `Fishbone' diagram is used to show the effectiveness of the actions considered by a QMS, which involve both the organization and the activities of the laboratory. Practical examples illustrate the benefits and improvements observed in the laboratory.

A 5 year longitudinal study of water quality for final rinsing in the single chamber washer-disinfector with a reverse osmosis plant.

PubMed

Uetera, Yushi; Kishii, Kozue; Yasuhara, Hiroshi; Kumada, Naohito; Moriya, Kyoji; Saito, Ryoichi; Okazaki, Mitsuhiro; Misawa, Yoshiki; Kawamura, Kunio

2013-01-01

This report deals with the construction and management of the reverse osmosis (RO) water system for final rinsing of surgical instruments in the washer-disinfector. Numerous operational challenges were encountered in our RO water system and these were analyzed utilizing the Ishikawa Fishbone diagram. The aim was to find potential problems and promote preventive system management for RO water. It was found that the measures that existed were inappropriate for preventing contamination in the heat-labile RO water system. The storage tank was found to be significantly contaminated and had to be replaced with a new one equipped with a sampling port and water drainage system. Additional filters and an UV treatment lamp were installed. The whole system disinfection started 1.5 years later using a peracetic acid-based compound after confirming the material compatibility. Operator errors were found when a new water engineer took over the duty from his predecessor. It was also found that there were some deficiencies in the standard operating procedures (SOPs), and that on-the-job training was not enough. The water engineer failed to disinfect the sampling port and water drainage system. The RO membrane had been used for 4 years, even though the SOP standard specified changing it as every 3 years. Various bacteria, such as Rothia mucilaginosa, were cultured from the RO water sampled from the equipment. Because Rothia mucilaginosa is a resident in the oral cavity and upper respiratory tract, it is believed that the bacteria were introduced into the system by the maintenance personnel or working environment. Therefore, the presence of R. mucilaginosa implied the failure of sanitary maintenance procedures. This study suggests that water systems should be designed based on the plans for profound system maintenance. It also suggests that SOP and on-the job training are essential to avoid any operator errors. These results must be carefully considered when either constructing new

Initial results from a multi-point mapping observation of thundercloud high-energy radiation in coastal area of Japan sea

NASA Astrophysics Data System (ADS)

Wada, Y.; Enoto, T.; Furuta, Y.; Nakazawa, K.; Yuasa, T.; Okuda, K.; Makishima, K.; Nakano, T.; Umemoto, D.; Tsuchiya, H.

2017-12-01

On-ground detections of Thunderstorm Radiation Bursts (TRB) which mainly consist of bremsstrahlung gamma rays with energy extending up to 20 MeV indicate powerful electron accelerations inside thunderclouds or along lightning discharge paths (e.g. Torii et al., 2002, Tsuchiya et al., 2007, Dwyer et al., 2004). In order to resolve time variation and structure of the electron accelerators, we have constructed a multi-point mapping observation network with the aim of tracing gamma rays from moving thunderclouds since 2015. In fiscal 2016, we developed low cost and small size detectors dedicated to our observation. The data acquisition system records energy and timing of individual gamma-ray photons by 4-ch and 50 MHz sampling electrical boards (9.5 cm x 9.5 cm), coupled with BGO scintillator crystals. The systems were installed in portable water-proof boxes. We operated 10 detectors in two areas (Ishikawa and Niigata) along the coast of Japan Sea from October 2016 to April 2017. During this period, detectors in Ishikawa detected in total 10 TRBs lasting for several minutes associated with passage of a thundercloud. Our previous single-site measurement at Niigata, has recorded 1.4 TRBs per year on average in 2006-2015. Therefore, our new multi-point observation detected 7 times as many events as the previous system. One of the TRB gamma-ray spectra was fitted well by a cutoff power-law model. We performed a Monte Carlo simulation, and revealed that this spectrum was explained as bremsstrahlung of a monochromatic 15 MeV electron beam generated at an altitude of 500 m. We also succeeded in tracing gamma rays from an identical moving thundercloud with two detectors, demonstrating performance of the multi-point observation. In addition, we detected "short TRBs" lasting for a few hundred milliseconds associated with lightning discharges from four independent detectors placed 500 m apart simultaneously, in January and February 2017 at Niigata. The results in 2016-2017 winter

Process capability improvement through DMAIC for aluminum alloy wheel machining

NASA Astrophysics Data System (ADS)

Sharma, G. V. S. S.; Rao, P. Srinivasa; Babu, B. Surendra

2017-07-01

This paper first enlists the generic problems of alloy wheel machining and subsequently details on the process improvement of the identified critical-to-quality machining characteristic of A356 aluminum alloy wheel machining process. The causal factors are traced using the Ishikawa diagram and prioritization of corrective actions is done through process failure modes and effects analysis. Process monitoring charts are employed for improving the process capability index of the process, at the industrial benchmark of four sigma level, which is equal to the value of 1.33. The procedure adopted for improving the process capability levels is the define-measure-analyze-improve-control (DMAIC) approach. By following the DMAIC approach, the C p, C pk and C pm showed signs of improvement from an initial value of 0.66, -0.24 and 0.27, to a final value of 4.19, 3.24 and 1.41, respectively.

A preliminary analysis of incident investigation reports of an integrated steel plant: some reflection.

PubMed

Verma, A; Maiti, J; Gaikwad, V N

2018-06-01

Large integrated steel plants employ an effective safety management system and gather a significant amount of safety-related data. This research intends to explore and visualize the rich database to find out the key factors responsible for the occurrences of incidents. The study was carried out on the data in the form of investigation reports collected from a steel plant in India. The data were processed and analysed using some of the quality management tools like Pareto chart, control chart, Ishikawa diagram, etc. Analyses showed that causes of incidents differ depending on the activities performed in a department. For example, fire/explosion and process-related incidents are more common in the departments associated with coke-making and blast furnace. Similar kind of factors were obtained, and recommendations were provided for their mitigation. Finally, the limitations of the study were discussed, and the scope of the research works was identified.

Evaluation of Regional Vulnerability to Disasters by People of Ishikawa, Japan: A Cross Sectional Study Using National Health Insurance Data

PubMed Central

Fujiu, Makoto; Morisaki, Yuma; Takayama, Junichi; Yanagihara, Kiyoko; Nishino, Tatsuya; Sagae, Masahiko; Hirako, Kohei

2018-01-01

The 2013 Partial Amendment of the Disaster Countermeasures Basic Law mandated that a roster of vulnerable persons during disasters be created, and further development of evacuation support is expected. In this study, the number of vulnerable people living in target analytical areas are identified in terms of neighborhood units by using the National Health Insurance Database to create a realistic and efficient evacuation support plan. Later, after considering the “vulnerability” of an area to earthquake disaster damage, a quantitative evaluation of the state of the disaster is performed using a principle component analysis that further divided the analytical target areas into neighborhood units to make a detailed determination of the number of disaster-vulnerable persons, the severity of the disaster, etc. The results of the disaster evaluation performed after considering the vulnerability of an area are that 628 disaster-vulnerable persons live in areas with a relatively higher disaster evaluation value. PMID:29534021

Kruppel-like Factor 9 is a Negative Regulator of Ligand-dependent Estrogen Receptor Alpha Signaling in Ishikawa Endometrial Adenocarcinoma Cells

USDA-ARS?s Scientific Manuscript database

Estrogen (E) and progesterone (P), acting through their respective receptors and other nuclear proteins, exhibit opposing activities in target cells. We previously reported that Krüppel-like factor 9 (KLF9) cooperates with progesterone receptor (PR) to facilitate P-dependent gene transcription in ut...

Wavelength and intensity dependence of recollision-enhanced multielectron effects in high-order harmonic generation

NASA Astrophysics Data System (ADS)

Abanador, Paul M.; Mauger, François; Lopata, Kenneth; Gaarde, Mette B.; Schafer, Kenneth J.

2018-04-01

Using a model molecular system (A2) with two active electrons restricted to one dimension, we examine high-order harmonic generation (HHG) enhanced by rescattering. Our results show that even at intensities well below the single ionization saturation, harmonics generated from the cation (A2+ ) can be significantly enhanced due to the rescattering of the electron that is initially ionized. This two-electron effect is manifested by the appearance of a secondary plateau and cutoff in the HHG spectrum, extending beyond the predicted cutoff in the single active electron approximation. We use our molecular model to investigate the wavelength dependence of rescattering enhanced HHG, which was first reported in a model atomic system [I. Tikhomirov, T. Sato, and K. L. Ishikawa, Phys. Rev. Lett. 118, 203202 (2017), 10.1103/PhysRevLett.118.203202]. We demonstrate that the HHG yield in the secondary cutoff is highly sensitive to the available electron rescattering energies as indicated by a dramatic scaling with respect to driving wavelength.

[Utilization of Big Data in Medicine and Future Outlook].

PubMed

Kinosada, Yasutomi; Uematsu, Machiko; Fujiwara, Takuya

2016-03-01

"Big data" is a new buzzword. The point is not to be dazzled by the volume of data, but rather to analyze it, and convert it into insights, innovations, and business value. There are also real differences between conventional analytics and big data. In this article, we show some results of big data analysis using open DPC (Diagnosis Procedure Combination) data in areas of the central part of JAPAN: Toyama, Ishikawa, Fukui, Nagano, Gifu, Aichi, Shizuoka, and Mie Prefectures. These 8 prefectures contain 51 medical administration areas called the second medical area. By applying big data analysis techniques such as k-means, hierarchical clustering, and self-organizing maps to DPC data, we can visualize the disease structure and detect similarities or variations among the 51 second medical areas. The combination of a big data analysis technique and open DPC data is a very powerful method to depict real figures on patient distribution in Japan.

SerpinE2, a poor biomarker of endometrial cancer, promotes the proliferation and mobility of EC cells.

PubMed

Shen, Yuan; Wang, Xiaoyu; Xu, Jianping; Lu, Lin

2017-07-04

The SerpinE2 pathway is evolutionarily conserved and plays an important role in tumorigenesis. SerpinE2 (a small ubiquitin-related modifier), like ubiquitin, conjugates SerpinE2 proteins onto lysine residues of target proteins. SerpinE2 over-expression has been found in several tumors. Here, we detected the level of SerpinE2 in 72 samples of EC tissue using immunohistochemistry to assess the role of SerpinE2 in EC prognosis. Meanwhile, we knocked down SerpinE2 by siRNA in the HTB-111 and Ishikawa EC cell lines and analyzed the viability and mobility change using an MTT assay, an annexin V/PI apoptosis assay, a wound scratch test and a transwell assay. A Kaplan-Meier analysis indicated a negative correlation between the level of SerpinE2 and the EC prognosis. Silencing SerpinE2 induced cell apoptosis and reduced the migration ability. Our data suggest SerpinE2 works as an oncogene in EC.

Application of Failure Mode and Effect Analysis (FMEA), cause and effect analysis, and Pareto diagram in conjunction with HACCP to a corn curl manufacturing plant.

PubMed

Varzakas, Theodoros H; Arvanitoyannis, Ioannis S

2007-01-01

The Failure Mode and Effect Analysis (FMEA) model has been applied for the risk assessment of corn curl manufacturing. A tentative approach of FMEA application to the snacks industry was attempted in an effort to exclude the presence of GMOs in the final product. This is of crucial importance both from the ethics and the legislation (Regulations EC 1829/2003; EC 1830/2003; Directive EC 18/2001) point of view. The Preliminary Hazard Analysis and the Fault Tree Analysis were used to analyze and predict the occurring failure modes in a food chain system (corn curls processing plant), based on the functions, characteristics, and/or interactions of the ingredients or the processes, upon which the system depends. Critical Control points have been identified and implemented in the cause and effect diagram (also known as Ishikawa, tree diagram, and the fishbone diagram). Finally, Pareto diagrams were employed towards the optimization of GMOs detection potential of FMEA.

Treatment of fingertip amputation: comparison of results between microsurgical replantation and pocket principle.

PubMed

Yabe, Tetsuji; Tsuda, Tomoyuki; Hirose, Shunsuke; Ozawa, Toshiyuki

2012-05-01

In this article, a comparison of replantation using microsurgical replantation (replantation) and the Brent method and its modification (pocket principle) in the treatment of fingertip amputation is reported. As a classification of amputation level, we used Ishikawa's subzone classification of fingertip amputation, and the cases of amputations only in subzone 2 were included in this study. Between these two groups, there was no statistical difference in survival rate, postoperative atrophy, or postoperative range of motion. In terms of sensory recovery, some records were lost and exact study was difficult. But there was no obvious difference between these cases. In our comparison of microsurgical replantation versus the pocket principle in treatment of subzone 2 fingertip amputation, there was no difference in postoperative results. Each method has pros and cons, and the surgeon should choose which technique to use based on his or her understanding of the characteristics of both methods. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Actual Condition of Paddy Field Levee Maintenance by Various Farm Households including Large-scale Farming in the Developed Land Renting Area

NASA Astrophysics Data System (ADS)

Sakata, Yasuyo

The survey of interview, resource acquisition, photographic operation, and questionnaire were carried out in the “n” Community in the “y” District in Hakusan City in Ishikawa Prefecture to investigate the actual condition of paddy field levee maintenance in the area where land-renting market was proceeding, large-scale farming was dominant, and the problems of geographically scattered farm-land existed. In the study zone, 1) an agricultural production legal person rent-cultivated some of the paddy fields and maintained the levees, 2) another agricultural production legal person rent-cultivated some of the soy bean fields for crop changeover and land owners maintained the levees. The results indicated that sufficient maintenance was executed on the levees of the paddy fields cultivated by the agricultural production legal person, the soy bean fields for crop changeover, and the paddy fields cultivated by the land owners. Each reason is considered to be the managerial strategy, the economic incentive, the mutual monitoring and cross-regulatory mechanism, etc.

Nonlinear dynamics analysis of the spur gear system for railway locomotive

NASA Astrophysics Data System (ADS)

Wang, Junguo; He, Guangyue; Zhang, Jie; Zhao, Yongxiang; Yao, Yuan

2017-02-01

Considering the factors such as the nonlinearity backlash, static transmission error and time-varying meshing stiffness, a three-degree-of-freedom torsional vibration model of spur gear transmission system for a typical locomotive is developed, in which the wheel/rail adhesion torque is considered as uncertain but bounded parameter. Meantime, the Ishikawa method is used for analysis and calculation of the time-varying mesh stiffness of the gear pair in meshing process. With the help of bifurcation diagrams, phase plane diagrams, Poincaré maps, time domain response diagrams and amplitude-frequency spectrums, the effects of the pinion speed and stiffness on the dynamic behavior of gear transmission system for locomotive are investigated in detail by using the numerical integration method. Numerical examples reveal various types of nonlinear phenomena and dynamic evolution mechanism involving one-period responses, multi-periodic responses, bifurcation and chaotic responses. Some research results present useful information to dynamic design and vibration control of the gear transmission system for railway locomotive.

Application of path analysis to urinary findings of cadmium-induced renal dysfunction.

PubMed

Abe, T; Kobayashi, E; Okubo, Y; Suwazono, Y; Kido, T; Shaikh, Z A; Nogawa, K

2001-01-01

In order to identify some causal relations among various urinary indices of cadmium-induced renal dysfunction, such as glucose, total protein, amino nitrogen, beta 2-microglobulin (beta 2-m), metallothionein (MT), and cadmium (Cd), we applied path analysis method to previous epidemiological studies targeting the residents of the Cd-polluted Kakehashi River basin of Ishikawa Prefecture, Japan. We obtained a diagram-termed path model, representing some causal relations among the above urinary indices. It shows that urinary Cd is located at the beginning point in the diagram, and Cd-induced renal dysfunction develops in the following order: Cd exposure-->increase of beta 2-m and/or MT excretion-->increase of amino-N and/or total protein excretion-->increase of glucose excretion. It was proved mathematically, that in the case of both males and females, increased excretions of beta 2-m and/or MT were the most sensitive urinary indices of the early stage of chronic Cd-induced renal dysfunction.

Phase Diagram in a Random Mixture of Two Antiferromagnets with Competing Spin Anisotropies. I

NASA Astrophysics Data System (ADS)

Someya, Yoshiko

1981-12-01

The phase diagram of a random mixture of two antiferromagnets with competing spin anisotropies (A1-xBx) has been analyzed by extending the theory of Matsubara and Inawashiro, and Oguchi and Ishikawa. In the model assumed, the anisotropy energies are expressed by the anisotropic exchange interactions. According to this formulation, it has been shown that the concentration dependence of TN becomes a function of \\includegraphics{dummy.eps}, where P, Q=A, B; SP is a magnitude of P-spin, and JPQη is a η component of exchange integral between P- and Q-spin). Further, the phase boundary between an AF phase and an OAF (oblique antiferromagnetic) phase at T{=}0 K has been shown to be determined by α({\\equiv}SB/SA), if \\includegraphics{dummy.eps} are given. The obtained phase diagrams for Fe1-xCoxCl2, K2Mn1-xFexF4 and Fe1-xCoxCl2\\cdot2H2O are compared with the experimental ones.

Development of Fieldwork Activities to Educate the Youth for the Biological and Cultural Preservation in Rural Communities of Ishikawa Prefecture, Japan

ERIC Educational Resources Information Center

Mammadova, Aida

2017-01-01

In order to achieve the regional sustainability and bio-cultural preservation, environmental education of youth will be critical, however due to the lack of the specific subject of regional studies at the educational curriculum, students are not able to achieve the skills to understand the local environment and feel isolated from nature. We…

Expression of GRIM-19 in adenomyosis and its possible role in pathogenesis.

PubMed

Wang, Jing; Deng, Xiaohui; Yang, Yang; Yang, Xingsheng; Kong, Beihua; Chao, Lan

2016-04-01

To study the expression of the gene associated with retinoid-interferon (IFN)-induced mortality 19 (GRIM-19) in the endometrial tissue of patients with adenomyosis and to describe the possible pathogenic mechanisms of this phenomenon. Experimental study using human samples and cell lines. University-affiliated hospital. Ectopic and eutopic endometrial tissues were obtained from 30 patients with adenomyosis, whereas normal endometrial specimens were obtained from 10 control patients without adenomyosis. Patients with rapid pathology report-confirmed adenomyosis were recruited, and eutopic and ectopic endometrial tissue samples were collected from patients who had undergone hysterectomies by either the transabdominal or laparoscopic method at Qilu Hospital. Normal endometrial tissue was collected from a group of control patients without adenomyosis. Immunohistochemistry (IHC) was performed to evaluate the expression of GRIM-19, phospho-signal transducer and activator of transcription 3 (Y705) (Y705) (pSTAT3(Y705)), and vascular endothelial growth factor (VEGF) in endometrial tissue samples. The protein levels of GRIM-19, pSTAT3(Y705), STAT3, and VEGF were detected by Western blot. Apoptosis in endometrial specimens was assayed by TUNEL. Immunohistochemistry with an antibody directed against CD34 was performed to detect new blood vessels in the endometrial tissue. GRIM-19 small interfering RNA and a recombinant plasmid carrying GRIM-19 were constructed to evaluate the effects of GRIM-19 on the downstream factors pSTAT3(Y705), STAT3, and VEGF in Ishikawa cells. The expression of GRIM-19 was down-regulated in the eutopic endometria of patients with adenomyosis compared with the endometria of patients in the control group, and it was further reduced in the endometrial glandular epithelial cells of adenomyotic lesions. Apoptosis was reduced in the eutopic endometrium compared with the control group, and it was significantly reduced in ectopic endometrial tissues. In

FOREWORD: Focus on Novel Nanoelectromechanical 3D Structures: Fabrication and Properties Focus on Novel Nanoelectromechanical 3D Structures: Fabrication and Properties

NASA Astrophysics Data System (ADS)

Yamada, Shooji; Yamaguchi, Hiroshi; Ishihara, Sunao

2009-06-01

Microelectromechanical systems (MEMS) are widely used small electromechanical systems made of micrometre-sized components. Presently, we are witnessing a transition from MEMS to nanoelectromechanical systems (NEMS), which comprise devices integrating electrical and mechanical functionality on the nanoscale and offer new exciting applications. Similarly to MEMS, NEMS typically include a central transistor-like nanoelectronic unit for data processing, as well as mechanical actuators, pumps, and motors; and they may combine with physical, biological and chemical sensors. In the transition from MEMS to NEMS, component sizes need to be reduced. Therefore, many fabrication methods previously developed for MEMS are unsuitable for the production of high-precision NEMS components. The key challenge in NEMS is therefore the development of new methods for routine and reproducible nanofabrication. Two complementary types of method for NEMS fabrication are available: 'top-down' and 'bottom-up'. The top-down approach uses traditional lithography technologies, whereas bottom-up techniques include molecular self-organization, self-assembly and nanodeposition. The NT2008 conference, held at Ishikawa High-Tech Conference Center, Ishikawa, Japan, between 23-25 October 2008, focused on novel NEMS fabricated from new materials and on process technologies. The topics included compound semiconductors, small mechanical structures, nanostructures for micro-fluid and bio-sensors, bio-hybrid micro-machines, as well as their design and simulation. This focus issue compiles seven articles selected from 13 submitted manuscripts. The articles by Prinz et al and Kehrbusch et al introduce the frontiers of the top-down production of various operational NEMS devices, and Kometani et al present an example of the bottom-up approach, namely ion-beam induced deposition of MEMS and NEMS. The remaining articles report novel technologies for biological sensors. Taira et al have used manganese nanoparticles

Effect of halogenated substituents on the metabolism and estrogenic effects of the equine estrogen, equilenin.

PubMed

Liu, Xuemei; Zhang, Fagen; Liu, Hong; Burdette, Joanna E; Li, Yan; Overk, Cassia R; Pisha, Emily; Yao, Jiaqin; van Breemen, Richard B; Swanson, Steven M; Bolton, Judy L

2003-06-01

Estrogen replacement therapy has been correlated with an increased risk for developing breast and endometrial cancers. One potential mechanism of estrogen carcinogenesis involves metabolism of estrogens to 2- and 4-hydroxylated catechols, which are further oxidized to electrophilic/redox active o-quinones that have the potential to both initiate and promote the carcinogenic process. Previously, we showed that the equine estrogens, equilin and equilenin, which are major components of the estrogen replacement formulation Premarin (Wyeth-Ayerst), are primarily metabolized to the catechol, 4-hydroxyequilenin. This catechol was found to autoxidize to an o-quinone causing oxidation and alkylation of DNA in vitro and in vivo. To block catechol formation from equilenin, 4-halogenated equilenin derivatives were synthesized. These derivatives were tested for their ability to bind to the estrogen receptor, induce estrogen sensitive genes, and their potential to form catechol metabolites. We found that the 4-fluoro derivatives were more estrogenic than the 4-chloro and 4-bromo derivatives as demonstrated by a higher binding affinity for estrogen receptors alpha and beta, an enhanced induction of alkaline phosphatase activity in Ishikawa cells, pS2 expression in S30 cells, and PR expression in Ishikawa cells. Incubation of these compounds with tyrosinase in the presence of GSH showed that the halogenated equilenin compounds formed less catechol GSH conjugates than the parent compounds, equilenin and 17beta-hydroxyequilenin. In addition, these halogenated compounds showed less cytotoxicity in the presence of tyrosinase than the parent compounds in S30 cells. Also, as stated above, the 4-fluoro derivatives showed similar estrogenic effects as compared with parent compounds; however, they were less toxic in S30 cells as compared to equilenin and 17beta-equilenin. Because 17beta-hydroxy-4-halogenated equilenin derivatives showed higher estrogenic effects than the halogenated

[Morbidity-mortality review in psychiatry: suicide or suicide attempts].

PubMed

Thomas, A; Combalbert, N; Fay, J; Paquis, J

2010-06-01

Further to the occurrence of three cases of suicide attempts or suicides within a few months, a psychiatric team introduced a method of evaluation of the professional practices on this subject. The objective aimed by the team was to collectively identify the risk factors of the acting out and the strategies to prevent it. The analysis and the treatment of unwanted events require an approach per problem. Because of the obligation for the doctors to perform an evaluation of their professional practices, a proposition to use a method presented by the High Authority of Health was looked for. Considering the necessity of favoring the exchanges between team members, the articulation of two methods was proposed: a morbidity mortality review (MMR) and an analysis of the detailed causes. The objective of the MMR is to analyze the deaths of certain predetermined morbid accidents within a service. The aim of the MMR is to highlight actions for improvement. The analysis of the causes allows the professionals to list all the causes of the problem identified, without limiting themselves to the immediate causes. In this case, a simple method was chosen: the Ishikawa diagram (or fishbone diagram, or also cause-and-effect diagram). A specific Ishikawa diagram for suicide was created by the coordinating physician and was proposed to the team. In the term of the first MMR, the tool was improved by the collective clinical experience and served as support of analysis for the studied events. Three cases related to the evaluation were prepared beforehand by the referent doctor and later presented by him in MMR sessions. For each case, approximately a dozen of professionals were invited to fill in the biography of the patient. A discussion was then engaged by the external doctor on the circumstances of self injuries or suicide attempts. The three detailed analyses of cases were transcribed into a virgin Ishikawa diagram. Furthermore, several points were discussed on the safety aspects

In-situ determination of residual specific activity in activated concrete walls of a PET-cyclotron room

NASA Astrophysics Data System (ADS)

Matsumura, H.; Toyoda, A.; Masumoto, K.; Yoshida, G.; Yagishita, T.; Nakabayashi, T.; Sasaki, H.; Matsumura, K.; Yamaya, Y.; Miyazaki, Y.

2018-06-01

In the decommissioning work for concrete walls of PET-cyclotron rooms, an in-situ measurement is expected to be useful for obtaining a contour map of the specific activity on the walls without destroying the structure. In this study, specific activities of γ-ray-emitting radionuclides in concrete walls were determined by using an in-situ measurement method employing a portable Ge semiconductor detector, and compared with the specific activity obtained using the sampling measurement method, at the Medical and Pharmacological Research Center Foundation in Hakui, Ishikawa, Japan. Accordingly, the specific activity could be determined by the in-situ determination method. Since there is a clear correlation between the total specific activity of γ-ray-emitting radionuclides and contact dose rate, the specific activity can be determined approximately by contact dose-rate measurement using a NaI scintillation survey meter. The specific activity of each γ-ray-emitting radionuclide can also be estimated from the contact dose rate using a NaI scintillation survey meter. The in-situ measurement method is a powerful tool for the decommissioning of the PET cyclotron room.

Medical applications of atomic force microscopy and Raman spectroscopy.

PubMed

Choi, Samjin; Jung, Gyeong Bok; Kim, Kyung Sook; Lee, Gi-Ja; Park, Hun-Kuk

2014-01-01

This paper reviews the recent research and application of atomic force microscopy (AFM) and Raman spectroscopy techniques, which are considered the multi-functional and powerful toolkits for probing the nanostructural, biomechanical and physicochemical properties of biomedical samples in medical science. We introduce briefly the basic principles of AFM and Raman spectroscopy, followed by diagnostic assessments of some selected diseases in biomedical applications using them, including mitochondria isolated from normal and ischemic hearts, hair fibers, individual cells, and human cortical bone. Finally, AFM and Raman spectroscopy applications to investigate the effects of pharmacotherapy, surgery, and medical device therapy in various medicines from cells to soft and hard tissues are discussed, including pharmacotherapy--paclitaxel on Ishikawa and HeLa cells, telmisartan on angiotensin II, mitomycin C on strabismus surgery and eye whitening surgery, and fluoride on primary teeth--and medical device therapy--collagen cross-linking treatment for the management of progressive keratoconus, radiofrequency treatment for skin rejuvenation, physical extracorporeal shockwave therapy for healing of Achilles tendinitis, orthodontic treatment, and toothbrushing time to minimize the loss of teeth after exposure to acidic drinks.

Implementation of the infinite-range exterior complex scaling to the time-dependent complete-active-space self-consistent-field method

NASA Astrophysics Data System (ADS)

Orimo, Yuki; Sato, Takeshi; Scrinzi, Armin; Ishikawa, Kenichi L.

2018-02-01

We present a numerical implementation of the infinite-range exterior complex scaling [Scrinzi, Phys. Rev. A 81, 053845 (2010), 10.1103/PhysRevA.81.053845] as an efficient absorbing boundary to the time-dependent complete-active-space self-consistent field method [Sato, Ishikawa, Březinová, Lackner, Nagele, and Burgdörfer, Phys. Rev. A 94, 023405 (2016), 10.1103/PhysRevA.94.023405] for multielectron atoms subject to an intense laser pulse. We introduce Gauss-Laguerre-Radau quadrature points to construct discrete variable representation basis functions in the last radial finite element extending to infinity. This implementation is applied to strong-field ionization and high-harmonic generation in He, Be, and Ne atoms. It efficiently prevents unphysical reflection of photoelectron wave packets at the simulation boundary, enabling accurate simulations with substantially reduced computational cost, even under significant (≈50 % ) double ionization. For the case of a simulation of high-harmonic generation from Ne, for example, 80% cost reduction is achieved, compared to a mask-function absorption boundary.

Bases of the Mantle-Carbonatite Conception of Diamond Genesis

NASA Astrophysics Data System (ADS)

Litvin, Yuriy; Spivak, Anna; Kuzyura, Anastasia

2016-04-01

In the mantle-carbonatite conception of diamond genesis, the results of physic-chemical experiments are coordinated with the data of analytic mineralogy of primary inclusions in natural diamonds. Generalization of the solutions of principal genetic problems constitutes the bases of the conception. The solutions are following: (1) it is grounded that diamond-parental melts of the upper mantle have peridotite/eclogite - carbonatite - carbon compositions, of the transition zone - (wadsleite↔ringwoodite) - majorite - stishovite - carbonatite - carbon compositions, and of the lower mantle - periclase/wustite - bridgmanite - Ca-perovskite -stishovite - carbonatite - carbon compositions; (2) a construction of generalized diagrams for the diamond-parental media, which reveal changeable compositions of the growth melts of diamonds and associated phases, their genetic relations to the mantle substance, and classification connections of the primary inclusions in natural diamonds; (3) experimental equilibrium phase diagrams of syngenesis of diamonds and primary inclusions, which characterize the nucleation and growth conditions of diamonds and a capture of paragenetic and xenogenetic minerals by the growing diamonds; (4) a determination of the phase diagrams of diamonds and inclusions syngenesis under the regime of fractional crystallization, which discover the regularities of ultrabasic-basic evolution and paragenesis transitions in the diamond-forming systems of the upper and lower mantle. The evidence of the physic-chemically united mode of diamond genesis at the mantle depths with different mineralogy is obtained. References. Litvin Yu.A. (2007). High-pressure mineralogy of diamond genesis. In: Advances in High-Pressure Mineralogy (edited by Eiji Ohtani), Geological Society of America Special paper 421, 83-103. Litvin Yu.A. (2012). Experimental study of physic-chemical conditions of natural diamond formation on an example of the eclogite

Increased AIF-1-mediated TNF-α expression during implantation phase in IVF cycles with GnRH antagonist protocol.

PubMed

Xu, Bufang; Zhou, Mingjuan; Wang, Jingwen; Zhang, Dan; Guo, Feng; Si, Chenchen; Leung, Peter C K; Zhang, Aijun

2018-06-12

Is allograft inflammatory factor-1 (AIF-1), a cytokine associated with inflammation and allograft rejection, aberrantly elevated in in vitro fertilization (IVF) cycles with gonadotropin-releasing hormone (GnRH) antagonist protocol with potential effects on endometrial receptivity? Our findings indicated AIF-1 is increased in IVF cycles with GnRH antagonist protocol and mediates greater TNF-α expression during implantation phase, which may be unfavorable for embryo implantation. Studies have shown that GnRH antagonist protocol cycles have lower implantation and clinical pregnancy rates than GnRH agonist long protocol cycles. Endometrial receptivity but not embryo quality is a key factor contributing to this phenomenon; however, the mechanism is still unknown. Implantation and pregnancy rates were studied in 238 patients undergoing their first cycle of IVF/ICSI between 2012 and 2014. Forty of these patients opted to have no fresh embryo replacement and were divided into two equal groups: (i) GnRH antagonist protocol and (ii) GnRH agonist long protocol, group 3 included 20 infertile women with a tubal factor in untreated cycles. During the same interval, endometrial tissues were taken from 18 infertile women with a tubal factor in the early proliferative phase, late proliferative phase, and mid-secretory phase of the menstrual cycle (n = 6/group). Microarray analysis, RT-qPCR, Western blot analysis, immunohistochemistry were used to investigate the expression levels of AIF-1 and the related cytokines (TNF-α, IL1β, IL1RA, IL6, IL12, IL15 and IL18). The effect of AIF-1 on uterine receptivity was modeled using in vitro adhesion experiments (coculture of JAR cells and Ishikawa cells). The expression of AIF-1 was the highest in early proliferative phase, decreasing thereafter in the late proliferative phase, and almost disappearing in the mid-secretory phase, indicating that low AIF-1 expression might be important for embryo implantation during implantation phase

Quantification of Ligand Binding to G-Protein Coupled Receptors on Cell Membranes by Ellipsometry

PubMed Central

Kriechbaumer, Verena; Nabok, Alexei; Widdowson, Robert; Smith, David P.; Abell, Ben M.

2012-01-01

G-protein-coupled receptors (GPCRs) are prime drug targets and targeted by approximately 60% of current therapeutic drugs such as β-blockers, antipsychotics and analgesics. However, no biophysical methods are available to quantify their interactions with ligand binding in a native environment. Here, we use ellipsometry to quantify specific interactions of receptors within native cell membranes. As a model system, the GPCR-ligand CXCL12α and its receptor CXCR4 are used. Human-derived Ishikawa cells were deposited onto gold coated slides via Langmuir-Schaefer film deposition and interactions between the receptor CXCR4 on these cells and its ligand CXCL12α were detected via total internal reflection ellipsometry (TIRE). This interaction could be inhibited by application of the CXCR4-binding drug AMD3100. Advantages of this approach are that it allows measurement of interactions in a lipid environment without the need for labelling, protein purification or reconstitution of membrane proteins. This technique is potentially applicable to a wide variety of cell types and their membrane receptors, providing a novel method to determine ligand or drug interactions targeting GPCRs and other membrane proteins. PMID:23049983

A DMAIC approach for process capability improvement an engine crankshaft manufacturing process

NASA Astrophysics Data System (ADS)

Sharma, G. V. S. S.; Rao, P. Srinivasa

2014-05-01

The define-measure-analyze-improve-control (DMAIC) approach is a five-strata approach, namely DMAIC. This approach is the scientific approach for reducing the deviations and improving the capability levels of the manufacturing processes. The present work elaborates on DMAIC approach applied in reducing the process variations of the stub-end-hole boring operation of the manufacture of crankshaft. This statistical process control study starts with selection of the critical-to-quality (CTQ) characteristic in the define stratum. The next stratum constitutes the collection of dimensional measurement data of the CTQ characteristic identified. This is followed by the analysis and improvement strata where the various quality control tools like Ishikawa diagram, physical mechanism analysis, failure modes effects analysis and analysis of variance are applied. Finally, the process monitoring charts are deployed at the workplace for regular monitoring and control of the concerned CTQ characteristic. By adopting DMAIC approach, standard deviation is reduced from 0.003 to 0.002. The process potential capability index ( C P) values improved from 1.29 to 2.02 and the process performance capability index ( C PK) values improved from 0.32 to 1.45, respectively.

A cross-sectional study on the relationship of job stress with natural killer cell activity and natural killer cell subsets among healthy nurses.

PubMed

Morikawa, Yuko; Kitaoka-Higashiguchi, Kazuyo; Tanimoto, Chie; Hayashi, Midori; Oketani, Reiko; Miura, Katsuyuki; Nishijo, Muneko; Nakagawa, Hideaki

2005-09-01

The present study investigated the effects of job stress on cellular immune function, such as NK cell activity and NK cell subsets. The participants were 61 female nurses aged 23-59, who worked in a public psychiatric hospital in Ishikawa, Japan. Each subject completed the Nursing Job Stressor Scale (NJSS) and their NK cell activity and lymphocyte surface antigens (CD16+56+) were evaluated as immune system parameters. The NJSS has seven subscales: conflict with other nursing staff, nursing role conflict, conflict with physicians or autonomy, conflict with death or dying, quantitative work load, qualitative work load and conflict with patients. Factors influencing NK cell activity, and the proportion and cell counts of CD16+56+ lymphocytes were evaluated. Increase in quantitative work load significantly decreased NK cell activity. Conversely, no linear relationship was observed between qualitative work load and immunological variables, with the highest percentage of CD16+56+ lymphocytes observed among participants in the medium work load group. The other five NJSS subscales did not relate to immune parameters. In conclusion, the results suggest that perceived job strains, particularly quantitative work load, decreased NK cell function.

Innovative Use of Quality Management Methods for Product Improvement

NASA Astrophysics Data System (ADS)

Midor, Katarzyna; Žarnovský, Jozef

2016-12-01

Organisations constantly look for new, innovative solutions and methods which could be used to improve their efficiency and increase the quality of their products. Identifying the causes for returns is an important issue for modern companies, as returns are the cause for the increase in production costs and, most importantly, the loss of credibility in the eyes of the client. Therefore, for the company to be able to sustain or strengthen its position on the market, it has to follow the rules of quality management. Especially important is the rule of constant improvement. This rule is primarily connected with preventing errors and defects from occurring at all the stages of the production process. To achieve that, one must, among other things, use quality management tools. The article presents an analysis of causes for returns of a vibrating screen produced by a company which manufactures machinery and equipment for the extractive industry, using quality management tools such as the Ishikawa diagram and Pareto analysis. The analysis allowed for the identification of the causes of client returns which could not be previously identified, and proposing solutions for them.

The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells.

PubMed

Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue; Wan, Xiao-Ping; He, Yin-Yan

2012-04-06

The selective ER modulator tamoxifen (TAM(1)) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17β-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus. Copyright © 2012 Elsevier Inc. All rights reserved.

Chemotherapeutic Effect of CD147 Antibody-labeled Micelles Encapsulating Doxorubicin Conjugate Targeting CD147-Expressing Carcinoma Cells.

PubMed

Asakura, Tadashi; Yokoyama, Masayuki; Shiraishi, Koichi; Aoki, Katsuhiko; Ohkawa, Kiyoshi

2018-03-01

CD147 (basigin/emmprin) is expressed on the surface of carcinoma cells. For studying the efficacy of CD147-targeting medicine on CD147-expressing cells, we studied the effect of anti-CD147-labeled polymeric micelles (CD147ab micelles) that encapsulated a conjugate of doxorubicin with glutathione (GSH-DXR), with specific accumulation and cytotoxicity against CD147-expressing A431 human epidermoid carcinoma cells, Ishikawa human endometrial adenocarcinoma cells, and PC3 human prostate carcinoma cells. By treatment of each cell type with CD147ab micelles for 1 h, a specific accumulation of CD147ab micelles in CD147-expressing cells was observed. In addition, the cytotoxicity of GSH-DXR-encapsulated micelles against each cell type was measured by treatment of the micelles for 1 h. The cytotoxic effect of CD147ab micelles carrying GSH-DXR was 3- to 10-fold higher for these cells than that of micelles without GSH-DXR. These results suggest that GSH-DXR-encapsulated CD147ab micelles could serve as an effective drug delivery system to CD147-expressing carcinoma cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Minimizing variability of cascade impaction measurements in inhalers and nebulizers.

PubMed

Bonam, Matthew; Christopher, David; Cipolla, David; Donovan, Brent; Goodwin, David; Holmes, Susan; Lyapustina, Svetlana; Mitchell, Jolyon; Nichols, Steve; Pettersson, Gunilla; Quale, Chris; Rao, Nagaraja; Singh, Dilraj; Tougas, Terrence; Van Oort, Mike; Walther, Bernd; Wyka, Bruce

2008-01-01

The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD).

Quality improvement primer part 1: Preparing for a quality improvement project in the emergency department.

PubMed

Chartier, Lucas B; Cheng, Amy H Y; Stang, Antonia S; Vaillancourt, Samuel

2018-01-01

Emergency medicine (EM) providers work in a fast-paced and often hectic environment that has a high risk for patient safety incidents and gaps in the quality of care. These challenges have resulted in opportunities for frontline EM providers to play a role in quality improvement (QI) projects. QI has developed into a mature field with methodologies that can dramatically improve the odds of having a successful project with a sustainable impact. However, this expertise is not yet commonly taught during professional training. In this first of three articles meant as a QI primer for EM clinicians, we will introduce QI methodology and strategic planning using a fictional case study as an example. We will review how to identify a QI problem, define components of an effective problem statement, and identify stakeholders and core change team members. We will also describe three techniques used to perform root cause analyses-Ishikawa diagrams, Pareto charts and process mapping-and how they relate to preparing for a QI project. The next two papers in this series will focus on the execution of the QI project itself using rapid-cycle testing and on the evaluation and sustainability of QI projects.

Improved Formula for the Stress Intensity Factor of Semi-Elliptical Surface Cracks in Welded Joints under Bending Stress

PubMed Central

Peng, Yang; Wu, Chao; Zheng, Yifu; Dong, Jun

2017-01-01

Welded joints are prone to fatigue cracking with the existence of welding defects and bending stress. Fracture mechanics is a useful approach in which the fatigue life of the welded joint can be predicted. The key challenge of such predictions using fracture mechanics is how to accurately calculate the stress intensity factor (SIF). An empirical formula for calculating the SIF of welded joints under bending stress was developed by Baik, Yamada and Ishikawa based on the hybrid method. However, when calculating the SIF of a semi-elliptical crack, this study found that the accuracy of the Baik-Yamada formula was poor when comparing the benchmark results, experimental data and numerical results. The reasons for the reduced accuracy of the Baik-Yamada formula were identified and discussed in this paper. Furthermore, a new correction factor was developed and added to the Baik-Yamada formula by using theoretical analysis and numerical regression. Finally, the predictions using the modified Baik-Yamada formula were compared with the benchmark results, experimental data and numerical results. It was found that the accuracy of the modified Baik-Yamada formula was greatly improved. Therefore, it is proposed that this modified formula is used to conveniently and accurately calculate the SIF of semi-elliptical cracks in welded joints under bending stress. PMID:28772527

On the road to a stronger public health workforce: visual tools to address complex challenges.

PubMed

Drehobl, Patricia; Stover, Beth H; Koo, Denise

2014-11-01

The public health workforce is vital to protecting the health and safety of the public, yet for years, state and local governmental public health agencies have reported substantial workforce losses and other challenges to the workforce that threaten the public's health. These challenges are complex, often involve multiple influencing or related causal factors, and demand comprehensive solutions. However, proposed solutions often focus on selected factors and might be fragmented rather than comprehensive. This paper describes approaches to characterizing the situation more comprehensively and includes two visual tools: (1) a fishbone, or Ishikawa, diagram that depicts multiple factors affecting the public health workforce; and (2) a roadmap that displays key elements-goals and strategies-to strengthen the public health workforce, thus moving from the problems depicted in the fishbone toward solutions. The visual tools aid thinking about ways to strengthen the public health workforce through collective solutions and to help leverage resources and build on each other's work. The strategic roadmap is intended to serve as a dynamic tool for partnership, prioritization, and gap assessment. These tools reflect and support CDC's commitment to working with partners on the highest priorities for strengthening the workforce to improve the public's health. Published by Elsevier Inc.

High-throughput screening and mechanism-based evaluation of estrogenic botanical extracts

PubMed Central

Overk, Cassia R.; Yao, Ping; Chen, Shaonong; Deng, Shixing; Imai, Ayano; Main, Matthew; Schinkovitz, Andreas; Farnsworth, Norman R.; Pauli, Guido F.; Bolton, Judy L.

2009-01-01

Symptoms associated with menopause can greatly affect the quality of life for women. Botanical dietary supplements have been viewed by the public as safe and effective despite a lack of evidence indicating a urgent necessity to standardize these supplements chemically and biologically. Seventeen plants were evaluated for estrogenic biological activity using standard assays: competitive estrogen receptor (ER) binding assay for both alpha and beta subtypes, transient transfection of the estrogen response element luciferase plasmid into MCF-7 cells expressing either ER alpha or ER beta, and the Ishikawa alkaline phosphatase induction assay for both estrogenic and antiestrogenic activities. Based on the combination of data pooled from these assays, the following was determined: a) a high rate of false positive activity for the competitive binding assays, b) some extracts had estrogenic activity despite a lack of ability to bind the ER, c) one extract exhibited selective estrogen receptor modulator (SERM) activity, and d) several extracts show additive/synergistic activity. Taken together, these data indicate a need to reprioritize the order in which the bioassays are performed for maximal efficiency of programs involving bioassay-guided fractionation. In addition, possible explanations for the conflicts in the literature over the estrogenicity of Cimicifuga racemosa (black cohosh) are suggested. PMID:18473738

Full genome analysis of bovine astrovirus from fecal samples of cattle in Japan: identification of possible interspecies transmission of bovine astrovirus.

PubMed

Nagai, Makoto; Omatsu, Tsutomu; Aoki, Hiroshi; Otomaru, Konosuke; Uto, Takehiko; Koizumi, Motoya; Minami-Fukuda, Fujiko; Takai, Hikaru; Murakami, Toshiaki; Masuda, Tsuneyuki; Yamasato, Hiroshi; Shiokawa, Mai; Tsuchiaka, Shinobu; Naoi, Yuki; Sano, Kaori; Okazaki, Sachiko; Katayama, Yukie; Oba, Mami; Furuya, Tetsuya; Shirai, Junsuke; Mizutani, Tetsuya

2015-10-01

A viral metagenomics approach was used to investigate fecal samples of Japanese calves with and without diarrhea. Of the different viral pathogens detected, read counts gave nearly complete astrovirus-related RNA sequences in 15 of the 146 fecal samples collected in three distinct areas (Hokkaido, Ishikawa, and Kagoshima Prefectures) between 2009 and 2015. Due to the lack of genetic information about bovine astroviruses (BoAstVs) in Japan, these sequences were analyzed in this study. Nine of the 15 Japanese BoAstVs were closely related to Chinese BoAstVs and clustered into a lineage (tentatively named lineage 1) in all phylogenetic trees. Three of 15 strains were phylogenetically separate from lineage 1, showing low sequence identities, and clustered instead with an American strain isolated from cattle with respiratory disease (tentatively named lineage 2). Interestingly, two of 15 strains clustered with lineage 1 in the open reading frame (ORF)1a and ORF1b regions, while they clustered with lineage 2 in the ORF2 region. Remarkably, one of 15 strains exhibited low amino acid sequence similarity to other BoAstVs and was clustered separately with porcine astrovirus type 5 in all trees, and ovine astrovirus in the ORF2 region, suggesting past interspecies transmission.

Prostaglandin E2 mediates phosphorylation and down-regulation of the tuberous sclerosis-2 tumor suppressor (tuberin) in human endometrial adenocarcinoma cells via the Akt signaling pathway.

PubMed

Sales, Kurt J; Battersby, Sharon; Williams, Alistair R W; Anderson, Richard A; Jabbour, Henry N

2004-12-01

Prostaglandin (PG) E2 promotes tumor growth via interaction with its G protein-coupled receptors and activation of intracellular signaling. Tuberous sclerosis 2 (tuberin) is a tumor suppressor, which negatively regulates cell growth. Its phosphorylation results in its inactivation and targeted down- regulation, thus lifting the growth inhibition effects. This study investigated the expression and localization of tuberin in neoplastic and normal endometrium and the effect of PGE2 on phosphorylation of tuberin via the Akt pathway. Quantitative RT-PCR and Western blot analysis demonstrated reduced expression of tuberin in neoplastic tissue, compared with normal endometrial tissue. Tuberin expression was localized by immunohistochemistry to the glandular epithelial compartment in neoplastic and normal endometrium. We investigated the effect of PGE2 on phosphorylation of tuberin via the Akt pathway. Treatment of neoplastic and normal endometrium with 100 nm PGE2 enhanced phosphorylated tuberin immunoreactivity in the glandular epithelium. PGE2 also phosphorylated Akt and tuberin in Ishikawa endometrial adenocarcinoma cells, leading to a reduction in expression of total tuberin protein. Cotreatment of cells with wortmannin or LY294002 inhibited the PGE2-induced phosphorylation of Akt and tuberin. These data suggest that PGE2 signaling may promote endometrial tumorigenesis by inactivation of tuberin after its phosphorylation via the Akt signaling pathway.

Examination of the relationship between the working conditions of young workers and the content of the meals they buy at convenience stores.

PubMed

Miyagoshi, Miki; Otsuka, Mika; Kato, Megumi; Kubo, Chiharu; Tsuchihashi, Kayoko; Toyoshima, Hiromi; Miyazaki, Eriko; Yoshie, Ayumu; Okura, Mika; Omote, Shizuko; Kido, Teruhiko

2008-05-01

The aim of this study was to investigate the relationship between the working conditions of young workers and the meals they buy at convenience stores, and to consider the prevention of obesity. The subjects of this study were 284 workers under 29 yr of age employed at a transportation company in Ishikawa prefecture. Questionnaires were sent to participants, and 193 valid responses were obtained. Working types, night duty and working time were correlated with convenience store patronage, although working situations were not obviously associated with the content of meal selection at convenience stores. The study results revealed a tendency for the proportion of the fat in meals to be greater than 25% for the majority of working situations. It was also shown that foods selected with high frequency contained a high proportion of fat. There results suggest that this situation increases the risk of obesity. In addition, the more days per week convenience stores were patronized, the greater the number of participants felt "The need to improve meals." Therefore, we believe it is essential that young workers consider the prevention of obesity by observing nutritional information when selecting foods. An environment in which such information is easy to obtain at convenience stores should be arranged.

Estrogen Receptor (ER) Subtype Selectivity Identifies 8-Prenylapigenin as an ERβ Agonist from Glycyrrhiza inflata and Highlights the Importance of Chemical and Biological Authentication.

PubMed

Hajirahimkhan, Atieh; Mbachu, Obinna; Simmler, Charlotte; Ellis, Sarah G; Dong, Huali; Nikolic, Dejan; Lankin, David C; van Breemen, Richard B; Chen, Shao-Nong; Pauli, Guido F; Dietz, Birgit M; Bolton, Judy L

2018-04-27

Postmenopausal women are increasingly using botanicals for menopausal symptom relief due to the increased breast cancer risk associated with traditional estrogen therapy. The deleterious effects of estrogens are associated with estrogen receptor (ER)α-dependent proliferation, while ERβ activation could enhance safety by opposing ERα effects. Three medicinal licorice species, Glycyrrhiza glabra ( G. glabra), G. uralensis, and G. inflata, were studied for their differential estrogenic efficacy. The data showed higher estrogenic potency for G. inflata in an alkaline phosphatase induction assay in Ishikawa cells (ERα) and an estrogen responsive element (ERE)-luciferase assay in MDA-MB-231/β41 breast cancer cells (ERβ). Bioassay-guided fractionation of G. inflata led to the isolation of 8-prenylapigenin (3). Surprisingly, a commercial batch of 3 was devoid of estrogenic activity. Quality control by MS and qNMR revealed an incorrect compound, 4'- O-methylbroussochalcone B (10), illustrating the importance of both structural and purity verification prior to any biological investigations. Authentic and pure 3 displayed 14-fold preferential ERβ agonist activity. Quantitative analyses revealed that 3 was 33 times more concentrated in G. inflata compared to the other medicinal licorice extracts. These data suggest that standardization of G. inflata to 3 might enhance the safety and efficacy of G. inflata supplements used for postmenopausal women's health.

Functional evaluation of synthetic flavonoids and chalcones for potential antiviral and anticancer properties.

PubMed

Mateeva, Nelly; Eyunni, Suresh V K; Redda, Kinfe K; Ononuju, Ucheze; Hansberry, Tony D; Aikens, Cecilia; Nag, Anita

2017-06-01

Flavonoids, stilbenes, and chalcones are plant secondary metabolites that often possess diverse biological activities including anti-inflammatory, anti-cancer, and anti-viral activities. The wide range of bioactivities poses a challenge to identify their targets. Here, we studied a set of synthetically generated flavonoids and chalcones to evaluate for their biological activity, and compared similarly substituted flavonoids and chalcones. Substituted chalcones, but not flavonoids, showed inhibition of viral translation without significantly affecting viral replication in cells infected with hepatitis C virus (HCV). We suggest that the chalcones used in this study inhibit mammalian target of rapamycin (mTOR) pathway by ablating phosphorylation of ribosomal protein 6 (rps6), and also the kinase necessary for phosphorylating rps6 in Huh7.5 cells (pS6K1). In addition, selected chalcones showed inhibition of growth in Ishikawa, MCF7, and MDA-MB-231 cells resulting an IC 50 of 1-6µg/mL. When similarly substituted flavonoids were used against the same set of cancer cells, we did not observe any inhibitory effect. Together, we report that chalcones show potential for anti-viral and anti-cancer activities compared to similarly substituted flavonoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

Root Cause Analysis: Learning from Adverse Safety Events.

PubMed

Brook, Olga R; Kruskal, Jonathan B; Eisenberg, Ronald L; Larson, David B

2015-10-01

Serious adverse events continue to occur in clinical practice, despite our best preventive efforts. It is essential that radiologists, both as individuals and as a part of organizations, learn from such events and make appropriate changes to decrease the likelihood that such events will recur. Root cause analysis (RCA) is a process to (a) identify factors that underlie variation in performance or that predispose an event toward undesired outcomes and (b) allow for development of effective strategies to decrease the likelihood of similar adverse events occurring in the future. An RCA process should be performed within the environment of a culture of safety, focusing on underlying system contributors and, in a confidential manner, taking into account the emotional effects on the staff involved. The Joint Commission now requires that a credible RCA be performed within 45 days for all sentinel or major adverse events, emphasizing the need for all radiologists to understand the processes with which an effective RCA can be performed. Several RCA-related tools that have been found to be useful in the radiology setting include the "five whys" approach to determine causation; cause-and-effect, or Ishikawa, diagrams; causal tree mapping; affinity diagrams; and Pareto charts. © RSNA, 2015.

Improving patient access to an interventional US clinic.

PubMed

Steele, Joseph R; Clarke, Ryan K; Terrell, John A; Brightmon, Tonya R

2014-01-01

A continuous quality improvement project was conducted to increase patient access to a neurointerventional ultrasonography (US) clinic. The clinic was experiencing major scheduling delays because of an increasing patient volume. A multidisciplinary team was formed that included schedulers, medical assistants, nurses, technologists, and physicians. The team created an Ishikawa diagram of the possible causes of the long wait time to the next available appointment and developed a flowchart of the steps involved in scheduling and completing a diagnostic US examination and biopsy. The team then implemented a staged intervention that included adjustments to staffing and room use (stage 1); new procedures for scheduling same-day add-on appointments (stage 2); and a lead technician rotation to optimize patient flow, staffing, and workflow (stage 3). Six months after initiation of the intervention, the mean time to the next available appointment had decreased from 25 days at baseline to 1 day, and the number of available daily appointments had increased from 38 to 55. These improvements resulted from a coordinated provider effort and had a net present value of more than $275,000. This project demonstrates that structural changes in staffing, workflow, and room use can substantially reduce scheduling delays for critical imaging procedures. © RSNA, 2014.

Mapping care processes within a hospital: from theory to a web-based proposal merging enterprise modelling and ISO normative principles.

PubMed

Staccini, Pascal; Joubert, Michel; Quaranta, Jean-François; Fieschi, Marius

2005-03-01

Today, the economic and regulatory environment, involving activity-based and prospective payment systems, healthcare quality and risk analysis, traceability of the acts performed and evaluation of care practices, accounts for the current interest in clinical and hospital information systems. The structured gathering of information relative to users' needs and system requirements is fundamental when installing such systems. This stage takes time and is generally misconstrued by caregivers and is of limited efficacy to analysts. We used a modelling technique designed for manufacturing processes (IDEF0/SADT). We enhanced the basic model of an activity with descriptors extracted from the Ishikawa cause-and-effect diagram (methods, men, materials, machines, and environment). We proposed an object data model of a process and its components, and programmed a web-based tool in an object-oriented environment. This tool makes it possible to extract the data dictionary of a given process from the description of its elements and to locate documents (procedures, recommendations, instructions) according to each activity or role. Aimed at structuring needs and storing information provided by directly involved teams regarding the workings of an institution (or at least part of it), the process-mapping approach has an important contribution to make in the analysis of clinical information systems.

Estradiol and tamoxifen induce cell migration through GPR30 and activation of focal adhesion kinase (FAK) in endometrial cancers with low or without nuclear estrogen receptor α (ERα).

PubMed

Tsai, Chia-Lung; Wu, Hsien-Ming; Lin, Chiao-Yun; Lin, Yi-Jun; Chao, Angel; Wang, Tzu-Hao; Hsueh, Swei; Lai, Chyong-Huey; Wang, Hsin-Shih

2013-01-01

Estrogens and tamoxifen (an antiestrogen) exert their actions by activation of estrogen receptor (ER) through genomic and non-genomic mechanisms and are implicated in the development of endometrial cancer. Previous reports have demonstrated that estradiol and tamoxifen induce proliferation of human endometrial cancer cells through GPR30 (non-genomic ER) signaling pathway. Herein, we demonstrate that phosphorylation of focal adhesion kinase (FAK) is involved in cell migration induced by estradiol, tamoxifen and G1 (a GPR30 agonist) through the transmembrane ER (GPR30) in endometrial cancer cell lines with or without ERα (Ishikawa and RL95-2). Additionally, the GPR30-mediated cell migration was further abolished by administration of either specific RNA interference targeting GPR30 or an FAK inhibitor. Moreover, we have validated that the signaling between GPR30 and phosphorylated FAK is indeed mediated by the EGFR/PI3K/ERK pathway. Clinically, a significant correlation between levels of GPR30 and phophorylated FAK (pFAK) observed in human endometrial cancer tissues with low or without ERα further suggested that estrogen-induced phosphorylation of FAK and cell migration were most likely triggered by GPR30 activation. These results provided new insights for understanding the pathophysiological functions of GPR30 in human endometrial cancers.

Soft X-ray study of solar wind charge exchange from the Earth's magnetosphere : Suzaku observations and a future X-ray imaging mission concept

NASA Astrophysics Data System (ADS)

Ezoe, Y.; Ishisaki, Y.; Ohashi, T.; Ishikawa, K.; Miyoshi, Y.; Fujimoto, R.; Terada, N.; Kasahara, S.; Fujimoto, M.; Mitsuda, K.; Nishijo, K.; Noda, A.

2013-12-01

Soft X-ray observations of solar wind charge exchange (SWCX) emission from the Earth's magnetosphere using the Japanese X-ray astronomy satellite Suzaku are shown, together with our X-ray imaging mission concept to characterize the solar wind interaction with the magnetosphere. In recent years, the SWCX emission from the Earth's magnetosphere, originally discovered as unexplained noise during the soft X-ray all sky survey (Snowden et al. 1994), is receiving increased attention on studying geospace. The SWCX is a reaction between neutrals in exosphere and highly charged ions in the magnetosphere originated from solar wind. Robertson et al. (2005) modeled the SWCX emission as seen from an observation point 50 Re from Earth. In the resulting X-ray intensities, the magnetopause, bow shock and cusp were clearly visible. High sensitivity soft X-ray observation with CCDs onboard recent X-ray astronomy satellites enables us to resolve SWCX emission lines and investigate time correlation with solar wind as observed with ACE and WIND more accurately. Suzaku is the 5th Japanese X-ray astronomy satellite launched in 2005. The line of sight direction through cusp is observable, while constraints on Earth limb avoidance angle of other satellites often limits observable regions. Suzaku firstly detected the SWCX emission while pointing in the direction of the north ecliptic pole (Fujimoto et al. 2007). Using the Tsyganenko 1996 magnetic field model, the distance to the nearest SWCX region was estimated as 2-8 Re, implying that the line of sight direction can be through magnetospheric cusp. Ezoe et al. (2010) reported SWCX events toward the sub-solar side of the magnetosheath. These cusp and sub-solar side magnetosheath regions are predicted to show high SWCX fluxes by Robertson et al. (2005). On the other hand, Ishikawa et al. (2013) discovered a similarly strong SWCX event when the line of sight direction did not transverse these two regions. Motivated by these detections

Scoring and ranking of metabolic trees to computationally ...

EPA Pesticide Factsheets

Increasing awareness about endocrine disrupting chemicals (EDCs) in the environment has driven concern about their potential impact on human health and wildlife. Tens of thousands of natural and synthetic xenobiotics are presently in commerce with little to no toxicity data and therefore uncertainty about their impact on estrogen receptor (ER) signaling pathways and other toxicity endpoints. As such, there is a need for strategies that make use of available data to prioritize chemicals for testing. One of the major achievements within the EPA’s Endocrine Disruptor Screening Program (EDSP), was the network model combining 18 ER in vitro assays from ToxCast to predict in vivo estrogenic activity. This model overcomes the limitations of single in vitro assays at different steps of the ER pathway. However, it lacks many relevant features required to estimate safe exposure levels and the composite assays do not consider the complex metabolic processes that might produce bioactive entities in a living system. This problem is typically addressed using in vivo assays. The aim of this work is to design a computational and in vitro approach to prioritize compounds and perform a quantitative safety assessment. To this end, we pursue a tiered approach taking into account bioactivity and bioavailability of chemicals and their metabolites using a human uterine epithelial cell (Ishikawa)-based assay. This biologically relevant fit-for-purpose assay was designed to quantitati

Purification and cDNA cloning of a protein derived from Flammulina velutipes that increases the permeability of the intestinal Caco-2 cell monolayer.

PubMed

Watanabe, H; Narai, A; Shimizu, M

1999-06-01

A new protein that decreases transepithelial electrical resistance (TEER) in the human intestinal Caco-2 cell monolayer was found in a water-soluble fraction of the mushroom Flammulina velutipes. This protein, termed TEER-decreasing protein (TDP), is not cytotoxic and does not induce cell detachment, but rapidly increases the tight junctional permeability for water-soluble marker substances such as Lucifer Yellow CH (Mr 457) through the paracellular pathway. TDP was isolated and purified from the aqueous extract of F. velutipes by chromatographic means. Purified TDP was found to be a simple, nonglycosylated protein without intermolecular disulfide bonds, and the apparent molecular mass as estimated by SDS/PAGE and gel filtration is 30 kDa. It was revealed that the N-terminal amino-acid sequence of purified TDP is identical to the recently reported N-terminal sequence of flammutoxin, a membrane-perturbing hemolytic protein, for which the complete primary structure has not yet been reported [Tomita, T., Ishikawa, D., Noguchi, T., Katayama, E., and Hashimoto, Y. (1998) Biochem. J. 333, 24794-24799]. The cDNA coding for TDP was cloned by 5' and 3' rapid amplification of cDNA ends. The ORF encodes a protein with 272 amino-acid residues showing no homology to known proteins. Relevant studies using TDP cDNA will provide insight into the structure-function relationships of membrane pore-forming toxins.

The Setting is the Service: How the Architecture of Sober Living Residences Supports Community Based Recovery

PubMed Central

Wittman, Fried; Jee, Babette; Polcin, Douglas L.; Henderson, Diane

2014-01-01

The architecture of residential recovery settings is an important silent partner in the alcohol/drug recovery field. The settings significantly support or hinder recovery experiences of residents, and shape community reactions to the presence of sober living houses (SLH) in ordinary neighborhoods. Grounded in the principles of Alcoholics Anonymous, the SLH provides residents with settings designed to support peer based recovery; further, these settings operate in a community context that insists on sobriety and strongly encourages attendance at 12-step meetings. Little formal research has been conducted to show how architectural features of the recovery setting – building appearance, spatial layouts, furnishings and finishes, policies for use of the facilities, physical care and maintenance of the property, neighborhood features, aspects of location in the city – function to promote (or retard) recovery, and to build (or detract from) community support. This paper uses a case-study approach to analyze the architecture of a community-based residential recovery service that has demonstrated successful recovery outcomes for its residents, is popular in its community, and has achieved state-wide recognition. The Environmental Pattern Language (Alexander, Ishikawa, & Silverstein, 1977) is used to analyze its architecture in a format that can be tested, critiqued, and adapted for use by similar programs in many communities, providing a model for replication and further research. PMID:25328377

The Setting is the Service: How the Architecture of Sober Living Residences Supports Community Based Recovery.

PubMed

Wittman, Fried; Jee, Babette; Polcin, Douglas L; Henderson, Diane

2014-07-01

The architecture of residential recovery settings is an important silent partner in the alcohol/drug recovery field. The settings significantly support or hinder recovery experiences of residents, and shape community reactions to the presence of sober living houses (SLH) in ordinary neighborhoods. Grounded in the principles of Alcoholics Anonymous, the SLH provides residents with settings designed to support peer based recovery; further, these settings operate in a community context that insists on sobriety and strongly encourages attendance at 12-step meetings. Little formal research has been conducted to show how architectural features of the recovery setting - building appearance, spatial layouts, furnishings and finishes, policies for use of the facilities, physical care and maintenance of the property, neighborhood features, aspects of location in the city - function to promote (or retard) recovery, and to build (or detract from) community support. This paper uses a case-study approach to analyze the architecture of a community-based residential recovery service that has demonstrated successful recovery outcomes for its residents, is popular in its community, and has achieved state-wide recognition. The Environmental Pattern Language (Alexander, Ishikawa, & Silverstein, 1977) is used to analyze its architecture in a format that can be tested, critiqued, and adapted for use by similar programs in many communities, providing a model for replication and further research.

Estrogen effects of Daldinia concentrica and Psathyrella efflorescens extracts in vitro.

PubMed

Benie, Tanon; Kouakou, Koffi; Thieulant, Marie-Lise

2008-02-28

Daldinia concentrica and Psathyrella efflorescens are two fungi used in African traditional medicine. In the present study, their extracts were evaluated for their steroid activities in estrogen- or androgen-dependent cell lines using as endpoints steroid-dependent transcriptional activity and cell proliferation. Treatment of human breast cancer MCF-7 cells with 15 or 30 microg/ml of Daldinia concentrica or Psathyrellaefflorescens extracts in the absence of 17beta-estradiol (E2) significantly increased the transcriptional activity of an estrogen receptor (ER)-dependent reporter gene, in the same range as E2. Similar data were obtained in gonadotrope cell line alpha-T3-1. All the effects were prevented by the pure estrogen antagonist, ICI 182,780. In the absence of steroid addition, the two extracts induced cell proliferation of ER-dependent MCF-7 and Ishikawa Var-I cell lines by approximately 100% of the E2 response. Combination treatments with E2 showed no competitive or additive effects in the two latter cell lines. Interestingly, the extracts had no androgen-like response in androgen receptor (AR)-positive and ER-negative MDA-MB231 cells, suggesting that fungi effects are estrogen specific and extracts are not toxic at used concentrations. Results provided evidence that Daldinia concentrica or Psathyrellaefflorescens extracts induce estrogen-like effects in ER-positive cell lines, which could be responsible of the effects observed in vivo.

Interferometric imaging of acoustical phenomena using high-speed polarization camera and 4-step parallel phase-shifting technique

NASA Astrophysics Data System (ADS)

Ishikawa, K.; Yatabe, K.; Ikeda, Y.; Oikawa, Y.; Onuma, T.; Niwa, H.; Yoshii, M.

2017-02-01

Imaging of sound aids the understanding of the acoustical phenomena such as propagation, reflection, and diffraction, which is strongly required for various acoustical applications. The imaging of sound is commonly done by using a microphone array, whereas optical methods have recently been interested due to its contactless nature. The optical measurement of sound utilizes the phase modulation of light caused by sound. Since light propagated through a sound field changes its phase as proportional to the sound pressure, optical phase measurement technique can be used for the sound measurement. Several methods including laser Doppler vibrometry and Schlieren method have been proposed for that purpose. However, the sensitivities of the methods become lower as a frequency of sound decreases. In contrast, since the sensitivities of the phase-shifting technique do not depend on the frequencies of sounds, that technique is suitable for the imaging of sounds in the low-frequency range. The principle of imaging of sound using parallel phase-shifting interferometry was reported by the authors (K. Ishikawa et al., Optics Express, 2016). The measurement system consists of a high-speed polarization camera made by Photron Ltd., and a polarization interferometer. This paper reviews the principle briefly and demonstrates the high-speed imaging of acoustical phenomena. The results suggest that the proposed system can be applied to various industrial problems in acoustical engineering.

An integrated, quality by design (QbD) approach for design, development and optimization of orally disintegrating tablet formulation of carbamazepine.

PubMed

Mishra, Saurabh M; Rohera, Bhagwan D

2017-11-01

The objective of the present study was to design and develop a formulation for orally disintegrating tablets (ODTs) of carbamazepine using quality by design principles. The target product profile (TPP) and quality target product profile (QTPP) of ODTs were identified. Risk assessment was carried out by leveraging prior knowledge and experience to define the criticality of factors based on their impact by Ishikawa fishbone diagram and preliminary hazard analysis tool. Box-Behnken response surface methodology was used to study the effect of critical factors on various attributes of ODTs. The independent factors selected were compression pressure (X 1 ), concentration of sublimating agent (volatile material) (X 2 ), disintegrant concentration (X 3 ) and the responses were tablet crushing strength, tablet porosity, disintegration time, water absorption time, tablet friability and drug dissolution. ANOVA and lack of fit test illustrated that selected independent variables had significant effect on the response variables, and excellent correlation was observed between actual and predicted values. Optimization by desirability function indicated that compression pressure, X 1 (1534 lbs), ammonium bicarbonate concentration, X 2 (7.68%) and Kollidon ® CL-SF concentration, X 3 (6%) were optimum to prepare ODT formulation of carbamazepine of desired attributes complying with QTPP. Thus, in the present study, a high level of assurance was established for ODT product quality and performance.

The Faculties of Pharmacy Schools Should Make an Effort to Network with Community Pharmacies.

PubMed

Matsushita, Ryo

2016-01-01

By law, medical faculties are mandated to have a designated partner hospital for the purposes of student practical training. In contrast, pharmacy faculties do not have such a legal requirement for student training in a community pharmacy setting. Nevertheless, there are several public and private universities that do have community pharmacies. However, there is no national university that has established both an educational hospital and a community pharmacy. When Kanazawa University (KU) established a graduate school with a clinical pharmacy course, the faculty of KU deemed it necessary to set up an independent community pharmacy for the purpose of practical training. Thus, in 2003, the Acanthus Pharmacy was set up as the first educational community pharmacy in Japan, managed by a nonprofit organization, with the permission of the Ishikawa Pharmaceutical Association and local community pharmacists. Since that time, Acanthus has managed a clinical pharmacy practice for students from both the undergraduate and graduate schools of KU. From 2006, the undergraduate pharmacy program was changed to a 6-year program, and the Acanthus Pharmacy has continued its roles in educating undergraduate pharmaceutical students, medical students, and as a site of early exposure for KU freshmen. From our experience, it is important to have a real clinical environment available to university pharmacy faculty and students, especially in training for community pharmacy practices.

Evaluating the Properties of Poly(lactic-co-glycolic acid) Nanoparticle Formulations Encapsulating a Hydrophobic Drug by Using the Quality by Design Approach.

PubMed

Kozaki, Masato; Kobayashi, Shin-Ichiro; Goda, Yukihiro; Okuda, Haruhiro; Sakai-Kato, Kumiko

2017-01-01

We applied the Quality by Design (QbD) approach to the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticle formulations encapsulating triamcinolone acetonide, and the critical process parameters (CPPs) were identified to clarify the correlations between critical quality attributes and CPPs. Quality risk management was performed by using an Ishikawa diagram and experiments with a fractional factorial design (ANOVA). The CPPs for particle size were PLGA concentration and rotation speed, and the CPP for relative drug loading efficiency was the poor solvent to good solvent volume ratio. By assessing the mutually related factors in the form of ratios, many factors could be efficiently considered in the risk assessment. We found a two-factor interaction between rotation speed and rate of addition of good solvent by using a fractional factorial design with resolution V. The system was then extended by using a central composite design, and the results obtained were visualized by using the response surface method to construct a design space. Our research represents a case study of the application of the QbD approach to pharmaceutical development, including formulation screening, by taking actual production factors into consideration. Our findings support the feasibility of using a similar approach to nanoparticle formulations under development. We could establish an efficient method of analyzing the CPPs of PLGA nanoparticles by using a QbD approach.

Solving the worldwide emergency department crowding problem - what can we learn from an Israeli ED?

PubMed

Pines, Jesse M; Bernstein, Steven L

2015-01-01

ED crowding is a prevalent and important issue facing hospitals in Israel and around the world, including North and South America, Europe, Australia, Asia and Africa. ED crowding is associated with poorer quality of care and poorer health outcomes, along with extended waits for care. Crowding is caused by a periodic mismatch between the supply of ED and hospital resources and the demand for patient care. In a recent article in the Israel Journal of Health Policy Research, Bashkin et al. present an Ishikawa diagram describing several factors related to longer length of stay (LOS), and higher levels of ED crowding, including management, process, environmental, human factors, and resource issues. Several solutions exist to reduce ED crowding, which involve addressing several of the issues identified by Bashkin et al. This includes reducing the demand for and variation in care, and better matching the supply of resources to demands in care in real time. However, what is needed to reduce crowding is an institutional imperative from senior leadership, implemented by engaged ED and hospital leadership with multi-disciplinary cross-unit collaboration, sufficient resources to implement effective interventions, access to data, and a sustained commitment over time. This may move the culture of a hospital to facilitate improved flow within and across units and ultimately improve quality and safety over the long-term.

QbD for pediatric oral lyophilisates development: risk assessment followed by screening and optimization.

PubMed

Casian, Tibor; Iurian, Sonia; Bogdan, Catalina; Rus, Lucia; Moldovan, Mirela; Tomuta, Ioan

2017-12-01

This study proposed the development of oral lyophilisates with respect to pediatric medicine development guidelines, by applying risk management strategies and DoE as an integrated QbD approach. Product critical quality attributes were overviewed by generating Ishikawa diagrams for risk assessment purposes, considering process, formulation and methodology related parameters. Failure Mode Effect Analysis was applied to highlight critical formulation and process parameters with an increased probability of occurrence and with a high impact on the product performance. To investigate the effect of qualitative and quantitative formulation variables D-optimal designs were used for screening and optimization purposes. Process parameters related to suspension preparation and lyophilization were classified as significant factors, and were controlled by implementing risk mitigation strategies. Both quantitative and qualitative formulation variables introduced in the experimental design influenced the product's disintegration time, mechanical resistance and dissolution properties selected as CQAs. The optimum formulation selected through Design Space presented ultra-fast disintegration time (5 seconds), a good dissolution rate (above 90%) combined with a high mechanical resistance (above 600 g load). Combining FMEA and DoE allowed the science based development of a product with respect to the defined quality target profile by providing better insights on the relevant parameters throughout development process. The utility of risk management tools in pharmaceutical development was demonstrated.

Time-Reversal Symmetry Breaking and Consequent Physical Responses Induced by All-In-All-Out Type Magnetic Order on the Pyrochlore Lattice

NASA Astrophysics Data System (ADS)

Arima, Taka-Hisa

2014-03-01

Pyrochlore-type 5d transition-metal oxide compounds Cd2Os2O7 and R2Ir2O7 (R =rare earth) undergo a metal-insulator transition accompanied by a magnetic transition. Recently, the magnetic structures of Cd2Os2O7 and Eu2Ir2O7 were investigated by means of resonant x-ray magnetic scattering. The x-ray data indicated the all-in/all-out type magnetic order. The all-in/all-out order breaks the time-reversal symmetry, while the spontaneous magnetization is essentially absent. The magnetic order can be viewed as ferroic magnetic octupolar order. The magnetic order is expected to provide several unique physical properties like quadratic magnetization. linear magneto-capacitance, linear magneto-resistance, linear magneto-mechanical coupling and so on. The symmetry breaking results in two non-equivalent domains, ``all-in/all-out'' and ``all-out/all-in.'' Interestingly, some theoretical works predict that a peculiar metallic state would appear on the domain wall. The observation and control of the domain distribution are essential for studying verious exotic physical responses. We have developed an x-ray technique for domain imaging and started studying the effects of external stimuli on the domain distribution. This work was performed in collaboration with S. Tardif, S. Takeshita, H. Ohsumi, D. Uematsu, H. Sagayama, J. J. Ishikawa, S. Nakatsuji, J. Yamaura, and Z. Hiroi.

Rural-Urban Disparity in Emergency Care for Acute Myocardial Infarction in Japan.

PubMed

Masuda, Jun; Kishi, Mikio; Kumagai, Naoto; Yamazaki, Toru; Sakata, Kenji; Higuma, Takumi; Ogimoto, Akiyoshi; Dohi, Kaoru; Tanigawa, Takashi; Hanada, Hiroyuki; Nakamura, Mashio; Sokejima, Shigeru; Takayama, Morimasa; Higaki, Jitsuo; Yamagishi, Masakazu; Okumura, Ken; Ito, Masaaki

2018-05-25

There are few reports examining regional differences between rural prefectures and metropolitan areas in the management of acute myocardial infarction (AMI) in Japan.Methods and Results:In the Rural AMI registry, a prospective, multi-prefectural registry of AMI in 4 rural prefectures (Ishikawa, Aomori, Ehime and Mie), a total of 1,695 consecutive AMI patients were registered in 2013. Among them, 1,313 patients who underwent primary percutaneous coronary intervention (PPCI) within 24 h of onset were enrolled in this study (Rural group), and compared with the cohort data from the Tokyo CCU Network registry for AMI in the same period (Metropolitan group, 2,075 patients). The prevalence of direct ambulance transport to PCI-capable facilities in the Rural group was significantly lower than that in the Metropolitan group (43.8% vs. 60.3%, P<0.01), which resulted in a longer onset-to-balloon time (OTB: 225 vs. 210 min, P=0.02) and lower prevalence of PPCI in a timely fashion (OTB ≤2 h: 11.5% vs. 20.7%, P<0.01) in the Rural group. Multivariate analysis revealed that direct ambulance transport was the strongest predictor for PPCI in a timely fashion (odds ratio=4.13, P<0.001). AMI patients in rural areas were less likely to be transported directly to PCI-capable facilities, resulting in time delay to PPCI compared with those in metropolitan areas.

Development and evaluation of paclitaxel nanoparticles using a quality-by-design approach.

PubMed

Yerlikaya, Firat; Ozgen, Aysegul; Vural, Imran; Guven, Olgun; Karaagaoglu, Ergun; Khan, Mansoor A; Capan, Yilmaz

2013-10-01

The aims of this study were to develop and characterize paclitaxel nanoparticles, to identify and control critical sources of variability in the process, and to understand the impact of formulation and process parameters on the critical quality attributes (CQAs) using a quality-by-design (QbD) approach. For this, a risk assessment study was performed with various formulation and process parameters to determine their impact on CQAs of nanoparticles, which were determined to be average particle size, zeta potential, and encapsulation efficiency. Potential risk factors were identified using an Ishikawa diagram and screened by Plackett-Burman design and finally nanoparticles were optimized using Box-Behnken design. The optimized formulation was further characterized by Fourier transform infrared spectroscopy, X-ray diffractometry, differential scanning calorimetry, scanning electron microscopy, atomic force microscopy, and gas chromatography. It was observed that paclitaxel transformed from crystalline state to amorphous state while totally encapsulating into the nanoparticles. The nanoparticles were spherical, smooth, and homogenous with no dichloromethane residue. In vitro cytotoxicity test showed that the developed nanoparticles are more efficient than free paclitaxel in terms of antitumor activity (more than 25%). In conclusion, this study demonstrated that understanding formulation and process parameters with the philosophy of QbD is useful for the optimization of complex drug delivery systems. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Answer to the dynamic (fretting effect) and static (oxide) behavior of electric contact surfaces: based on a five-year infrared thermographic study

NASA Astrophysics Data System (ADS)

Paez-Leon, Cristobal D.; Patino, Antonio R.; Aguillon, Luis

1991-03-01

This paper describes the results of a five-year study carried out in 38 power substations (230, 115, 34.5 and 13.8 Kv), located in the Western power electric system of CADAFE (Venezuela's national Electric Utility). A total of 154 hot spots were found between 1980 and 1982, a time span considered a reliable source of information in connection with methodology, term and results. The distribution of hot spots found during those years was 77, 33 and 44. The reduction of the spot/substation parameter was found to be 4.1, 3.3 and 3.1, respectively. Every item detected could have been the cause of major interruptions, locally and regionally, or even the system's blackout. The methodology used to determine the major concentration of findings and their location on the equipment, followed the sequence of Pareto's Diagram and Ishikawa's Graphic. Based on the results of the study whose results are presented here, a lubricant and compound-aid connector for Al-Al and bimetallic electric connections was formulated, developed, manufactured, tested (at IREQ laboratories) and traded (CONECTECH CAC- 01). To date, the whole process represents 12 years of work. The connector's behavior and reliability are being tested throughout Venezuela's national electric system (responsible for the supply of around 50,000 Gwh/year) with the use of 12 Tons of CONECTECH CAC-01.

Expression and function of activin receptors in human endometrial adenocarcinoma cells.

PubMed

Tanaka, Tetsuji; Toujima, Saori; Otani, Tsutomu; Minami, Sawako; Yamoto, Mareo; Umesaki, Naohiko

2003-09-01

Menstrual cycle-dependent expressions of activin A in normal human endometrial tissues have been reported. Expression of activin receptor mRNAs and increased activin A production were also observed in human endometrial adenocarcinoma tissues, suggesting that activin A might enhance cell proliferation and inhibit apoptotic signaling in endometrial cancer cells. In this study, we have examined the effects of activin A on cell proliferation, anticancer drug-induced apoptosis and Fas-mediated apoptosis in 3 differentiated human endometrial adenocarcinoma cell lines, namely HEC-1, HHUA and Ishikawa. Flow cytometric analyses revealed moderate expressions of all 4 types of activin receptor subunits on the cell surfaces of the 3 cell lines. The proliferations of the 3 endometrial cancer cells were completely unaffected by activin A, whereas it suppressed the cell proliferation of a human ovarian endometrioid adenocarcinoma cell line, OVK-18, in a dose-dependent manner. Moreover, activin A did not affect the apoptotic changes in the 3 endometrial adenocarcinoma cells treated with 4 different anticancer drugs, namely CDDP, paclitaxel, etoposide and SN38. The apoptotic changes in HHUA cells treated with anti-Fas IgM were also unaffected by activin A. These results indicate that the increased activin A production in human endometrial adenocarcinoma tissues in vivo may not stimulate carcinoma cell proliferation or inhibit apoptotic signaling in carcinoma cells. Insensitivity to the usual growth suppression signals induced by activin A might be one of the mechanisms of immortality of human endometrial adenocarcinoma cells.

CD147 Induces Epithelial-to-Mesenchymal Transition by Disassembling Cellular Apoptosis Susceptibility Protein/E-Cadherin/β-Catenin Complex in Human Endometriosis.

PubMed

Wang, Chaoqun; Zhang, Jieting; Fok, Kin Lam; Tsang, Lai Ling; Ye, Mei; Liu, Jianni; Li, Fanghong; Zhao, Allan Zijian; Chan, Hsiao Chang; Chen, Hao

2018-04-06

Epithelial-to-mesenchymal transition (EMT) is postulated to be a prerequisite for the establishment of endometriosis (EMS), a common reproductive disorder in women. Our previous studies have demonstrated the elevated expression of transmembrane glycoprotein CD147 and its prosurvival effect on abnormal cells in endometriosis. Intriguingly, CD147 is known to promote EMT in cancers. However, the involvement of CD147 in EMT during the establishment of endometriosis remains incompletely understood. We found that CD147 promotes EMT in human endometrial adenocarcinoma cell line Ishikawa. We identified a novel CD147-interacting partner, cellular apoptosis susceptibility protein (CAS), which stabilized the interaction between E-cadherin (E-cad) and β-catenin (β-cat) by forming the CAS/E-cad/β-cat complex. Down-regulation of CAS led to the release and nuclear translocation of β-cat from E-cad, resulting in the overexpression of the EMT-promoting gene SNAIL. Interestingly, overexpression of CD147 impaired the interaction between CAS and E-cad and triggered the release of β-cat from the CAS/E-cad/β-cat complex, which in turn led to EMT. Furthermore, CAS was down-regulated in EMS, with elevated levels of CD147 and nuclear β-cat. These findings suggest a previously undefined role of CAS in regulating EMT and reveal the involvement of a CD147-induced EMT signaling pathway in pathogenic progression of EMS. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

MicroRNA-93 Promotes Epithelial–Mesenchymal Transition of Endometrial Carcinoma Cells

PubMed Central

Sun, Kai-Xuan; Xiu, Yin-Ling; Liu, Bo-Liang; Feng, Miao-Xiao; Sang, Xiu-Bo; Zhao, Yang

2016-01-01

MicroRNA-93, derived from a paralog (miR-106b-25) of the miR-17-92 cluster, is involved in the tumorigenesis and progression of many cancers such as breast, colorectal, hepatocellular, lung, ovarian, and pancreatic cancer. However, the role of miR-93 in endometrial carcinoma and the potential molecular mechanisms involved remain unknown. Our results showed that miR-93 was overexpressed in endometrial carcinoma tissues than normal endometrial tissues. The endometrial carcinoma cell lines HEC-1B and Ishikawa were transfected with miR-93-5P, after which cell migration and invasion ability and the expression of relevant molecules were detected. MiR-93 overexpression promoted cell migration and invasion, and downregulated E-cadherin expression while increasing N-cadherin expression. Dual-luciferase reporter assay showed that miR-93 may directly bind to the 3′ untranslated region of forkhead box A1 (FOXA1); furthermore, miR-93 overexpression downregulated FOXA1 expression while miR-93 inhibitor transfection upregulated FOXA1 expression at both mRNA and protein level. In addition, transfection with the most effective FOXA1 small interfering RNA promoted both endometrial cancer cell migration and invasion, and downregulated E-cadherin expression while upregulating N-cadherin expression. Therefore, we suggest that miR-93 may promote the process of epithelial–mesenchymal transition in endometrial carcinoma cells by targeting FOXA1. PMID:27829043

Risk assessment and experimental design in the development of a prolonged release drug delivery system with paliperidone.

PubMed

Iurian, Sonia; Turdean, Luana; Tomuta, Ioan

2017-01-01

This study focuses on the development of a drug product based on a risk assessment-based approach, within the quality by design paradigm. A prolonged release system was proposed for paliperidone (Pal) delivery, containing Kollidon ® SR as an insoluble matrix agent and hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC), or sodium carboxymethyl cellulose as a hydrophilic polymer. The experimental part was preceded by the identification of potential sources of variability through Ishikawa diagrams, and failure mode and effects analysis was used to deliver the critical process parameters that were further optimized by design of experiments. A D-optimal design was used to investigate the effects of Kollidon SR ratio ( X 1 ), the type of hydrophilic polymer ( X 2 ), and the percentage of hydrophilic polymer ( X 3 ) on the percentages of dissolved Pal over 24 h ( Y 1 - Y 9 ). Effects expressed as regression coefficients and response surfaces were generated, along with a design space for the preparation of a target formulation in an experimental area with low error risk. The optimal formulation contained 27.62% Kollidon SR and 8.73% HPMC and achieved the prolonged release of Pal, with low burst effect, at ratios that were very close to the ones predicted by the model. Thus, the parameters with the highest impact on the final product quality were studied, and safe ranges were established for their variations. Finally, a risk mitigation and control strategy was proposed to assure the quality of the system, by constant process monitoring.

Organizational factors affecting length of stay in the emergency department: initial observational study.

PubMed

Bashkin, Osnat; Caspi, Sigalit; Haligoa, Rachel; Mizrahi, Sari; Stalnikowicz, Ruth

2015-01-01

Length of stay (LOS) is considered a key measure of emergency department throughput, and from the perspective of the patient, it is perceived as a measure of healthcare service quality. Prolonged LOS can be caused by various internal and external factors. This study examined LOS in the emergency department and explored the main factors that influence LOS and cause delay in patient care. Observations of 105 patients were performed over a 3-month period at the emergency room of a community urban hospital. Observers monitored patients from the moment of entrance to the department until discharge or admission to another hospital ward. Analysis revealed a general average total emergency department LOS of 438 min. Significant differences in average LOS were found between admitted patients (Mean = 544 min, SD = 323 min) and discharged patients (Mean = 291 min, SD = 286 min). In addition, nurse and physician change of shifts and admissions to hospital wards were found to be significant factors associated with LOS. Using an Ishikawa causal diagram, we explored various latent organizational factors that may prolong this time. The study identified several factors that are associated with high average emergency department LOS. High LOS may lead to increases in expenditures and may have implications for patient safety, whereas certain organizational changes, communication improvement, and time management may have a positive effect on it. Interdisciplinary methods can be used to explore factors causing prolonged emergency department LOS and contribute to a better understanding of them.

Two novel GPER agonists induce gene expression changes and growth effects in cancer cells.

PubMed

Lappano, R; Rosano, C; Santolla, M F; Pupo, M; De Francesco, E M; De Marco, P; Ponassi, M; Spallarossa, A; Ranise, A; Maggiolini, M

2012-06-01

Although the action of estrogens has been traditionally explained by the binding to and transactivation of the nuclear estrogen receptor (ER)α and ERβ, recently the G protein-coupled receptor GPR30/GPER has been involved in the rapid estrogen signaling. We investigated the ability of two original molecules, which were named GPER-L1 and GPERL2, to bind to and activate the GPER transduction pathway in cancer cells. Competition assays, docking simulations, transfection experiments, real-time PCR, immunoblotting, gene silencing technology and growth assays were performed to ascertain the selective action of GPER-L1 and GPER-L2 in activating the GPER-mediated signaling. Both compounds, which did not show any ability to bind to and activate the classical ERs, were able to bind to GPER and to trigger the rapid activation of the GPER/EGFR/ERK transduction pathway which led to the up-regulation of GPER-target genes. Notably, GPER-L1 and GPER-L2 induced the proliferation of SkBr3 breast and Ishikawa endometrial cancer cells at nM concentrations through GPER, hence providing further evidence on their capability to elicit relevant biological responses mediated by GPER. The identification and characterization of these novel compounds as selective GPER agonists represent a valuable tool to further dissect the pharmacology of this novel estrogen receptor and to better differentiate the specific functions elicited by each estrogen receptor subtype in cancer cells.

Microbial Immobilization of Si, Mn, Fe, and Sr Ions in the Nacreous Layer of Sinohyliopsis schlegeli and Environmental Factors

NASA Astrophysics Data System (ADS)

Tazaki, Kazue; Morii, Issei

Environmental changes recorded in the shell nacre of Sinohyliopsis schlegeli were observed with elemental factors of characteristic water and nutrition for eight months in a cultivated drainage pond at Kanazawa University, Ishikawa Prefecture, Japan. Tetracycline as an indicator was injected into the shell nacre once every month from May to November in 2007. Water qualities such as the pH, redox potential, electrical conductivity, dissolved oxygen concentration, and water temperature were measured periodically, and the suspended solids in the water were removed by filtration for optical microscopy, X-ray fluorescence analysis, and scanning electron microscopy-energy dispersive X-ray (SEM-EDX) observations. X-ray fluorescence chemical analysis of shell nacre indicated layers with strong tetracycline accumulation corresponding to high concentrations of Si, Mn, Fe, and Sr ions. The redox potential and dissolved oxygen concentration measurements supported the existence of layers in the nacre. The suspended materials in the drainage pond water comprised mainly of Si, Mn, and Fe elements, which were the same elements involved in microbial immobilization in the shell nacre during the summer of 2007. SEM-EDX analyses confirmed that the ions originated from diatoms, Siderocapsa sp. and Gallionella ferruginea in the stomach. There was little microbial immobilization of the ions in winter. The results suggested elemental immobilization in the layered shell nacre and indicated that Sinohyliopsis schlegeli fed on the ions, to grow the nacre during summer. Sinohyliopsis schlegeli with these biogenic oxides might contribute to the scavenging of heavy metals in natural water.

Genetic Analyses of an H3N8 Influenza Virus Isolate, Causative Strain of the Outbreak of Equine Influenza at the Kanazawa Racecourse in Japan in 2007.

PubMed

Ito, Mika; Nagai, Makoto; Hayakawa, Yuji; Komae, Hirofumi; Murakami, Naruto; Yotsuya, Syouichi; Asakura, Shingo; Sakoda, Yoshihiro; Kida, Hiroshi

2008-09-01

In August 2007, an outbreak of equine influenza occurred among vaccinated racehorses with Japanese commercial equine influenza vaccine at Kanazawa Racecourse in Ishikawa prefecture in Japan. Apparent symptoms were pyrexia (38.2-41.0 degrees C) and nasal discharge with or without coughing, although approximately half of the infected horses were subclinical. All horses had been shot with a vaccine that contained two inactivated H3N8 influenza virus strains [A/equine/La Plata/93 (La Plata/93) of American lineage and A/equine/Avesta/93 (Avesta/93) of European lineage] and an H7N7 strain (A/equine/Newmarket/1/77). Influenza virus, A/equine/Kanazawa/1/2007 (H3N8) (Kanazawa/07), was isolated from one of the nasal swab samples of diseased horses. Phylogenetic analysis indicated that Kanazawa/07 was classified into the American sublineage Florida. In addition, four amino acid substitutions were found in the antigenic sites B and E in the HA1 subunit protein of Kanazawa/07 in comparison with that of La Plata/93. Hemagglutination-inhibition (HI) test using 16 serum samples from recovering horses revealed that 1.4- to 8-fold difference in titers between Kanazawa/07 and either of the vaccine strains. The present findings suggest that Japanese commercial inactivated vaccine contributed to reducing the morbidity rate and manifestation of the clinical signs of horses infected with Kanazawa/07 that may be antigenically different from the vaccine strains.

Testing the time-of-flight model for flagellar length sensing.

PubMed

Ishikawa, Hiroaki; Marshall, Wallace F

2017-11-07

Cilia and flagella are microtubule-based organelles that protrude from the surface of most cells, are important to the sensing of extracellular signals, and make a driving force for fluid flow. Maintenance of flagellar length requires an active transport process known as intraflagellar transport (IFT). Recent studies reveal that the amount of IFT injection negatively correlates with the length of flagella. These observations suggest that a length-dependent feedback regulates IFT. However, it is unknown how cells recognize the length of flagella and control IFT. Several theoretical models try to explain this feedback system. We focused on one of the models, the "time-of-flight" model, which measures the length of flagella on the basis of the travel time of IFT protein in the flagellar compartment. We tested the time-of-flight model using Chlamydomonas dynein mutant cells, which show slower retrograde transport speed. The amount of IFT injection in dynein mutant cells was higher than that in control cells. This observation does not support the prediction of the time-of-flight model and suggests that Chlamydomonas uses another length-control feedback system rather than that described by the time-of-flight model. © 2017 Ishikawa and Marshall. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Relationships between health literacy, motivation and diet and physical activity in people with type 2 diabetes participating in peer-led support groups.

PubMed

Juul, Lise; Rowlands, Gill; Maindal, Helle Terkildsen

2018-03-17

To investigate associations between health literacy (HL) and diet and physical activity, and motivation and diet and physical activity in Danish people with type 2 diabetes. We used a cross-sectional design including 194 individuals with type 2 diabetes participating in peer-led support groups provided by the Danish Diabetes Association between January-December 2015. The participants completed a questionnaire at the first meeting including; The Summary of Diabetes Self-Care Activities (SDSCA) measure, The Treatment Self-Regulation Questionnaire (TSRQ) (Self-Determination Theory) measuring type of motivation, and two HL scales: The HLS-EU-Q16, and the Diabetes Health Literacy scale (Ishikawa, H). Data were analyzed using linear regression models adjusting for age, gender, educational level, diabetes duration, motivation and HL. The adjusted β (95%CI) showed that autonomous motivation and functional HL were associated with following recommended diet: autonomous motivation; 0.43 (0.06; 0.80) and functional HL; 0.52 (0.02; 1.00). Autonomous motivation was related to following physical activity recommendations; β (95%CI) 0.56 (0.16; 0.96). This study indicates that, for people with type 2 diabetes, functional HL and autonomous motivation may be important drivers for following diet recommendations, and autonomous motivation may be the most important factor for following recommendations regarding physical activity. These concepts may therefore be highly relevant to address in interventions to people with type 2 diabetes. Different interventions are suggested. Copyright © 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Phase 0 and phase III transport in various organs: combined concept of phases in xenobiotic transport and metabolism.

PubMed

Döring, Barbara; Petzinger, Ernst

2014-08-01

The historical phasing concept of drug metabolism and elimination was introduced to comprise the two phases of metabolism: phase I metabolism for oxidations, reductions and hydrolyses, and phase II metabolism for synthesis. With this concept, biological membrane barriers obstructing the accessibility of metabolism sites in the cells for drugs were not considered. The concept of two phases was extended to a concept of four phases when drug transporters were detected that guided drugs and drug metabolites in and out of the cells. In particular, water soluble or charged drugs are virtually not able to overcome the phospholipid membrane barrier. Drug transporters belong to two main clusters of transporter families: the solute carrier (SLC) families and the ATP binding cassette (ABC) carriers. The ABC transporters comprise seven families with about 20 carriers involved in drug transport. All of them operate as pumps at the expense of ATP splitting. Embedded in the former phase concept, the term "phase III" was introduced by Ishikawa in 1992 for drug export by ABC efflux pumps. SLC comprise 52 families, from which many carriers are drug uptake transporters. Later on, this uptake process was referred to as the "phase 0 transport" of drugs. Transporters for xenobiotics in man and animal are most expressed in liver, but they are also present in extra-hepatic tissues such as in the kidney, the adrenal gland and lung. This review deals with the function of drug carriers in various organs and their impact on drug metabolism and elimination.

Personnel training experience in the radioactive waste management: 10 years of Moscow SIA 'RADON' international education training centre

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

Batyukhnova, Olga; Dmitriev, Sergey; Arustamov, Artur

Available in abstract form only. Full text of publication follows: The education service for specialists dealing with radioactive waste was established in Russia (former USSR) in 1983 and was based on the capabilities of two organisations: the Moscow Scientific and Industrial Association 'Radon' (SIA 'Radon') and the Chemical Department of Lomonosov's Moscow State University. These two organizations are able to offer training programs in the science fundamentals, applied research and in practical operational areas of the all pre-disposal activities of the radioactive waste management. Since 1997 this system was upgraded to the international level and now acts as International Educationmore » Training Centre (IETC) at SIA 'Radon' under the guidance of the IAEA. During 10 years more than 300 specialists from 26 European and Asian countries enhanced their knowledge and skills in radioactive waste management. The IAEA supported specialized regional training courses and workshops, fellowships, on-the-job training, and scientific visits are additional means to assure development of personnel capabilities. Efficiency of training was carefully analysed using the structural adaptation of educational process as well as factors, which have influence on education quality. Social-psychological aspects were also taken into account in assessing the overall efficiency. The analysis of the effect of individual factors and the efficiency of education activity were carried out based on attestation results and questioning attendees. A number of analytical methods were utilised such as Ishikawa's diagram method and Pareto's principle for improving of training programs and activities. (authors)« less

Prostaglandin F2alpha-F-prostanoid receptor signaling promotes neutrophil chemotaxis via chemokine (C-X-C motif) ligand 1 in endometrial adenocarcinoma.

PubMed

Wallace, Alison E; Sales, Kurt J; Catalano, Roberto D; Anderson, Richard A; Williams, Alistair R W; Wilson, Martin R; Schwarze, Jurgen; Wang, Hongwei; Rossi, Adriano G; Jabbour, Henry N

2009-07-15

The prostaglandin F(2alpha) (PGF(2alpha)) receptor (FP) is elevated in endometrial adenocarcinoma. This study found that PGF(2alpha) signaling via FP regulates expression of chemokine (C-X-C motif) ligand 1 (CXCL1) in endometrial adenocarcinoma cells. Expression of CXCL1 and its receptor, CXCR2, are elevated in cancer tissue compared with normal endometrium and localized to glandular epithelium, endothelium, and stroma. Treatment of Ishikawa cells stably transfected with the FP receptor (FPS cells) with 100 nmol/L PGF(2alpha) increased CXCL1 promoter activity, mRNA, and protein expression, and these effects were abolished by cotreatment of cells with FP antagonist or chemical inhibitors of Gq, epidermal growth factor receptor, and extracellular signal-regulated kinase. Similarly, CXCL1 was elevated in response to 100 nmol/L PGF(2alpha) in endometrial adenocarcinoma explant tissue. CXCL1 is a potent neutrophil chemoattractant. The expression of CXCR2 colocalized to neutrophils in endometrial adenocarcinoma and increased neutrophils were present in endometrial adenocarcinoma compared with normal endometrium. Conditioned media from PGF(2alpha)-treated FPS cells stimulated neutrophil chemotaxis, which could be abolished by CXCL1 protein immunoneutralization of the conditioned media or antagonism of CXCR2. Finally, xenograft tumors in nude mice arising from inoculation with FPS cells showed increased neutrophil infiltration compared with tumors arising from wild-type cells or following treatment of mice bearing FPS tumors with CXCL1-neutralizing antibody. In conclusion, our results show a novel PGF(2alpha)-FP pathway that may regulate the inflammatory microenvironment in endometrial adenocarcinoma via neutrophil chemotaxis.

Prostaglandin F2α–F-Prostanoid Receptor Signalling Promotes Neutrophil Chemotaxis via Chemokine (CXC motif) Ligand-1 in Endometrial Adenocarcinoma

PubMed Central

Wallace, Alison E; Sales, Kurt J; Catalano, Roberto D; Anderson, Richard A; Williams, Alistair RW; Wilson, Martin R; Schwarze, Jurgen; Wang, Hongwei; Rossi, Adriano G; Jabbour, Henry N

2009-01-01

The prostaglandin F2α (PGF2α) receptor (FP) is elevated in endometrial adenocarcinoma. This study found that PGF2α signalling via FP regulates expression of chemokine (C-X-C motif) ligand 1 (CXCL1) in endometrial adenocarcinoma cells. Expression of CXCL1 and its receptor, CXCR2, are elevated in cancer tissue as compared to normal endometrium and localised to glandular epithelium, endothelium and stroma. Treatment of Ishikawa cells stably transfected with the FP receptor (FPS cells) with 100nM PGF2α increased CXCL1 promoter activity, mRNA and protein expression, and these effects were abolished by co-treatment of cells with FP antagonist or chemical inhibitors of Gq, EGFR and ERK. Similarly, CXCL1 was elevated in response to 100 nM PGF2α in endometrial adenocarcinoma explant tissue. CXCL1 is a potent neutrophil chemoattractant. The expression of CXCR2 colocalised to neutrophils in endometrial adenocarcinoma and increased neutrophils were present in endometrial adenocarcinoma compared with normal endometrium. Conditioned media from PGF2α-treated FPS cells stimulated neutrophil chemotaxis which could be abolished by CXCL1 protein immunoneutralisation of the conditioned media or antagonism of CXCR2. Finally, xenograft tumours in nude mice arising from inoculation with FPS cells showed increased neutrophil infiltration compared to tumours arising from wild-type cells or following treatment of mice bearing FPS tumours with CXCL1-neutralising antibody. In conclusion, our results demonstrate a novel PGF2α-FP pathway that may regulate the inflammatory microenvironment in endometrial adenocarcinoma via neutrophil chemotaxis. PMID:19549892

Applying Lean-Six-Sigma Methodology in radiotherapy: Lessons learned by the breast daily repositioning case.

PubMed

Mancosu, Pietro; Nicolini, Giorgia; Goretti, Giulia; De Rose, Fiorenza; Franceschini, Davide; Ferrari, Chiara; Reggiori, Giacomo; Tomatis, Stefano; Scorsetti, Marta

2018-05-01

Lean Six Sigma Methodology (LSSM) was introduced in industry to provide near-perfect services to large processes, by reducing improbable occurrence. LSSM has been applied to redesign the 2D-2D breast repositioning process (Lean) by the retrospective analysis of the database (Six Sigma). Breast patients with daily 2D-2D matching before RT were considered. The five DMAIC (define, measure, analyze, improve, and control) LSSM steps were applied. The process was retrospectively measured over 30 months (7/2014-12/2016) by querying the RT Record&Verify database. Two Lean instruments (Poka-Yoke and Visual Management) were considered for advancing the process. The new procedure was checked over 6 months (1-6/2017). 14,931 consecutive shifts from 1342 patients were analyzed. Only 0.8% of patients presented median shifts >1 cm. The major observed discrepancy was the monthly percentage of fractions with almost zero shifts (AZS = 13.2% ± 6.1%). Ishikawa fishbone diagram helped in defining the main discrepancy con-causes. Procedure harmonization involving a multidisciplinary team to increase confidence in matching procedure was defined. AZS was reduced to 4.8% ± 0.6%. Furthermore, distribution symmetry improvement (Skewness moved from 1.4 to 1.1) and outlier reduction, verified by Kurtosis diminution, demonstrated a better "normalization" of the procedure after the LSSM application. LSSM was implemented in a RT department, allowing to redesign the breast repositioning matching procedure. Copyright © 2018 Elsevier B.V. All rights reserved.

Benzotriazole Enhances Cell Invasive Potency in Endometrial Carcinoma Through CTBP1-Mediated Epithelial-Mesenchymal Transition.

PubMed

Wang, Yiquan; Dai, Chencheng; Zhou, Cheng; Li, Wenqu; Qian, Yujia; Wen, Juan; Wang, Yang; Han, Bing; Ma, Jingjing; Xu, Juan; Fu, Ziyi; Ruan, Hongjie; Tong, Hua; Jia, Xuemei

2017-01-01

Benzotriazole (BTR) and its derivatives, such as intermediates and UV stabilizers, are important man-made organic chemicals found in everyday life that have been recently identified as environmental toxins and a threat to female reproductive health. Previous studies have shown that BTR could act as a carcinogen by mimicking estrogen. Environmental estrogen mimics could promote the initiation and development of female cancers, such as endometrial carcinoma, a type of estrogenic-sensitive malignancy. However, there is little information on the relationship between BTR and endometrial carcinoma. In this study, we aimed to demonstrate the biological function of BTR in endometrial carcinoma and explored the underlying mechanism. The CCK-8 assay was performed to detect cell viability; transwell-filter assay was used to assess cell invasion; gene microarray analysis was employed to determine gene expression patterns in response to BTR treatment; western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were carried out to detect the expression levels of BTR-related genes. Our data showed that BTR could induce the invasion and migration of endometrial carcinoma cells (Ishikawa and HEC-1-B). In addition, BTR increased the expression level of CTBP1, which could enhance the epithelial-mesenchymal transition (EMT) in cancer cells. Moreover, CTBP1 silencing reversed the effect of BTR on EMT progression in endometrial carcinoma cells. This study indicates that BTR could act as a carcinogen to promote the development of endometrial carcinoma mainly through CTBP1-mediated EMT, which deserves more attention. © 2017 The Author(s). Published by S. Karger AG, Basel.

High throughput screening of natural products for anti-mitotic effects in MDA-MB-231 human breast carcinoma cells

PubMed Central

Mazzio, E; Badisa, R; Mack, N; Deiab, S; Soliman, KFA

2013-01-01

Some of the most effective anti-mitotic microtubule-binding agents, such as paclitaxel (Taxus brevifolia) were originally discovered through robust NCI botanical screenings. In this study, a high-through microarray format was utilized to screen 897 aqueous extracts of commonly used natural products (0.00015–0.5 mg/ml) relative to paclitaxel for anti-mitotic effects (independent of toxicity) on proliferation of MDA-MB-231 cells. The data obtained showed that less than 1.34 % tested showed inhibitory growth (IG50) properties <0.0183 mg/ml. The most potent anti-mitotics (independent of toxicity) were Mandrake root (Podophyllum peltatum), Truja Twigs (Thuja occidentalis), Colorado desert mistletoe (Phoradendron flavescens), Tou Gu Cao Speranskia Herb (Speranskia tuberculata), Bentonite Clay, Bunge Root (Pulsatilla chinensis), Brucea Fruit (Brucea javanica), Madder Root (Rubia tinctorum), Gallnut of Chinese Sumac (Melaphis chinensis), Elecampane Root (Inula Helenium), Yuan Zhi Root (Polygala tenuifolia), Pagoda Tree Fruit (Melia Toosendan), Stone Root (Collinsonia Canadensis) and others such as American Witchhazel, Arjun and Bladderwrack. The strongest tumoricidal herbs identified from amongst the subset evaluated for anti-mitotic properties were wild yam (Dioscorea villosa), beth-root (Trillium Pendulum) and alkanet-root (Lithospermum canescens). Additional data was obtained on a lesser-recognized herb: (Speranskia tuberculata) which showed growth inhibition on BT-474 (human ductal breast carcinoma) and Ishikawa (human endometrial adenocarcinoma) cells with ability to block replicative DNA synthesis leading to G2 arrest in MDA-MB-231 cells. In conclusion, these findings present relative potency of natural anti-mitotic resources effective against human breast carcinoma MDA-MB-231 cell division. PMID:24105850

Pigmentation abnormalities in systemic scleroderma examined by using a colorimeter (Choromo Meter CR-200).

PubMed

Maeda, M; Kachi, H; Matubara, K; Mori, S; Kitajima, Y

1996-03-01

Cutaneous colors of the dorsum of the hands (A), the distal forearms (B; 5 cm from the wrists), the proximal forearm (C; proximal 1/3 from the elbow) and sternal skin region (D) in patients with systemic scleroderma (73 cases; M:F = 16:57) systemic lupus erythematosus (SLE) or dermatomyositis (27 cases; M:F = 7:20) and healthy controls (HC) (36 cases; M:F = 8:28) was characterized by a XYZ colorimetric system (CIE, 1931) using a colorimeter (Choromo Meter CR-200, Minolta Camera Co. Ltd., Osaka). The index Y, which means color value shows a lower value in male HC and in patients with systemic scleroderma, especially in the more severe type with hyperpigmentation (score 5-6; the system proposed by Ishikawa) than that of female HC. The values of indices x and y, which relate to reddish (erythema with hyperpigmentation) and greenish color (pale), respectively, were higher in the exposed portion of the severe type of systemic scleroderma with hyperpigmentation, especially male and older patients, and in unexposed portions of the female group without hyperpigmentation. Histopathologically, there was prominent pigmentation in the upper dermis of the forearm in the severe type of systemic scleroderma, so that melanin quantity may be closely related to the decrease in index Y. There was no statistical significance in the value of indices Y, x and y between HC, SLE and dermatomyositis. This method may contribute not only to diagnosis of systemic scleroderma and differentiation from other collagen diseases, but also studies of clinical follow-up and effects of medication.

Synthesis, characterization and cytotoxicity studies of 1,2,3-triazoles and 1,2,4-triazolo [1,5-a] pyrimidines in human breast cancer cells.

PubMed

Gilandoust, Maryam; Harsha, Kachigere B; Mohan, Chakrabhavi Dhananjaya; Raquib, Ainiah Rushdiana; Rangappa, Shobith; Pandey, Vijay; Lobie, Peter E; Basappa; Rangappa, Kanchugarakoppal S

2018-05-09

Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) is essential for physiological functions of tissues and neovasculature. VEGFR signaling is associated with the progression of pathological angiogenesis in various types of malignancies, making it an attractive therapeutic target in cancer treatment. In the present work, we report the synthesis of 1,4-disubstituted 1,2,3-triazoles and 1,2,4-triazolo[1, 5-a]pyrimidine derivatives via copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and screened for their anticancer activity against MCF7 cells. We identified 1-(2'-ethoxy-4'-fluoro-[1,1'-biphenyl]-4-yl)-4-phenyl-1H-1,2,3-triazole (EFT) as lead cytotoxic agent against MCF7 cell lines with an IC 50 value of 1.69 µM. Further evaluation revealed that EFT induces cytotoxicity on Ishikawa, MDA-MB-231 and BT474 cells with IC 50 values of 1.97, 4.81 and 4.08 µM respectively. However, EFT did not induce cytotoxicity in normal lung epithelial (BEAS-2B) cells. Previous reports suggested that 1,2,3-triazoles are the inhibitors of VEGFR1 and therefore, we evaluated the effect of EFT on the expression of VEGFR1. The results demonstrated that EFT downregulates the expression of VEGFR1 in MCF7 cells. In summary, we identified a potent cytotoxic agent that imparts its antiproliferative activity by targeting VEGFR1 in breast cancer cells. The novel compound could serve as a lead structure in developing VEGFR1 inhibitors. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Systematic Approach of Employing Quality by Design Principles: Risk Assessment and Design of Experiments to Demonstrate Process Understanding and Identify the Critical Process Parameters for Coating of the Ethylcellulose Pseudolatex Dispersion Using Non-Conventional Fluid Bed Process.

PubMed

Kothari, Bhaveshkumar H; Fahmy, Raafat; Claycamp, H Gregg; Moore, Christine M V; Chatterjee, Sharmista; Hoag, Stephen W

2017-05-01

The goal of this study was to utilize risk assessment techniques and statistical design of experiments (DoE) to gain process understanding and to identify critical process parameters for the manufacture of controlled release multiparticulate beads using a novel disk-jet fluid bed technology. The material attributes and process parameters were systematically assessed using the Ishikawa fish bone diagram and failure mode and effect analysis (FMEA) risk assessment methods. The high risk attributes identified by the FMEA analysis were further explored using resolution V fractional factorial design. To gain an understanding of the processing parameters, a resolution V fractional factorial study was conducted. Using knowledge gained from the resolution V study, a resolution IV fractional factorial study was conducted; the purpose of this IV study was to identify the critical process parameters (CPP) that impact the critical quality attributes and understand the influence of these parameters on film formation. For both studies, the microclimate, atomization pressure, inlet air volume, product temperature (during spraying and curing), curing time, and percent solids in the coating solutions were studied. The responses evaluated were percent agglomeration, percent fines, percent yield, bead aspect ratio, median particle size diameter (d50), assay, and drug release rate. Pyrobuttons® were used to record real-time temperature and humidity changes in the fluid bed. The risk assessment methods and process analytical tools helped to understand the novel disk-jet technology and to systematically develop models of the coating process parameters like process efficiency and the extent of curing during the coating process.

The G protein-coupled receptor GPR30 mediates the proliferative and invasive effects induced by hydroxytamoxifen in endometrial cancer cells

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

Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue

2012-04-06

Highlights: Black-Right-Pointing-Pointer We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. Black-Right-Pointing-Pointer GPR30 mediates the proliferative effects induced by OHT. Black-Right-Pointing-Pointer GPR30 mediates the invasive effects induced by OHT. Black-Right-Pointing-Pointer GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in themore » activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17{beta}-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.« less

Assessing Estrogen-Induced Proliferative Response in an Endometrial Cancer Cell Line Using a Universally Applicable Methodological Guide.

PubMed

Parkes, Christina; Kamal, Areege; Valentijn, Anthony J; Alnafakh, Rafah; Gross, Stephane R; Barraclough, Roger; Moss, Diana; Kirwan, John; Hapangama, Dharani K

2018-01-01

Translational endometrial cancer (EC) research benefits from an in vitro experimental approach using EC cell lines. We demonstrated the steps that are required to examine estrogen-induced proliferative response, a simple yet important research question pertinent to EC, and devised a pragmatic methodological workflow for using EC cell lines in experimental models. Comprehensive review of all commercially available EC cell lines was carried out, and Ishikawa cell line was selected to study the estrogen responsiveness with HEC1A, RL95-2, and MFE280 cell lines as comparators where appropriate, examining relevant differential molecular (steroid receptors) and functional (phenotype, anchorage-independent growth, hormone responsiveness, migration, invasion, and chemosensitivity) characteristics in 2-dimensional and 3-dimensional cultures in vitro using immunocytochemistry, immunofluorescence, quantitative polymerase chain reaction, and Western blotting. In vivo tumor, formation, and chemosensitivity were also assessed in a chick chorioallantoic membrane model. Short tandem repeat analysis authenticated the purchased cell lines, whereas gifted cells deviated significantly from the published profile. We demonstrate the importance of prior assessment of the suitability of each cell line for the chosen in vitro experimental technique. Prior establishment of baseline, nonenriched conditions was required to induce a proliferative response to estrogen. The chorioallantoic membrane model was a suitable in vivo multicellular animal model for EC for producing rapid and reproducible data. We have developed a methodological guide for EC researchers when using endometrial cell lines to answer important translational research questions (exemplified by estrogen-responsive cell proliferation) to facilitate robust data, while saving time and resources.

[The factors involved in invasive ability of endometrial carcinoma cells].

PubMed

Mori, Y; Mizuuchi, H; Sato, K; Okamura, N; Kudo, R

1994-06-01

The in vitro invasive ability, the expression of cell adhesion molecule E-cadherin, activity of matrix metalloproteinase (MMP) and K-ras point mutation were investigated in eight human endometrial carcinoma cell lines. 1) In vitro invasive abilities of endometrial carcinoma cell lines depend on the degree of cell differentiation and the origin of cell lines. A poorly-differentiated carcinoma cell line (NUE-1) and a cell line derived from metastatic lymph node (SNG-M) were more invasive than moderately-(HEC-1A, HEC-1BE) and well-differentiated (HEC-6, Ishikawa) cell lines. 2) Immunohistochemically, less or non-invasive cell lines expressed E-cadherin strongly, whereas a highly invasive cell line (NUE-1) expressed E-cadherin weakly. 3) When cultured on Matrigel-coated dishes, the tumor cells derived from moderately- and well-differentiated carcinoma aggregated with each other and did not invade Matrigel in the invasion assay. The aggregated cells expressed E-cadherin more strongly when cultured on Matrigel. 4) 72-kD gelatinase (MMP-2) was secreted in serum-free conditioned medium of all cell lines. In an invasive cell line (NUE-1,SNG-M), the activity of MMP-2 was stronger than in other cell lines. And the activity of 92-kDa gelatinase (MMP-9) was detected in most invasive cell line (NUE-1). 5) Point mutation of K-ras codon 12 was detected in four of eight (50%) cell lines by the PCR-RFLP method. The changes in the DNA sequence were identified, but K-ras point mutation was not correlated with in vitro invasiveness of the tumor cells.

Risk assessment and experimental design in the development of a prolonged release drug delivery system with paliperidone

PubMed Central

Iurian, Sonia; Turdean, Luana; Tomuta, Ioan

2017-01-01

This study focuses on the development of a drug product based on a risk assessment-based approach, within the quality by design paradigm. A prolonged release system was proposed for paliperidone (Pal) delivery, containing Kollidon® SR as an insoluble matrix agent and hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC), or sodium carboxymethyl cellulose as a hydrophilic polymer. The experimental part was preceded by the identification of potential sources of variability through Ishikawa diagrams, and failure mode and effects analysis was used to deliver the critical process parameters that were further optimized by design of experiments. A D-optimal design was used to investigate the effects of Kollidon SR ratio (X1), the type of hydrophilic polymer (X2), and the percentage of hydrophilic polymer (X3) on the percentages of dissolved Pal over 24 h (Y1–Y9). Effects expressed as regression coefficients and response surfaces were generated, along with a design space for the preparation of a target formulation in an experimental area with low error risk. The optimal formulation contained 27.62% Kollidon SR and 8.73% HPMC and achieved the prolonged release of Pal, with low burst effect, at ratios that were very close to the ones predicted by the model. Thus, the parameters with the highest impact on the final product quality were studied, and safe ranges were established for their variations. Finally, a risk mitigation and control strategy was proposed to assure the quality of the system, by constant process monitoring. PMID:28331293

[Appropriateness of ketorolac use in a trauma hospital].

PubMed

Angeles González-Fernández, M

2009-06-01

To evaluate the suitability of ketorolac and non-steroidal anti-inflamatory drugs (NSAIDs) and other analgesic drugs currently used in the hospital. We have followed the steps to develop a PDCA cycle (plan, do, check, act) or quality improvement cycle. The quality problem was analysed using an Ishikawa diagram. We defined both qualitative quality indicators, those that measure prescription quality, and quantitative ones (defined daily dose, DDD/100BDs), which measure drug consumption, being the objectives to achieve. The study was conducted in all patients admitted to the hospital and who were admitted to orthopaedic and trauma surgery and plastic surgery departments with unit-dose dispensing systems. The strategy used was to give information to physicians through meetings and documentation. Finally, the results were analysed and compared with the initial objectives. The study was performed on 260 patients in the first study period and 292 in the second. Qualitative indicators: intravenous ketorolac use < or =2 days, increased in 25.5% (p<0.001); in patients > or =65 years old at dose < or =60 mg/day it increased 27.7% (p<0.05). Quantitative indicators: in the second study period, ketorolac use decreased (plastic surgery department: 61.8 DDD/100BDs to 14.8), whereas tramadol, ibuprofen and metamizole increased (plastic surgery department: 0 to 14.1 in tramadol, 8.7 to 48.6 in ibuprofen and 50.1 to 71 in metamizole). Appropriateness of ketorolac, NSAIDs and tramadol use has been achieved, thus improving patient safety. Strategies have been effective.

Quality by Design (QbD) Approach for Development of Co-Processed Excipient Pellets (MOMLETS) By Extrusion-Spheronization Technique.

PubMed

Patel, Hetal; Patel, Kishan; Tiwari, Sanjay; Pandey, Sonia; Shah, Shailesh; Gohel, Mukesh

2016-01-01

Microcrystalline cellulose (MCC) is an excellent excipient for the production of pellets by extrusion spheronization. However, it causes slow release rate of poorly water soluble drugs from pellets. Co-processed excipient prepared by spray drying (US4744987; US5686107; WO2003051338) and coprecipitation technique (WO9517831) are patented. The objective of present study was to develop co-processed MCC pellets (MOMLETS) by extrusion-spheronization technique using the principle of Quality by Design (QbD). Co-processed excipient core pellets (MOMLETS) were developed by extrusion spheronization technique using Quality by Design (QbD) approach. BCS class II drug (telmisartan) was layered onto it in a fluidized bed processor. Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA) for pellets were identified. Risk assessment was reported using Ishikawa diagram. Plackett Burman design was used to check the effect of seven independent variables; superdisintegrant, extruder speed, ethanol: water, spheronizer speed, extruder screen, pore former and MCC: lactose; on percentage drug release at 30 min. Pareto chart and normal probability plot was constructed to identify the significant factors. Box-Behnken design (BBD) using three most significant factors (Extruder screen size, type of superdisintegrant and type of pore former) was used as an optimization design. The control space was identified in which desired quality of the pellets can be obtained. Co-processed excipient core pellets (MOMLETS) were successfully developed by QbD approach. Versatility, Industrial scalability and simplicity are the main features of the proposed research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Unit operation optimization for the manufacturing of botanical injections using a design space approach: a case study of water precipitation.

PubMed

Gong, Xingchu; Chen, Huali; Chen, Teng; Qu, Haibin

2014-01-01

Quality by design (QbD) concept is a paradigm for the improvement of botanical injection quality control. In this work, water precipitation process for the manufacturing of Xueshuantong injection, a botanical injection made from Notoginseng Radix et Rhizoma, was optimized using a design space approach as a sample. Saponin recovery and total saponin purity (TSP) in supernatant were identified as the critical quality attributes (CQAs) of water precipitation using a risk assessment for all the processes of Xueshuantong injection. An Ishikawa diagram and experiments of fractional factorial design were applied to determine critical process parameters (CPPs). Dry matter content of concentrated extract (DMCC), amount of water added (AWA), and stirring speed (SS) were identified as CPPs. Box-Behnken designed experiments were carried out to develop models between CPPs and process CQAs. Determination coefficients were higher than 0.86 for all the models. High TSP in supernatant can be obtained when DMCC is low and SS is high. Saponin recoveries decreased as DMCC increased. Incomplete collection of supernatant was the main reason for the loss of saponins. Design space was calculated using a Monte-Carlo simulation method with acceptable probability of 0.90. Recommended normal operation region are located in DMCC of 0.38-0.41 g/g, AWA of 3.7-4.9 g/g, and SS of 280-350 rpm, with a probability more than 0.919 to attain CQA criteria. Verification experiment results showed that operating DMCC, SS, and AWA within design space can attain CQA criteria with high probability.

Enhancing quality practice for prevention and diagnosis of urinary tract infection during inpatient spinal cord rehabilitation.

PubMed

Alavinia, Seyed Mohammad; Omidvar, Maryam; Farahani, Farnoosh; Bayley, Mark; Zee, Joana; Craven, Beverley Catharine

2017-11-01

To reduce the incidence of Urinary Tract Infection (UTI) in subacute SCI individuals admitted for tertiary inpatient rehabilitation. A quality improvement team was assembled to improve UTI prevention/diagnosis. To plan data collection, UTI-related factors were mapped in an Ishikawa (fishbone) driver diagram. Data including patient demographics, presence and frequency of signs and/or symptoms of UTI and antibiotic initiation from August to December 2015 were recorded. Sensitivity, Specificity, Positive and Negative Predictive Values (PPV, NPV), and Likelihood Ratios (LR) were calculated for each sign and symptom. Tertiary SCI Rehabilitation Results: Among 55 inpatients with subacute SCI who had signs/symptoms prompting urine culture and sensitivity (C&S), 32 (58.18%) were diagnosed with a UTI. The most frequent symptoms were foul smelling urine (41%), change in urine color (31%), and incontinence (25%), and the most common sign was fever (34%). Most UTIs (81%) occurred among individuals using Clean Intermittent Catheterization (CIC), with 46% of catheterizations performed by nurses. Foul smelling urine had the highest sensitivity (0.50, 95% CI: 0.31-0.69), and new incontinence had the highest specificity (0.88, 95% CI: 0.69-0.97) for UTI diagnosis. The highest PPV belonged to the cloudy urine (0.71, 95% CI: 0.42-0.92). The combination of cloudy and foul smelling urine increased the PPV to 78% (95% CI: (0.40-0.97). The concurrent presence of cloudy and foul smelling urine is predicted of UTI diagnosis inpatients tertiary setting. SCI inpatients are susceptible to UTI when learning CIC technique from nurses.

Multivariate Approaches for Simultaneous Determination of Avanafil and Dapoxetine by UV Chemometrics and HPLC-QbD in Binary Mixtures and Pharmaceutical Product.

PubMed

2016-04-07

Multivariate UV-spectrophotometric methods and Quality by Design (QbD) HPLC are described for concurrent estimation of avanafil (AV) and dapoxetine (DP) in the binary mixture and in the dosage form. Chemometric methods have been developed, including classical least-squares, principal component regression, partial least-squares, and multiway partial least-squares. Analytical figures of merit, such as sensitivity, selectivity, analytical sensitivity, LOD, and LOQ were determined. QbD consists of three steps, starting with the screening approach to determine the critical process parameter and response variables. This is followed by understanding of factors and levels, and lastly the application of a Box-Behnken design containing four critical factors that affect the method. From an Ishikawa diagram and a risk assessment tool, four main factors were selected for optimization. Design optimization, statistical calculation, and final-condition optimization of all the reactions were Carried out. Twenty-five experiments were done, and a quadratic model was used for all response variables. Desirability plot, surface plot, design space, and three-dimensional plots were calculated. In the optimized condition, HPLC separation was achieved on Phenomenex Gemini C18 column (250 × 4.6 mm, 5 μm) using acetonitrile-buffer (ammonium acetate buffer at pH 3.7 with acetic acid) as a mobile phase at flow rate of 0.7 mL/min. Quantification was done at 239 nm, and temperature was set at 20°C. The developed methods were validated and successfully applied for simultaneous determination of AV and DP in the dosage form.

SOX15 regulates proliferation and migration of endometrial cancer cells.

PubMed

Rui, Xiaohui; Xu, Yun; Jiang, Xiping; Guo, Caixia; Jiang, Jingting

2017-10-31

The study aimed to investigate the effects of Sry-like high mobility group box 15 ( SOX15 ) on proliferation and migration of endometrial cancer (EC) cells. Immunohistochemistry (IHC) was applied to determine the expression of SOX15 in EC tissues and adjacent tissues. We used cell transfection method to construct the HEC-1-A and Ishikawa cell lines with stable overexpression and low expression SOX15 Reverse-transcription quantitative real-time PCR (RT-qPCR) and Western blot were performed to examine expression of SOX15 mRNA and SOX15 protein, respectively. By conducting a series of cell proliferation assay and migration assay, we analyzed the influence of SOX15 overexpression or low expression on EC cell proliferation and migration. The expression of SOX15 mRNA and protein in EC tissues was significantly lower than that in adjacent tissues. After lentivirus-transfecting SOX15 , the expression level of SOX15 mRNA and protein was significantly increased in cells of SOX15 group, and decreased in sh- SOX15 group. Overexpression of SOX15 could suppress cell proliferation, while down-regulation of SOX15 increased cell proliferation. Flow cytometry results indicated that overexpression of SOX15 induced the ratio of cell-cycle arrest in G 1 stage. In addition, Transwell migration assay results showed that SOX15 overexpression significantly inhibited cell migration, and also down-regulation of SOX15 promoted the migration. As a whole, SOX15 could regulate the proliferation and migration of EC cells and up- regulation of SOX15 could be valuable for EC treatment. © 2017 The Author(s).

Genistein effects on stromal cells determines epithelial proliferation in endometrial co-cultures.

PubMed

Sampey, Brante P; Lewis, Terrence D; Barbier, Claire S; Makowski, Liza; Kaufman, David G

2011-06-01

Estrogen is the leading etiologic factor for endometrial cancer. Estrogen-induced proliferation of endometrial epithelial cells normally requires paracrine growth factors produced by stromal cells. Epidemiologic evidence indicates that dietary soy prevents endometrial cancer, and implicates the phytoestrogen genistein in this effect. However, results from previous studies are conflicting regarding the effects of genistein on hormone responsive cancers. The effects of estrogen and genistein on proliferation of Ishikawa (IK) endometrial adenocarcinoma cells were examined in co-cultures of IK cells with endometrial stromal cells, recapitulating the heterotypic cell-to-cell interactions observed in vivo. The roles of estrogen receptor (ER)α and ERβ were evaluated using ERα and ERβ specific agonists. ER activation and cell proliferation in the IK epithelial cells were determined by alkaline phosphatase assay and Coulter counter enumeration, respectively. Both estrogen and genistein increased estrogen receptor-induced gene activity in IK cells over a range of concentrations. Estrogen alone but not genistein increased IK proliferation in co-cultures. When primed by estrogen treatment, increasing concentrations of genistein produced a biphasic effect on IK proliferation: nM concentrations inhibited estrogen-induced proliferation while μM concentrations increased proliferation. Studies with an ERβ-specific agonist produced similar results. Genistein did not influence the effects of estrogen on IK proliferation in monoculture. Our study indicates that nutritionally relevant concentrations (nM) of genistein inhibit the proliferative effects of estrogen on endometrial adenocarcinoma cells presumably through activation of stromal cell ERβ. We believe that sub-micromolar concentrations of genistein may represent a novel adjuvant for endometrial cancer treatment and prevention. Copyright © 2011 Elsevier Inc. All rights reserved.

Evaluating the "recovery level" of endangered species without prior information before alien invasion.

PubMed

Watari, Yuya; Nishijima, Shota; Fukasawa, Marina; Yamada, Fumio; Abe, Shintaro; Miyashita, Tadashi

2013-11-01

For maintaining social and financial support for eradication programs of invasive species, quantitative assessment of recovery of native species or ecosystems is important because it provides a measurable parameter of success. However, setting a concrete goal for recovery is often difficult owing to lack of information prior to the introduction of invaders. Here, we present a novel approach to evaluate the achievement level of invasive predator management based on the carrying capacity of endangered species estimated using long-term monitoring data. In Amami-Oshima Island, Japan, where the eradication project of introduced small Indian mongoose is ongoing since 2000, we surveyed the population densities of four endangered species threatened by the mongoose (Amami rabbit, the Otton frog, Amami tip-nosed frog, and Amami Ishikawa's frog) at four time points ranging from 2003 to 2011. We estimated the carrying capacities of these species using the logistic growth model combined with the effects of mongoose predation and environmental heterogeneity. All species showed clear tendencies toward increasing their density in line with decreased mongoose density, and they exhibited density-dependent population growth. The estimated carrying capacities of three endangered species had small confidence intervals enough to measure recovery levels by the mongoose management. The population density of each endangered species has recovered to the level of the carrying capacity at about 20-40% of all sites, whereas no individuals were observed at more than 25% of all sites. We propose that the present approach involving appropriate monitoring data of native organism populations will be widely applicable to various eradication projects and provide unambiguous goals for management of invasive species.

A meta-analysis of randomized trials assessing the effects of probiotic preparations on oral candidiasis in the elderly.

PubMed

Ai, Ruixue; Wei, Jiao; Ma, Danhua; Jiang, Lu; Dan, Hongxia; Zhou, Yu; Ji, Ning; Zeng, Xin; Chen, Qianming

2017-11-01

Oral candidiasis is the most common fungal infection and can be attributed in part to dysbiosis, an imbalance in the resident oral microflora. Therefore, probiotics, which counter pathogenic microorganisms through competitive, antagonistic, and immunological effects, have been used by some clinicians. To date, the effect of probiotics in preventing oral candidiasis in the elderly is controversial. A systematic review that summarizes and critically appraises the available clinical trials is therefore necessary. Electronic searches were performed using the Pubmed, Embase, and Cochrane databases. Only randomized controlled trials were included. The Mantel-Haenszel test was used to appraise the odds ratio for single studies and an overall combined odds ratio for all studies combined. Three studies matched the inclusion criteria and were homogeneous. The data from one study that estimated candida growth from plaque and saliva were subdivided, thus a total of four studies with 595 people were included. The overall combined odds ratio was 0.54 (95% CI: 0.38-0.77). Three studies provided that active treatment reduced the risk of oral candidiasis more than placebo: Hatakka et al. (OR 0.51, 95% CI 0.26 to 0.97; 192 participants, plaque); Kraft-Bodi et al. (OR 0.46, 95% CI 0.24 to 0.86; 174 participants, palatal); Kraft-Bodi et al. (OR 0.50, 95% CI 0.26 to 0.98; 174 participants, plaque), while one study provided reverse result: Ishikawa et al. (OR 1.24, 95% CI 0.48 to 3.58; 55 participants, saliva). Probiotics have a preventative effect on oral candidiasis in the elderly. Copyright © 2017. Published by Elsevier Ltd.

Deuteration Effect on the Nh/nd Stretch Band of the Jet-Cooled 7-AZAINDOLE and its Tautomeric Dimers: Relation to the Ground-State Double Proton-Transfer Reaction

NASA Astrophysics Data System (ADS)

Ishikawa, Haruki; Nakano, Takumi; Takashima, Tsukiko; Yabuguchi, Hiroki; Fuke, Kiyokazu

2013-06-01

In order to investigate the deuteration effect on the vibrational dynamics of the NH and/or ND stretch excited levels of the 7-azaindole (7-AI) normal dimer and its tautomeric dimer, we have carried out infrared spectroscopy of three isotopic species for each dimers; undeuterated one (NH-NH) and one or two hydrogen atom(s) of the NH groups is deuterated ones (NH-ND and ND-ND, respectively). It is found that the ND stretch band profiles of the NH-ND and ND-ND tautomeric dimers are very similar with each other. This result is very distinct from the result of the comparison of the NH stretch band profiles of the NH-NH and NH-ND dimers in our previous study. For a further discussion, we have examined the deuteration effect in the case of the 7-AI normal dimer. It is found that the NH stretch band profiles of the NH-NH and the NH-ND dimers and also the ND stretch band profiles of the NH-ND and the ND-ND dimers exhibit similar patterns, respectively. These facts indicates that the vibrational relaxation from the NH/ND stretch level of the normal dimer basically proceed within a monomer unit. The large deuteration effect of the NH stretch band profile observed previously is found to be characteristic of the tautomeric dimer. This behavior is related to a large anharmonicity of the potential energy surface originating from an existence of the double-proton transfer reaction barrier. H. Ishikawa, H. Yabuguchi, Y. Yamada, A. Fujihara, K. Fuke, J. Phys. Chem. A 114, 3199 (2010).

Evaluation of clinical measurements and development of new diagnostic criteria for Takayasu arteritis in a Chinese population.

PubMed

Kong, X; Ma, L; Wu, L; Chen, H; Ma, L; Sun, Y; Wu, W; Ji, Z; Zhang, Z; Yang, C; Ye, S; Chen, S; Dai, S; Xue, Y; Qin, G; Zou, Y; Yu, Q; Jiang, L

2015-01-01

Takayasu arteritis (TA) is a chronic granulomatous large-vessel vasculitis. When diagnosing TA, the criteria designed by the American College of Rheumatology (ACR) are used commonly but they were just classification criteria. There is an urgent need for a new set of diagnostic criteria. One hundred and thirty-one TA patients and 132 control patients with other types of vascular disease were enrolled and both groups were distributed into a "training set" and a "validation set". All general information as well as clinical, laboratory and imaging data were collected. After comparing all the medical records of two groups in the training set, logistic regression and clinical judgment were used to form the new criteria for TA. The new criteria were tested by the validation set. New TA diagnostic criteria within total score 26 include age (<40 years), female, chest pain/chest distress, amaurosis, vascular bruits, a decreased/absent pulse, involvement of the aortic arch or its major branches, and involvement of the abdominal aorta or its branches. Patients with a score ≥ 8 were diagnosed as TA. The sensitivity and specificity of our new criteria were 91.92% and 93.94%, respectively, higher than those of the ACR criteria (75.76%, 85.86%) and the Ishikawa criteria (56.57%, 94.95%). The areas under the ROC curves of the new criteria and ACR criteria were 0.981 and 0.868, respectively (p<0.001). Sensitivity and specificity tested in the validation set were 90.63% and 96.97%, respectively. The new diagnostic criteria exhibited high sensitivity and specificity and have demonstrated to be feasible in the diagnosis of TA.

Formal quality improvement curriculum and DMAIC method results in interdisciplinary collaboration and process improvement in renal transplant patients.

PubMed

Leaphart, Cynthia L; Gonwa, Thomas A; Mai, Martin L; Prendergast, Mary B; Wadei, Hani M; Tepas, Joseph J; Taner, C Burcin

2012-09-01

Broad-based formal quality improvement curriculum emphasizing Six Sigma and the DMAIC approach developed by our institution is required for physicians in training. DMAIC methods evaluated the common outcome of postoperative hyponatremia, thus resulting in collaboration to prevent hyponatremia in the renal transplant population. To define postoperative hyponatremia in renal transplant recipients, a project charter outlined project aims. To measure postoperative hyponatremia, serum sodium at admission and immediately postoperative were recorded by retrospective review of renal transplant recipient charts from June 29, 2010 to December 31, 2011. An Ishikawa diagram was generated to analyze potential causative factors. Interdisciplinary collaboration and hospital policy assessment determined necessary improvements to prevent hyponatremia. Continuous monitoring in control phase was performed by establishing the goal of <10% of transplant recipients with abnormal serum sodium annually through quarterly reduction of hyponatremia by 30% to reach this goal. Of 54 transplant recipients, postoperative hyponatremia occurred in 92.6% of patients. These potential causes were evaluated: 1) Hemodialysis was more common than peritoneal dialysis. 2) Alemtuzumab induction was more common than antithymocyte globulin. 3) A primary diagnosis of diabetes existed in 16 patients (30%). 4) Strikingly, 51 patients received 0.45% sodium chloride intraoperatively, suggesting this as the most likely cause of postoperative hyponatremia. A hospital policy change to administer 0.9% sodium chloride during renal transplantation resulted in normal serum sodium levels postoperatively in 59 of 64 patients (92.2%). The DMAIC approach and formal quality curriculum for trainees addresses core competencies by providing a framework for problem solving, interdisciplinary collaboration, and process improvement. Copyright © 2012 Elsevier Inc. All rights reserved.

Collective hydrodynamics of swimming micro-organisms

NASA Astrophysics Data System (ADS)

Pedley, Timothy

2007-11-01

Since the work of Kessler in the 1980s, and before, there has been considerable interest among fluid dynamicists and physicists in the collective behaviour of swimming micro-organisms in suspension. Since all such cells are denser than the water in which they swim, bioconvection patterns result from upswimming of cells in a chamber of finite depth and from gyrotaxis of bottom-heavy cells in a uniform fluid. Bioconvection has been analysed for dilute suspensions; the theory will be briefly re-examined with emphasis on the additional stress induced by the cells' swimming motions (each cell can be regarded as a force-dipole, or stresslet), because of the new instabilities revealed by Simha & Ramaswamy (2002) for uniform suspensions in the absence of gravity. Even more fascinating coherent structures arise in concentrated suspensions, of bacteria for example, in which cell-cell interactions cannot be ignored. The hypothesis is that such structures emerge from purely hydrodynamic interactions between cells. A variety of models have been developed, which are outlined briefly, but particular attention will be paid to our own model in which cells are represented as inertia-free ``spherical squirmers,'' whose behaviour is dominated by near-field hydrodynamics. Pairwise interactions are computed precisely, and Stokesian dynamics in a periodic box is used to simulate an infinite suspension. Trajectories are computed deterministically, but the long-time spreading of a 3D suspension, from random initial conditions, is diffusive; scaling arguments can be used to estimate the effective diffusivity. However, in 2D there is a strong tendency towards aggregation into clumps or bands. [Recent work reported here has been performed in collaboration with T Ishikawa and J T Locsei.

The elastic ratio: introducing curvature into ratio-based image segmentation.

PubMed

Schoenemann, Thomas; Masnou, Simon; Cremers, Daniel

2011-09-01

We present the first ratio-based image segmentation method that allows imposing curvature regularity of the region boundary. Our approach is a generalization of the ratio framework pioneered by Jermyn and Ishikawa so as to allow penalty functions that take into account the local curvature of the curve. The key idea is to cast the segmentation problem as one of finding cyclic paths of minimal ratio in a graph where each graph node represents a line segment. Among ratios whose discrete counterparts can be globally minimized with our approach, we focus in particular on the elastic ratio [Formula: see text] that depends, given an image I, on the oriented boundary C of the segmented region candidate. Minimizing this ratio amounts to finding a curve, neither small nor too curvy, through which the brightness flux is maximal. We prove the existence of minimizers for this criterion among continuous curves with mild regularity assumptions. We also prove that the discrete minimizers provided by our graph-based algorithm converge, as the resolution increases, to continuous minimizers. In contrast to most existing segmentation methods with computable and meaningful, i.e., nondegenerate, global optima, the proposed approach is fully unsupervised in the sense that it does not require any kind of user input such as seed nodes. Numerical experiments demonstrate that curvature regularity allows substantial improvement of the quality of segmentations. Furthermore, our results allow drawing conclusions about global optima of a parameterization-independent version of the snakes functional: the proposed algorithm allows determining parameter values where the functional has a meaningful solution and simultaneously provides the corresponding global solution.

Chromophores from Photolyzed Ammonia Reacting with Acetylene: Application to Jupiter’s Great Red Spot

NASA Astrophysics Data System (ADS)

Carlson, Robert W.; Baines, K. H.; Anderson, M. S.; Filacchione, G.

2012-10-01

The production mechanisms of chromophores at Jupiter, and notably at the Great Red Spot (GRS), have been long-standing puzzles. A clue to the formation of the GRS coloring agent may be the great height of this storm, which can upwell ammonia to pressure levels of a few hundred mbar where solar photons capable of dissociating NH3 penetrate. Acetylene formed at higher altitudes can diffuse down and react with the NH3 photodissociation products, forming a deposit that absorbs in the ultraviolet and visible region (Ferris and Ishikawa, J. Amer. Chem. Soc. 110, 4306-4312, 1988). We have investigated the system NH3 + C2H2 + CH4 using a Zn lamp emitting at 214 nm to produce NH2 + H and subsequent reaction products. The deposits produced in these reactions were analyzed by optical and infrared spectroscopy and soft-ionization (He*) time-of-flight mass spectroscopy. The combination of NH3 + CH4 produced no visibly absorbing material, but NH3 + C2H2 and NH3 + C2H2 + CH4 mixtures both produced a yellow-orange film whose transmission spectra are similar to that of the GRS obtained by Cassini VIMS. Infrared spectra show a strong band at 2056 wavenumbers which may arise from nitrile (-CN), isonitrile (-NC), or diazide (-CNN) functional groups. The high-resolution mass spectra are consistent with compounds of the form CnH2n+1Nm, similar to the products formed in NH3 + CH4 spark discharges (Molton and Ponnamperuma, Icarus 21, 166-174, 1974). We thank NASA's Planetary Atmospheres Program for support.

FOREWORD: Focus on the Degradation and Stability of Polymers

NASA Astrophysics Data System (ADS)

Terano, Minoru

2008-06-01

Modern society is so reliant on polymers that products incorporating these macromolecules are almost 'invisible'. Polymers are indispensable materials used for manufacturing compact disks, clothes, lightweight airplanes, automobiles, footware and even the humble polystyrene boxes for packing our favorite hamburgers and fries. But, like many other materials, polymers degrade and become unstable, so a deeper understanding of the physical mechanisms responsible for degradation is necessary to address issues such as potential applications, recycling and the impact of polymer-products on the environment. In particular, polymers are highly vulnerable to oxidative degradation at elevated temperatures and in sunlight. Unfortunately, in spite of extensive research on polymer degradation, our knowledge is still incomplete. The analysis of polymer degradation and stability has recently become harder and more complicated because of the wider range of polymer applications, including blends and composites. Notably, composites with nanofillers are being studied for automotive, electrical and other industrial applications. With this background, the 1st International Symposium on Ultimate Stability of NanoStructured Polymers and Composites (NT2007) was held in October at the Japan Advanced Institute of Science and Technology in Ishikawa Prefecture. The meeting provided a forum to discuss advanced research achievements to resolve problems in this field of research. The papers selected for this focus issue describe recent discoveries on the stability, weatherability and flame retardancy of polymers, as well as providing an insight into degradation mechanisms of nanostructured polymers and composites. We hope that this focus issue will serve as a timely source of information about one of the most important topics in polymer science and related technologies.

Evaluating the “recovery level” of endangered species without prior information before alien invasion

PubMed Central

Watari, Yuya; Nishijima, Shota; Fukasawa, Marina; Yamada, Fumio; Abe, Shintaro; Miyashita, Tadashi

2013-01-01

For maintaining social and financial support for eradication programs of invasive species, quantitative assessment of recovery of native species or ecosystems is important because it provides a measurable parameter of success. However, setting a concrete goal for recovery is often difficult owing to lack of information prior to the introduction of invaders. Here, we present a novel approach to evaluate the achievement level of invasive predator management based on the carrying capacity of endangered species estimated using long-term monitoring data. In Amami-Oshima Island, Japan, where the eradication project of introduced small Indian mongoose is ongoing since 2000, we surveyed the population densities of four endangered species threatened by the mongoose (Amami rabbit, the Otton frog, Amami tip-nosed frog, and Amami Ishikawa's frog) at four time points ranging from 2003 to 2011. We estimated the carrying capacities of these species using the logistic growth model combined with the effects of mongoose predation and environmental heterogeneity. All species showed clear tendencies toward increasing their density in line with decreased mongoose density, and they exhibited density-dependent population growth. The estimated carrying capacities of three endangered species had small confidence intervals enough to measure recovery levels by the mongoose management. The population density of each endangered species has recovered to the level of the carrying capacity at about 20–40% of all sites, whereas no individuals were observed at more than 25% of all sites. We propose that the present approach involving appropriate monitoring data of native organism populations will be widely applicable to various eradication projects and provide unambiguous goals for management of invasive species. PMID:24363899

Lipid Identification by Untargeted Tandem Mass Spectrometry Coupled with Ultra-High-Pressure Liquid Chromatography.

PubMed

Gugiu, Gabriel B

2017-01-01

Lipidomics refers to the large-scale study of lipids in biological systems (Wenk, Nat Rev Drug Discov 4(7):594-610, 2005; Rolim et al., Gene 554(2):131-139, 2015). From a mass spectrometric point of view, by lipidomics we understand targeted or untargeted mass spectrometric analysis of lipids using either liquid chromatography (LC) (Castro-Perez et al., J Proteome Res 9(5):2377-2389, 2010) or shotgun (Han and Gross, Mass Spectrom Rev 24(3):367-412, 2005) approaches coupled with tandem mass spectrometry. This chapter describes the former methodology, which is becoming rapidly the preferred method for lipid identification owing to similarities with established omics workflows, such as proteomics (Washburn et al., Nat Biotechnol 19(3):242-247, 2001) or genomics (Yadav, J Biomol Tech: JBT 18(5):277, 2007). The workflow described consists in lipid extraction using a modified Bligh and Dyer method (Bligh and Dyer, Can J Biochem Physiol 37(8):911-917, 1959), ultra high pressure liquid chromatography fractionation of lipid samples on a reverse phase C18 column, followed by tandem mass spectrometric analysis and in silico database search for lipid identification based on MSMS spectrum matching (Kind et al., Nat Methods 10(8):755-758, 2013; Yamada et al., J Chromatogr A 1292:211-218, 2013; Taguchi and Ishikawa, J Chromatogr A 1217(25):4229-4239, 2010; Peake et al., Thermoscientifices 1-3, 2015) and accurate mass of parent ion (Sud et al., Nucleic Acids Res 35(database issue):D527-D532, 2007; Wishart et al., Nucleic Acids Res 35(database):D521-D526, 2007).

Fibulin-4 is associated with prognosis of endometrial cancer patients and inhibits cancer cell invasion and metastasis via Wnt/β-catenin signaling pathway

PubMed Central

Wang, Tiantian; Wang, Mei; Fang, Shuang; Wang, Qiang; Fang, Rui; Chen, Jie

2017-01-01

Fibulin-4, an extracellular glycoprotein, which plays significant roles in elastic fiber assembly, is correlated to the progression of some cancers. However, the role of fibulin-4 in endometrial cancer cell invasion and metastasis remains unexplored. In our study, fibulin-4 expression was assessed by immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in normal endometrial tissues and endometrial carcinoma tissues. Using single cell cloning, strongly, and weakly, invasive subclones were derived from KLE and Ishikawa endometrial carcinoma cell lines. RT-qPCR, western blotting, and immunocytochemistry (ICC) were used to assess mRNA and protein expressions of fibulin-4 in primary cultured endometrial cells, 4 types of endometrial cancer cell lines, and the different invasive subclones. Using lentivirus transfection, fibulin-4 shRNA and pLVX-fibulin-4 were constructed and used to infect the strongly and weakly invasive subclones. The effects of fibulin-4 on the biological characteristics of endometrial carcinoma cells were detected by cell functional assays in vitro and in vivo. Using Wnt signaling pathway inhibitor XAV-939 and activator LiCl, we detected the role of fibulin-4 in the Wnt/β-catenin pathway and the relationship with epithelial to mesenchymal transition (EMT). Fibulin-4 was decreased in endometrial carcinoma tissues, and loss of fibulin-4 expression was significantly related with poor differentiation, lymph node metastasis, and poor prognosis of endometrial carcinoma. Fibulin-4 significantly inhibited endometrial carcinoma cell proliferation, invasion, metastasis, and EMT through the Wnt/β-catenin pathway. Fibulin-4 has the ability to suppress endometrial cancer progression. These results can contribute to the development of a new potential therapeutic target for patients with endometrial carcinoma. PMID:28177909

Imiquimod Induces Apoptosis in Human Endometrial Cancer Cells In vitro and Prevents Tumor Progression In vivo

PubMed Central

Almomen, Aliyah; Jarboe, Elke A.; Dodson, Mark K.; Peterson, C. Matthew; Owen, Shawn C.; Janát-Amsbury, Margit M.

2016-01-01

Purpose The increasing incidence of endometrial cancer (EC), in younger age at diagnosis, calls for new tissue-sparing treatment options. This work aims to evaluate the potential of imiquimod (IQ) in the treatment of low-grade EC. Methods Effects of IQ on the viabilities of Ishikawa and HEC-1A cells were evaluated using MTT assay. The ability of IQ to induce apoptosis was evaluated by testing changes in caspase 3/7 levels and expression of cleaved caspase-3, using luminescence assay and western blot. Apoptosis was confirmed by flow cytometry and the expression of cleaved PARP. Western blot was used to evaluate the effect of IQ on expression levels of Bcl-2, Bcl-xL, and BAX. Finally, the in vivo efficacy of IQ was tested in an EC mouse model. Results There was a decrease in EC cell viability following IQ treatment as well as increased caspase 3/7 activities, cleaved caspase-3 expression, and Annexin-V/ 7AAD positive cell population. Western blot results showed the ability of IQ in cleaving PARP, decreasing Bcl-2 and Bcl-xL expressions, but not affecting BAX expression. In vivo study demonstrated IQ’s ability to inhibit EC tumor growth and progression without significant toxicity. Conclusions IQ induces apoptosis in low-grade EC cells in vitro, probably through its direct effect on Bcl-2 family protein expression. In, vivo, IQ attenuates EC tumor growth and progression, without an obvious toxicity. Our study provides the first building block for the potential role of IQ in the non-surgical management of low-grades EC and encouraging further investigations. PMID:27245465

Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients.

PubMed

Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria

2018-01-02

Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy.

The lesser of two adverse reactions.

PubMed

Chakraborti, Chayan; Egan, John

2010-01-01

Fundamental to complex systems are interconnected processes involved in providing high-quality patient care. A case study and a root cause analysis (RCA) illustrate a patient safety effort with unintended consequences. A 38-year-old woman presented to the hospital for odynophagia and vomiting. The patient developed Mobitz type 2, second-degree heart block temporally associated with the administration of intravenous ondansetron. RESPONSE TO THE EVENT: An Ishikawa, or fishbone, diagram conducted to enumerate potential contributing factors indicated that a key factor appeared to be an institutional restriction against using intravenous (i.v.) promethazine, which resulted in ondansetron being the only readily available i.v. anti-emetic on formulary. The anesthesia department requested that i.v. promethazine be removed from all operating and recovery room automated medication dispensing machines. The pharmacy department, given the realization that individual departments were taking independent action regarding promethazine, discussed the matter with the medical director, who issued a memo banning the use of i.v. promethazine. An institutional ban on i.v. anti-emetics such as promethazine may have resulted in an increase in the use of ondansetron and contributed to this adverse reaction. The reason to restrict promethazine is not well reported in the literature. In limiting the use of promethazine for patient safety concerns, the inadvertent increase in adverse reactions of the alternative medication, ondansetron, may have been overlooked. The resultant RCA underscores the need for careful cataloguing of adverse medication effects. Stakeholders should anticipate as many "downstream effects" of quality and patient safety improvements as possible. Comprehensive reporting of adverse medication effects will augment the emerging science of patient safety.

[Evaluation and improvement of the management of informed consent in the emergency department].

PubMed

del Pozo, P; García, J A; Escribano, M; Soria, V; Campillo-Soto, A; Aguayo-Albasini, J L

2009-01-01

To assess the preoperative management in our emergency surgical service and to improve the quality of the care provided to patients. In order to find the causes of non-compliance, the Ishikawa Fishbone diagram was used and eight assessment criteria were chosen. The first assessment includes 120 patients operated on from January to April 2007. Corrective measures were implemented, which consisted of meetings and conferences with doctors and nurses, insisting on the importance of the informed consent as a legal document which must be signed by patients, and the obligation of giving a copy to patients or relatives. The second assessment includes the period from July to October 2007 (n=120). We observed a high non-compliance of C1 signing of surgical consent (CRITERION 1: all patients or relatives have to sign the surgical informed consent for the operation to be performed [27.5%]) and C2 giving a copy of the surgical consent (CRITERION 2: all patients or relatives must have received a copy of the surgical informed consent for the Surgery to be performed [72.5%]) and C4 anaesthetic consent copy (CRITERION 4: all patients or relatives must have received a copy of the Anaesthesia informed consent corresponding to the operation performed [90%]). After implementing corrective measures a significant improvement was observed in the compliance of C2 and C4. In C1 there was an improvement without statistical significance. The carrying out of an improvement cycle enabled the main objective of this paper to be achieved: to improve the management of informed consent and the quality of the care and information provided to our patients.

[Not Available].

PubMed

Abril, Encarnación; Gómez-Conesa, Antonia; Gutiérrez-Santos, Manuel

2008-05-01

To assess the quality of physiotherapeutic care in patients treated for low back pain in a Primary Health Care physiotherapy unit, and to improve the quality of the care provided to these patients. The first assessment includes all patients treated in 2002 (n=83). Five criteria corresponding to the initial physiotherapeutic assessment were chosen: C1, pain; C2, disability; C3, mobility, muscle examination, and C5, palpation. In order to detect non-compliance, the Ishikawa Fishbone diagram was used. Corrective measures were established in November 2003: publication of an Oswestry questionnaire model for assessing disability and reflecting on the results obtained. The second assessment includes the period of time from 1st November 2003 to 6th April 2004 (n=32). In the initial assessment, compliances observed were: C1: 21.69%; C2: 0; C3: 69.87%; C4: 78.31%, and C5: 84.33%. After implementing corrective measures a significant improvement was observed in the compliance of C1, C2, and C3. In C4 there was an improvement, and in C5 there was a decrease in compliance, both of them without statistical significance. The carrying out of an improvement cycle has enabled non-compliances in the application of this protocol to be detected and corrected. The corrective measures implemented have led to a reduction of the variability in the records. It is advisable to ensure that compliance does not decrease in the areas that initially showed a high level of compliance. Copyright © 2008 Sociedad Española de Calidad Asistencial. Published by Elsevier Espana. All rights reserved.

Virtual Telemedicine Visits in Pediatric Home Parenteral Nutrition Patients: A Quality Improvement Initiative.

PubMed

Raphael, Bram P; Schumann, Caitlin; Garrity-Gentille, Sara; McClelland, Jennifer; Rosa, Carolyn; Tascione, Christina; Gallotto, Mary; Takvorian-Bené, Melissa; Carey, Alexandra N; McCarthy, Patrick; Duggan, Christopher; Ozonoff, Al

2018-05-04

Despite being less costly than prolonged hospitalization, home parenteral nutrition (HPN) is associated with high rates of post-discharge complications, including frequent readmissions and central line-associated bloodstream infections (CLABSIs). Telemedicine has been associated with improved outcomes and reduced healthcare utilization in other high-risk populations, but no studies to date have supported effectiveness of telemedicine in pediatric HPN. We prospectively collected data on pediatric patients managed at a single HPN program who participated in postdischarge telemedicine visits from March 1, 2014 to March 30, 2016. We excluded patients with a history of HPN and strictly palliative care goals. Univariate analysis was performed for primary outcomes: Community-acquired CLABSI and 30-day readmission rate. Twenty-six families participated in the pilot initiative with median (interquartile range) patient age 1.5 (5.7) years old, diagnosis of short bowel syndrome in 16 (62%), and in-state residence in 17 (55%). Ishikawa (fishbone) diagram identified causes of post-discharge HPN complications. Areas of focus during telemedicine visit included central venous catheter care methods, materials, clinical concerns, and equipment. Compared to historical comparison group, the telemedicine group experienced CLABSI rates of 1.0 versus 2.7 per 1,000 line days and readmission rates of 38% versus 17% (p = 0.03, 0.02, respectively). Telemedicine visits identified opportunities for improvement for families newly discharged on HPN. In a small cohort of patients who experienced telemedicine visits, we found lower CLABSI rates alongside higher readmission rates compared with a historical comparison group. Further studies are needed to optimize telemedicine in delivering care to this high-risk population.

Validity and reliability of the Japanese version of the Newest Vital Sign: a preliminary study.

PubMed

Kogure, Takamichi; Sumitani, Masahiko; Suka, Machi; Ishikawa, Hirono; Odajima, Takeshi; Igarashi, Ataru; Kusama, Makiko; Okamoto, Masako; Sugimori, Hiroki; Kawahara, Kazuo

2014-01-01

Health literacy (HL) refers to the ability to obtain, process, and understand basic health information and services, and is thus needed to make appropriate health decisions. The Newest Vital Sign (NVS) is comprised of 6 questions about an ice cream nutrition label and assesses HL numeracy skills. We developed a Japanese version of the NVS (NVS-J) and evaluated the validity and reliability of the NVS-J in patients with chronic pain. The translation of the original NVS into Japanese was achieved as per the published guidelines. An observational study was subsequently performed to evaluate the validity and reliability of the NVS-J in 43 Japanese patients suffering from chronic pain. Factor analysis with promax rotation, using the Kaiser criterion (eigenvalues ≥1.0), and a scree plot revealed that the main component of the NVS-J consists of three determinative factors, and each factor consists of two NVS-J items. The criterion-related validity of the total NVS-J score was significantly correlated with the total score of Ishikawa et al.'s self-rated HL Questionnaire, the clinical global assessment of comprehensive HL level, cognitive function, and the Brinkman index. In addition, Cronbach's coefficient for the total score of the NVS-J was adequate (alpha = 0.72). This study demonstrated that the NVS-J has good validity and reliability. Further, the NVS-J consists of three determinative factors: "basic numeracy ability," "complex numeracy ability," and "serious-minded ability." These three HL abilities comprise a 3-step hierarchical structure. Adequate HL should be promoted in chronic pain patients to enable coping, improve functioning, and increase activities of daily living (ADLs) and quality of life (QOL).

Enhancer of zeste homolog 2 blockade by RNA interference is implicated with inhibited proliferation, invasion and promoted apoptosis in endometrial carcinoma.

PubMed

Wang, Juan; Ai, Zhihong; Chen, Jing; Teng, Yincheng; Zhu, Jieping

2018-06-01

Endometrial carcinoma is the most common gynecological malignancy of the female genital tract worldwide (2012). Enhancer of zeste homolog 2 (EZH2), a critical component of the polycomb repressive complex 2, has been found to be associated with multiple biological processes and is overexpressed in multiple types of cancer. Previous studies have demonstrated that EZH2 is associated with endometrial carcinoma. The present study investigated the expression and biology function of EZH2 in endometrial cancer (EC). It was found that EZH2 levels were markedly increased in endometrial cancer tissues compared with that in adjacent normal tissues. EZH2 was significantly overexpressed in 3 separate endometrial cancer cell lines (Ishikawa, RL95-2 and HEC1-A) when compared with the normal endometrial cell line ESC. Additionally, small interfering RNA was used to investigate the role of EZH2 in endometrial carcinoma cell proliferation, and the results showed that EZH2 knockdown suppressed the proliferation of endometrial carcinoma cells in vitro . Furthermore, EZH2 knockdown induced apoptosis of human EC cells by promoting the expression of pro-apoptosis protein caspase 3, caspase 9, BCL2 associated X and decreasing the expression of anti-apoptosis protein Bcl-2. Finally, the present study demonstrated that EZH2 knockdown suppressed the invasion of EC cells through downregulation of the epithelial-mesenchymal transition. Collectively, these data demonstrate that EZH2 is frequently overexpressed in EC cells and its overexpression is associated with promoting the proliferation and invasion and decreasing the apoptosis of EC cells, suggesting that EZH2 may provide potential therapeutic targets for treatment of endometrial carcinoma.

QbD-Enabled Development of Novel Stimuli-Responsive Gastroretentive Systems of Acyclovir for Improved Patient Compliance and Biopharmaceutical Performance.

PubMed

Singh, Bhupinder; Kaur, Anterpreet; Dhiman, Shashi; Garg, Babita; Khurana, Rajneet Kaur; Beg, Sarwar

2016-04-01

The current studies entail systematic quality by design (QbD)-based development of stimuli-responsive gastroretentive drug delivery systems (GRDDS) of acyclovir using polysaccharide blends for attaining controlled drug release profile and improved patient compliance. The patient-centric quality target product profile was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies, carried out through Ishikawa fish bone diagram and failure mode, effect, and criticality analysis, helped in identifying the plausible risks or failure modes affecting the quality attributes of the drug product. A face-centered cubic design was employed for systematic development and optimization of the concentration of sodium alginate (X 1) and gellan (X 2) as the critical material attributes (CMAs) in the stimuli-responsive formulations, which were evaluated for CQAs viz. viscosity, gel strength, onset of floatation, and drug release characteristics. Mathematical modeling was carried out for generation of design space, and optimum formulation was embarked upon, exhibiting formulation characteristics marked by excellent floatation and bioadhesion characteristics along with promising drug release control up to 24 h. Drug-excipient compatibility studies through FTIR and DSC revealed absence of any interaction(s) among the formulation excipients. In vivo pharmacokinetic studies in Wistar rats corroborated extension in the drug absorption profile from the optimized stimuli-responsive GR formulations vis-à-vis the marketed suspension (ZOVIRAX®). Establishment of in vitro/in vivo correlation (IVIVC) revealed a high degree of correlation between the in vitro and in vivo data. In a nutshell, the present investigations report the successful development of stimuli-responsive GRDDS of acyclovir, which can be applicable as a platform approach for other drugs too.

QbD-enabled systematic development of gastroretentive multiple-unit microballoons of itopride hydrochloride.

PubMed

Bansal, Sanjay; Beg, Sarwar; Asthana, Abhay; Garg, Babita; Asthana, Gyati Shilakari; Kapil, Rishi; Singh, Bhupinder

2016-01-01

The objectives of present studies were to develop the systematically optimized multiple-unit gastroretentive microballoons, i.e. hollow microspheres of itopride hydrochloride (ITH) employing quality by design (QbD)-based approach. Initially, the patient-centric QTPP and CQAs were earmarked, and preliminary studies were conducted to screen the suitable polymer, solvent, solvent ratio, pH and temperature conditions. Microspheres were prepared by non-aqueous solvent evaporation method employing Eudragit S-100. Risk assessment studies carried out by constructing Ishikawa cause-effect fish-bone diagram, and techniques like risk estimation matrix (REM) and failure mode effect analysis (FMEA) facilitated the selection of plausible factors affecting the drug product CQAs, i.e. percent yield, entrapment efficiency (EE) and percent buoyancy. A 3(3) Box-Behnken design (BBD) was employed for optimizing CMAs and CPPs selected during factor screening studies employing Taguchi design, i.e. drug-polymer ratio (X1), stirring temperature (X2) and stirring speed (X3). The hollow microspheres, as per BBD, were evaluated for EE, particle size and drug release characteristics. The optimum formulation was embarked upon using numerical desirability function yielding excellent floatation characteristics along with adequate drug release control. Drug-excipient compatibility studies employing FT-IR, DSC and powder XRD revealed absence of significant interaction among the formulation excipients. The SEM studies on the optimized formulation showed hollow and spherical nature of the prepared microspheres. In vivo X-ray imaging studies in rabbits confirmed the buoyant nature of the hollow microspheres for 8 h in the upper GI tract. In a nutshell, the current investigations report the successful development of gastroretentive floating microspheres for once-a-day administration of ITH.

Sustainable Water Use System of Artesian Water in Alluvial Fan

NASA Astrophysics Data System (ADS)

Kishi, K.; Tsujimura, M.; Tase, N.

2013-12-01

The traditional water use system, developed with the intelligence of the local residents, usually takes advantage of local natural resources and is considered as a sustainable system, because of its energy saving(only forces of nature). For this reason, such kind of water use system is also recommended in some strategic policies for the purpose of a symbiosis between nature and human society. Therefore, it is important to clarify the relationship between human activities and water use systems. This study aims to clarify the mechanism of traditional water use processes in alluvial fan, and in addition, to investigate the important factors which help forming a sustainable water use system from the aspects of natural conditions and human activities. The study area, an alluvial fan region named Adogawa, is located in Shiga Prefecture, Japan and is in the west of Biwa Lake which is the largest lake in Japan. In this alluvial region where the land use is mainly occupied by settlements and paddy fields, a groundwater flowing well system is called "kabata" according to local tradition. During field survey, we took samples of groundwater, river water and lake water as well as measured the potential head of groundwater. The results showed that the upper boundary of flowing water was approximately 88m amsl, which is basically the same as the results reported by Kishi and Kanno (1966). In study area, a rapid increase of water pumping for domestic water use and melting snow during last 50 years, even if the irrigation area has decreased about 30% since 1970, and this fact may cause a decrease in recharge rate to groundwater. However, the groundwater level didn't decline based on the observed results, which is probably contributed by some water conservancy projects on Biwa Lake which maintained the water level of the lake. All the water samples are characterized by Ca-HCO3 type and similar stable isotopic value of δD and δ18O. Groundwater level in irrigation season is higher

Decreased PECAM1-mediated TGF-β1 expression in the mid-secretory endometrium in women with recurrent implantation failure.

PubMed

Guo, Feng; Si, Chenchen; Zhou, Mingjuan; Wang, Jingwen; Zhang, Dan; Leung, Peter C K; Xu, Bufang; Zhang, Aijun

2018-05-01

Is recurrent implantation failure (RIF) associated with decreased expression of platelet and endothelial cell adhesion molecule 1 (PECAM1) and transforming growth factor β1 (TGF-β1) in the endometrium during the implantation window? The present study demonstrates that the expression of PECAM1 and TGF-β1 is significantly decreased in the mid-secretory endometrium in women with RIF, which may account for embryo implantation failure. RIF has become a bottleneck issue that hampers the improvement of pregnancy rates in IVF-embryo transfer (IVF-ET). The causes of RIF are complex and may involve the dysregulation of various growth factors, metabolites, and inflammatory cytokines. At present, the precise pathogenesis of RIF has not been elucidated. This was a prospective case-control study. Endometrial tissue samples were obtained from January 2014 to December 2016 from two groups of women who had undergone IVF (RIF group, 22 women who underwent ≥3 ETs including a total of ≥4 good-quality embryos without pregnancy, control group, 18 women who conceived in their first treatment cycle). At the same time, samples were obtained from 18 women with infertility secondary to tubal factor in the early proliferative, late proliferative and mid-secretory phases of the menstrual cycle (n = 6 per group). Samples used for isolation of primary human endometrial epithelial cells and stromal cells (HEECs and HESCs) were collected in December 2017 from six women with infertility secondary to tubal factor. We investigated gene expression using integrative whole genome expression microarray analysis, including differentially expressed gene screening, principal component analysis, and functional enrichment analysis. RT-qPCR, western blotting, immunohistochemistry, immunofluorescence co-localization analysis and short hairpin RNA (shRNA) plasmid transfection in Ishikawa cell line, HEECs and HESCs were used to investigate the expression of PECAM1 and TGF-β1. Integrative data mining of

Blog Posting After Lung Cancer Notification: Content Analysis of Blogs Written by Patients or Their Families.

PubMed

Sato, Akira; Aramaki, Eiji; Shimamoto, Yumiko; Tanaka, Shiro; Kawakami, Koji

2015-05-18

anxiety in 495 sentences. Our results showed that there were substantially more posts concerning "Way of living, reasons for living, set of values" and "Relationships with medical staff (own hospital)" than in previous studies (Analysis B). This study provides insight into the feelings of dissatisfaction and anxieties held by lung cancer patients and their families, including those regarding the "Way of living, reasons for living, set of values" and "Relationship with medical staff (own hospital)," which were inaccessible in previous survey analyses. When comparing information obtained from patients' voluntary records and those from previous surveys conducted by health care institutions, it is likely that the former would be more indicative of patients' actual opinions and feelings. Therefore, it is important to utilize such records as an information resource. ©Akira Sato, Eiji Aramaki, Yumiko Shimamoto, Shiro Tanaka, Koji Kawakami. , 18.05.2015.

Pancreatic α-Amylase Controls Glucose Assimilation by Duodenal Retrieval through N-Glycan-specific Binding, Endocytosis, and Degradation*

PubMed Central

Date, Kimie; Satoh, Ayano; Iida, Kaoruko; Ogawa, Haruko

2015-01-01

α-Amylase, a major pancreatic protein and starch hydrolase, is essential for energy acquisition. Mammalian pancreatic α-amylase binds specifically to glycoprotein N-glycans in the brush-border membrane to activate starch digestion, whereas it significantly inhibits glucose uptake by Na+/glucose cotransporter 1 (SGLT1) at high concentrations (Asanuma-Date, K., Hirano, Y., Le, N., Sano, K., Kawasaki, N., Hashii, N., Hiruta, Y., Nakayama, K., Umemura, M., Ishikawa, K., Sakagami, H., and Ogawa, H. (2012) Functional regulation of sugar assimilation by N-glycan-specific interaction of pancreatic α-amylase with glycoproteins of duodenal brush border membrane. J. Biol. Chem. 287, 23104–23118). However, how the inhibition is stopped was unknown. Here, we show a new mechanism for the regulation of intestinal glucose absorption. Immunohistochemistry revealed that α-amylase in the duodena of non-fasted, but not fasted, pigs was internalized from the pancreatic fluid and immunostained. We demonstrated that after N-glycan binding, pancreatic α-amylase underwent internalization into lysosomes in a process that was inhibited by α-mannoside. The internalized α-amylase was degraded, showing low enzymatic activity and molecular weight at the basolateral membrane. In a human intestinal Caco-2 cell line, Alexa Fluor 488-labeled pancreatic α-amylase bound to the cytomembrane was transported to lysosomes through the endocytic pathway and then disappeared, suggesting degradation. Our findings indicate that N-glycan recognition by α-amylase protects enterocytes against a sudden increase in glucose concentration and restores glucose uptake by gradual internalization, which homeostatically controls the postprandial blood glucose level. The internalization of α-amylase may also enhance the supply of amino acids required for the high turnover of small intestine epithelial cells. This study provides novel and significant insights into the control of blood sugar during the absorption

SU-E-T-50: A Multi-Institutional Study of Independent Dose Verification Software Program for Lung SBRT

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

Kawai, D; Takahashi, R; Kamima, T

2015-06-15

Purpose: The accuracy of dose distribution depends on treatment planning system especially in heterogeneity-region. The tolerance level (TL) of the secondary check using the independent dose verification may be variable in lung SBRT plans. We conducted a multi-institutional study to evaluate the tolerance level of lung SBRT plans shown in the AAPM TG114. Methods: Five institutes in Japan participated in this study. All of the institutes used a same independent dose verification software program (Simple MU Analysis: SMU, Triangle Product, Ishikawa, JP), which is Clarkson-based and CT images were used to compute radiological path length. Analytical Anisotropic Algorithm (AAA), Pencilmore » Beam Convolution with modified Batho-method (PBC-B) and Adaptive Convolve (AC) were used for lung SBRT planning. A measurement using an ion-chamber was performed in a heterogeneous phantom to compare doses from the three different algorithms and the SMU to the measured dose. In addition to it, a retrospective analysis using clinical lung SBRT plans (547 beams from 77 patients) was conducted to evaluate the confidence limit (CL, Average±2SD) in dose between the three algorithms and the SMU. Results: Compared to the measurement, the AAA showed the larger systematic dose error of 2.9±3.2% than PBC-B and AC. The Clarkson-based SMU showed larger error of 5.8±3.8%. The CLs for clinical plans were 7.7±6.0 % (AAA), 5.3±3.3 % (AC), 5.7±3.4 % (PBC -B), respectively. Conclusion: The TLs from the CLs were evaluated. A Clarkson-based system shows a large systematic variation because of inhomogeneous correction. The AAA showed a significant variation. Thus, we must consider the difference of inhomogeneous correction as well as the dependence of dose calculation engine.« less

SU-E-T-762: Toward Volume-Based Independent Dose Verification as Secondary Check

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

Tachibana, H; Tachibana, R

2015-06-15

Purpose: Lung SBRT plan has been shifted to volume prescription technique. However, point dose agreement is still verified using independent dose verification at the secondary check. The volume dose verification is more affected by inhomogeneous correction rather than point dose verification currently used as the check. A feasibility study for volume dose verification was conducted in lung SBRT plan. Methods: Six SBRT plans were collected in our institute. Two dose distributions with / without inhomogeneous correction were generated using Adaptive Convolve (AC) in Pinnacle3. Simple MU Analysis (SMU, Triangle Product, Ishikawa, JP) was used as the independent dose verification softwaremore » program, in which a modified Clarkson-based algorithm was implemented and radiological path length was computed using CT images independently to the treatment planning system. The agreement in point dose and mean dose between the AC with / without the correction and the SMU were assessed. Results: In the point dose evaluation for the center of the GTV, the difference shows the systematic shift (4.5% ± 1.9 %) in comparison of the AC with the inhomogeneous correction, on the other hands, there was good agreement of 0.2 ± 0.9% between the SMU and the AC without the correction. In the volume evaluation, there were significant differences in mean dose for not only PTV (14.2 ± 5.1 %) but also GTV (8.0 ± 5.1 %) compared to the AC with the correction. Without the correction, the SMU showed good agreement for GTV (1.5 ± 0.9%) as well as PTV (0.9% ± 1.0%). Conclusion: The volume evaluation for secondary check may be possible in homogenous region. However, the volume including the inhomogeneous media would make larger discrepancy. Dose calculation algorithm for independent verification needs to be modified to take into account the inhomogeneous correction.« less

SU-E-T-49: A Multi-Institutional Study of Independent Dose Verification for IMRT

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

Baba, H; Tachibana, H; Kamima, T

2015-06-15

Purpose: AAPM TG114 does not cover the independent verification for IMRT. We conducted a study of independent dose verification for IMRT in seven institutes to show the feasibility. Methods: 384 IMRT plans in the sites of prostate and head and neck (HN) were collected from the institutes, where the planning was performed using Eclipse and Pinnacle3 with the two techniques of step and shoot (S&S) and sliding window (SW). All of the institutes used a same independent dose verification software program (Simple MU Analysis: SMU, Triangle Product, Ishikawa, JP), which is Clarkson-based and CT images were used to compute radiologicalmore » path length. An ion-chamber measurement in a water-equivalent slab phantom was performed to compare the doses computed using the TPS and an independent dose verification program. Additionally, the agreement in dose computed in patient CT images between using the TPS and using the SMU was assessed. The dose of the composite beams in the plan was evaluated. Results: The agreement between the measurement and the SMU were −2.3±1.9 % and −5.6±3.6 % for prostate and HN sites, respectively. The agreement between the TPSs and the SMU were −2.1±1.9 % and −3.0±3.7 for prostate and HN sites, respectively. There was a negative systematic difference with similar standard deviation and the difference was larger in the HN site. The S&S technique showed a statistically significant difference between the SW. Because the Clarkson-based method in the independent program underestimated (cannot consider) the dose under the MLC. Conclusion: The accuracy would be improved when the Clarkson-based algorithm should be modified for IMRT and the tolerance level would be within 5%.« less

Discovery of diethyl 2,5-diaminothiophene-3,4-dicarboxylate derivatives as potent anticancer and antimicrobial agents and screening of anti-diabetic activity: synthesis and in vitro biological evaluation. Part 1.

PubMed

Bozorov, Khurshed; Ma, Hai-Rong; Zhao, Jiang-Yu; Zhao, Hai-Qing; Chen, Hua; Bobakulov, Khayrulla; Xin, Xue-Lei; Elmuradov, Burkhon; Shakhidoyatov, Khusnutdin; Aisa, Haji A

2014-09-12

Series of diethyl 2,5-diaminothiophene-3,4-dicarboxylate (DDTD) derivatives: azomethines of DDTD (2a-l) have been synthesized and screened for their anticancer, antimicrobial and anti-diabetic activities. The novel synthesized compounds were characterized by (1)H, (13)C NMR, MS and FT-IR analyses. All compounds were evaluated for their antiproliferative activity against three types of cancer cell line such as T47D and MCF-7 (human breast cancer), Hela (human cervical cancer) and Ishikawa (human endometrial cancer) lines. The results showed that most compounds exhibited significant antiproliferative activity against breast cancer cells. The majority of azomethines DDTD influenced strongly against breast cancer cells T47D and MCF-7, among them compounds 2b (2.3 μM), 2c (12.1 μM), 2e (13.2 μM), 2i (14.9 μM), 2j (16.0 μM), 2k (7.1 μM), 2l (8.6 μM) manifest potent anticancer activity against cancer cell T47D than Doxorubicin (DOX, 15.5 μM). Compound 2j has shown potent activity on all three types of cancer cells concurrently and IC50 values were considerably low in comparison with positive control DOX. In addition, all compounds were tested for antimicrobial activity against Staphylococcus aureus ATCC 6538 (Gram positive bacteria), Escherichia coli ATCC 11229 (Gram negative bacteria) and Candida albicans ATCC 10231 (Fungi) strains and 2j which contains in the ring nitrofurfural fragment, showed the highest effect on the three species of microbial pathogens simultaneously. Some compounds induced enzymatic inhibition in a concentration-dependent manner on PTP-1B inhibitor. Copyright © 2014. Published by Elsevier Masson SAS.

Inhibition of osteopontin suppresses in vitro and in vivo angiogenesis in endometrial cancer.

PubMed

Du, Xue-lian; Jiang, Tao; Sheng, Xiu-gui; Gao, Rong; Li, Qing-shui

2009-12-01

Osteopontin (OPN) has been found to play an important role in tumor angiogenesis in recent years. Our previous studies have shown that OPN is overexpressed in tumor-associated human endometrial endothelial cells (HEECs) isolated from tissue samples of patients with endometrial cancer. In the present study, we aimed to further determine the role of OPN in endometrial cancer-associated angiogenesis. We knock down OPN expression in HEECs and human endometrial cancer Ishikawa (ISK) cells using the small interference RNA method, and then evaluate the effects of OPN on endometrial cancer-associated angiogenesis by in vivo mouse studies and in vitro assays. Our results revealed that proliferative activity of HEECs and ISK cells in vitro was not affected by transfection with the siOPN-RNA (P>0.05). Inhibition of OPN expression in HEECs reduced the cell migration, with the percentage of repaired area of 36.32+/-2.88 vs. 8.54+/-1.13 (P=0.007). HEEC/siOPN and ISK/siOPN demonstrated 67.4% and 51.2% decreased invasiveness compared with controls, respectively (P<0.05). The number of branched points per well was obviously lower in HEEC/siOPN than that in HEEC/Control (32.46+/-17.10 vs. 53.15+/-15.44, P=0.021). Furthermore, ISK cells transfected with OPN siRNA formed smaller tumor in mice and led to a lower microvessel density, i.e., angiogenesis, in transplanted tumors of mice than scrambled siRNA controls (12.88+/-7.14 vs. 28.42+/-9.69 vessels per HPF, P=0.019). These data confirm the positive role of OPN in endometrial cancer-associated angiogenesis and might be of great benefit for finding rational approach in endometrial cancer therapy.

IL-17A contributes to the pathogenesis of endometriosis by triggering pro-inflammatory cytokines and angiogenic growth factors

PubMed Central

Ahn, Soo Hyun; Edwards, Andrew K.; Singh, Sukhbir S.; Young, Steven L.; Lessey, Bruce A.; Tayade, Chandrakant

2015-01-01

Endometriosis is a chronic, inflammatory disease characterized by the growth of endometrial tissue in aberrant locations outside the uterus. Neo-angiogenesis or establishment of new blood supply is one of the fundamental requirements of endometriotic lesion survival in the peritoneal cavity. IL-17A is emerging as a potent angiogenic and pro-inflammatory cytokine involved in the pathophysiology of several chronic inflammatory diseases such as rheumatoid arthritis and psoriasis. However, sparse information is available in the context of endometriosis. In this study, we demonstrate the potential importance of IL-17A in the pathogenesis and pathophysiology of endometriosis. The data show a differential expression of IL-17A in human ectopic endometriotic lesions and matched eutopic endometrium from women with endometriosis. Importantly, surgical removal of lesions resulted in significantly reduced plasma IL-17A concentrations. Immunohistochemistry revealed localization of IL-17A primarily in the stroma of matched ectopic and eutopic tissue samples. In vitro stimulation of endometrial epithelial carcinoma cells, Ishikawa cells and human umbilical vein endothelial cells with IL-17A revealed significant increase in angiogenic (VEGF, IL-8), pro-inflammatory (IL-6, IL-1β) and chemotactic cytokines (G-CSF, CXCL12, CXCL1, CX3CL1). Furthermore, IL-17A promoted tubulogenesis of HUVECs plated on matrigel in a dose-dependent manner. Thus we provide the first evidence that endometriotic lesions produce IL-17A and that the removal of the lesion via laparoscopic surgery leads to the significant reduction in the systemic levels of IL-17A. Taken together, our data shows a likely important role of IL-17A in promoting angiogenesis and pro-inflammatory environment in the peritoneal cavity for the establishment and maintenance of endometriosis lesions. PMID:26259585

Transcriptional expression of type-I interferon response genes and stability of housekeeping genes in the human endometrium and endometriosis.

PubMed

Vestergaard, Anna L; Knudsen, Ulla B; Munk, Torben; Rosbach, Hanne; Martensen, Pia M

2011-04-01

Endometriosis is a painful chronic female disease defined by the presence of endometrial tissue implants in ectopic (Ec) locations. The pathogenesis is much debated, and type-I interferons (IFNs) could be involved. The expression of genes of the type-I IFN response were profiled by a specific PCR array of RNA obtained from Ec and eutopic (Eu) endometrium collected from nine endometriosis patients and nine healthy control women. Transcriptional expression levels of selected IFN-regulated and housekeeping genes (HKGs) were investigated by real-time quantitative reverse transcriptase PCR (qRT-PCR). Stably expressed HKGs for valid normalization of transcriptional studies of endometrium and endometriosis have not yet been published. Here, seven HKGs were evaluated for stability using the GeNorm and NormFinder software. A normalization factor based on HMBS, TBP and YWHAZ expression was suitable for normalization of qRT-PCR studies of Eu versus Ec endometrium. In the endometrial cell lines HEC1A, HEC1B, Ishikawa and RL95-2, HMBS and HPRT1 were the most stably expressed. The IFN-specific PCR array indicated significantly different expression of the genes BST2, COL16A1, HOXB2 and ISG20 between the endometrial tissue types. However, by correctly normalized qRT-PCR, levels of BST2, COL16A1 and the highly type-I IFN-stimulated genes ISG12A and 6-16 displayed insignificant variations. Conversely, HOXB2 and ISG20 transcriptions were significantly reduced in endometriosis lesions compared with endometrium from endometriosis patients and healthy controls. In conclusion, appropriate HKGs for normalization of qRT-PCR studies of endometrium and endometriosis have been identified here. Abolished expression of ISG20 and HOX genes could be important in endometriosis.

Novel software for analysis of root gravitropism: comparative response patterns of Arabidopsis wild-type and axr1 seedlings

NASA Technical Reports Server (NTRS)

Ishikawa, H.; Evans, M. L.

1997-01-01

In an earlier study (Evans, Ishikawa & Estelle 1994, Planta 194, 215-222) we used a video digitizer system to compare the kinetics of auxin action on root elongation in wild-type seedlings and seedlings of auxin response mutants of Arabidopsis thaliana (L.) Heynh. We have since modified the system software to allow determination of elongation on opposite sides of vertical or gravistimulated roots and to allow continuous measurement of the angle of orientation of sequential subsections of the root during the response. We used this technology to compare the patterns of differential growth that generate curvature in roots of the Columbia ecotype and in the mutants axr1-3, axr1-12 and axr2, which show reduced gravitropic responsiveness and reduced sensitivity to inhibition by auxin. The pattern of differential growth during gravitropism differed in roots of wild-type and axr1 seedlings. In wild-type roots, initial curvature resulted from differential inhibition of elongation in the distal elongation zone (DEZ). This was followed by an acceleration of elongation along the top side of the DEZ. In roots of axr1-3, curvature resulted from differential stimulation of elongation whereas in roots of axr1-12 the response was variable. Roots of axr2 did not exhibit gravitropic curvature. The observation that the pattern of differential growth causing curvature is dramatically altered by a change in sensitivity to auxin is consistent with the classical Cholodny-Went theory of gravitropism which maintains that differential growth patterns induced by gravistimulation are mediated primarily by gravi-induced shifts in auxin distribution. The new technology introduced with this report allows automated determination of stimulus response patterns in the small but experimentally popular roots of Arabidopsis.

SU-F-T-267: A Clarkson-Based Independent Dose Verification for the Helical Tomotherapy

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

Nagata, H; Juntendo University, Hongo, Tokyo; Hongo, H

2016-06-15

Purpose: There have been few reports for independent dose verification for Tomotherapy. We evaluated the accuracy and the effectiveness of an independent dose verification system for the Tomotherapy. Methods: Simple MU Analysis (SMU, Triangle Product, Ishikawa, Japan) was used as the independent verification system and the system implemented a Clarkson-based dose calculation algorithm using CT image dataset. For dose calculation in the SMU, the Tomotherapy machine-specific dosimetric parameters (TMR, Scp, OAR and MLC transmission factor) were registered as the machine beam data. Dose calculation was performed after Tomotherapy sinogram from DICOM-RT plan information was converted to the information for MUmore » and MLC location at more segmented control points. The performance of the SMU was assessed by a point dose measurement in non-IMRT and IMRT plans (simple target and mock prostate plans). Subsequently, 30 patients’ treatment plans for prostate were compared. Results: From the comparison, dose differences between the SMU and the measurement were within 3% for all cases in non-IMRT plans. In the IMRT plan for the simple target, the differences (Average±1SD) were −0.70±1.10% (SMU vs. TPS), −0.40±0.10% (measurement vs. TPS) and −1.20±1.00% (measurement vs. SMU), respectively. For the mock prostate, the differences were −0.40±0.60% (SMU vs. TPS), −0.50±0.90% (measurement vs. TPS) and −0.90±0.60% (measurement vs. SMU), respectively. For patients’ plans, the difference was −0.50±2.10% (SMU vs. TPS). Conclusion: A Clarkson-based independent dose verification for the Tomotherapy can be clinically available as a secondary check with the similar tolerance level of AAPM Task group 114. This research is partially supported by Japan Agency for Medical Research and Development (AMED)« less

A Lean Six Sigma approach to the improvement of the selenium analysis method.

PubMed

Cloete, Bronwyn C; Bester, André

2012-11-02

Reliable results represent the pinnacle assessment of quality of an analytical laboratory, and therefore variability is considered to be a critical quality problem associated with the selenium analysis method executed at Western Cape Provincial Veterinary Laboratory (WCPVL). The elimination and control of variability is undoubtedly of significant importance because of the narrow margin of safety between toxic and deficient doses of the trace element for good animal health. A quality methodology known as Lean Six Sigma was believed to present the most feasible solution for overcoming the adverse effect of variation, through steps towards analytical process improvement. Lean Six Sigma represents a form of scientific method type, which is empirical, inductive and deductive, and systematic, which relies on data, and is fact-based. The Lean Six Sigma methodology comprises five macro-phases, namely Define, Measure, Analyse, Improve and Control (DMAIC). Both qualitative and quantitative laboratory data were collected in terms of these phases. Qualitative data were collected by using quality-tools, namely an Ishikawa diagram, a Pareto chart, Kaizen analysis and a Failure Mode Effect analysis tool. Quantitative laboratory data, based on the analytical chemistry test method, were collected through a controlled experiment. The controlled experiment entailed 13 replicated runs of the selenium test method, whereby 11 samples were repetitively analysed, whilst Certified Reference Material (CRM) was also included in 6 of the runs. Laboratory results obtained from the controlled experiment was analysed by using statistical methods, commonly associated with quality validation of chemistry procedures. Analysis of both sets of data yielded an improved selenium analysis method, believed to provide greater reliability of results, in addition to a greatly reduced cycle time and superior control features. Lean Six Sigma may therefore be regarded as a valuable tool in any laboratory, and

Cytokine stimulation of MUC4 expression in human female reproductive tissue carcinoma cell lines and endometrial cancer.

PubMed

Chapela, Patricia J; Broaddus, Russell R; Hawkins, Shannon M; Lessey, Bruce A; Carson, Daniel D

2015-11-01

MUC4, a transmembrane glycoprotein, interferes with cell adhesion, and promotes EGFR signaling in cancer. Studies in rat models have demonstrated steroid hormonal regulation of endometrial MUC4 expression. In this study, qRT-PCR screening of mouse tissues determined that Muc4 mRNA also was robustly expressed in mouse uteri. Previous studies from our labs have demonstrated MUC4 mRNA was expressed at levels <1% of MUC1 mRNA in human endometrium and endometriotic tissue. Multiple human endometrial adenocarcinoma cell lines were assayed for MUC4 mRNA expression revealing extremely low basal expression in the Ishikawa, RL-95-2, AN3CA, and KLE lines. Moderate to high expression was observed in HEC50 and HEC-1A cells. MUC4 mRNA expression was not affected by progesterone and/or estrogen treatment, but was greatly stimulated at both mRNA and protein levels by proinflammatory cytokines (IFN-γ and TNF-α), particularly when used in combination. In endometrial tissue, MUC4 mRNA levels did not change significantly between normal or cancerous samples; although, a subset of patients with grade 1 and 2 tumors displayed substantially higher expression. Likewise, immunostaining of human endometrial adenocarcinoma tissues revealed little to no staining in many patients (low MUC4), but strong staining in some patients (high MUC4) independent of cancer grade. In cases where staining was observed, it was heterogeneous with some cells displaying robust MUC4 expression and others displaying little or no staining. Collectively, these observations demonstrate that while MUC4 is highly expressed in the mouse uterus, it is not a major mucin in normal human endometrium. Rather, MUC4 is a potential marker of endometrial adenocarcinoma in a subset of patients. © 2015 Wiley Periodicals, Inc.

Organo-Nitrogen Reactions on Jupiter

NASA Astrophysics Data System (ADS)

Lamothe, V. L.; Moses, J. I.

2000-10-01

Because the altitude regions for CH4 and NH3 photodissociation are physically separated from each other in the Jovian atmosphere, the possibility of forming organo-nitrogen compounds on Jupiter has been an uncertain problem [1,2,3,4,5]. Carbon- and nitrogen-bearing species do not interact significantly in laboratory experiments involving ultraviolet irradiation of CH4-NH3-H2 mixtures [6,7]. However, HCN and a variety of complex organo-nitrogen molecules are produced when methane in the above experiments is replaced by unsaturated hydrocarbons such as C2H2 or CH3C2H [8,9]. To determine the formation efficiency of organo-nitrogen compounds on Jupiter, we have added the reaction schemes proposed by [3,8,9] to a photochemical model of the Jovian troposphere and stratosphere. We find that HCN does not form in observable quantities unless a large tropospheric source of C2H2 exists (e.g., via lightning-induced chemistry, see [10]). Organo-nitrogen reactions are unlikely to be important on Jupiter --- chromophores are most likely due to inorganic compounds. References: [1] Strobel, D. F. (1973), J. Atmos. Sci. 30, 1205; [2] Kaye, J. A., and D. F. Strobel (1983a), Icarus\\ 55, 399; [3] Kaye, J. A., and D. F. Strobel (1983b), Icarus\\ 54, 417; [4] Tokunaga, A. T. et al./ (1981), Icarus\\ 48, 283; [5] Bézard, B. et al./ (1995), Icarus\\ 118, 384; [6] Raulin, F. et al. (1979), Icarus\\ 38, 358; [7] Ferris, J. P., and J. Y. Morimoto (1981), Icarus\\ 48, 118; [8] Ferris, J. P., and Y. Ishikawa (1988), J. Am. Chem. Soc. 110, 4306; [9] Ferris, J. et\\ al. (1992), Icarus\\ 95, 54; [10] Bétremieux, Y., and R. V. Yelle (1999), BAAS\\ 31, 1180.

Probing of the pseudogap via thermoelectric properties in the Au-Al-Gd quasicrystal approximant

NASA Astrophysics Data System (ADS)

Ishikawa, Asuka; Takagiwa, Yoshiki; Kimura, Kaoru; Tamura, Ryuji

2017-03-01

The pseudogap of the recently discovered Au-Al-Gd quasicrystal approximant crystal (AC) is investigated over a wide electron-per-atom (e /a ) ratio of ˜0.5 using thermoelectric properties as an experimental probe. This Au-Al-Gd AC provides an ideal platform for fine probing of the pseudogap among a number of known ACs because the Au-Al-Gd AC possesses an extraordinarily wide single-phase region with respect to the variation in the electron concentration [A. Ishikawa, T. Hiroto, K. Tokiwa, T. Fujii, and R. Tamura, Phys. Rev. B 93, 024416 (2016), 10.1103/PhysRevB.93.024416], in striking contrast to, for instance, binary stoichiometric C d6R ACs. As a result, a salient peak structure is observed in the Seebeck coefficient, S , with the composition as well as that of the power factor S2σ , in addition to a gradual variation in the conductivity, σ , and S . These two features are directly associated with rapid and slow variations, respectively, of spectral conductivity σ (E ) , and hence the fine structure inside the pseudogap, in the vicinity of the Fermi level EF. Based on the observed continuous variation of the Fermi wave vector reported in the previous experimental work, fine tuning of EF toward an optimal position was attempted, which led to the successful observation of a sharp peak in S2σ with a value of ˜270 μ W /m .K2 at 873 K. This is the highest value ever reported among both Tsai-type and Bergman-type compounds. The dimensionless figure of merit was determined as 0.026 at 873 K, which is also the highest reported among both Tsai-type and Bergman-type compounds.

Novel orally active selective progesterone receptor modulator CP8947 inhibits leiomyoma cell proliferation without adversely affecting endometrium or myometrium

PubMed Central

Catherino, William H.; Malik, Minnie; Driggers, Paul; Chappel, Scott; Segars, James; Davis, Joseph

2012-01-01

Context Uterine leiomyomas are highly prevalent and often symptomatic. Current medical therapies are limited. A novel, potent, selective, orally active therapy is needed. Objective and Methods To determine the progesterone receptor (PR) specificity and activation, endometrial response, and impact on proliferation and extracellular matrix (ECM) production of the novel non-steroidal selective progesterone receptor modulators (SPRMs) CP8863 and CP8947 in human immortalized leiomyoma and patient-matched myometrial cells. Receptor binding in vitro was assessed using LNCaP, Ishikawa, T-47D, and HeLa cell extracts for AR, ER-α, PR, and GR, respectively. Progestational activity assessed by alkaline phosphatase assay in T47D cells and ER-α expression in human leiomyoma and myometrial cells. In vivo progestational activity assayed by the McPhail assay. Proliferation and gene expression studies (q RT-PCR and western blot) were performed in immortalized leiomyoma and myometrial cells. Results Both CP8863 and CP8947 is highly selective for PR but not for ER-α, AR, and GR. Both induced alkaline phosphatase comparably to progesterone, while CP8947 induced ER-α in leiomyoma cells but not myometrial cells. CP8947 was progestational in rabbit endometrium. Nanomolar CP8947 treatment inhibited human leiomyoma but not myometrial cell proliferation. The decreased proliferation correlated with increased TRAIL and caspase -7, suggesting induction of apoptosis in leiomyoma cells. ECM components were decreased in leiomyoma cells, including COL1A1 and COL7A1 at nanomolar concentrations. Conclusions CP8947 was a potent novel non-steroidal SPRM that was selective for PR, showed progestational activity in endometrium, inhibited leiomyoma cell proliferation (potentially via induction of apoptosis), and decreased ECM component production, without disrupting myometrial cell proliferation. PMID:20493256

Progesterone-induced miR-133a inhibits the proliferation of endometrial epithelial cells.

PubMed

Pan, J-L; Yuan, D-Z; Zhao, Y-B; Nie, L; Lei, Y; Liu, M; Long, Y; Zhang, J-H; Blok, L J; Burger, C W; Yue, L-M

2017-03-01

This study aimed to understand the role of miR-133a in progesterone actions, explore the regulative mechanism of the progesterone receptor, and investigate the effects of miR-133a on the progesterone-inhibited proliferation of mouse endometrial epithelial cells. The expression of miR-133a induced by progesterone was detected by quantitative real-time PCR both in vivo and in vitro. Ishikawa subcell lines stably transfected with progesterone receptor subtypes were used to determine the receptor mechanism of progesterone inducing miR-133a. Specific miR-133a mimics or inhibitors were transfected into mouse uteri and primary cultured endometrial epithelial cells to overexpress or downregulate the miR-133a. The roles of miR-133a in the cell cycle and proliferation of endometrial epithelial cells were analysed by flow cytometry and Edu incorporation analysis. The protein levels of cyclinD2 in uterine tissue sections and primary cultured endometrial epithelial cells were determined by immunohistochemistry and Western blot analysis. Progesterone could induce miR-133a expression in a PRB-dependent manner in endometrial epithelial cells. miR-133a inhibited endometrial epithelial cell proliferation by arresting cell cycle at the G 1 -S transition. Moreover, miR-133a acted as an inhibitor in downregulating cyclinD2 in endometrial epithelial cells. We showed for the first time that progesterone-induced miR-133a inhibited the proliferation of endometrial epithelial cells by downregulating cyclinD2. Our research indicated an important mechanism for progesterone inhibiting the proliferation of endometrial epithelial cells by inducing special miRNAs to inhibit positive regulatory proteins in the cell cycle. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients

PubMed Central

Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria

2018-01-01

Background Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. Methods We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. Results EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. Conclusions EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy. PMID:29416671

Double-Resonance Facilitated Decomposion of Emission Spectra

NASA Astrophysics Data System (ADS)

Kato, Ryota; Ishikawa, Haruki

2016-06-01

Emission spectra provide us with rich information about the excited-state processes such as proton-transfer, charge-transfer and so on. In the cases that more than one excited states are involved, emission spectra from different excited states sometimes overlap and a decomposition of the overlapped spectra is desired. One of the methods to perform a decomposition is a time-resolved fluorescence technique. It uses a difference in time evolutions of components involved. However, in the gas-phase, a concentration of the sample is frequently too small to carry out this method. On the other hand, double-resonance technique is a very powerful tool to discriminate or identify a common species in the spectra in the gas-phase. Thus, in the present study, we applied the double-resonance technique to resolve the overlapped emission spectra. When transient IR absorption spectra of the excited state are available, we can label the population of the certain species by the IR excitation with a proper selection of the IR wavenumbers. Thus, we can obtain the emission spectra of labeled species by subtracting the emission spectra with IR labeling from that without IR. In the present study, we chose the charge-transfer emission spectra of cyanophenyldisilane (CPDS) as a test system. One of us reported that two charge-transfer (CT) states are involved in the intramolecular charge-transfer (ICT) process of CPDS-water cluster and recorded the transient IR spectra. As expected, we have succeeded in resolving the CT emission spectra of CPDS-water cluster by the double resonance facilitated decomposion technique. In the present paper, we will report the details of the experimental scheme and the results of the decomposition of the emission spectra. H. Ishikawa, et al., Chem. Phys. Phys. Chem., 9, 117 (2007).

[Improvement in health care quality for patients from the thoracic/chest pain unit in a regional hospital].

PubMed

Castellano Ortega, M A; Romero de Castilla, R J; Rus Mansilla, C; Cortez Quiroga, G A; Bayona Gómez, A J; Duran Torralba, M C

2011-01-01

The evaluation of an improvement cycle in patients suffering thoracic/chest pain in hospital emergencies, especially in those who could benefit from the early Bruce Treadmill Test. A multidisciplinary group care protocol was designed, which identified improvement opportunities and gave priority to the fact that «an early Bruce Treadmill Test was carried out on fewer occasions than recommended». Causes were analysed (Ishikawa diagram) and six quality criteria were defined. These criteria were evaluated in a random sample of 30 patients out of the total of 180 who used the ergometer at the Hospital in the first six months of 2007, as well as questionnaire for the doctors. Corrective measures were introduced: circulation, accessibility through intranet and explicit information for new employees (doctors). The second evaluation was carried out during the first six-months of 2008 using another random sample of 30 patients from a total of 120. In the first evaluation, the classification of the risk according to the protocol was very low (100% non-compliance) and patients whose admission to the Chest Pain Unit was recommended and an early Bruce Treadmill Test (74% criteria failure) were referred to cardiology clinics. After implementation of the corrective measures, we obtain a general improvement in all the criteria, but very significant from the previous ones, with non-compliances being reduced to 17% in classification and to the 23% in referrals. The structured cycle has helped resolve the priority problem in the short-term. The adopted measures have mainly been organisational, dependent on the professionals involved, and at a very low cost. Simple but organised methodological approaches should be taken into account before the incorporation of higher cost technologies. Copyright © 2010 SECA. Published by Elsevier Espana. All rights reserved.

Developing a tool for assessing competency in root cause analysis.

PubMed

Gupta, Priyanka; Varkey, Prathibha

2009-01-01

Root cause analysis (RCA) is a tool for identifying the key cause(s) contributing to a sentinel event or near miss. Although training in RCA is gaining popularity in medical education, there is no published literature on valid or reliable methods for assessing competency in the same. A tool for assessing competency in RCA was pilot tested as part of an eight-station Objective Structured Clinical Examination that was conducted at the completion of a three-week quality improvement (QI) curriculum for the Mayo Clinic Preventive Medicine and Endocrinology fellowship programs. As part of the curriculum, fellows completed a QI project to enhance physician communication of the diagnosis and treatment plan at the end of a patient visit. They had a didactic session on RCA, followed by process mapping of the information flow at the project clinic, after which fellows conducted an actual RCA using the Ishikawa fishbone diagram. For the RCA competency assessment, fellows performed an RCA regarding a scenario describing an adverse medication event and provided possible solutions to prevent such errors in the future. All faculty strongly agreed or agreed that they were able to accurately assess competency in RCA using the tool. Interrater reliability for the global competency rating and checklist scoring were 0.96 and 0.85, respectively. Internal consistency (Cronbach's alpha) was 0.76. Six of eight of the fellows found the difficulty level of the test to be optimal. Assessment methods must accompany education programs to ensure that graduates are competent in QI methodologies and are able to apply them effectively in the workplace. The RCA assessment tool was found to be a valid, reliable, feasible, and acceptable method for assessing competency in RCA. Further research is needed to examine its predictive validity and generalizability.

Identifying barriers to the availability and use of Magnesium Sulphate Injection in resource poor countries: a case study in Zambia.

PubMed

Ridge, Anna L; Bero, Lisa A; Hill, Suzanne R

2010-12-16

Pre-eclampsia and eclampsia are serious complications of pregnancy and major causes of maternal mortality and morbidity worldwide. According to systematic reviews and WHO guidelines magnesium sulphate injection (MgSO4) should be the first -line treatment for severe pre-eclampsia and eclampsia. Studies have shown that this safe and effective medicine is unavailable and underutilized in many resource poor countries. The objective of this study was to identify barriers to the availability and use of MgSO4 in the Zambian Public Health System. A 'fishbone' (Ishikawa) diagram listing probable facilitators to the availability and use of MgSO4 identified from the literature was used to develop an assessment tool. Barriers to availability and use of MgSO4 were assessed at the regulatory/government, supply, procurement, distribution, health facility and health professional levels. The assessment was completed during August 2008 using archival data, and observations at a pragmatic sample of health facilities providing obstetric services in Lusaka District, Zambia. The major barrier to the availability of MgSO4 within the public health system in Zambia was lack of procurement by the Ministry of Health. Other barriers identified included a lack of demand by health professionals at the health centre level and a lack of in-service training in the use of MgSO4. Where there was demand by obstetricians, magnesium sulphate injection was being procured from the private sector by the hospital pharmacy despite not being registered and licensed for use for the treatment of severe pre-eclampsia and eclampsia by the national Pharmaceutical Regulatory Authority. The case study in Zambia highlights the complexities that underlie making essential medicines available and used appropriately. The fishbone diagram is a useful theoretical framework for illustrating the complexity of translating research findings into clinical practice. A better understanding of the supply system and of the pattern

In situ targeting of dendritic cells sets tolerogenic environment and ameliorates CD4+ T-cell response in the postischemic liver.

PubMed

Funken, Dominik; Ishikawa-Ankerhold, Hellen; Uhl, Bernd; Lerchenberger, Maximilian; Rentsch, Markus; Mayr, Doris; Massberg, Steffen; Werner, Jens; Khandoga, Andrej

2017-11-01

CD4 + T cells recruited to the liver play a key role in the pathogenesis of ischemia/reperfusion (I/R) injury. The mechanism of their activation during alloantigen-independent I/R is not completely understood. We hypothesized that liver-resident dendritic cells (DCs) interact with CD4 + T cells in the postischemic liver and that modulation of DCs or T-cell-DC interactions attenuates liver inflammation. In mice, warm hepatic I/R (90/120-240 min) was induced. Tolerogenic DCs were generated in situ by pretreatment of animals with the vitamin D analog paricalcitol. A mAb-CD44 was used for blockade of CD4 + T-cell-DC interactions. As shown by 2-photon in vivo microscopy as well as confocal microscopy, CD4 + T cells were closely colocalized with DCs in the postischemic liver. Pretreatment with paricalcitol attenuated I/R-induced maturation of DCs (flow cytometry), CD4 + T-cell recruitment into the liver (intravital microscopy), and hepatocellular/microvascular damage (intravital microscopy, alanine aminotransferase/aspartate aminotransferase, histology). However, interruption of T-cell-DC interaction increased proinflammatory DC maturation and even enhanced tissue damage. Simultaneous treatment with an anti-CD44mAb completely abolished the beneficial effect of paricalcitol on T-cell migration and tissue injury. Our study demonstrates for the first time that hepatic DCs interact with CD4 + T cells in the postischemic liver in vivo ; modulation of DCs and/or generation of tolerogenic DCs attenuates intrahepatic CD4 + T-cell recruitment and reduces I/R injury; and interruption of CD44-dependent CD4 + T-cell-DC interactions enhances tissue injury by preventing the modulatory effect of hepatic DCs on T cells, especially type 1 T helper effector cells. Thus, hepatic DCs are strongly involved in the promotion of CD4 + T-cell-dependent postischemic liver inflammation.-Funken, D., Ishikawa-Ankerhold, H., Uhl, B., Lerchenberger, M., Rentsch, M., Mayr, D., Massberg, S., Werner, J

Negative Effect of Ellagic Acid on Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Cancer Cells.

PubMed

Abdelazeem, Khalid N M; Singh, Yogesh; Lang, Florian; Salker, Madhuri S

2017-01-01

Key properties of tumor cells include enhanced glycolytic flux with excessive consumption of glucose and formation of lactate. As glycolysis is highly sensitive to cytosolic pH, maintenance of glycolysis requires export of H+ ions, which is in part accomplished by Na+/H+ exchangers, such as NHE1. The carrier is sensitive to oxidative stress. Growth of tumor cells could be suppressed by the polyphenol Ellagic acid, which is found in various fruits and vegetables. An effect of Ellagic acid on transport processes has, however, never been reported. The present study thus elucidated an effect of Ellagic acid on cytosolic pH (pHi), NHE1 transcript levels, NHE1 protein abundance, Na+/H+ exchanger activity, and lactate release. Experiments were performed in Ishikawa cells without or with prior Ellagic acid (20 µM) treatment. NHE1 transcript levels were determined by qRT-PCR, NHE1 protein abundance by Western blotting, pHi utilizing (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein [BCECF] fluorescence, Na+/H+ exchanger activity from Na+ dependent realkalinization after an ammonium pulse, cell volume from forward scatter in flow cytometry, reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein fluorescence, glucose uptake utilizing 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose, and lactate concentration in the supernatant utilizing a colorimetric (570 nm)/ fluorometric enzymatic assay. A 48 hour treatment with Ellagic acid (20 µM) significantly decreased NHE1 transcript levels by 75%, NHE1 protein abundance by 95%, pHi from 7.24 ± 0.01 to 7.02 ± 0.01, Na+/H+ exchanger activity by 77%, forward scatter by 10%, ROS by 82%, glucose uptake by 58%, and lactate release by 15%. Ellagic acid (20µM) markedly down-regulates ROS formation and NHE1 expression leading to decreased Na+/H+ exchanger activity, pHi, glucose uptake and lactate release in endometrial cancer cells. Those effects presumably contribute to reprogramming and growth

SU-F-T-609: Impact of Dosimetric Variation for Prescription Dose Using Analytical Anisotropic Algorithm (AAA) in Lung SBRT

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

Kawai, D; Takahashi, R; Kamima, T

Purpose: Actual irradiated prescription dose to patients cannot be verified. Thus, independent dose verification and second treatment planning system are used as the secondary check. AAA dose calculation engine has contributed to lung SBRT. We conducted a multi-institutional study to assess variation of prescription dose for lung SBRT when using AAA in reference to using Acuros XB and Clarkson algorithm. Methods: Six institutes in Japan participated in this study. All SBRT treatments were planed using AAA in Eclipse and Adaptive Convolve (AC) in Pinnacle3. All of the institutes used a same independent dose verification software program (Simple MU Analysis: SMU,more » Triangle Product, Ishikawa, Japan), which implemented a Clarkson-based dose calculation algorithm using CT image dataset. A retrospective analysis for lung SBRT plans (73 patients) was performed to compute the confidence limit (CL, Average±2SD) in dose between the AAA and the SMU. In one of the institutes, a additional analysis was conducted to evaluate the variations between the AAA and the Acuros XB (AXB). Results: The CL for SMU shows larger systematic and random errors of 8.7±9.9 % for AAA than the errors of 5.7±4.2 % for AC. The variations of AAA correlated with the mean CT values in the voxels of PTV (a correlation coefficient : −0.7) . The comparison of AXB vs. AAA shows smaller systematic and random errors of −0.7±1.7%. The correlation between dose variations for AXB and the mean CT values in PTV was weak (0.4). However, there were several plans with more than 2% deviation of AAPM TG114 (Maximum: −3.3 %). Conclusion: In comparison for AC, prescription dose calculated by AAA may be more variable in lung SBRT patient. Even AXB comparison shows unexpected variation. Care should be taken for the use of AAA in lung SBRT. This research is partially supported by Japan Agency for Medical Research and Development (AMED)« less

Vibrio algivorus sp. nov., an alginate- and agarose-assimilating bacterium isolated from the gut flora of a turban shell marine snail.

PubMed

Doi, Hidetaka; Chinen, Akito; Fukuda, Hiroo; Usuda, Yoshihiro

2016-08-01

An agarose- and alginate-assimilating, Gram-reaction-negative, non-motile, rod-shaped bacterium, designated strain SA2T, was isolated from the gut of a turban shell sea snail (Turbo cornutus) collected near Noto Peninsula, Ishikawa Prefecture, Japan. The 16S rRNA gene sequence of strain SA2T was 99.59 % identical to that of Vibrio rumoiensis DSM 19141T and 98.19 % identical to that of Vibrio litoralis DSM 17657T. This suggested that strain SA2T could be a subspecies of V. rumoiensis or V. litoralis. However, DNA-DNA hybridization results showed only 37.5 % relatedness to DSM 19141T and 44.7 % relatedness to DSM 17657T, which was far lower than the 70 % widely accepted to define common species. Strain SA2T could assimilate agarose as a sole carbon source, whereas strains DSM 19141T and DSM 17657T could not assimilate it at all. Furthermore, results using API 20NE and API ZYM kits indicated that their enzymic and physiological phenotypes were also different. These results suggested that strain SA2T represented a novel species within the genus Vibrio. The major isoprenoid quinone in SA2T was Q-8, and its major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. The major fatty acids were summed feature 3, (comprising C16 : 1ω6c and/or C16 : 1ω7c), C16 : 0, and summed feature 8 (comprising C18 : 1ω6c and/or C18 : 1ω7c). The DNA G+C content of SA2T was 40.7 mol%. The name proposed for this novel species of the genus Vibrio is Vibrio algivorus sp. nov., with the type strain designated SA2T (=DSM 29824T=NBRC 111146T).

miR-145-dependent targeting of junctional adhesion molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness.

PubMed

Götte, M; Mohr, C; Koo, C-Y; Stock, C; Vaske, A-K; Viola, M; Ibrahim, S A; Peddibhotla, S; Teng, Y H-F; Low, J-Y; Ebnet, K; Kiesel, L; Yip, G W

2010-12-16

Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regulate cell motility, we aimed at investigating a potential role for miR-145 in breast cancer cell motility and invasiveness. Assisted by Affymetrix array technology, we demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to a downregulation of the cell-cell adhesion protein JAM-A and of the actin bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145 overexpression. These miR-145-dependent expression changes drastically decreased cancer cell motility, as revealed by time-lapse video microscopy, scratch wound closure assays and matrigel invasion assays. Immunofluorescence microscopy demonstrated restructuring of the actin cytoskeleton and a change in cell morphology by miR-145 overexpression, resulting in a more cortical actin distribution, and reduced actin stress fiber and filopodia formation. Nuclear rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells, accompanied by a reduction of perinuclear actin. Luciferase activation assays confirmed direct miR-145-dependent regulation of the 3'UTR of JAM-A, whereas siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. Our data provide a rationale for future miR-145-targeted approaches of antimetastatic cancer therapy.

Cell-like features imprinted in the physical nano- and micro-topography of the environment modify the responses to anti-cancer drugs of endometrial cancer cells.

PubMed

Tan, Li Hui; Sykes, Peter H; Alkaisi, Maan M; Evans, John J

2017-02-14

Topographical features of cells at nanometre resolution were fabricated in polystyrene. The study investigated the effect of physical topography on the response of cancer cells to the common anticancer drugs, paclitaxel and doxorubicin. Human endometrial cancer cells (Ishikawa) were incubated on substrates containing cell-like features that had been fabricated using our bioimprint methodology to create moulds of cells with positive (convex) and negative (concave) topography. Control cultures were performed on flat substrates. Effects of the drugs on caspase-3 expression, proliferating nuclear antigen (PCNA) expression, cell number and vascular endothelial growth factor (VEGF) secretion were determined. Results revealed that the topography influenced the cell responses in a drug-dependent manner i.e. paclitaxel effects were sensitive to topography differently to those of doxorubicin. In addition, function signalling pathways were sensitive to the detailed topography i.e. positive imprint and negative imprint induced distinct response patterns. The results in this study show for the first time that a culture surface with cell-like topography, that has both nano- and micro-resolution, influences endometrial cancer cell responses to chemotherapy drugs. The effects are dependent on the topography and also on the chemotherapy drug. In particular, the platforms described have potential to provide substrates with high physical relevancy on which to undertake preclinical testing of new drugs. The method also allows for use of different cell types to provide cell-specific topography. The results imply that physical architecture of the cancer cell environment may be a suitable prospective target to enhance clinical activity of traditional drugs. Additionally or alternatively we provide compelling support for the notion that understanding the physical component of the nano- and micro-environment may encourage a redirection of drug development. Further, our observation that the

Jovian Tropospheric Photohemistry: Constraints from Recent Cassini and Galileo Observations and from Laboratory Experiment Simulations

NASA Astrophysics Data System (ADS)

Moses, Julianne I.; Sperier, A. D.; Keane, T. C.

2008-09-01

We use the Caltech/JPL KINETICS code (Allen et al. 1981, JGR 86, 3617) to develop 1-D (in altitude) photochemical models for Jupiter's troposphere that are consistent with available Cassini, Galileo, Voyager, and Earth-based observations of ammonia and phosphine, and upper limits for HCN. As a test of the adopted chemical reaction list, we simulate laboratory experiments of coupled NH3-PH3 and NH3-C2H2 photochemistry (Ferris et al. 1984, J. Am. Chem. Soc. 106, 318; Ferris and Ishikawa 1988, J. Am. Chem. Soc. 110, 4306; Keane et al. 1996, Icarus 122, 205). We find that the vertical profile of PH3 is sensitive to the assumed tropospheric eddy diffusion coefficient and aerosol extinction, both of which are loosely constrained by observations and seem to vary with latitude. The NH3 profile is controlled by condensation and is relatively insensitive to the eddy diffusion coefficient. As was determined by previous photochemical models, the dominant products of Jovian tropospheric chemistry are P2H4, N2H4, red phosphorus, NH2PH2, and N2. All of these species except N2 will condense. Diphosphine (P2H4) is an underappreciated condensate that will likely be more important than N2H4 as an aerosol component on Jupiter as well as Saturn. Little is known about the chemistry and properties of NH2PH2, but this product could also be an important condensable constituent. Coupled NH3-C2H2 photochemistry does not readily occur in Jupiter's troposphere due to the low predicted (and observed) tropospheric C2H2 abundance. The models therefore produce only a small amount of HCN (well within upper limits), and even smaller amounts of the nitriles, hydrazones, and other organo-nitrogen molecules identified in the laboratory experiments mentioned above. This work was supported by the NASA Planetary Atmospheres Program (NNX08AF05G) and the Lunar and Planetary Institute/USRA.

Mechanism for the Coupled Photochemistry of Ammonia and Acetylene: Implications for Giant Planets, Comets and Interstellar Organic Synthesis

NASA Astrophysics Data System (ADS)

Keane, Thomas C.

2017-09-01

Laboratory studies provide a fundamental understanding of photochemical processes in planetary atmospheres. Photochemical reactions taking place on giant planets like Jupiter and possibly comets and the interstellar medium are the subject of this research. Reaction pathways are proposed for the coupled photochemistry of NH3 (ammonia) and C2H2 (acetylene) within the context Jupiter's atmosphere. We then extend the discussion to the Great Red Spot, Extra-Solar Giant Planets, Comets and Interstellar Organic Synthesis. Reaction rates in the form of quantum yields were measured for the decomposition of reactants and the formation of products and stable intermediates: HCN (hydrogen cyanide), CH3CN (acetonitrile), CH3CH = N-N = CHCH3 (acetaldazine), CH3CH = N-NH2 (acetaldehyde hydrazone), C2H5NH2 (ethylamine), CH3NH2 (methylamine) and C2H4 (ethene) in the photolysis of NH3/C2H2 mixtures. Some of these compounds, formed in our investigation of pathways for HCN synthesis, were not encountered previously in observational, theoretical or laboratory photochemical studies. The quantum yields obtained allowed for the formulation of a reaction mechanism that attempts to explain the observed results under varying experimental conditions. In general, the results of this work are consistent with the initial observations of Ferris and Ishikawa (1988). However, their proposed reaction pathway which centers on the photolysis of CH3CH = N-N = CHCH3 does not explain all of the results obtained in this study. The formation of CH3CH = N-N = CHCH3 by a radical combination reaction of CH3CH = N• was shown in this work to be inconsistent with other experiments where the CH3CH = N• radical is thought to form but where no CH3CH = N-N = CHCH3 was detected. The importance of the role of H atom abstraction reactions was demonstrated and an alternative pathway for CH3CH = N-N = CHCH3 formation involving nucleophilic reaction between N2H4 and CH3CH = NH is advanced.

Developing Connectivist Schemas for Geological and Geomorphological Education

NASA Astrophysics Data System (ADS)

Whalley, B.

2012-12-01

Teaching geology is difficult; students need to grasp changes in time over three dimensions. Furthermore, the scales and rates of change in four dimensions may vary over several orders of magnitude. Geological explanations incorporate ideas from physics, chemistry, biology and engineering, lectures and textbooks provide a basic framework but they need to be amplified by laboratories and fieldwork involving active student participation and engagement. Being shown named 'things' is only a start to being able to being able to inculcate geological thinking that requires a wide and focused viewpoints. Kastens and Ishikawa (2006) suggested five aspects of thinking geologically, summarised as: 1. Observing, describing, recording, communicating geologically entities (ie basic cognitive skills) 2. (mentally) manipulating these entities 3. interpreting them via causal relationships 4. predicting other aspects using the basic knowledge (to create new knowledge) 5. using cognitive strategies to develop new ways of interpreting gained knowledge. These steps can be used follow the sequence from 'known' through 'need to know' to using knowledge to gain better geologic explanation, taken as enquiry-based or problem solving modes of education. These follow ideas from Dewey though Sternberg's 'thinking styles' and Siemens' connectivist approaches. Implementation of this basic schema needs to be structured for students in a complex geological world in line with Edelson's (2006) 'learning for' framework. In a geomorphological setting, this has been done by showing students how to interpret a landscape (landform, section etc) practice their skills and thus gain confidence with a tutor at hand. A web-based device, 'Virtorial' provides scenarios for students to practice interpretation (or even be assessed with). A cognitive tool is provided for landscape interpretation by division into the recognition of 'Materials' (rock, sediments etc), Processes (slope, glacial processes etc) and

An integrated quality by design and mixture-process variable approach in the development of a capillary electrophoresis method for the analysis of almotriptan and its impurities.

PubMed

Orlandini, S; Pasquini, B; Stocchero, M; Pinzauti, S; Furlanetto, S

2014-04-25

The development of a capillary electrophoresis (CE) method for the assay of almotriptan (ALM) and its main impurities using an integrated Quality by Design and mixture-process variable (MPV) approach is described. A scouting phase was initially carried out by evaluating different CE operative modes, including the addition of pseudostationary phases and additives to the background electrolyte, in order to approach the analytical target profile. This step made it possible to select normal polarity microemulsion electrokinetic chromatography (MEEKC) as operative mode, which allowed a good selectivity to be achieved in a low analysis time. On the basis of a general Ishikawa diagram for MEEKC methods, a screening asymmetric matrix was applied in order to screen the effects of the process variables (PVs) voltage, temperature, buffer concentration and buffer pH, on critical quality attributes (CQAs), represented by critical separation values and analysis time. A response surface study was then carried out considering all the critical process parameters, including both the PVs and the mixture components (MCs) of the microemulsion (borate buffer, n-heptane as oil, sodium dodecyl sulphate/n-butanol as surfactant/cosurfactant). The values of PVs and MCs were simultaneously changed in a MPV study, making it possible to find significant interaction effects. The design space (DS) was defined as the multidimensional combination of PVs and MCs where the probability for the different considered CQAs to be acceptable was higher than a quality level π=90%. DS was identified by risk of failure maps, which were drawn on the basis of Monte-Carlo simulations, and verification points spanning the design space were tested. Robustness testing of the method, performed by a D-optimal design, and system suitability criteria allowed a control strategy to be designed. The optimized method was validated following ICH Guideline Q2(R1) and was applied to a real sample of ALM coated tablets

Hydrothermal Alteration of the Mt Unzen Conduit (Shimabara/Japan)

NASA Astrophysics Data System (ADS)

Yilmaz, T. I.; Mayer, K.; Hess, K. U.; Janots, E.; Gilg, H. A.; Dingwell, D. B.

2016-12-01

Investigations were carried out on hydrothermally altered coherent dacitic dykes samples from (USDP-4) drill core at Mt Unzen stratovolcano (Shimabara/Japan). XRF, XRD, EMPA, and C-O-isotope analysis led to insights concerning chemistry, mineralogy, and intensity of alteration as well as the origin of carbonate-precipitating fluids. Additionally a textural characterization of the occurring replacement features in the magma conduit zone was performed. The occurrence of the main secondary phases such as chlorite, pyrite, carbonates, and R1 (Reichweite parameter) illite-smectite indicate a weak to moderate propylitic to phyllic hydrothermal alteration. The dacitic samples of the dykes show different hydrothermal alteration features: (i) carbonate pseudomorphs after hornblende as well as core and zonal textures due to replacement of plagioclase by R1 illite-smectite, (ii) colloform banded fracture fillings and fillings in dissolution vugs, and (iii) chlorite and R1 illite-smectite in the groundmass. Carbonates in fractures comprise iron-rich dolomite solid solutions ("ankerite") and calcite. Isotopic values of d13Cvpdb = -4.59 ± 0.6‰ and d18Ovpdb = -21.73 ± 0.5‰ indicate a hydrothermal-magmatic origin for the carbonate formation. The chlorite-carbonate-pyrite index (CCPI) and the Ishikawa alteration index (AI), applied to the investigated samples show significant differences (CCPI=52.7-57.8; AI=36.1-40.6) indicating their different degree of alteration. According to Nakada et al., 2005, the C13 to C16 dykes represent the feeder dyke from the latest eruption (1991-1995) whereas C8 represents an earlier dyke feeder dyke from an older eruption. Weakest conduit alteration, which was obtained in samples C16-1-5 and C13-2-5, correlates with the alteration degree of the pristine dome rocks. Highest CCPI value was determined for sample C14-1-5 and the highest AI value was determined for sample C15-2-6. The degrees of alteration do not indicate highest alteration of the

Risk management and statistical multivariate analysis approach for design and optimization of satranidazole nanoparticles.

PubMed

Dhat, Shalaka; Pund, Swati; Kokare, Chandrakant; Sharma, Pankaj; Shrivastava, Birendra

2017-01-01

Rapidly evolving technical and regulatory landscapes of the pharmaceutical product development necessitates risk management with application of multivariate analysis using Process Analytical Technology (PAT) and Quality by Design (QbD). Poorly soluble, high dose drug, Satranidazole was optimally nanoprecipitated (SAT-NP) employing principles of Formulation by Design (FbD). The potential risk factors influencing the critical quality attributes (CQA) of SAT-NP were identified using Ishikawa diagram. Plackett-Burman screening design was adopted to screen the eight critical formulation and process parameters influencing the mean particle size, zeta potential and dissolution efficiency at 30min in pH7.4 dissolution medium. Pareto charts (individual and cumulative) revealed three most critical factors influencing CQA of SAT-NP viz. aqueous stabilizer (Polyvinyl alcohol), release modifier (Eudragit® S 100) and volume of aqueous phase. The levels of these three critical formulation attributes were optimized by FbD within established design space to minimize mean particle size, poly dispersity index, and maximize encapsulation efficiency of SAT-NP. Lenth's and Bayesian analysis along with mathematical modeling of results allowed identification and quantification of critical formulation attributes significantly active on the selected CQAs. The optimized SAT-NP exhibited mean particle size; 216nm, polydispersity index; 0.250, zeta potential; -3.75mV and encapsulation efficiency; 78.3%. The product was lyophilized using mannitol to form readily redispersible powder. X-ray diffraction analysis confirmed the conversion of crystalline SAT to amorphous form. In vitro release of SAT-NP in gradually pH changing media showed <20% release in pH1.2 and pH6.8 in 5h, while, complete release (>95%) in pH7.4 in next 3h, indicative of burst release after a lag time. This investigation demonstrated effective application of risk management and QbD tools in developing site-specific release

Risk Assessment Integrated QbD Approach for Development of Optimized Bicontinuous Mucoadhesive Limicubes for Oral Delivery of Rosuvastatin.

PubMed

Javed, Md Noushad; Kohli, Kanchan; Amin, Saima

2018-04-01

Statins are widely prescribed for hyperlipidemia, cancer, and Alzheimer's disease but are facing some inherent challenges such as low solubility and drug loading, higher hepatic metabolism, as well as instability at gastric pH. So, relatively higher circulating dose, required for exerting the therapeutic benefits, leads to dose-mediated severe toxicity. Furthermore, due to low biocompatibility, high toxicity, and other regulatory caveats such as product conformity, reproducibility, and stability of conventional formulations as well as preferentially higher bioabsorption of lipids in their favorable cuboidal geometry, enhancement in in vivo biopharmaceutical performance of Rosuvastatin could be well manifested in Quality by Design (QbD) integrated cuboidal-shaped mucoadhesive microcrystalline delivery systems (Limicubes). Here, quality-target-product-profile (QTPPs), critical quality attributes (CQAs), Ishikawa fishbone diagram, and integration of risk management through risk assessment matrix for failure mode and effects analysis (FMEA) followed by processing of Plackett-Burman design matrix using different statistical test for the first time established an approach to substantiate the claims that controlling levels of only these three screened out independent process variables, i.e., Monoolein (B = 800-1100 μL), Poloxamer (C = 150-200 mg), and stirring speed (F = 700-1000 rpm) were statistically significant to modulate and improve the biopharmaceutical performance affecting key attributes, viz., average particle size (Y 1  = 1.40-2.70 μ), entrapment efficiency (Y 2  = 62.60-88.80%), and drug loading (Y 3  = 0.817-1.15%), in QbD-enabled process. The optimal performance of developed Limicubes exhibited an average particle size of 1.8 ± 0.2 μ, entrapment efficiency 80.32 ± 2.88%, and drug loading 0.93 ± 0.08% at the level of 1100 μL (+ 1), 200 mg (+ 1), and 700 rpm (- 1) for Monoolein, Poloxamer, and stirring

Development of a validated liquid chromatographic method for quantification of sorafenib tosylate in the presence of stress-induced degradation products and in biological matrix employing analytical quality by design approach.

PubMed

Sharma, Teenu; Khurana, Rajneet Kaur; Jain, Atul; Katare, O P; Singh, Bhupinder

2018-05-01

The current research work envisages an analytical quality by design-enabled development of a simple, rapid, sensitive, specific, robust and cost-effective stability-indicating reversed-phase high-performance liquid chromatographic method for determining stress-induced forced-degradation products of sorafenib tosylate (SFN). An Ishikawa fishbone diagram was constructed to embark upon analytical target profile and critical analytical attributes, i.e. peak area, theoretical plates, retention time and peak tailing. Factor screening using Taguchi orthogonal arrays and quality risk assessment studies carried out using failure mode effect analysis aided the selection of critical method parameters, i.e. mobile phase ratio and flow rate potentially affecting the chosen critical analytical attributes. Systematic optimization using response surface methodology of the chosen critical method parameters was carried out employing a two-factor-three-level-13-run, face-centered cubic design. A method operable design region was earmarked providing optimum method performance using numerical and graphical optimization. The optimum method employed a mobile phase composition consisting of acetonitrile and water (containing orthophosphoric acid, pH 4.1) at 65:35 v/v at a flow rate of 0.8 mL/min with UV detection at 265 nm using a C 18 column. Response surface methodology validation studies confirmed good efficiency and sensitivity of the developed method for analysis of SFN in mobile phase as well as in human plasma matrix. The forced degradation studies were conducted under different recommended stress conditions as per ICH Q1A (R2). Mass spectroscopy studies showed that SFN degrades in strongly acidic, alkaline and oxidative hydrolytic conditions at elevated temperature, while the drug was per se found to be photostable. Oxidative hydrolysis using 30% H 2 O 2 showed maximum degradation with products at retention times of 3.35, 3.65, 4.20 and 5.67 min. The absence of any

Inhibition of Wnt Signaling Pathways Impairs Chlamydia trachomatis Infection in Endometrial Epithelial Cells

PubMed Central

Kintner, Jennifer; Moore, Cheryl G.; Whittimore, Judy D.; Butler, Megan; Hall, Jennifer V.

2017-01-01

Chlamydia trachomatis infections represent the predominant cause of bacterial sexually transmitted infections. As an obligate intracellular bacterium, C. trachomatis is dependent on the host cell for survival, propagation, and transmission. Thus, factors that affect the host cell, including nutrition, cell cycle, and environmental signals, have the potential to impact chlamydial development. Previous studies have demonstrated that activation of Wnt/β-catenin signaling benefits C. trachomatis infections in fallopian tube epithelia. In cervical epithelial cells chlamydiae sequester β-catenin within the inclusion. These data indicate that chlamydiae interact with the Wnt signaling pathway in both the upper and lower female genital tract (FGT). However, hormonal activation of canonical and non-canonical Wnt signaling pathways is an essential component of cyclic remodeling in another prominent area of the FGT, the endometrium. Given this information, we hypothesized that Wnt signaling would impact chlamydial infection in endometrial epithelial cells. To investigate this hypothesis, we analyzed the effect of Wnt inhibition on chlamydial inclusion development and elementary body (EB) production in two endometrial cell lines, Ishikawa (IK) and Hec-1B, in nonpolarized cell culture and in a polarized endometrial epithelial (IK)/stromal (SHT-290) cell co-culture model. Inhibition of Wnt by the small molecule inhibitor (IWP2) significantly decreased inclusion size in IK and IK/SHT-290 cultures (p < 0.005) and chlamydial infectivity (p ≤ 0.01) in both IK and Hec-1B cells. Confocal and electron microscopy analysis of chlamydial inclusions revealed that Wnt inhibition caused chlamydiae to become aberrant in morphology. EB formation was also impaired in IK, Hec-1B and IK/SHT-290 cultures regardless of whether Wnt inhibition occurred throughout, in the middle (24 hpi) or late (36 hpi) during the development cycle. Overall, these data lead us to conclude that Wnt signaling in

The Deep Carbon Cycle and CO2 Sequestration

NASA Astrophysics Data System (ADS)

Filipovitch, N. B.; Mao, W. L.; Chou, I.; Mu, K.

2009-12-01

.G., Gormley, Deirdre, Nunez, Ryan, Carpenter, R.W., Squires, Kyle, Wolf, George, 2006, Carbon Sequestration via Aqueous Olivine Mineral Carbonation: Role of Passivating Layer Formation, Environ. Sci. Technol., Vol. 40, pp 4802-4808 3. Wolf, George H., Chizmeshya, Andrew V. G., Diefenbacher, Jason, McKelvy, Michael J., 2004, In Situ Observation of CO2 Sequestration Reactions Using a Novel Microreaction System, Environmental Science & Technology, Vol.38, No.3, pp 932-936 4. O’Connor, W. K., Dahlin, D. C., Nilsen, D.N., Rush, G.E., Walters, R.P., and Turner, P. C., 2000, “CO2 Storage in Solid Form: A Study of Direct Mineral Carbonation,” Proc. of the 5th International Conference on Greenhouse Gas Technologies, Cairns, Australia, August 14-18, pp. 1-7 5. Isshiki, Maiko, Irifune, Tetsuo, Hirose, Kei, Ono, Shigeaki, Ohishi, Yasuo, Watanuki, Tetsu, Nishibori, Eiji, Takata, Masaki, Sakata, Makoto, 2004, Stability of magnesite and its high-pressure form in the lowermost mantle, Nature, Vol. 427, pp. 60-63 6. Kawano, Jun, Miyake, Akira, Shimobayashi, Norimasa, Kitamura, Masao, 2009, Molecular dynamics simulation of the phase transition between calcite and CaCO3-II , Journal of Physics: Condensed Matter, Vol. 21, pp. 1-11

Identifying barriers to the availability and use of Magnesium Sulphate Injection in resource poor countries: A case study in Zambia

PubMed Central

2010-01-01

Background Pre-eclampsia and eclampsia are serious complications of pregnancy and major causes of maternal mortality and morbidity worldwide. According to systematic reviews and WHO guidelines magnesium sulphate injection (MgSO4) should be the first -line treatment for severe pre-eclampsia and eclampsia. Studies have shown that this safe and effective medicine is unavailable and underutilized in many resource poor countries. The objective of this study was to identify barriers to the availability and use of MgSO4 in the Zambian Public Health System. Methods A 'fishbone' (Ishikawa) diagram listing probable facilitators to the availability and use of MgSO4 identified from the literature was used to develop an assessment tool. Barriers to availability and use of MgSO4 were assessed at the regulatory/government, supply, procurement, distribution, health facility and health professional levels. The assessment was completed during August 2008 using archival data, and observations at a pragmatic sample of health facilities providing obstetric services in Lusaka District, Zambia. Results The major barrier to the availability of MgSO4 within the public health system in Zambia was lack of procurement by the Ministry of Health. Other barriers identified included a lack of demand by health professionals at the health centre level and a lack of in-service training in the use of MgSO4. Where there was demand by obstetricians, magnesium sulphate injection was being procured from the private sector by the hospital pharmacy despite not being registered and licensed for use for the treatment of severe pre-eclampsia and eclampsia by the national Pharmaceutical Regulatory Authority. Conclusions The case study in Zambia highlights the complexities that underlie making essential medicines available and used appropriately. The fishbone diagram is a useful theoretical framework for illustrating the complexity of translating research findings into clinical practice. A better understanding

Comparison of the effects of gemfibrozil and clofibric acid on peroxisomal enzymes and cholesterol synthesis of rat hepatocytes.

PubMed

Hashimoto, F; Taira, S; Hayashi, H

1998-11-01

We studied whether the peroxisomal proliferation, induction of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and activation of cholesterol synthesis by gemfibrozil shown in whole body (Hashimoto F., Ishikawa T., Hamada S. and Hayashi H., Biochemical. Pharm., 49, 1213-1221 (1995)) is also detected at a culture cell level, and we made a comparative analysis of the effects of clofibric acid. Gemfibrozil at 0.25 mM increased the activity of some peroxisomal enzymes (catalase and the cyanide-insensitive fatty acyl-CoA oxidizing system) after incubation for 72 h. However, contrary to whole body experiments, gemfibrozil decreased the activity of HMG-CoA reductase and cholesterol synthesis from [14C]acetate. At 1 mM, gemfibrozil decreased not only the activity of HMG-CoA reductase and cholesterol synthesis, but also the protein content of the cells and peroxisomal enzyme activity, indicating nonspecific inhibition at this concentration. Clofibric acid (0.25 and 1 mM) increased the activity of peroxisomal enzymes, but decreased the activity of HMG-CoA reductase and cholesterol synthesis. With respect to the direct effect on HMG-CoA reductase in the cell homogenate, gemfibrozil at 0.25 mm did not affect the activity, but it clearly inhibited the activity at 2 mM and above. Clofibric acid at 2 mM hardly affected the activity, but it clearly decreased the activity at 5 mM and over. That is, gemfibrozil directly inhibited the activity more strongly than clofibric acid. The direct inhibition of the enzyme itself required higher concentrations of both agents than did inhibition at the culture cell level. These results suggest that the cytotoxicity of gemfibrozil is greater than that of clofibric acid, and that gemfibrozil, as well as clofibric acid, can induce peroxisomal enzymes in the culture cell level. In contrast to whole body results, gemfibrozil may suppress cholesterol synthesis from [14C]acetate through the inhibition of HMG-CoA reductase at the culture

Osmium isotope variations in the Pacific mantle: implications for the distribution of heterogeneity in the convecting mantle

NASA Astrophysics Data System (ADS)

Ishikawa, A.; Senda, R.; Suzuki, K.; Tani, K.; Ishii, T.

2015-12-01

Recent accumulation of Os isotope data obtained either from abyssal peridotites or from ocean island peridotite xenoliths has clearly demonstrated that the modern convecting mantle is substantially heterogeneous in Os-isotope composition. Unlike other radiogenic isotope heterogeneities observed in oceanic basalts, largely controlled by incorporation of recycled crustal materials, it seems likely that the observed range of Os-isotope compositions in oceanic peridotites directly reflect varying degrees of ancient melt extraction from peridotitic mantle. Hence, global variations of Os-isotope compositions in oceanic peridotites may provide an important piece of information in unraveling the geochemical and geodynamic evolution of the convecting mantle. Here we present the Os-isotope variations in peridotite-serpentinite recovered from the Pacific area because the number of data available is yet scarce when compared with data from other oceans (Atlantic, Arctic and Indian Ocean). Our primary purpose is to test whether mantle domains underlying four major oceans are distinct in terms of Os isotope variations, reflecting the pattern of mantle convection or mixing efficiency. We examined 187Os/188Os ratios and highly siderophile element concentrations in serpentinized harzburgite recovered from Hess Deep in the East Pacific Rise, a mantle section in the Taitao ophiolite, Chile (Schulte et al., 2009), serpentinized harzburgite bodies in the Izu-Ogasawara and Tonga forearc (Parkinson et al., 1998), peridotite xenoliths from the Pali-Kaau vent in O'ahu island, Hawaii (Bizimis et al., 2007), and low-temperature type peridotite xenoliths from Malaita, Solomon Islands (Ishikawa et al., 2011). The results demonstrate that samples from each area display very similar Os-isotope variations with a pronounced peak in 187Os/188Os = 0.125-0.128. Moreover, the relatively larger datasets obtained from Hess Deep, Taitao and Malaita clearly exhibit the presence of secondary peak in 187Os

Chemistry, mineralogy and alteration intensity of hydrothermal altered Mt Unzen conduit rocks (Shimabara/Japan)

NASA Astrophysics Data System (ADS)

Hess, Kai-Uwe; Yilmaz, Tim; Gilg, H. Albert; Janots, Emilie; Mayer, Klaus; Nakada, Setsuya; Dingwell, Donald

2017-04-01

Investigations were carried out on hydrothermally altered coherent dacitic dykes samples from (USDP-4) drill core at Mt Unzen stratovolcano (Shimabara/Japan). XRF, XRD, EMPA, C-O-isotope, hot-cathode CL and SEM analysis led to insights concerning chemistry, mineralogy, and intensity and type of alteration as well as the origin of carbonate-precipitating fluids. Additionally a textural characterization of the occurring replacement features in the volcanic conduit rocks was performed. The occurrence of the main secondary phases such as chlorite, pyrite, carbonates, and R1 (Reichweite parameter) illite-smectite and kaolinite group minerals indicate a weak to moderate propylitic to phyllic hydrothermal alteration. The dacitic samples of the dykes show different hydrothermal alteration features: (i) carbonate and chlorite pseudomorphs after hornblende as well as core and zonal textures due to replacement of plagioclase by R1 illite-smectite as well as kaolinite group minerals, (ii) colloform banded fracture fillings and fillings in dissolution vugs, and (iii) chlorite, R1 illite-smectite as well as kaolinite group minerals in the groundmass. Late chlorite veins crosscut precipitates of R1 illite-smectite as well as kaolinite group minerals. Carbonates in fractures and in pseudomorphs after hornblende comprise iron-rich dolomite solid solutions ("ankerite") and calcite. Isotopic values indicate a hydrothermal-magmatic origin for the carbonate formation. The chlorite-carbonate-pyrite index (CCPI) and the Ishikawa alteration index (AI), applied to the investigated samples show significant differences (CCPI=52.7-57.8; AI=36.1-40.6) indicating their different degree of alteration. According to Nakada et al., 2005, the C13 to C16 dykes represent the feeder dyke from the latest eruption (1991-1995) whereas C8 represents an earlier dyke feeder dyke from an older eruption. Weakest alteration, which was obtained in samples C16-1-5 and C13-2-5, correlates with the alteration

Mechanism for the Coupled Photochemistry of Ammonia and Acetylene: Implications for Giant Planets, Comets and Interstellar Organic Synthesis.

PubMed

Keane, Thomas C

2017-09-01

Laboratory studies provide a fundamental understanding of photochemical processes in planetary atmospheres. Photochemical reactions taking place on giant planets like Jupiter and possibly comets and the interstellar medium are the subject of this research. Reaction pathways are proposed for the coupled photochemistry of NH 3 (ammonia) and C 2 H 2 (acetylene) within the context Jupiter's atmosphere. We then extend the discussion to the Great Red Spot, Extra-Solar Giant Planets, Comets and Interstellar Organic Synthesis. Reaction rates in the form of quantum yields were measured for the decomposition of reactants and the formation of products and stable intermediates: HCN (hydrogen cyanide), CH 3 CN (acetonitrile), CH 3 CH = N-N = CHCH 3 (acetaldazine), CH 3 CH = N-NH 2 (acetaldehyde hydrazone), C 2 H 5 NH 2 (ethylamine), CH 3 NH 2 (methylamine) and C 2 H 4 (ethene) in the photolysis of NH 3 /C 2 H 2 mixtures. Some of these compounds, formed in our investigation of pathways for HCN synthesis, were not encountered previously in observational, theoretical or laboratory photochemical studies. The quantum yields obtained allowed for the formulation of a reaction mechanism that attempts to explain the observed results under varying experimental conditions. In general, the results of this work are consistent with the initial observations of Ferris and Ishikawa (1988). However, their proposed reaction pathway which centers on the photolysis of CH 3 CH = N-N = CHCH 3 does not explain all of the results obtained in this study. The formation of CH 3 CH = N-N = CHCH 3 by a radical combination reaction of CH 3 CH = N• was shown in this work to be inconsistent with other experiments where the CH 3 CH = N• radical is thought to form but where no CH 3 CH = N-N = CHCH 3 was detected. The importance of the role of H atom abstraction reactions was demonstrated and an alternative pathway for CH 3 CH = N-N = CHCH 3 formation involving nucleophilic reaction

The basal part of the Oman ophiolitic mantle: a fossil Mantle Wedge?

NASA Astrophysics Data System (ADS)

Prigent, Cécile; Guillot, Stéphane; Agard, Philippe; Godard, Marguerite; Chauvet, Alain; Dubacq, Benoit; Monié, Patrick; Yamato, Philippe

2014-05-01

Although the Oman ophiolite is classically regarded as being the direct analog of oceanic lithosphere created at fast spreading ridges, the geodynamic context of its formation is still highly debated. The other alternative end-member model suggests that this ophiolite entirely formed in a supra-subduction zone setting. Fluids involved in the hydration of the oceanic lithosphere and in the presence of a secondary boninitic and andesitic volcanism may provide a way to discriminate between these two interpretations: are they descending near-axis hydrothermal fluxes (first model) or ascending from a subducting slab (second model)? We herein focus on the base of the ophiolitic mantle in order to characterize the origin of fluids and decipher hydration processes. Samples were taken along hecto- to kilometre-long sections across the basal banded unit directly overlying the amphibolitic/granulitic metamorphic sole. We carried out a petrological, structural and geochemical study on these rocks and their constitutive minerals. Our results show that, unlike the generally refractory character of Oman harzburgites, all the basal mantle rocks display secondary crystallization of clinopyroxene and amphibole through metasomatic processes. The microstructures and the chronology of these secondary mineralizations (clinopyroxene, pargasitic amphibole, antigorite and then lizardite/chrysotile) suggest that these basal rocks have been affected by cooling from mantle temperatures (<1200°C) to low-T serpentinisation (<300°C). Furthermore, major elements required to crystallize these minerals and the observed fluid-mobile elements (FMEs) enrichments in the clinopyroxenes and in the amphiboles (B, Pb, Sr), as well as in the serpentines (B, Sr, Rb, Ba, As), are consistent with amphibolite-derived fluids (Ishikawa et al., 2005) and cannot be easily explained by other sources. Based on these observations, we propose a geodynamic model in which intense and continuous metasomatism of the

A Modern History of 'Imperial Medicine' Surrounding Hansen's Disease: Strategies to Manage Public Opinion in Modern Japanese Media.

PubMed

Seo, Gijae

2017-12-01

was controlled by the director of the sanatorium. Consequently, the research tends to perceive the problem within the frame of antagonism between the agent of imperialism and the victims of exploitation by the hands of imperialism. Hence, it has limitations in that it has not fully addressed the problem of the people who were not Hansen's disease patients and as such, existed somewhere in between the two extremes in the process of administering medicine under the imperial rule. The purpose of this study is to identify the direction of imperial medicine in the history of Hansen's disease in Japan and to comprehend the characteristics of policy on Hansen's disease developed by Mitsuda Kensuke, who was behind the policy of imperial medicine, and examine the process of imperial medicine reaching out to the people (of Japan and its colonies). To achieve the goal, this study explores how the agent of imperial medicine gain the favor the public, who are not Hansen's disease patients, by means of the mass media. Specifically, this paper examines data in the Japanese language related to Korean patients of Hansen's disease including the mass media data on Hansen's disease in the source book titled The Collection of Data on Hansen's Disease in Joseon under the Colonial Rule(8 volumes) compiled by Takio Eiji, which has not been studied until now. It also reviews the cultural and popular magazines published in Japan and Joseon at that time.

The effect of tamoxifen and raloxifene on estrogen metabolism and endometrial cancer risk.

PubMed

Williams-Brown, Marian Y; Salih, Sana M; Xu, Xia; Veenstra, Timothy D; Saeed, Muhammad; Theiler, Shaleen K; Diaz-Arrastia, Concepcion R; Salama, Salama A

2011-09-01

Selective estrogen receptor modulators (SERMs) demonstrate differential endometrial cancer (EC) risk. While tamoxifen (TAM) use increases the risk of endometrial hyperplasia and malignancy, raloxifene (RAL) has neutral effects on the uterus. How TAM increases the risk of EC and why TAM and RAL differentially modulate the risk for EC, however, remain elusive. Here, we tested the hypothesis that TAM increases the risk for EC, at least in part, by enhancing the local estrogen biosynthesis and directing estrogen metabolism towards the formation of genotoxic and hormonally active estrogen metabolites. In addition, the differential effects of TAM and RAL in EC risk are attributed to their differential effect on estrogen metabolism/metabolites. The endometrial cancer cell line (Ishikawa cells) and the nonmalignant immortalized human endometrial glandular cell line (EM1) were used for the study. The profile of estrogen/estrogen metabolites (EM), depurinating estrogen-DNA adducts, and the expression of estrogen-metabolizing enzymes in cells treated with 17β-estradiol (E2) alone or in combination with TAM or RAL were investigated using high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS(2)), ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS), and Western blot analysis, respectively. TAM significantly increased the total EM and enhanced the formation of hormonally active and carcinogenic estrogen metabolites, 4-hydroxestrone (4-OHE1) and 16α-hydroxyestrone, with concomitant reduction in the formation of antiestrogenic and anticarcinogenic 2-hydroxyestradiol and 2-methoxyestradiol. Furthermore, TAM increased the formation of depurinating estrogen-DNA adducts 4-OHE1 [2]-1-N7Guanine and 4-OHE1 [2]-1-N3 Adenine. TAM-induced alteration in EM and depurinating DNA adduct formation is associated with altered expression of estrogen metabolizing enzymes CYP1A1, CYP1B1, COMT, NQO1, and SF-1 as revealed by

Boron isotope systematics during magma-carbonate interaction: an experimental study from Merapi (Indonesia) and Vesuvius (Italy)

NASA Astrophysics Data System (ADS)

Deegan, F. M.; Jolis, E. M.; Troll, V. R.; Freda, C.; Whitehouse, M.

2011-12-01

mass transfer in subduction zones, where B is frequently employed as a tracer of deep crustal recycling [8]. [1] Chadwick et al. (2007) J. Petrol. 48, 1793-1812. [2] Deegan et al. (2010) J. Petrol. 51, 1027-1051. [3] Freda et al. (2010) Bull. Volcanol. 73, 241-256. [4] Jolis et al. (2011) in prep. [5] Leeman & Sisson (1996) Rev. Min. 33, 645-707. [6] Ishikawa & Nakamura (1993) Earth Planet Sci. Lett. 117, 567-580. [7] Deegan et al. (2011) Geology Today 27, 63-64. [8] Rose et al. (2001) Science 293, 281-283.

Heterostructure-based high-speed/high-frequency electronic circuit applications

NASA Astrophysics Data System (ADS)

Zampardi, P. J.; Runge, K.; Pierson, R. L.; Higgins, J. A.; Yu, R.; McDermott, B. T.; Pan, N.

1999-08-01

With the growth of wireless and lightwave technologies, heterostructure electronic devices are commodity items in the commercial marketplace [Browne J. Power-amplifier MMICs drive commercial circuits. Microwaves & RF, 1998. p. 116-24.]. In particular, HBTs are an attractive device for handset power amplifiers at 900 MHz and 1.9 GHz for CDMA applications [Lum E. GaAs technology rides the wireless wave. Proceedings of the 1997 GaAs IC Symposium, 1997. p. 11-13; "Rockwell Ramps Up". Compound Semiconductor, May/June 1997.]. At higher frequencies, both HBTs and p-HEMTs are expected to dominate the marketplace. For high-speed lightwave circuit applications, heterostructure based products on the market for OC-48 (2.5 Gb/s) and OC-192 (10 Gb/s) are emerging [http://www.nb.rockwell.com/platforms/network_access/nahome.html#5.; http://www.nortel.com/technology/opto/receivers/ptav2.html.]. Chips that operate at 40 Gb/ have been demonstrated in a number of research laboratories [Zampardi PJ, Pierson RL, Runge K, Yu R, Beccue SM, Yu J, Wang KC. hybrid digital/microwave HBTs for >30 Gb/s optical communications. IEDM Technical Digest, 1995. p. 803-6; Swahn T, Lewin T, Mokhtari M, Tenhunen H, Walden R, Stanchina W. 40 Gb/s 3 Volt InP HBT ICs for a fiber optic demonstrator system. Proceedings of the 1996 GaAs IC Symposium, 1996. p. 125-8; Suzuki H, Watanabe K, Ishikawa K, Masuda H, Ouchi K, Tanoue T, Takeyari R. InP/InGaAs HBT ICs for 40 Gbit/s optical transmission systems. Proceedings of the 1997 GaAs IC Symposium, 1997. p. 215-8]. In addition to these two markets, another area where heterostructure devices are having significant impact is for data conversion [Walden RH. Analog-to digital convertor technology comparison. Proceedings of the 1994 GaAs IC Symposium, 1994. p. 217-9; Poulton K, Knudsen K, Corcoran J, Wang KC, Nubling RB, Chang M-CF, Asbeck PM, Huang RT. A 6-b, 4 GSa/s GaAs HBT ADC. IEEE J Solid-State Circuits 1995;30:1109-18; Nary K, Nubling R, Beccue S, Colleran W

Analysis of the barriers and enablers to implementing lifestyle management practices for women with PCOS in Singapore.

PubMed

Ko, Henry; Teede, Helena; Moran, Lisa

2016-06-16

Polycystic ovary syndrome (PCOS) is a condition that affects women of reproductive age and manifests with adverse reproductive, metabolic and psychological consequences. Evidence-based PCOS guidelines recommend lifestyle management first line for infertility. In Singapore women with PCOS can attend the PCOS Clinic at the Kandang Kerbau Women and Children's Hospital for infertility treatment. However lifestyle integration into infertility management is currently limited and barriers and enablers to progress remain unclear. All PCOS clinic staff undertook semi-structured interviews to investigate perceived barriers for staff and consumers for the integration of lifestyle into infertility management. This study utilised various tools including an 8P Ishikawa diagram model to identify and categorise barriers. A modified Hanlon method was then used to prioritise barriers within the Singaporean context considering organisational, cultural and financial constraints. Propriety, economics, acceptability, resources and legality (PEARL) criteria were also incorporated into this decision-making tool. In the 8P model, there were five factors contributing to the 'procedure (consultations and referral processes)' barrier, one 'policy (government and hospitals)' factor, five 'place' factors, two 'product (lifestyle management programme)' barriers, two 'people (programme capacity)' factors, four 'process (integration)' factors, three 'promotion' barriers and three 'price' factors. Of the prioritised barriers, two were identified across each of 'procedures', 'place', 'product' and 'people' and four related to 'processes'. There were no barriers identified that for 'policies', 'promotion' and 'price' that can be addressed. There is a clear need to integrate lifestyle into infertility management in PCOS, in line with current national and international evidence-based guidelines. The highest priority identified improvement opportunity was to develop a collaborative lifestyle management

Ferrian Ilmenites: Investigating the Magnetic Phase Diagram

NASA Astrophysics Data System (ADS)

Lagroix, F.

2007-12-01

The main objective of this study is to investigate the magnetic phase changes within the hematite-ilmenite solid solution, yFeTiO3·(1-y)·Fe2O3. Two sets of synthetic ferrian ilmenites of y-values equal to 0.7, 0.8, 0.9, and 1.0 were available for this study. As currently drawn, the magnetic phase diagram, proposed by Ishikawa et al. [1985, J. Phys. Soc. Jpn. v.54, 312-325], predicts for increasing y values (0.5

Glucose-Specific Enzyme IIA of the Phosphoenolpyruvate:Carbohydrate Phosphotransferase System Modulates Chitin Signaling Pathways in Vibrio cholerae.

PubMed

Yamamoto, Shouji; Ohnishi, Makoto

2017-09-15

In Vibrio cholerae , the genes required for chitin utilization and natural competence are governed by the chitin-responsive two-component system (TCS) sensor kinase ChiS. In the classical TCS paradigm, a sensor kinase specifically phosphorylates a cognate response regulator to activate gene expression. However, our previous genetic study suggested that ChiS stimulates the non-TCS transcriptional regulator TfoS by using mechanisms distinct from classical phosphorylation reactions (S. Yamamoto, J. Mitobe, T. Ishikawa, S. N. Wai, M. Ohnishi, H. Watanabe, and H. Izumiya, Mol Microbiol 91:326-347, 2014, https://doi.org/10.1111/mmi.12462). TfoS specifically activates the transcription of tfoR , encoding a small regulatory RNA essential for competence gene expression. Whether ChiS and TfoS interact directly remains unknown. To determine if other factors mediate the communication between ChiS and TfoS, we isolated transposon mutants that turned off tfoR :: lacZ expression but possessed intact chiS and tfoS genes. We demonstrated an unexpected association of chitin-induced signaling pathways with the glucose-specific enzyme IIA (EIIA glc ) of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) for carbohydrate uptake and catabolite control of gene expression. Genetic and physiological analyses revealed that dephosphorylated EIIA glc inactivated natural competence and tfoR transcription. Chitin-induced expression of the chb operon, which is required for chitin transport and catabolism, was also repressed by dephosphorylated EIIA glc Furthermore, the regulation of tfoR and chb expression by EIIA glc was dependent on ChiS and intracellular levels of ChiS were not affected by disruption of the gene encoding EIIA glc These results define a previously unknown connection between the PTS and chitin signaling pathways in V. cholerae and suggest a strategy whereby this bacterium can physiologically adapt to the existing nutrient status. IMPORTANCE The EIIA glc

The Coupled Photochemistry of Ammonia and Acetylene: Applications to the Atmospheric Chemistry on Jupiter

NASA Astrophysics Data System (ADS)

Keane, Thomas Christopher

1995-01-01

The existence of hydrogen cyanide (HCN) in the highly reducing atmosphere of Jupiter was a surprising discovery (Tokunaga et al., 1981). Previous studies that tested the theoretical proposal of Kaye and Strobel (1983a) that the HCN observed on Jupiter is the result of NH _3 photolysis in the presence of C _2H_2 established that acetonitrile (CH_3CN) and acetaldazine (CH _3CH=NN=CHCH_3) are important intermediates in HCN formation (Ferris and Ishikawa, 1988). In this study the rates of formation of these compounds, and of other recently detected intermediates, have been determined in static photolysis experiments at 296 K and at temperatures which are closer to those found in the Jovian atmosphere. Experiments were also performed, using a photochemical flow reactor, that allowed for a better approximation of the mixing ratios of reactant gases (8 times 10^{ -4} for NH_3 and 1 times 10^{-5} for C_2H_2) and the process of advection in the Jovian atmosphere. An overall reaction pathway for HCN formation is proposed. Major intermediates and products found in these laboratory simulations that have not yet been observed on Jupiter are acetonitrile (CH_3CN), acetaldazine (CH_3CH=NN=CHCH _3), acetaldehyde hydrazone (CH_3 CH=NNH_2), N-ethylethylideneimine (CH_3CH=NC_2H _5), ethylamine (C_2H _5NH_2) and methylamine (CH _3NH_2). HCN is formed by the photolysis of NH_3/C _2H_2 mixtures (40:5 torr) at 296 K and at low temperature (208 K, 195 K and 180 K) with the highest quantum efficiency for HCN formation observed at 180 K. In static experiments using a high partial pressure of H_2 the quantum yield for HCN formation decreased three-fold relative to the 296 K photolyses when no H_2 was used. An additional ten-fold decrease in the quantum yield for HCN formation occurred when using the flow system. The quantum yields for acetaldazine and acetaldehyde hydrazone formation were found to vary inversely to that for HCN formation. For those static experiments which best simulate

PREFACE: 22nd International Congress on X-Ray Optics and Microanalysis

NASA Astrophysics Data System (ADS)

Falkenberg, Gerald; Schroer, Christian G.

2014-04-01

fees low and to distribute eight student travel grants. The Wednesday was devoted to an outing to DESY with guided tours to PETRA III and FLASH experiments and to the European XFEL construction site. A lecture was given by Henry Chapman introducing to structural imaging at X-ray free-electron lasers. Talks highlighting the current status and future of nanoanalysis at the leading synchrotron facilities APS (J Maser), ESRF (P Cloetens) and SPRing8 (Ishikawa) were given in the DESY auditorium offering other DESY scientists the opportunity to follow the talks. Participants A higher quality version of this image is available in supplementary data Further information about ICXOM22, including a detailed program and electronic abstract book, can be found on the congress website www.icxom22.de. We thank all the participants of ICXOM22, everybody who helped in the organization and are looking forward to hearing about further progress during ICXOM23, which will be organized by Brookhaven National Laboratory in Uptown, New York. Gerald Falkenberg ICXOM22 conference chair Christian Schroer ICXOM22 co-chair

Transport of carbon-bearing dusts from Iraq to Japan during Iraq's War

NASA Astrophysics Data System (ADS)

Tazaki, Kazue; Wakimoto, Rie; Minami, Yukiya; Yamamoto, Masayoshi; Miyata, Koshirou; Sato, Kazuhiro; Saji, Ichiro; Chaerun, S. Khodijah; Zhou, Guoping; Morishita, Tomoaki; Asada, Ryuji; Segawa, Hiromi; Imanishi, Hiroki; Kato, Rie; Otani, Yusuke; Watanabe, Tomoko

Rainwater collected during the period of February-April, 2003 in Kanazawa University and Hakui, Ishikawa Prefecture, Japan, was investigated by ion chromatography of the dissolved ions, and Scanning electron microscopy equipped with energy dispersive analyzer (SEM-EDX), electron microprobe analyzer (EPMA), transmission electron microscopy, and X-ray powder diffraction (XRD) analyses of the filtered samples. The pH, Eh, EC, dissolved oxygen (DO) and depleted U (DU) of the rainwater were also measured. The results show a rare case with low pH value of rain and high value of electrical conductivity (EC) in the rainwater during certain period. The NO 3-, SO 42- and NH 4+ concentrations on 26th March, show quite high values after oil field fires on 21st March 2003. The powdery dust and carbon-bearing nm sized particles contained in the rainwater have characteristics different from that of the Asian dust (Kosa). Since 21 March, 2003 the Iraq plunged into the war, the 9 oil field fires were reported on 25 March, 2003 in Rumaylah oil field near the borderline of Kuwait. The first precipitation was caught in Kanazawa on 24 March, 2003. The pH value of the rainwater indicated a strong acid rain (pH 3.6) with black powdery dusts. The acid rain on 27th March to 2nd April (pH 3.4-4.3; 5-17 mm) associated with WNW wind (2.7-4.1 m/s) has continued to the first 10 days of April in Kanazawa, during the 9 oil fields were burning in Iraq. The EC in rainwater collected from 24 March to 15 April, 2003, shows high concentrations of ions, suggesting high contents of water soluble-carbon particles and soot. In the meantime, it was the highest season of sandstorms at bare dried land in Iraq from the end of March to the beginning of April. Westerly wind blew around 5500 m high, and the sandstorm with 2000 m wide was transported by strong wind to Zagros 3000 m high mountains. The hot wind hit the Zagros Mountains and easily to join and rise to Westerly wind high by a rising air current. The

Glassy and Metastable Crystalline BaTi2O5 by Containerless Processing

NASA Astrophysics Data System (ADS)

Yoda, Shinichi; Kentei Yu, Yu; Kumar, Vijaya; Kameko, Masashi

metastable a-and b-BaTi2 O5 are constructed with non-centrosymmetric geometry TiO5 polyhedra, which provides higher potential for yielding high dielectric constants, pyroelectric and nonlinear op-tical properties than that of normal 4-or 6-coordinate Ti-O polyhedra. In addition, all lanthanide elements can be doped into the unusual glassy BaTi2 O5 structure to open up new possibilities for creating new bulk glasses, metastable phases and nano-crystalline ceramics with peculiar electronic and optical properties, such as giant permittivity and strong upconversion luminescence. References [1] Y. Akishige, K. Fukano, and H. Shigematsu, Jpn. J. Appl. Phys. p2, 42, L946 (2003). [2] J. Yu, Y. Arai, T. Masaki, T. Ishikawa, S. Yoda, S. Kohara, H. Taniguchi, M. Itoh, and Y. Kuroiwa, Chem. Matter. 18 p.2169 (2006) [3] J. Yu, S. Kohara, S. Nozawa, K. Itoh, S. Miyoshi, Y. Arai, A. Masuno, H. Taniguchi, M. Itoh, M. Takata, T. Fukunaga, S. Koshihara, Y. Kuroiwa, and S. Yoda, Chem. Matter. 21, p259 (2009).

Sediment dynamics and the changing nature of the subduction component beneath the Kurile volcanic Arc

NASA Astrophysics Data System (ADS)

Dreyer, B.; Morris, J.; Tera, F.; Gill, J.

2006-12-01

Strong slab signatures in the lavas of the of the Kurile volcanic arc and their systematic changes across this unusually wide (~120-200km above the downgoing slab) arc provide excellent leverage for investigating the changing nature of subduction components and mixing processes across volcanic arcs. Results of new and published geochemical transects of the Kurile arc indicate a waning fluid subduction component across the arc (Bailey et al., Contrib. Mineral. Petrol., 1987; Zhuralev et al., Chem. Geol., 1987; Ryan et al., Science, 1995; Noll, et al., Geochimica et Cosmochimica Acta, 1996; Ishikawa and Tera, Earth Planet. Sci. Lett., 1997; Morris and Ryan, Treatise on Geochemistry, 2003); little geochemical change is observed along the arc. Boron, Sb, As, Pb, Cs, Ba, and Be, are progressively distilled from the slab in approximately decreasing efficiency. When the effects of decreasing degree of partial melting towards the rear-arc are minimized, Cs, Ba, and Be do not return to Pacific MORB values, indicating that they are still being added to the mantle wedge beneath the rear-arc. Despite the longer transit times, and hence additional decay of cosmogenic 10Be (t1/2=1.5Ma), 10Be/9Be ratios in the rear arc are frequently greater than or comparable to those measured at the front and requires (young, <10Ma) sediment contribution across the width of the arc, which likely reflects a greater proportion of sediment Be in rear-arc lavas, possibly as a melt or supercritical fluid (Johnson and Plank, G3, 1999). To characterize the incoming sediment and clarify the sediment dynamics beneath the Kurile arc and, new trace element, radiogenic isotope, and 10Be concentration data have been measured for a 250 meter section of marine sediments from ODP Site 1179 ~550 km outboard of the trench; these data are integrated with those of the Kurile arc lavas. Initial calculations suggest a maximum 10Be inventory of ~1.5x1013 atoms/cm2 in the incoming sediment column, which translates to

PREFACE: Atomically controlled fabrication technology: new physics and functional device realization Atomically controlled fabrication technology: new physics and functional device realization

NASA Astrophysics Data System (ADS)

Kuwahara, Yuji; Kasai, Hideaki

2011-10-01

, J L Hutchison, D C Smith, P Ashburn and C H de Groot Mechanism of atomic-scale passivation and flattening of semiconductor surfaces by wet-chemical preparationsKenta Arima, Katsuyoshi Endo, Kazuto Yamauchi, Kikuji Hirose, Tomoya Ono and Yasuhisa Sano Real-space calculations for electron transport properties of nanostructuresTomoya Ono, Shigeru Tsukamoto, Yoshiyuki Egami and Yoshitaka Fujimoto Thermally activated magnetization reversal in monatomic magnetic chains on surfaces studied by classical atomistic spin-dynamics simulationsDavid S G Bauer, Phivos Mavropoulos, Samir Lounis and Stefan Blügel An atomically controlled Si film formation process at low temperatures using atmospheric-pressure VHF plasmaK Yasutake, H Kakiuchi, H Ohmi, K Inagaki, Y Oshikane and M Nakano Single-nanometer focusing of hard x-rays by Kirkpatrick-Baez mirrorsKazuto Yamauchi, Hidekazu Mimura, Takashi Kimura, Hirokatsu Yumoto, Soichiro Handa, Satoshi Matsuyama, Kenta Arima, Yasuhisa Sano, Kazuya Yamamura, Koji Inagaki, Hiroki Nakamori, Jangwoo Kim, Kenji Tamasaku, Yoshinori Nishino, Makina Yabashi and Tetsuya Ishikawa Surface magnetism in O2 dissociation—from basics to applicationY Kunisada, M C Escaño and H Kasai Real-space finite-difference approach for multi-body systems: path-integral renormalization group method and direct energy minimization methodAkira Sasaki, Masashi Kojo, Kikuji Hirose and Hidekazu Goto Electrical conduction of organic ultrathin films evaluated by an independently driven double-tip scanning tunneling microscopeK Takami, S Tsuruta, Y Miyake, M Akai-Kasaya, A Saito, M Aono and Y Kuwahara

The Chondrite Neagari: Petrography, Mineralogy, Chemical Compositions, and Cosmogenic Nuclides

NASA Astrophysics Data System (ADS)

Okada, A.; Komura, K.; Nagao, K.; Nishiizumi, K.; Miyamoto, Y.; Sakamoto, K.; Ebihara, M.; Shima, M.

1995-09-01

The Neagari meteorite fell on Feb. 18, 1995 at Neagari-machi, Nomi-gun, Ishikawa-ken, Japan (geographical coordinate: 36 degrees 26.9'N, 136 degrees 27.9'E). It was broken into several pieces when it hit a car upon falling. The largest piece weighing about 325 g and a small piece weighing 39 g were brought to the Kanazawa University for the measurements of gamma-rays emitted by cosmogenic nuclides only 2.7 days after the fall. Thereafter, the measurement was repeated several times. Other small pieces were used for petrographic, mineralogical and chemical studies. Noble gas mass spectrometry and AMS were also conducted. The Neagari meteorite shows a distinct, recrystallized structure under the microscopic observation of the thin section. Chondrules, 0.6 to 1.0 mm in diameter, are all present as relicts, buried in the well-recrystallized matrix. The chondrule-matrix boundaries are scarcely discernible in the granulated matrix. Olivine (Fa: 25.3 +/- 0.6 mole%) and orthopyroxene (Fs: 20.6 +/- 0.6 mole%) are the most abundant minerals both in matrix and in the chondrule relicts. Diopside is present as individual grains in the granular matrix. Interstitial feldspar crystal (Or(sub)6.3Ab (sub)88.0 An(sub)5.8) are common in the matrix and chondrule relicts, and often enclose minute pyroxene grains. Main opaque minerals are kamacite, taenite, troilite and chromite, and the metal phase is more abundant than the sulfide phase in the section. Both Fa and Fs values indicate that the Neagari meteorite is an L chondrite. The well-crystallized structure of the matrix, poorly defined outline of relict chondrules in the matrix, the prevalence of clear and well-developed plagioclase grains in the matrix and chondrule relicts and the absence of glass and monoclinic low-Ca pyroxene indicate the petrologic type to be 6. By the non-destructive gamma-ray measurement of the meteorite, eleven cosmogenic nuclides (^44mSc, ^52Mn, ^48V, ^51Cr, ^7Be, ^56Co, ^46Sc, ^57Co, ^54Mn, ^22Na, and ^26Al

EDITORIAL: Invited papers from ISAMMA 2010 (Sendai, Japan, 12-16 July 2010) Invited papers from ISAMMA 2010 (Sendai, Japan, 12-16 July 2010)

NASA Astrophysics Data System (ADS)

Takahashi, M.; Saito, H.

2011-02-01

Yanagihara, Yuta Toyoda and Eiji Kita Monte Carlo simulations of the magnetocaloric effect in magnetic Ni-Mn-X (X = Ga, In) Heusler alloys V D Buchelnikov, V V Sokolovskiy, S V Taskaev, V V Khovaylo, A A Aliev, L N Khanov, A B Batdalov, P Entel, H Miki and T Takagi Changes in electronic states and magnetic free energy in La1-zCez(FexSi1-x)13 magnetic refrigerants A Fujita, S Fujieda and K Fukamichi Garnet composite films with Au particles fabricated by repetitive formation for enhancement of Faraday effect H Uchida, Y Mizutani, Y Nakai, A A Fedyanin and M Inoue Control of magnetic domain wall displacement using spin current in small in-plane magnetic field in Permalloy nanowires Yoshihiko Togawa, Takashi Kimura, Ken Harada, Akira Tonomura and Yoshichika Otani Magnetic-field tunable transmittance in a ferrofluid-filled silicon nitride photonic crystal slab H M Lee, L Horng and J C Wu Evaluation of a miniature magnetostrictive actuator using Galfenol under tensile stress Toshiyuki Ueno, Hidemitsu Miura and Sotoshi Yamada Sub-nm resolution depth profiling of the magnetic structure of thin films by the depth-resolved x-ray magnetic circular dichroism technique K Amemiya and M Sakamaki

Titanium (IV) sol-gel chemistry in varied gravity environments

NASA Astrophysics Data System (ADS)

Hales, Matthew; Martens, Wayde; Steinberg, Theodore

. The test systems and experimental results obtained will be presented. 1. Okubo, T., Tsuchida, A., Okuda, T., Fujitsuna, K., Ishikawa, M., Morita, T., Tada, T. , Kinetic Analyses of Colloidal Crystallization in Microgravity -Aircraft Experiments. . Colloids and Surfaces A: Physicochemical and Engineering Aspects, 1999. 153: p. 515-524. 2. Okubo, T., Tsuchida, A., Kobayashi, K., Kuno, A., Morita, T., Fujishima, M., Kohno, Y., Kinetic Study of the Formation Reaction of Colloidal Silica Spheres in Microgravity Using Aircraft. Colloid Polymer Science, 1999. 277(5): p. 474-478. 3. Pienaar, C.L., Chiffoleau, G. J. A., Follens, L. R. A., Martens, J. A., Kirschhock, C. E. A., Steinberg, T. A., Effect of Gravity on the Gelation of Silica Sols. Chem. Mater., 2007. 19(4): p. 660-664. 4. Smith, D.D., et al., Effect of Microgravity on the Growth of Silica Nanostructures. Langmuir, 2000. 16(26): p. 10055-10060. 5. Zhang, X., Johnson, D.P., Manerbino, A.R., Moore, J.J., Schowengerdt, F. , Recent Mi-crogravity Results in the Synthesis of Porous Materials. AIP Conference Proceedings (Space Technology and Applications International Forum-1999, Pt. 1), 1999. 458: p. 88-93. 6. Dunbar, P.B., Bendzko, N.J.,, 1H and 13C NMR observation of the reaction of acetic acid with titanium isopropoxide. Materials Chemistry and Physics, 1999. 59: p. 26-35. 7. Krunks, M., Oja, I., T˜nsuaadu, K., Es-Souni, M., Gruselle, M., Niinistü,. L, Thermoanalytical study of acetylacetonate-modified titanium (iv) isopropoxide as precursor for TiO2 films. Journal of Thermal Analysis and Calorimetry, 2005: p. 483-488. 8. Moran, P.D., Bowmaker, G. A., Cooney, R. P., Vibrational Spectra and Molecular Associa-tion of Titanium Tetraisopropoxide. Inorg. Chem., 1998. 37(1): p. 2741-2748. 9. Somogyvari, A., Serpone, N.,, Evidence for five-coordination in titanium(1V) complexes. A nuclear magnetic resonance investigation. Canadian Journal of Chemistry, 1977. 56: p. 316-319.

The oceanic carbon cycle implicated in the d13Ccarb and the d13Corg variations from the terminal Ediacaran to the Early Cambrian

NASA Astrophysics Data System (ADS)

Ishikawa, T.; Ueno, Y.; Komiya, T.; Shu, D.; Li, Y.; Yoshida, N.; Maruyama, S.

2009-04-01

The terminal Neoproterozoic and its transition into the Cambrian witnessed major evolutionary and geochemical changes (e.g. Knoll, 1994). Evolutionary features include extinction and subsequent radiation events (e.g. Brasier, 1994; Knoll, 1994; Knoll and Carroll, 1999; Shu 2008). Geochemical changes comprise secular variations of the global carbon cycle expressed as variations of the d13C isotope records. A representative d13C curve for inorganic carbon (d13Ccarb) across the Precambrian/Cambrian boundary (Pc/C boundary) shows the existence of large fluctuations (e.g. Kirschvink et al., 1991; Narbonne et al., 1994; Kaufman et al., 1995; Amthor et al., 2003; Maloof et al., 2005, Ishikawa et al., 2008). This indicates a significant change of the oceanic carbon cycle at that time. On the other hand, the d13C values for total organic carbon (d13Corg) have rarely been reported together with the d13Ccarb across the boundary. Therefore, the precise relation between the d13Ccarb and the d13Corg and the global carbon cycle at the Pc/C boundary are still ambiguous. This work presents a first high-resolution d13Corg chemostratigraphy of drill core samples across the Pc/C boundary in the Three Gorges area, South China. Based on the results, this work additionally proposes variations of the sizes of the oceanic carbon reservoirs by a calculation of the carbon cycle model at the Pc/C boundary. The Three Gorges section extends from the uppermost Ediacaran dolostone (Dengying Formation), through the lowermost Early Cambrian muddy limestone (Yanjiahe Formation) to the middle Early Cambrian calcareous black shale (Shuijingtuo Formation). The ^13Corg values exhibit relatively invariant values averaging at -31 permil. By comparison between the d13Ccarb and d13Corg, we recognize two different terms in this period. The first term from the Pc/C boundary to the early Nemakit-Daldynian (ND) is characterized by the decoupling of d13Corg and d13Ccarb, stable d13Corg and the significant

A revision of the family Ameroseiidae (Acari, Mesostigmata), with some data on Slovak fauna

PubMed Central

Mašán, Peter

2017-01-01

Abstract The family Ameroseiidae Evans, 1961 (Acari: Mesostigmata) includes a total of 12 valid and adequately described genera, namely Afrocypholaelaps Elsen, 1972, Ameroseiella Bregetova, 1977, Ameroseius Berlese, 1904, Asperolaelaps Womersley, 1956, Brontispalaelaps Womersley, 1956, Epicriopsis Berlese, 1916, Hattena Domrow, 1963, Kleemannia Oudemans, 1930, Neocypholaelaps Vitzthum, 1942, Pseudoameroseius gen. n., Sertitympanum Elsen & Whitaker, 1985 and Sinoseius Bai & Gu, 1995. One of these genera includes subgenera, namely Kleemannia (Primoseius) Womersley, 1956. All genera are reviewed and re-diagnosed, and a dichotomous key is provided for their identification. Ameroseius (50 species), Kleemannia (28 species) and Neocypholaelaps (22 species) are the largest genera in the family. Ameroseiella, Kleemannia, Kleemannia (Primoseius) and Sinoseius are considered to be valid taxa and, in presented systematic classification, they are removed from synonymy with Ameroseius. The genus Pseudoameroseius gen. n., with type species Ameroseius michaelangeli Moraza, 2006 (from Canary Islands), is newly erected to further refine broad primary concept of Ameroseius as understood by some former authors (Karg, Bregetova). Asperolaelaps is removed from synonymy with Neocypholaelaps. Three new species are here described, namely Ameroseius renatae sp. n. (based on specimens from Slovakia), Kleemannia dolichochaeta sp. n. (from Spain) and Kleemannia miranda sp. n. (from U.S.A.). The following new junior synonymies are proposed: Ameroseius apodius Karg, 1971 = Ameroseiella macrochelae (Westerboer, 1963); Ameroseius bregetovae Livshits & Mitrofanov, 1975 = Neocypholaelaps favus Ishikawa, 1968; Ameroseius chinensis Khalili-Moghadam & Saboori, 2016 = Ameroseius guyimingi Ma, 1997; Ameroseius crassisetosus Ye & Ma, 1993, Ameroseius qinghaiensis Li & Yang, 2000 and Ameroseius norvegicus Narita, Abduch & Moraes, 2015 = Ameroseius corbiculus (Sowerby, 1806); Ameroseius dubitatus Berlese

Fungal Planet description sheets: 469-557.

PubMed

Crous, P W; Wingfield, M J; Burgess, T I; Hardy, G E St J; Crane, C; Barrett, S; Cano-Lira, J F; Le Roux, J J; Thangavel, R; Guarro, J; Stchigel, A M; Martín, M P; Alfredo, D S; Barber, P A; Barreto, R W; Baseia, I G; Cano-Canals, J; Cheewangkoon, R; Ferreira, R J; Gené, J; Lechat, C; Moreno, G; Roets, F; Shivas, R G; Sousa, J O; Tan, Y P; Wiederhold, N P; Abell, S E; Accioly, T; Albizu, J L; Alves, J L; Antoniolli, Z I; Aplin, N; Araújo, J; Arzanlou, M; Bezerra, J D P; Bouchara, J-P; Carlavilla, J R; Castillo, A; Castroagudín, V L; Ceresini, P C; Claridge, G F; Coelho, G; Coimbra, V R M; Costa, L A; da Cunha, K C; da Silva, S S; Daniel, R; de Beer, Z W; Dueñas, M; Edwards, J; Enwistle, P; Fiuza, P O; Fournier, J; García, D; Gibertoni, T B; Giraud, S; Guevara-Suarez, M; Gusmão, L F P; Haituk, S; Heykoop, M; Hirooka, Y; Hofmann, T A; Houbraken, J; Hughes, D P; Kautmanová, I; Koppel, O; Koukol, O; Larsson, E; Latha, K P D; Lee, D H; Lisboa, D O; Lisboa, W S; López-Villalba, Á; Maciel, J L N; Manimohan, P; Manjón, J L; Marincowitz, S; Marney, T S; Meijer, M; Miller, A N; Olariaga, I; Paiva, L M; Piepenbring, M; Poveda-Molero, J C; Raj, K N A; Raja, H A; Rougeron, A; Salcedo, I; Samadi, R; Santos, T A B; Scarlett, K; Seifert, K A; Shuttleworth, L A; Silva, G A; Silva, M; Siqueira, J P Z; Souza-Motta, C M; Stephenson, S L; Sutton, D A; Tamakeaw, N; Telleria, M T; Valenzuela-Lopez, N; Viljoen, A; Visagie, C M; Vizzini, A; Wartchow, F; Wingfield, B D; Yurchenko, E; Zamora, J C; Groenewald, J Z

2016-12-01

caatingaensis (endophyte from Tacinga inamoena ), Geastrum ishikawae on sandy soil, Geastrum pusillipilosum on soil, Gymnopus pygmaeus on dead leaves and sticks, Inonotus hymenonitens on decayed angiosperm trunk, Pyricularia urashimae on Urochloa brizantha , and Synnemellisia aurantia on Passiflora edulis . Chile : Tubulicrinis australis on Lophosoria quadripinnata. France : Cercophora squamulosa from submerged wood, and Scedosporium cereisporum from fluids of a wastewater treatment plant. Hawaii : Beltraniella acaciae , Dactylaria acaciae , Rhexodenticula acaciae , Rubikia evansii and Torula acaciae (all on Acacia koa ) . India : Lepidoderma echinosporum on dead semi-woody stems, and Rhodocybe rubrobrunnea from soil. Iran : Talaromyces kabodanensis from hypersaline soil. La Réunion : Neocordana musarum from leaves of Musa sp. Malaysia : Anungitea eucalyptigena on Eucalyptus grandis × pellita , Camptomeriphila leucaenae (incl. Camptomeriphila gen. nov.) on Leucaena leucocephala , Castanediella communis on Eucalyptus pellita , Eucalyptostroma eucalypti (incl. Eucalyptostroma gen. nov.) on Eucalyptus pellita , Melanconiella syzygii on Syzygium sp., Mycophilomyces periconiae (incl. Mycophilomyces gen. nov.) as hyperparasite on Periconia on leaves of Albizia falcataria , Synnemadiella eucalypti (incl. Synnemadiella gen. nov.) on Eucalyptus pellita , and Teichospora nephelii on Nephelium lappaceum. Mexico : Aspergillus bicephalus from soil. New Zealand : Aplosporella sophorae on Sophora microphylla , Libertasomyces platani on Platanus sp., Neothyronectria sophorae (incl. Neothyronectria gen. nov.) on Sophora microphylla , Parastagonospora phoenicicola on Phoenix canariensis , Phaeoacremonium pseudopanacis on Pseudopanax crassifolius , Phlyctema phoenicis on Phoenix canariensis , and Pseudoascochyta novae-zelandiae on Cordyline australis. Panama : Chalara panamensis from needle litter of Pinus cf. caribaea . South Africa : Exophiala eucalypti on leaves of Eucalyptus sp

Shallow Moho with aseismic upper crust and deep Moho with seismic lower crust beneath the Japanese Islands obtained by seismic tomography using data from dense seismic network

NASA Astrophysics Data System (ADS)

Matsubara, Makoto; Obara, Kazushige

2015-04-01

. The Moho discontinuity deepens over 35 km in the collision zone like as Kanto Mountains, the volcanic underplating zone as the Tohoku backbone range, and non-tension region like as Chugoku Mountains. These regions associated with deep Moho are characterized by the crustal seismicity within the depth range from 20 to 30 km. The iso-depth contour of 35 km beneath the southwestern Japan is consistent with that derived from the receiver function method (Shiomi et al. 2006). There are nonvolcanic tremors and short-time slow slip events (SSE) beneath the southwestern Japan (eg. Obara, 2002). Matsubara et al. (2009) consider that the tremors and SSEs occur along the contact zone of Moho discontinuity beneath the Eurasian plate and the subducting Philippine Sea plate beneath southwestern Japan. Our Moho model is consistent with this since they exist along the southern edge of the Moho discontinuity of the continental Eurasian plate. Reference: Hirata, N., Sakai, S., Nakagawa, S., Ishikawa, M., Sato, H., Kasahara, K., Kimura, H. and Honda, R. (2012) A new tomographic image on the Philippine Sea Slab beneath Tokyo - Implication to seismic hazard in the Tokyo metropolitan region, EOS, Transactions, AGU, T11C-06. Kita, S., T. Okada, A. Hasegawa, J. Nakajima, and T. Matsuzawa (2010) Anomalous deepening of a seismic belt in the upper-plane of the double seismic zone in the Pacific slab beneath the Hokkaido corner: Possible evidence for thermal shielding caused by subducted forearc crust materials, Earth Planet. Science Lett., 290, 415-426. Matsubara, M. and K. Obara (2011) The 2011 Off the Pacific Coast of Tohoku earthquake related to a strong velocity gradient with the Pacific plate, Earth Planets Space, 63, 663-667. Matsubara, M., K. Obara, and K. Kasahara (2009) High-Vp/Vs zone accompanying non-volcanic tremors and slow-slip events beneath southwestern Japan, Tectonophysics, 472, 6-17, doi:10.1016/j.tecto.2008.06.013. Obara, K. (2002) Nonvolcanic deep tremor associated with

PREFACE: 6th International Conference on Aperiodic Crystals (APERIODIC'09)

NASA Astrophysics Data System (ADS)

Grimm, Uwe; McGrath, Rónán; Degtyareva, Olga; Sharma, Hem Raj

2010-04-01

on quasicrystals (Eiji Abe), complex metal alloys (Alessandra Beni) and incommensurately modulated structures (Gervais Chapuis). While these were mainly aimed at younger researchers in the field, the lectures were very well attended and appreciated by the participants. The main programme ran from Monday morning until Friday lunchtime. It comprised 13 invited and 40 contributed plenary talks, and more than 40 posters, which were presented at two afternoon/evening poster sessions. The topics covered in the programme range from mathematical foundations, mathematical models, new materials, sample preparation, structure determination, physical properties and surface properties to industrial applications. Every presenter was invited to submit an article for this proceedings volume, and the 36 peer-reviewed papers in this volume present a cross-section of the range of presentations at the conference. They have been arranged into four categories, (i) quasicrystals, (ii) modulated structures, (iii) mathematical and theoretical aspects of aperiodic order, and (iv) approximants and complex phases. Prizes for best student presentations were awarded to Heinrich Orsini-Rosenberg (ETH Zurich) for his poster Tailor-made sevenfold approximants: ab-initio investigations on formation and stability and to Holger Euchner (Universität Stuttgart) for his contributed talk on Lattice dynamics in complex metallic alloys - vibrational properties of Zn11Mg2. In addition to a cash prize, Heinrich Orsini-Rosenberg received an icosahedral teapot, which was manufactured and donated by David Warrington, and Holger Euchner received a book prize. The meeting started with a welcome reception in the University's recently refurbished Victoria Gallery and Museum. A public lecture Simple sets of shapes that tile the plane but cannot ever repeat by Professor Sir Roger Penrose FRS attracted a wide audience and gave a fascinating insight into the discovery of the Penrose tiling, which is still the paradigm

Preface: Introductory Remarks: Linear Scaling Methods

NASA Astrophysics Data System (ADS)

Bowler, D. R.; Fattebert, J.-L.; Gillan, M. J.; Haynes, P. D.; Skylaris, C.-K.

2008-07-01

Haynes, Chris-Kriton Skylaris, Arash Mostofi and Mike Payne A miscellaneous overview of SIESTA algorithms Jose M Soler Wavelets as a basis set for electronic structure calculations and electrostatic problems Stefan Goedecker Wavelets as a basis set for linear scaling electronic structure calculationsMark Rayson O(N) Krylov subspace method for large-scale ab initio electronic structure calculations Taisuke Ozaki Linear scaling calculations with the divide-and-conquer approach and with non-orthogonal localized orbitals Weitao Yang Toward efficient wavefunction based linear scaling energy minimization Valery Weber Accurate O(N) first-principles DFT calculations using finite differences and confined orbitals Jean-Luc Fattebert Linear-scaling methods in dynamics simulations or beyond DFT and ground state properties An O(N) time-domain algorithm for TDDFT Guan Hua Chen Local correlation theory and electronic delocalization Joseph Subotnik Ab initio molecular dynamics with linear scaling: foundations and applications Eiji Tsuchida Towards a linear scaling Car-Parrinello-like approach to Born-Oppenheimer molecular dynamics Thomas Kühne, Michele Ceriotti, Matthias Krack and Michele Parrinello Partial linear scaling for quantum Monte Carlo calculations on condensed matter Mike Gillan Exact embedding of local defects in crystals using maximally localized Wannier functions Eric Cancès Faster GW calculations in larger model structures using ultralocalized nonorthogonal Wannier functions Paolo Umari Other approaches for linear-scaling, including methods formetals Partition-of-unity finite element method for large, accurate electronic-structure calculations of metals John E Pask and Natarajan Sukumar Semiclassical approach to density functional theory Kieron Burke Ab initio transport calculations in defected carbon nanotubes using O(N) techniques Blanca Biel, F J Garcia-Vidal, A Rubio and F Flores Large-scale calculations with the tight-binding (screened) KKR method Rudolf Zeller

EDITORIAL: Focus on Attosecond Physics

NASA Astrophysics Data System (ADS)

Bandrauk, André D.; Krausz, Ferenc; Starace, Anthony F.

2008-02-01

future involve using overdense plasmas. Electronic processes on sub-atomic spatio-temporal scales are the basis of chemical physics, atomic, molecular, and optical physics, materials science, and even some life science processes. Research in these areas using the new attosecond tools will advance together with the ability to control electrons themselves. Indeed, we expect that developments will advance in a way that is similar to advances that have occurred on the femtosecond time scale, in which much previous experimental and theoretical work on the interaction of coherent light sources has led to the development of means for 'coherent control' of nuclear motion in molecules. This focus issue of New Journal of Physics is centered on experimental and theoretical advances in the development of new methodologies and tools for electron control on the attosecond time scale. Topics such as the efficient generation of harmonics; the generation of attosecond pulses, including those having only a few cycles and those produced from overdense plasmas; the description of various nonlinear, nonperturbative laser-matter interactions, including many-electron effects and few-cycle pulse effects; the analysis of ultrashort propagation effects in atomic and molecular media; and the development of inversion methods for electron tomography, as well as many other topics, are addressed in the current focus issue dedicated to the new field of 'Attosecond Physics'. Focus on Attosecond Physics Contents Observing the attosecond dynamics of nuclear wavepackets in molecules by using high harmonic generation in mixed gases Tsuneto Kanai, Eiji J Takahashi, Yasuo Nabekawa and Katsumi Midorikawa Core-polarization effects in molecular high harmonic generation G Jordan and A Scrinzi Interferometric autocorrelation of an attosecond pulse train calculated using feasible formulae Y Nabekawa and K Midorikawa Attosecond pulse generation from aligned molecules—dynamics and propagation in H2+ E Lorin, S

EDITORIAL: Cluster issue on Heusler compounds and devices Cluster issue on Heusler compounds and devices

NASA Astrophysics Data System (ADS)

Felser, Claudia; Hillebrands, Burkard

2009-04-01

of the spin-Hall effect, spin-torque investigations and CPP GMR (current perpendicular plane giant magnetoresistance). Schneider et al have studied the Hall effect of laser ablated Co2(MnFe)Si thin films. Recently Inomata's group has reported on a high CPP GMR effect based on CFSA [19]. In this issue a theoretical study by Dai et al reports on the interfaces between CCFA and very thin chromium layers. Here the interface stays half-metallic which is a promising result regarding the realization of potential GMR devices. For spin-torque applications special requirements concerning the materials are necessary. Low damping constants, low magnetic moments and a perpendicular anisotropy are favourable properties. Ferrimagnetic Heusler compounds are candidates for low magnetic moments despite a high spin polarization and a high Curie temperature [20, 21]. Mn3Ga shows additionally a tetragonal distortion, which is favourable for perpendicular anisotropy [21]. The stability of Heusler compounds versus structural distortion is a well known phenomenon in shape memory alloys [22]. We hope this cluster of papers will inspire many researchers in the field of spintronics and motivate some of them to use these advanced materials for new devices. References [1] Heusler F 1903 Verh. Dtsch. Phys. Ges. 12 219 [2] de Groot R A, Müller F M, van Engen P G and Buschow K H J 1983 Phys. Rev. Lett. 50 2024 [3] Kübler J, Williams A R, Sommers C B 1983 Phys. Rev. B 28 1745 [4] Block T, Felser C and Jakob G 2003 J. Solid State Chem. 176 646 [5] Galanakis I, Mavropoulos Ph and Dederichs P H 2006 J. Phys. D: Appl. Phys. 39 765 [6] Kandpal H C, Fecher G H and Felser C 2007 J. Phys. D: Appl. Phys. 40 1507 [7] Wurmehl S, Fecher G H, Kandpal H C, Ksenofontov V, Felser C and Lin H J 2006 Appl. Phys. Lett. 86 032503 [8] Kämmerer S, Thomas A, Hütten A and Reiss G 2004 Appl. Phys. Lett. 85 79 [9] Yamato M, Marukame T, Ishikawa T, Matsuda K, Uemura T and Arita M 2006 J. Phys. D: Appl. Phys. 39 824 [10