(To see other currencies, click on price)
MORE ABOUT THIS BOOK
Main description:
This book contains the proceedings of a conference devoted to the study of the structure and function of Terminal deoxynucleotidyl Transferase (TdT) and its utilization as biochemical marker in immuno biology and leukemia, held in Elba, Italy on May 28-31, 1981. The en zyme has been known to nucleic acid biochemists for more than 20 years and has proved to be an excellent tool for making deoxypolymers, label ing DNA fragments, and adding homopolymer tails to restriction endonu clease fragments from DNA. Since the discovery of its peculiar tissue distribution, normally restricted to the thymus and bone marrow, and of its abnormal occur rence in human leukemic lymphoblasts, TdT has become one of the most widely used markers in the study of lymphocyte differentiation and in the classification of hematopoietic neoplasia. The subject seemed most appropriate for a meeting where molecular and cellular biologists, immunologists and hematologists could convene for the first time to discuss both basic research and the clinical aspects of the problem. Among the goals achieved by this workshop was the sharing of in formation about the enzymology of TdT, biochemical and immunological methodology and the correlation of TdT with other markers in the diag nosis of leukemia. The remarkable accordance of results, presented here by five independent hematological institutions, from analysis of TdT in several thousands of leukemic patients, marks the importance of this enzyme as a diagnostic and prognostic tool in these diseases.
Contents:
Section I Structures and Properties of Terminal Deoxynucleotidyl Transferase.- Terminal Transferase: Past to Present.- Purification of Terminal Deoxynucleotidyl Transferase from Pig Thymus: Identification of 42,000 and 57,000 Dalton Species.- Purification of Terminal Deoxynucleotidyl Transferase of 60,000 Dalton from Mannalian Thymus and Thymoma by Immunoadsorbent Column and Comparison of Peptide Structures.- Structure of Calf Thymus Terminal Deoxynucleotidyl Transferase.- Purification and Characterization of Multiple Forms of Terminal Transferase from Human Leukemic Cells.- Purification and Properties of Chick Terminal Deoxynucleotidyl Transferase (TdT).- Restriction Analysis of Cloned Heteropolymeric DNA Synthesized in vitro by TdT.- Terminal Deoxynucleotidyl Transferase Helps DNA Polymerase ? Bypass Thymine Dimer.- Inhibitors of DNA Polymerases: Their Selectivity and Mode of Action.- Section II Development of Immunological Reagents for Detection of Terminal Deoxynucleotidyl Transferase.- Development of Antibodies and Immunological Methods for Terminal Transferase Assay..- Use of Immimoflurorescence Tests for TdT in Human Hematologic Malignancy.- Section III Use of Terminal Deoxynucleotidyl Transferase as a Marker for Studies on Differentiation of Lymphocytes.- Ontogeny of Terminal Deoxynucleotidyl Transferase Containing Lymphocytes in R ts Mice.- Effects of Biological Response Modifiers on the Growth and Differentiation of Terminal Deoxynucleotidyl Transferase Containing Lymphocytes.- Murine Thymocyte Subpopulations: Two and Three Parameter Analysis with Various Markers.- Terminal Transferase Positive Cells in the Human Bone Marrow and Thymus.- Disappearance of Nuclear TdT in RPMI-8402 Following TPA Treatment.- Terminal Deoxynucleotidyl Transferase in Human Fetal Tissues.- Effect of Nucleosides on Human T and B Lymphoblastoid Cell Lines.- 20?-Hydroxysteroid Dehydrogenase (20?SDH) - A New Enzymatic Marker for Pre-T and T Lymphocytes.- Hybrids Between Myeloma Cells and Thymocytes - An Attempt to Approach the Biological Function of Terminal Transferase.- Section IV Terminal Transferase as a Marker for Malignant Lymphoid Cells.- The Bollum Enzyme in Leukemia and Lymphoma Cells: the First Decade.- Prognostic Significance of Terminal Transferase Activity and Other Factors in Childhood Acute Lymphoblastic Leukemia.- The Prognostic Significance of Terminal Deoxynucleotidyl Transferase (TdT) in Patients with Leukemias and Malignant Lymphomas.- Clinical Relevance of Terminal Transferase and Adenosine Deaminase in Leukemia.- Studies of Terminal Deoxynucleotidyl Transferase in Normal and Neoplastic Human Cells.- Nuclear Terminal Deoxynucleotidyl Transferase (TdT) in Leukemic Infiltrates of Testicular Tissue.- Phenotypic Changes During Blast Crisis of CML Characterized by Occurrence and Loss of TdT.- Enrichment of Terminal Deoxynucleotidyl Transferase Activity by Cell Separation.- TdT-Positive and TdT Negative Human Leukemic Cells: Specific Density and Morphology.- Normal Mononuclear Blood Cells in Diffusion Chambers: Occurrence of cALLA and TdT.- Enzymatic Properties in Pericellular Membranes of Leukemia Cells.
PRODUCT DETAILS
Publisher: Springer (Springer-Verlag New York Inc.)
Publication date: June, 2012
Pages: 393
Weight: 773g
Availability: Available
Subcategories: Biochemistry
From the same series
Marcello Costa
Gianfranco Donelli
Peter D Wagner
Amato Giaccia
Juan Antonio Rosado
Thomas J. Conlon
Mieczyslaw Pokorski
Gianfranco Donelli
Vered Stearns
Matthew Hirsch
David K. Harrison
Mieczyslaw Pokorski
Gaetano Santulli
Janos Minarovits
Dagmar Wilhelm
Gaetano Santulli
Mieczyslaw Pokorski
Aamir Ahmad
Mieczyslaw Pokorski
Gaetano Santulli
Arthur N. Popper
Luiz E. Bertassoni
Roberto Scatena
Joseph A. Sisneros
Ayache Bouakaz
John Ash
Feridoun Karimi-Busheri
Elisabetta Baldi
Mercedes Serabian
Christopher Ahern
Colin A. Nurse
John D. Lambris
Stephen P. Schoenberger
Marco Canepari
Mieczyslaw Pokorski
Mieczyslaw Pokorski
Mieczyslaw Pokorski
Richard Bronson
Charles Harris
Olga Gursky
Neville Vassallo
Mieczyslaw Pokorski
Patricia A. Ganz
Eugene G. Hrycay
Mieczyslaw Pokorski
Moneeb Ehtesham
Gil Atzmon, PhD
Maziar Divangahi
Stephen W. Schaffer
Ben Berkhout
Mieczyslaw Pokorski
Maria Spies
Heiko Enderling
Jean Champagnat
Maria Diakonova, PhD
Samir Zakhari
Mieczyslaw Pokorski
Mieczyslaw Pokorski
Mieczyslaw Pokorski
Mieczyslaw Pokorski
Mieczyslaw Pokorski
Mieczyslaw Pokorski
Mieczyslaw Pokorski
Mieczyslaw Pokorski
Marek Kimmel
Panayiotis Vlamos, PhD
Panayiotis Vlamos, PhD
Panayiotis Vlamos, PhD
Dongqing Wei
Gianfranco Donelli
Gianfranco Donelli
Hugo Merchant
Mindy Levin
William Horsnell
William V Holt
Donald Gullberg
Stefan Grimm
Lubo Zhang
Helen E. Scharfman
Alisa G. Woods
Eugenie S. Kleinerman
Bernard Fried
Bharat B. Aggarwal
Duane F. Bruley
David Capco
John Ash
Rameshwar Adhikari
Rameshwar Adhikari
Jackie Butler
Duane F. Bruley
Eric Schirmer
Toby K. Eisenstein
Jorg Reichrath
Christiane Ferran
Jaroslava T. Halper
Xin Zhang
Robert Snyder
Setsuro Fujii
Gregory R. Bowman
Christian Landry
David Klachko
Ernesto Porta
Uday Kishore
Laurent Nguyen
Natalia Maltsev
Maurice Landers
Amato Giaccia
Marco Fioroni
Marta Filizola
W. Holmes
Allan R. Brasier
John D. Lambris
Stephen P. Schoenberger
Richard Bott
Barbara Hoffman
S. Samuel Kim
M. R. Escobar
D. M. Klachko
P.J. Schollmeyer
G. Prodi
Paul Mandel
Sami Malek
Charlotte M. Witmer
Mladen Vranic
Pier Mannuccio Mannucci
Shaul Massry
Elisabetta Baldi, Ph.D.
Amrik Sahota
Morton Grossman
Yehezkel Ben-Ari
Mieczyslaw Pokorski
Stephen A. Zderic
George P. Chrousos
Nepomuk Zollner
Dirk Linke
Duane F. Bruley
Alexander Tzagoloff
Ryan J. Huxtable
Daniel Capelluto
Geneviève Spik
Richard L. Hughson
Santosh Nigam
Charles N. Serhan
Giuseppe Porcellati
Wolfgang L. Gross
Chi-Tang Ho
Kenneth V. Honn
Helmut Greim
Harry LeVine
Ryan J. Huxtable
Lauren S. Jackson
Roland Leclercq
W. Hildemann
R. Ekholm
Stefan Pohlmann
Mohan K. Raizada
Andrew J. Clifford
Junichi Azuma
David A. Lane
Stephen W. Schaffer
Mendel Friedman
Maryce M. Jacobs
Avigdor Shafferman
William E. Paul
Maryce M. Jacobs
Erik A. Richter
Sergio Gorini
Charles Day
Prem S. Paul
Jesús del Mazo
Ulrich Dirnagl
George R. Waller
Vijay V. Kakkar
Roger M. Enoka
Thomas Dittmar
Brian C. J. Moore
Duane F. Bruley
K. Abe
Srinivasan Damodaran
Darlene A. Dartt
H. Friedman
Lori R. Walsh
Louis Miller
Paola Ricciardi-Castagnoli
I. David Goldman
Sergio Gorini
Paola S. Timiras
Bela Buslig
June E. Ayling
Nanduri R. Prabhakar
Martin Hildebrandt
Jürgen Langner
V. Ter Meulen
Patti A. Quant
James Olcese
Lawrence Corey
Gary B. Calandra
Thomas Dittmar
K. Mikanagi
M. Mochizuki
Oded Sperling
Duane F. Bruley
John A. Mol
Alexander S. Kauffman
Hiroshi Maeda
J. E. Kudlow
Berthold Koletzko
Emmanuelle E. Wollmann
Herman Friedman
V. Cristofalo
Jürgen Langner
Mikael Skurnik
Adrianne Bendich
Nagy Habib
Karen B. Helle
Ryan J. Huxtable
Maziar Divangahi
A. Lowenthal
Albert M. Wu
Rodolfo Paoletti
Stephen P. Schoenberger
Calixto Machado
Oded Sperling
Abdeslem El Idrissi
Joe G. Hollyfield
Abdeslem El Idrissi
Abdeslem El Idrissi
Ulf Schmitz
Dariusz Leszczynski
David Wallach
H. V. Samis
Hubert Laude
Michael Dunn
Michael Riley
Wafik S. El-Deiry
A. Strano
Stewart G. Wolf
Shaul G. Massry
Mathias M. Muller
Arthur H. Rossof
Martin Reivich
W. L. Nyhan
G. Arden
F. Kreuzer
Jurgon Grote
Robert W. Ledeen
Bernard Haber
Colin Bloor
G. Manning
George Breese
Lowell Greenbaum
R. Camerini-Davalos
Jiri Mestecky
Jacob W. Streilein
Kerry Yasunobu
Illani Atwater
Shaul G. Massry
Alberto Amerio
Alberto Amerio
Chris H. De Bruyn
Shimon Gatt
Pierre Busson
J. Piiper
Peter D Wagner
David Kritchevky
Darlene A. Dartt
W. Stinebring
Claude L. Malmendier
Paul Nieuwenhuis
N. Bazan
A. Benedict
M. Klingberg
Francesco Bossa
H. Hidaka
Israel Hanin
V. Zappia
Michael Feldman
Nathan Back
K. Lindahl-Kiessling
Herbert Berman
Eric Chantler
Jarma Palo
David Kritchevsky
Sudhir Gupta
M. W. Miller
B. Jankovic
F. Sicuteri
M. Zouhair Atassi
L. Fiore-Donati
Paola S. Timiras
Krzysztof Palczewski
Edward K.L. Chan
Germana Meroni
Hamid R. Arabnia
Pierre Henkart
Chris H. De Bruyn
A. Rapado
L. Sandberg
H. J. Day
William R. Clark
Laurence Hedlund
V. Cosi
David M. Klachko
I. Silver
Maryce M. Jacobs
Sanat Dhar
B. Kahan
Robert Fitzgerald
Stewart Wolf
Darlene A. Dartt
A. B. Chandler
Mathias M. Muller
Robert Schwarcz
David Kessel
Ronald A. Pattillo
M. Zouhair Atassi
Sigbjorn Fossum
Eugenia Rosemberg
David Cavanagh
Walter H. Horl
Stewart Wolf
Shaul G. Massry
Stewart Wolf
P. J. Rottier
Ronald T. Acton
Barry B. Bercu
G. Schrauzer
A. Rapado
Haim I. Bicher
Tatiana Assaykeen
Shaul G. Massry
L. Hinshaw
David Kritchevsky
Lowell Greenbaum
F. Kreuzer
John J. Spitzer
Wendell W. Leavitt
Paul Actor
Herman Friedman
Andor Szentivanyi
K. Mikanagi
Maria Spies
K. Abe
Michael E. Maragoudakis
Graziella Allegri
Anthony J. Hannan
Edwin L. Cooper
John R. DeLoach
Heiko Enderling
Gerald Huether
Jeffrey Dunn
David T. Delpy
Peter D Wagner
Manuel Posada De La Paz
Dilson E. Rassier
Peter Hackett
Peter Vaupel
David T. Delpy
Uwe Proske
Peter Chiba
Andrzej Mackiewicz
Lazaros C. Triarhou
Christian Alzheimer
Vicente Felipo
E. Heinen
Chaim Hershko
Lee K. Opresko
American Institute for Cancer Research
Kalwant S. Authi
Constancio Gonzalez
Edward A. Dennis
G.J.L. Kaspers
Duane F. Bruley
Kenji Takahashi
Naranjan S. Dhalla
James E. Estes
M. Zouhair Atassi
Jiri Mestecky
Herman Friedman
Gerald H. Pollack
Rebecca Matsas
Stephen W. Schaffer
C. Tissa Kappagoda
Wolfram Sterry
Aaron I. Vinik
James P. Karr
Nicolas G. Bazan
David Ginsburg
Eduard W. A. Kamperdijk
T. William Hutchens
Thomas K. Goldstick
Hans H. Zingg
Adolf-Friedrich Holstein
F.D. Rose
Jerry R. McGhee
Rafael Beyar
Pawel Migula
Vincenzo Zappia
John S. Axford
Youcef M. Rustum
Ronan G. O'Regan
Claes-Goran Ostenson
Joseph C. LaManna
Donald Armstrong
Cecil R. Pace-Asciak
Carmel Mallia
Barry P. Rosen
Dominique Bagnard
Laurence S. Baskin
David Kritchevsky
Laurence S. Baskin
Yogesh C. Patel
Peter D Wagner
Aubie Angel
Alec Sehon
Roberto L. Ceriani
Carlos Eyzaguirre
Herman Friedman
Ehud Lavi
Bernard Robaire
Alberto Zanchetti
John S. Axford
Helmut Greim
Azita Alavi
Michael H. Tunick
Brian J. Whipp
M. Zouhair Atassi
Gary A. Levy
Jacques Banchereau
Jean-Marie Andrieu
Vicente Felipo
Constancio Gonzalez
Hanudatta S. Atreya
I.J.D. Lindley
Jiri Mestecky
Michael N.G. James
Kenneth V. Honn
Sangkot Marzuki
David S. Newburg
Chi-Sang Poon
David F. Wilson
Stephen W. Schaffer
Frank Roels
Prem S. Paul
Vicente Felipo
American Institute for Cancer Research
W. McIntyre Burnham
Arturo Leone
Mary W. Trucksess
Lawrence Corey
William E. Paul
Rodolfo Paoletti
Markus Tolnay
Janet A. Novotny
Shamim I. Ahmad
Chaim Hershko
Lauren S. Jackson
Yigal H. Ehrlich
American Institute for Cancer Research
Gilbert C. White II
Y. Murat Elçin
John D. Lambris
C. Yan Cheng
Lubov T. Timchenko
Stephen A. Zderic
Nicanor I. Moldovan
Laszlo Vecsei
Adam Karpf
Patrick C. Hallenbeck
M. Wolman
Darrell Salk
M. Zouhair Atassi
Ralph Bradshaw
Duane F. Bruley
Jolanta Baranska
Tim Schedl
Horst-Dieter Dellmann
Norbert W. Seidler
Mieczyslaw Pokorski
Lester R. Drewes
Nesrin Hasirci
Mieczyslaw Pokorski
Orkun Soyer
R.W.E. Watts
Alzira Maria Paiva de Almeida
F. Messiha
Gerald Pollack
Charlotte M. Witmer
Robert Schwarcz
Henri Begleiter
Rahul Jandial
Bernhard Kadenbach
V. Cristofalo
C. E. Finch
J. C. Petricciani
Bert O'Malley
Wolfgang Muller-Ruchholtz
Ryan J. Huxtable
Kunio Oota
N. Zöllner
M. R. Escobar
Claude L. Malmendier
David Kritchevsky
Jacqueline M. Matthews
Md. Shahidul Islam
Andrea Becchetti
Ramkrishna Sen
Rahul Jandial
Edwin Michael
Perumana R. Sudhakaran
Sigurd J. Normann
Lars Svennerholm
N. Back
Ikuo Homma
A. Bondi
Stewart Wolf
M. Z. Atassi
Ryuya Yamanaka
Hans U. Lutz
M. Lai
Stewart Wolf
Cesare Sirtori
Howard M. Eisenberg
Mendel Friedman
George Brewer
Edward Majchrowicz
Shahidul Islam
Harold Morris
Alexander Kohn
George Brewer
I.J.D. Lindley
Ian S. Longmuir
Nachman Brautbar
Lester Packer
Vicente Felipo
Shozo Kito
Rafael A. Camerini-Davalos
Athena P. Kourtis
George Karpati
J. R. McGhee
Robert H. Cox
Edward A. Dennis
George P. Chrousos
Noberto C. Gonzalez
B.A. Askonas
Bernard Roizman
Thomas K. Goldstick
William Wagner
Ivan Furda
Daniela Jezova
John N. Diana
Nejat Duzgunes
Thomas J.J. Blanck
M. Zouhair Atassi
Haim I. Bicher
Suad Efendic
Springer
Mauro Magnani
Charles N. Serhan
Alex F. Roche
Claus W. Heizmann
Adrian W. Zorgniotti
Steven Specter
William E. Paul
Robert S. Moreland
Henry F. Epstein
Carlos Lopez-Larrea
Jean-Francois Jeannin
Katalin Balogh
Vladimir Berezin
Carlos A. Guzman
Stewart Wolf
Herman Friedman
Jose Luis Pedraz
Inke S. Nathke
Mendel Friedman
Padraic G. Fallon
Kenneth Maiese
Yongwon Choi
Duane F. Bruley
Srinivasa T. Reddy
Michael R. Kreutz
Michael Balls
William S. Spielman
Roberto Scatena
August Heidland
Jean Francois Jasmin
Carlos Lopez-Larrea
Carlos Lopez-Larrea
Anil B. Mukherjee
Duane F. Bruley
Makoto Kuro-o
Gwendolyn P. Quinn
Jorg Reichrath
Michael G. Rossmann
Duane F. Bruley
John Ash
Arthur N. Popper
Monika Fuxreiter
Igor I. Goryanin
Lily C. Tang
Uday Kishore
Shamim I. Ahmad
Ralph Anderson
Lionel A. Poirier
Edwin L. Cooper
Claude L. Malmendier
Albert M. Wu
Can Ince
Howard M. Reisner
American Institute for Cancer Research
Larry K. Pickering
Bruce Kleger
Michael R. Shurin
Itzhak Kahane
Bal Ram Singh
Herman Friedman
John D. Lambris
Joao L. Ascensao
Koichi Suzuki
Graziella Allegri
George R. Waller
Stephen P. Schoenberger
L. Ashley Cowart
Lesley J. Collins
Amir Hussain
Albert M. Wu
Dirk Linke
Antonio Rodriguez-Moreno
Thomas Dittmar
Dean D. Metcalfe
Duane F. Bruley
Thomas Dittmar
Mark W. Robinson
John P. Fisher
Esteban Ballestar
Lev M. Berstein
Shahidul Islam
Hemanta K. Majumder
Simon Yona
Kenneth Söderhäll
Robin L. Thurmond
Maria Teresa Giardi
David Wallach
Torben Heick Jensen
Helge Grosshans
David C. Chhieng
Paul Okunieff
Nigel G. Laing
Esther Zoref-Shani
John D. Lambris
Peter Gunning
Vincenzo Zappia
Bela Buslig
Devin K. Binder
Christos Zouboulis
Maureen S. Thorniley
Iqbal S. Grewal
American Institute for Cancer Research
Stephen P. Schoenberger
Peter D Wagner
William E. Paul
Jonathan J. Li
Benjamin J. Blencowe
Alberto Mantovani
Simo S. Oja
Joe G. Hollyfield
Miguel Maroto
Alexander I. Agoulnik
Dihua Yu
Mathias Bahr
Roya Khosravi-Far
Stephen W. Schaffer
Fabrizio d'Adda di Fagagna
Gail Ruth Goldberg
Miguel Maroto
Shamim I. Ahmad
Warren C.W. Chan
Jorg Reichrath
Stephen P. Schoenberger
Ryutaro Utsumi
Jon F. Wilkins
Duane F. Bruley
Per Liss
Julie Owens
John D. Lambris
Alexander Sigalov
Nasimul Ahsan
Peter D Wagner
Stanley Perlman
Richard Blumberg
Andrew Berchuck
Marc Poulin
Dominique Bagnard
Peter D Wagner
Simone Mocellin
Gerard Pasterkamp
Bharat B. Aggarwal
Vicente Felipo
Gáspár Jékely
Constancio Gonzalez
Berthold Koletzko
Hamid R. Arabnia
Manuel Posada De La Paz
Dilson E. Rassier
Timothy G. Geary
Talila Volk
Eran Meshorer
Charles Chalfant
Nektarios Tavernarakis
Claudio Hetz
Patrick C. Hallenbeck
Stephen P. Schoenberger
Robert B. Raffa
Jean S. Deutsch
Randy Y.C. Poon
Shamim I. Ahmad
Jeremy H. Lakey
Steeve Hervé Thany
Anna Catania
Edwin Michael
Andrea Becchetti
Shahidul Islam
Joe G. Hollyfield
Jeremy P. T. Ward
Ikuo Homma
Ramkrishna Sen
Rahul Jandial
Jose Luis Pedraz
Vladimir Berezin
Vassilis Cutsuridis
Duane F. Bruley
Srinivasa T. Reddy
Katalin Balogh
Jean-Francois Jeannin
Yongwon Choi
Kenneth Maiese
Padraic G. Fallon
Carmen Espinos
Inke S. Nathke
Carlos A. Guzman
Uday Kishore
Carlos Lopez-Larrea
Pierre Ferrier
R. Jeroen Pasterkamp
Constancio Gonzalez
Susan Valle
Iqbal S. Grewal
Dagmar Sternad
Per Liss
Stephen W. Schaffer
Gail Ruth Goldberg
Nigel G. Laing
Stephen P. Schoenberger
Peter Gunning
Alexander Sigalov
John D. Lambris
C.Y. Cheng
Gary B. Huffnagle
Miguel Maroto
Miguel Maroto
Shamim I. Ahmad
Ryutaro Utsumi
Lev M. Berstein
Andrew Berchuck
Gerhard Martin Technau
H. Kenneth Hudnell
Jonathan J. Li
Jorg Reichrath
Jon F. Wilkins
Benjamin J. Blencowe
Hemanta K. Majumder
Duane F. Bruley
Dominique Bagnard
Roya Khosravi-Far
Peter D Wagner
Joe G. Hollyfield
Alberto Mantovani
Warren C.W. Chan
Alexander I. Agoulnik
Richard Wilson
Yongwon Choi
Robert D. Perry
Gáspár Jékely
Dihua Yu
John D. Lambris
Duane F. Bruley
Michael R. Shurin
Fabrizio d'Adda di Fagagna
Gerard Pasterkamp
Bharat B. Aggarwal
Vicente Felipo
Setsuro Ebashi
Stephen P. Schoenberger
Simone Mocellin
Peter D Wagner
John P. Fisher
Stanley Perlman
Jean-Pierre Saint-Jeannet
Simo S. Oja
Duane F. Bruley
John D. Lambris
Constantine Tsoukas
Nagy A. Habib
Uwe Lendeckel
Constancio Gonzalez
Joseph T. Coyle
Richard Blumberg
Nasimul Ahsan
Marelyn Wintour-Coghlan
Joe G. Hollyfield
















































































































































































































































































































































































































































































































































































































































































































































































































































































































































