Ran Canetti, Oded Goldreich, Shafi Goldwasser, Silvio Micali
We introduce the notion of Resettable Zero-Knowledge (rZK), a new security measure for cryptographic protocols which strengthens the classical notion of zero-knowledge. In essence, an rZK protocol is one that remains zero knowledge even if an adversary can interact with the prover many times, each time resetting the prover to its initial state and forcing it to use the same random tape. All known examples of zero-knowledge proofs and arguments are trivially breakable in this setting. Moreover, by definition, all zero-knowledge proofs of knowledge are breakable in this setting. Under general complexity assumptions, which hold for example if the Discrete Logarithm Problem is hard, we construct:
Jürgen U. Linder, Thomas Hoffmann, Ursula Kurz, Joachim E. Schultz
Paramecium has a 280-kDa guanylyl cyclase. The N terminus resembles a P-type ATPase, and the C terminus is a guanylyl cyclase with the membrane topology of canonical mammalian adenylyl cyclases, yet with the cytosolic loops, C1 and C2, inverted compared with the mammalian order. We expressed in Escherichia coli the cytoplasmic domains of the protozoan guanylyl cyclase, independently and linked by a peptide, as soluble proteins. The His6-tagged proteins were enriched by affinity chromatography and analyzed by immunoblotting. Guanylyl cyclase activity was reconstituted upon mixing of the recombinant C1a- and C2-positioned domains and in a linked C1a-C2 construct. Adenylyl cyclase activity was minimal. The nucleotide substrate specificity was switched from GTP to ATP upon mutation of the substrate defining amino acids Glu1681 and Ser1748 in the C1-positioned domain to the adenylyl cyclase specific amino acids Lys and Asp. Using the C2 domains of mammalian adenylyl cyclases type II or IX and the C2-positioned domain from the Paramecium guanylyl cyclase we reconstituted a soluble, all C2 adenylyl cyclase. All enzymes containing protozoan domains were not affected by Gαs/GTP or forskolin, and P site inhibitors were only slightly effective. Paramecium has a 280-kDa guanylyl cyclase. The N terminus resembles a P-type ATPase, and the C terminus is a guanylyl cyclase with the membrane topology of canonical mammalian adenylyl cyclases, yet with the cytosolic loops, C1 and C2, inverted compared with the mammalian order. We expressed in Escherichia coli the cytoplasmic domains of the protozoan guanylyl cyclase, independently and linked by a peptide, as soluble proteins. The His6-tagged proteins were enriched by affinity chromatography and analyzed by immunoblotting. Guanylyl cyclase activity was reconstituted upon mixing of the recombinant C1a- and C2-positioned domains and in a linked C1a-C2 construct. Adenylyl cyclase activity was minimal. The nucleotide substrate specificity was switched from GTP to ATP upon mutation of the substrate defining amino acids Glu1681 and Ser1748 in the C1-positioned domain to the adenylyl cyclase specific amino acids Lys and Asp. Using the C2 domains of mammalian adenylyl cyclases type II or IX and the C2-positioned domain from the Paramecium guanylyl cyclase we reconstituted a soluble, all C2 adenylyl cyclase. All enzymes containing protozoan domains were not affected by Gαs/GTP or forskolin, and P site inhibitors were only slightly effective. nitrilotriacetic acid heterotrimeric guanine nucleotide-binding protein, GTPγS, guanosine 5′-O-(3-thiophosphate) guanylyl cyclase fromParamecium Adenylyl and guanylyl cyclases are key proteins in intracellular signaling of essentially all eukaryotic cells. In the freshwater protozoans Paramecium and Tetrahymena cAMP and cGMP levels depend on the ion composition of the extracellular milieu. Whereas adenylyl cyclase activity in vivo is stimulated by membrane hyperpolarization (1.Schultz J.E. Klumpp S. Benz R. Schürhof-Goeters W. Schmid A. Science. 1992; 255: 600-603Crossref PubMed Scopus (128) Google Scholar, 2.Schultz J.E. Schönborn C. FEBS Lett. 1994; 356: 322-326Crossref PubMed Scopus (17) Google Scholar), cGMP formation is enhanced by a depolarizing Ca2+ inward current (3.Schultz J.E. Pohl T. Klumpp S. Nature. 1986; 322: 271-273Crossref Scopus (48) Google Scholar). Recently, we reported on a group of guanylyl cyclases of 280 kDa that is present in the ciliates Paramecium and Tetrahymena but also in the genome of the malaria parasite Plasmodium (4.Linder J.U. Engel P. Reimer A. Krüger T. Plattner H. Schultz A. Schultz J.E. EMBO J. 1999; 18: 4222-4232Crossref PubMed Scopus (80) Google Scholar). This novel signal transduction protein is bifunctional. It has a 155-kDa N-terminal P-type ATPase-like domain and a 115-kDa C-terminal guanylyl cyclase domain. Both are linked by a cytosolic loop of about 110 amino acids (see Fig. 1 A). Surprisingly, the guanylyl cyclase domain is topologically identical to mammalian adenylyl cyclases,i.e. it is composed of two pseudosymmetric modules of six putative transmembrane spans (M1 and M2) that serve as membrane anchors for the cytosolic, catalytic segments C1 and C2 (4.Linder J.U. Engel P. Reimer A. Krüger T. Plattner H. Schultz A. Schultz J.E. EMBO J. 1999; 18: 4222-4232Crossref PubMed Scopus (80) Google Scholar). The sequences of both cytosolic subdomains are similar to each other and resemble the catalytic regions of metazoan adenylyl and, to a lesser extent, guanylyl cyclases. Sequence comparisons show that the order of the protozoan C1a- and C2-positioned loops is reversed compared with the corresponding mammalian adenylyl cyclase loops (4.Linder J.U. Engel P. Reimer A. Krüger T. Plattner H. Schultz A. Schultz J.E. EMBO J. 1999; 18: 4222-4232Crossref PubMed Scopus (80) Google Scholar). Data based on the crystal structure of a soluble adenylyl cyclase type VC1a/type IIC2 chimera demonstrated that Lys938 and Asp1018 in the catalytic pocket of the C2 domain (adenylyl cyclase type II numbering) are responsible for ATP substrate specificity (5.Zhang G. Liu Y. Ruoho A.E. Hurley J.H. Nature. 1997; 386: 247-253Crossref PubMed Scopus (326) Google Scholar, 6.Tesmer J.J.G. Sunahara R.K. Gilman A.G. Sprang S.R. Science. 1997; 278: 1907-1916Crossref PubMed Scopus (680) Google Scholar). In theParamecium guanylyl cyclase, those two amino acids have evolved as Glu1681 and Ser1748 in the C1-positioned domain, i.e. specify GTP as a substrate, whereas the surrounding amino acid residues are more akin to metazoan adenylyl cyclases (see Fig. 1 B for an abbreviated sequence alignment). The expressed membrane-bound Paramecium guanylyl cyclase domain uses MgGTP as a substrate; it accepts MnATP as a substrate only slightly and is inactive with MgATP (4.Linder J.U. Engel P. Reimer A. Krüger T. Plattner H. Schultz A. Schultz J.E. EMBO J. 1999; 18: 4222-4232Crossref PubMed Scopus (80) Google Scholar). Following successful strategies by others to produce soluble heterodimeric adenylyl cyclases (7.Tang W.-J. Gilman A.G. Science. 1995; 268: 1769-1772Crossref PubMed Scopus (165) Google Scholar, 8.Whisnant R.E. Gilman A.G. Dessauer C.W. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 6621-6625Crossref PubMed Scopus (117) Google Scholar, 9.Dessauer C.W. Gilman A.G. J. Biol. Chem. 1996; 271: 16967-16974Crossref PubMed Scopus (86) Google Scholar, 10.Dessauer C.W. Scully T.T. Gilman A.G. J. Biol. Chem. 1997; 272: 22272-22277Crossref PubMed Scopus (109) Google Scholar, 11.Dessauer C.W. Gilman A.G. J. Biol. Chem. 1997; 272: 27787-27795Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar, 12.Scholich K. Barbier A.J. Mullenix J.B. Patel T.B. Proc. Natl. Acad. Sci. 1997; 94: 2915-2920Crossref PubMed Scopus (64) Google Scholar, 13.Tang W.-J. Stanzel M. Gilman A.G. Biochemistry. 1995; 34: 14563-14572Crossref PubMed Scopus (111) Google Scholar), we wished to assemble a protozoan heterodimeric guanylyl cyclase by expression inEscherichia coli of the catalytic domains either separately or covalently connected by a peptide linker. Here, we report on the expression and activity of such constructs. We then changed the purine nucleotide substrate specificity in this ciliate guanylyl cyclase with mammalian adenylyl cyclase topology by site-directed mutagenesis of two amino acids in the C1-positioned cytosolic loop. The inversion of the cytosolic loops was definitively proven by the successful generation of active adenylyl cyclase chimeras, which consisted only of cytosolic C2 cyclase domains, i.e. the mammalian adenylyl cyclase IIC2 or IXC2 and the C2-positioned domain of the Paramecium guanylyl cyclase. Radiochemicals were purchased from ICN or Amersham-Pharmacia Biotech; pQE vectors and nickel-NTA1 resin were from Qiagen. All enzymes were from Roche Molecular Biochemicals and New England Biolabs. To obtain the soluble constructs of theParamecium guanylyl cyclase cytosolic loops, we used a clone as a template in which all TAA/TAG-Gln codons had been mutated to the universal CAA/CAG-Gln triplets (GenBankTM accession numberAJ238859; Ref. 4.Linder J.U. Engel P. Reimer A. Krüger T. Plattner H. Schultz A. Schultz J.E. EMBO J. 1999; 18: 4222-4232Crossref PubMed Scopus (80) Google Scholar). For cloning purposes the C1a- (ParaGC-C1a) and C2- (ParaGC-C2) positioned cytosolic domains were fitted withSalI, MluI, and AscI restriction sites. The exact segment boundaries including the N-terminal His6-sequence and N- and C-terminal stuffer amino acids added to accommodate respective restriction sites are depicted in Fig.2 A. Conventional experimental protocols in molecular biology were followed to obtain the DNA constructs. A list of oligonucleotide sense and antisense primers and of synthetic mutagenic primers that were used in this study is available on request. The peptide linker AAGGPPAAGG in the construct ParaGC-C1aLParaGC-C2 was generated with two complementary oligonucleotide primers. The correctness of all constructs was verified by double-stranded DNA-sequencing. The constructs were cloned into a pQE30 expression vector that was modified to contain only a 5′-SalI and a 3′-AscI/HindIII cloning site. The C2 clone from rat type II adenylyl cyclase (GenBankTMaccession number M80550; IIC2) and a mouse type IX adenylyl cyclase clone (GenBankTM accession number Z50190) were kindly provided by Dr. C. Kleuss (Berlin) and Dr. F. Antoni (Glasgow), respectively. The C2 regions were cloned the with respective as and specific with and restriction sites for cloning of the into the pQE30 expression vector (see Fig. mutagenesis and was by the of and 1992; PubMed Scopus Google the site-directed mutagenesis and by to the C1a- and C2-positioned loops of the cyclase cloned into II as The constructs in the pQE30 expression were into the were in of containing and and with of were and in For C.W. Gilman A.G. J. Biol. Chem. 1996; 271: 16967-16974Crossref PubMed Scopus (86) Google were in of containing a of inhibitors from were and were and were and the was for was by The were in and of was the resin was into a and with A with A with and were with of C containing The of the recombinant proteins with to adenylyl and guanylyl cyclase was Using we were to the protozoan constructs active upon on or by The of activity affected all protozoan constructs and not from to and on adenylyl or guanylyl cyclase were and all were from the affinity of activity was not to the proteins as analyzed by but to The proteins were analyzed by a mouse or a mouse Molecular were for in a of either or and 1 of were used as an of recombinant and The recombinant cyclase domains were on for to the by of and were and chromatography S. Schultz J.E. J. PubMed Scopus Google Scholar, Y. C. M. PubMed Scopus Google Scholar). The membrane-bound guanylyl cyclase from the Paramecium of two domains 1 A). The 155-kDa N-terminal domain resembles a P-type ATPase, and the C-terminal for a guanylyl cyclase of kDa with a structure of canonical mammalian adenylyl cyclases yet with reversed cytosolic C1a- and C2-positioned loops (4.Linder J.U. Engel P. Reimer A. Krüger T. Plattner H. Schultz A. Schultz J.E. EMBO J. 1999; 18: 4222-4232Crossref PubMed Scopus (80) Google Scholar). For soluble constructs of cytosolic adenylyl cyclase loops have been (7.Tang W.-J. Gilman A.G. Science. 1995; 268: 1769-1772Crossref PubMed Scopus (165) Google Scholar, 8.Whisnant R.E. Gilman A.G. Dessauer C.W. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 6621-6625Crossref PubMed Scopus (117) Google Scholar, 9.Dessauer C.W. Gilman A.G. J. Biol. Chem. 1996; 271: 16967-16974Crossref PubMed Scopus (86) Google Scholar, 10.Dessauer C.W. Scully T.T. Gilman A.G. J. Biol. Chem. 1997; 272: 22272-22277Crossref PubMed Scopus (109) Google Scholar, 11.Dessauer C.W. Gilman A.G. J. Biol. Chem. 1997; 272: 27787-27795Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar, 12.Scholich K. Barbier A.J. Mullenix J.B. Patel T.B. Proc. Natl. Acad. Sci. 1997; 94: 2915-2920Crossref PubMed Scopus (64) Google Scholar, 13.Tang W.-J. Stanzel M. Gilman A.G. Biochemistry. 1995; 34: 14563-14572Crossref PubMed Scopus (111) Google Scholar, W.-J. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar, R.K. Dessauer C.W. R.E. Kleuss C. Gilman A.G. J. Biol. Chem. 1997; 272: PubMed Scopus Google Scholar, C.W. J.J.G. Sprang S.R. Gilman A.G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). We wished to a soluble protozoan guanylyl cyclase from and C2-positioned loops and expressed the recombinant proteins in coli either or linked by a peptide in to W.-J. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar, R.K. Dessauer C.W. R.E. Kleuss C. Gilman A.G. J. Biol. Chem. 1997; 272: PubMed Scopus Google Scholar, C.W. J.J.G. Sprang S.R. Gilman A.G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). We used a construct with an molecular of kDa i.e. amino acid in of the which to a slightly for in C2 of rat type II adenylyl cyclase. The protozoan C2-positioned loop with an molecular of kDa consisted of the of the transmembrane A). of the recombinant a the as the proteins and only a of a was present in Guanylyl cyclase activity of catalytic loops was not whereas a of the C1a- and C2-positioned loops had activity either or MgGTP as substrate the protozoan guanylyl cyclase loops had a affinity for each other to a active This is in to with the catalytic domains from mammalian adenylyl cyclases of soluble adenylyl cyclase activity mixing of cytosolic domains from and the of C.W. Gilman A.G. J. Biol. Chem. 1996; 271: 16967-16974Crossref PubMed Scopus (86) Google and guanylyl cyclase of type and mutated constructs of Paramecium were with of the respective or and of each recombinant cytosolic domain or of the linked all affinity in were and in the C1-positioned domain and in the C2-positioned domain of the Paramecium guanylyl cyclase. not The of the was Data are from with similar The were of the C2-positioned in a were with of the respective or and of each recombinant cytosolic domain or of the linked all affinity in were and in the C1-positioned domain and in the C2-positioned domain of the Paramecium guanylyl cyclase. not The of the was Data are from with similar The were of the C2-positioned It was demonstrated that the activity of soluble constructs of mammalian adenylyl cyclases is or the catalytic loops are linked by a peptide (7.Tang W.-J. Gilman A.G. Science. 1995; 268: 1769-1772Crossref PubMed Scopus (165) Google Scholar). we linked the protozoan cytosolic domains a the order of the domains present in the reversed compared with mammalian adenylyl cyclases Fig. A). affinity the was by as a guanylyl cyclase activity was it not that in a of the expressed loops The of the of for MgGTP and were and and not from the with the linked construct and and to for the membrane-bound guanylyl cyclase domain expressed in or for the (4.Linder J.U. Engel P. Reimer A. Krüger T. Plattner H. Schultz A. Schultz J.E. EMBO J. 1999; 18: 4222-4232Crossref PubMed Scopus (80) Google Scholar, S. Schultz J.E. J. PubMed Scopus Google Scholar). of substrate were from to MgGTP and not from a substrate GTP The was to with the In with GTP as a substrate a of ATP guanylyl cyclase a specificity for GTP as a The of was A of was from the of an To the substrate specificity of the soluble guanylyl cyclase, we all constructs for adenylyl cyclase activity Using MgATP as a substrate, adenylyl cyclase activity was or of the respective guanylyl cyclase activity MnATP adenylyl cyclase activity was about of guanylyl cyclase and was similar to that with GTP as a substrate The crystal structure of a rat adenylyl cyclase type IIC2 and of a and rat to and and two or amino acids in the cyclases as responsible for purine nucleotide specificity (5.Zhang G. Liu Y. Ruoho A.E. Hurley J.H. Nature. 1997; 386: 247-253Crossref PubMed Scopus (326) Google Scholar, 6.Tesmer J.J.G. Sunahara R.K. Gilman A.G. Sprang S.R. Science. 1997; 278: 1907-1916Crossref PubMed Scopus (680) Google W.-J. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar, R.K. A. J.J.G. Sprang S.R. Gilman A.G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Hurley J.H. Hurley J.B. Proc. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). amino acids are all mammalian adenylyl and guanylyl cyclases and are In adenylyl cyclases Lys938 and the IIC2 catalytic domain with the and of the J.J.G. Sunahara R.K. Gilman A.G. Sprang S.R. Science. 1997; 278: 1907-1916Crossref PubMed Scopus (680) Google Scholar, Sunahara R.K. G. Gilman A.G. Sprang S.R. Science. 1999; PubMed Scopus Google Scholar). In guanylyl cyclases the corresponding amino acids are and to the of rat soluble guanylyl which with the and the of the guanine of amino acid residues the respective substrate of mammalian guanylyl and adenylyl cyclases R.K. A. J.J.G. Sprang S.R. Gilman A.G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Hurley J.H. Hurley J.B. Proc. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). to the Paramecium guanylyl cyclase, the C1-positioned domain is the of the catalytic of soluble guanylyl cyclases. Glu1681 in the C1-positioned loop is to and Ser1748 is to 1 In the a that is in mammalian guanylyl cyclases 1 This not the specific of GTP in the a the of the guanine and the This was a mutation the guanylyl cyclase activity to the of the A. C. J. Schultz G. Biochemistry. 1997; PubMed Scopus Google Scholar). To the of Glu1681 and Ser1748 in theParamecium domain in substrate we mutated to the adenylyl cyclase specific residues Lys and In we generated the the was not The constructs were enriched by affinity chromatography and by All recombinant proteins the molecular and were more or of Ser1748 to all cyclase of ATP or GTP as with as a guanylyl cyclase activity was by more and adenylyl cyclase activity was by more the of the adenylyl and guanylyl cyclase was only which that substrate was The then that the with the amino acid corresponding to to the for ATP or GTP substrate and to substrate The was in a purine nucleotide cyclase. in of two amino acids in mammalian membrane-bound or soluble guanylyl cyclases and in the mammalian had all of cyclase activity R.K. A. J.J.G. Sprang S.R. Gilman A.G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Hurley J.H. Hurley J.B. Proc. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). In the guanylyl cyclase the nucleotide specificity was switched from GTP to of guanylyl cyclase were of type whereas adenylyl cyclase activity to and This demonstrated the inversion of the of the cytosolic loops in the ciliate guanylyl cyclase the amino acids were in the domain, whereas in mammalian adenylyl cyclases are in the C2 domain R.K. A. J.J.G. Sprang S.R. Gilman A.G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). it demonstrated that which a that is in all mammalian guanylyl cyclases, is and a to had the In it the that the Paramecium guanylyl cyclase with a mammalian adenylyl cyclase membrane topology is a guanylyl cyclase we substrate specificity by site-directed mutagenesis of the protozoan domain as by the available of the mammalian adenylyl cyclase C2 (5.Zhang G. Liu Y. Ruoho A.E. Hurley J.H. Nature. 1997; 386: 247-253Crossref PubMed Scopus (326) Google Scholar, 6.Tesmer J.J.G. Sunahara R.K. Gilman A.G. Sprang S.R. Science. 1997; 278: 1907-1916Crossref PubMed Scopus (680) Google Sunahara R.K. G. Gilman A.G. Sprang S.R. Science. 1999; PubMed Scopus Google Scholar). A novel for a cyclase with a canonical mammalian adenylyl cyclase topology was the in purine nucleotide This has been only for mammalian guanylyl cyclases R.K. A. J.J.G. Sprang S.R. Gilman A.G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Hurley J.H. Hurley J.B. Proc. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). The to the substrate specificity of a soluble mammalian adenylyl cyclase in a purine nucleotide cyclase R.K. A. J.J.G. Sprang S.R. Gilman A.G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In the C1 domain of adenylyl cyclases type adenylyl was as a of for substrate by and by (5.Zhang G. Liu Y. Ruoho A.E. Hurley J.H. Nature. 1997; 386: 247-253Crossref PubMed Scopus (326) Google Scholar, R.K. A. J.J.G. Sprang S.R. Gilman A.G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Hurley J.H. Hurley J.B. Proc. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). In adenylyl cyclases this is of a In soluble guanylyl cyclases the corresponding is an which to in the Paramecium C2-positioned loop. we mutated is in guanylyl in the ciliate C2-positioned domain to the adenylyl cyclase B and The construct was expressed in to a protein on a of the type with the guanylyl cyclase activity to and with MgGTP and the is adenylyl this have been it was to that also the adenylyl cyclase activity was to and with MgATP and MnATP as the of guanylyl to adenylyl cyclase that the of the C1-positioned loop is not all in substrate We that the was inactive which the The in which all residues and specific for were not cAMP formation that with the are in with substrate of the adenylyl cyclase chimera in which the Sunahara R.K. G. Gilman A.G. Sprang S.R. Science. 1999; PubMed Scopus Google Scholar). we the that a of the to substrate in other cyclase (see In theParamecium guanylyl cyclase the amino acid residues for substrate to for guanylyl cyclase adenylyl cyclase cyclase activity were with of the respective or Guanylyl cyclase activity was not with either All the domain were residues are in (see for in a were with of the respective or Guanylyl cyclase activity was not with either All the domain were residues are in (see for In the protozoan the molecular of the cytosolic and C2-positioned loops is reversed (see and J.U. Engel P. Reimer A. Krüger T. Plattner H. Schultz A. Schultz J.E. EMBO J. 1999; 18: 4222-4232Crossref PubMed Scopus (80) Google Scholar). To the of on we the of the C2-positioned domain for of cyclase activity with the catalytic C2 loop from mammalian adenylyl cyclases of rat type II and mouse type IX Fig. expression and IIC2 as a on a whereas the of IXC2 by of guanylyl cyclase activity was in protozoan C2 chimeras, whereas adenylyl cyclase were in with either IIC2 or IXC2 The were with MnATP as a substrate as compared with MgATP This was in the which was more active with MnATP the inversion of the cytosolic loops in the Paramecium guanylyl cyclase has been on an the C2-positioned domain from the ciliate guanylyl cyclase for a mammalian adenylyl cyclase domain. of the sequence theParamecium C2-positioned and mammalian domains, the which are to a were in the ciliate C2 loop. we used the for adenylyl cyclase with IIC2 or Whereas adenylyl cyclase activity was the for MnATP as a substrate was This that the to the of the C1 and C2 domains in adenylyl cyclases, not the domain not an active cyclase with mammalian domains not All membrane-bound mammalian adenylyl cyclases by the of and the forskolin, and by P site of M. Google Scholar). we the of canonical adenylyl cyclase or affected of the guanylyl cyclase constructs. This was not of the Paramecium guanylyl cyclase sequence that amino acid residues to for cyclase by and for such as (adenylyl cyclase numbering) are J.J.G. Sunahara R.K. Gilman A.G. Sprang S.R. Science. 1997; 278: 1907-1916Crossref PubMed Scopus (680) Google Scholar). all were also by and In respective an of a was not The are of a chimera of and the of a soluble rat guanylyl cyclase, which also was to the adenylyl cyclase S. Kleuss C. Biochemistry. 1999; PubMed Scopus Google Scholar). adenylyl cyclase by and to constructs the mammalian C1 and C2 P site inhibitors the of the cyclases with C.W. Gilman A.G. J. Biol. Chem. 1997; 272: 27787-27795Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar). is M. Google Scholar). The available P site for adenylyl cyclases is with of 1 for the and in the upon by In a similar guanylyl cyclase is by R.K. A. J.J.G. Sprang S.R. Gilman A.G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). We the of and on the constructs generated In P site soluble Paramecium guanylyl cyclase constructs was 1 not guanylyl cyclase and 1 by about guanylyl cyclase was with as a i.e. in a activity guanylyl cyclase activity was with as an i.e. in a activity was more i.e. was and specific as as the purine was The of the by the in the of a soluble guanylyl cyclase had on the of we the adenylyl cyclase reconstituted from the mutated Paramecium domains and and from the chimeras, i.e. and 1 adenylyl cyclase of all reconstituted enzymes by about was 1 i.e. we that substrate and P site specificity to in constructs as reported for mammalian constructs R.K. A. J.J.G. Sprang S.R. Gilman A.G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The of the of the P site inhibitors compared with mammalian cyclases. The then of this was the The protein that is in for the of the group of the nucleotide in with the of two Sunahara R.K. G. Gilman A.G. Sprang S.R. Science. 1999; PubMed Scopus Google Scholar). The amino acids are of the C1 and in the domain and and IIC2 Sunahara R.K. G. Gilman A.G. Sprang S.R. Science. 1999; PubMed Scopus Google Scholar). from respective sequence all of amino acid residues are present in the corresponding C2- and C1-positioned domains of the protozoan guanylyl cyclase. are of the C2-positioned and in the C2-positioned loop and and in the catalytic C1-positioned loop (see the abbreviated in we that the amino acid for the site is present in the protozoan guanylyl cyclase and that the of of P site inhibitors has a In mammalian adenylyl cyclases loops a substrate ATP to a specific and active site and the heterotrimeric proteins either or such a which the substrate group and the catalytic residues Sunahara R.K. G. Gilman A.G. Sprang S.R. Science. 1999; PubMed Scopus Google Scholar). all of the amino acid residues for such a are present in theParamecium guanylyl cyclase, we that it in a similar to that of a mammalian adenylyl cyclase. it is that it also an to the into a activity which then affected by P site inhibitors mammalian adenylyl cyclases have to for the of of the heterotrimeric protein in Paramecium U. T. U. and J. In in the of a and a protein that the substrate, have been we have to for the of a protozoan protein that the Ca2+ in the guanylyl cyclase S. Schultz J.E. J. PubMed Scopus Google Scholar). In this the of the 155-kDa N-terminal P-type domain the more The of a P-type with a guanylyl cyclase as a mammalian adenylyl cyclase in a sequence to novel as M. Science. 1999; PubMed Scopus Google of cyclase by with 1 cyclase cyclase and was used in all residues are in (see for in a and was used in all residues are in (see for We C. Kleuss and (Berlin) for a clone of the adenylyl cyclase type IIC2 and a of and Dr. F. for a clone of the mouse type IX adenylyl cyclase.
The important issue, for both central and local governments in the 2000's is financial reconstruction and administrative reform. And, pursuing a policy of government decentralization has been regarded as an important issue in 1990's, and since 1999 it has received much attention at the central government and local government levels. In 1999,the Government Decentralization Law was passed. As expected, that the relationship between the central and local government has changed drastically. This report gives a study of Basic Concepts of Reform of Public Sector Accounting System in Local Government, and so on, is presented as follows : 1. Introduction. 2. Central Public Finance and Local Public Finance : An Overview. 3. Issues of Public Sector Accounting System in Local Government. 4. Conversion of Public Sector Accounting System in Local Government. 5. Development of Public Sector Accounting System in Local Government. 6. New Public Management. 7. Conclusion.
The study of maths curriculum in the last grades of secondary schools in France along 30 years brings to light important variations that took place since 1962 in the contents of calculus at this level. These evolutions concern the objects of calculus that are taught as well as the procedures used by students and teachers. The suggested methods affect the knowledge that students are likely to use when doing the given tasks; and we observe that since the 90ths', the tasks given to students do not valorise validation. We study the possibilities of establishing an real relationship to the knowledge in calculus, at this level of teaching, and to allow the students to build appropriate methods.<br />We study the question of validation in teaching analysis through the following directions:<br />- the mathematical theory; its organisation; the methods of proof and the formalization; how these methods can be introduced in the teaching, in a way that students can understand;<br />- the existence of fundamental situations concerning the concepts of function and limit, and the possibility of implement such situations in the class.<br /><br />Besides, the study of the different settings of representation that are at stake to build a suitable environment for the teaching of function and limit makes new potentialities come to light, particularly in the graphic and formal settings.<br />The experimentation is carried through the building of situations with an a-didactical component for the teaching of function and limit, and through the observation of their implementation in a scientific class of 17 years-old students. This makes us first question the knowledge and professional knowing a teacher uses to manage a teaching situation in analysis, with an a-didactical component, and then draw a pattern to the teacher's milieu.<br />We also submit a test to the students and analyse the results with statistic tools so as to test the main features of the learning.<br />In the last chapter we study lectures at undergraduate level, and student's papers with lots of errors about calculus definitions. This leads us to question the knowledge that is compulsory at University level; we wonder how it is possible to link it with Secondary school's knowledge and habits.<br />As a conclusion, we shall suggest some remarks about the balance between definitive knowledge and what students must get as an experience in the teaching of a new mathematical theory; this balance affects the possibilities of validation and finally, the future prospects of teaching analysis from Secondary Schools to University.
Bitcoin is the first digital medium to allow global, "purely peer-to-peer" exchange. At the height of the Great Recession, Bitcoin's pseudonymous creator introduced the electronic cash to sidestep political and economic institutions. Today, it is praised as an opportunity for the unbanked, a liberating force, and a pioneering technology. It is also infamously associated with volatility, illicit activities, and profligate energy consumption. Bitcoin has also flown under the radar of political science, whereas computer scientists, economists, and legal scholars have written extensively about it. To address the gap in the literature, I describe Bitcoin as an actor in global affairs, explain how Bitcoin and blockchain technology work, and discuss why Bitcoin is relevant to political science as the archetypal case of blockchain technology. I argue that Bitcoin is a form of contentious politics uniquely suited to the twenty-first century. Examining Bitcoin as a form of contentious politics sheds light on how a purportedly borderless technology has actually fared in subverting state authority: not entirely well. Nonetheless, Bitcoin has succeeded in at least two respects: it is an unprecedented form of untraceable electronic cash that coordinates unrivaled levels of computing resources from voluntary contributors and it has become a resilient, global social movement. As an archetype of blockchain technology, Bitcoin inspires research of blockchain's capacity to facilitate collective action, uses in international cooperation and competition, and prospects for human development. The thesis concludes with a set of implications for blockchain research and policy.
Guillém López i Casasnovas, Esther Martínez Garcia
The authors analyse the magnitude and composition of the fiscal imbalance between Catalonia and the Spanish Central government for 1995-1998, and its evolution since 1986. A flow approach is adopted, whereas the usual incidence hypothesis is followed in alloating tax revenues. The results show a rather stable net contribution of Catalonia to the Spanish Central government in 1998 of 1.3 trillion pesetas (8.37% of Catalan GDP). Calalonia participated in 19.60 % of Central government revenues, but received only 15.03% of expenditures. Catalan population is 15.5% of the Spanish total. Overall, in 1994 constant terms, the evolution of the per capita imbalance rises from 117,133 PTAs. in 1986, to 192,294 PTAs. in 1998. The authors also introduce an explicit way to deal with the effects of Central government budget deficits on fiscal revenues, in computing the financial distortions of the political and economic central role of Madrid, different tax compliance among regions, the impact of inflation differentials, and the evaluation of the social security flows on regional imbalances. In general, the authors favour an estimation of the amount of revenues at the disposal of Catalonia in order to finance its own expenditure, without the mediation of the Central government, but maintaining a single Spanish fiscal system. This approach may force the contribution of Catalonia as any other region to finance the joint expenditures of the Central government, and/or to finance its owm public sector, but in a rather more dear way. As a result, with regard to the financial decentralization system, territorial solidarity and social cohesion is enhanced, at the same time that autonomy and self-governance,
in a better way than it is today.
This Article argues that the restoration of a communitarian approach to taxation can help soften the widespread anti-tax sentiment that has engulfed the United States. It proposes and analyzes a concrete plan for the collection of revenue that taps into the same sense of shared community sacrifice that was invoked in fourteenth-century England. It proposes that the United States adopt a modernized, decentralized system of revenue collection modeled after the requisition, which was the chief means of raising revenue in the early American republic. Whereas the federal government currently collects approximately seventy percent of the nation's tax dollars, and the state and local governments collect the remaining thirty percent, this Article contemplates how the United States, and the individual states themselves, might differ if those numbers were reversed. The article begins by explaining why, due to the historical peculiarities of America's fiscal history, a decentralized approach to collecting revenues is not currently under consideration. Further, the article proposes a tax system in which the federal government would abolish the individual income tax, and discusses the likely effects of such a program on governmental spending by the states and on citizen mobility. The Article then explores the justifications for such an approach to taxation. The Article also consists of a utilitarian analysis of the costs and benefits of shifting to requisitions finance. Finally, the Article confronts the serious policy challenges that would arise if society were to implement requisitions finance, and ends with a discussion of several variations on the requisitions finance model that can address several of the communitarian and utilitarian criticisms.
Counterfeit products, especially in the pharmaceutical sector, have plagued the international community for decades. To combat this problem, many anti-counterfeiting approaches have been proposed. They use either Radio Frequency Identification (RFID) or Near Field Communication (NFC) physical tags affixed to the products. Current anti-counterfeiting approaches detect two counterfeiting attacks: (1) modifications to a product's tag details, such as changing the expiration date; and (2) cloning of a genuine product's details to reuse on counterfeit products. In addition, these anti-counterfeiting approaches track-and-trace the physical locations of products as the products flow through supply chains. Existing approaches suffer from two main drawbacks. They cannot detect tag reapplication attacks, wherein a counterfeiter removes a legitimate tag from a genuine product and reapplies it to a counterfeit or expired product. Second, most existing approaches typically rely on a central server to authenticate products. This is not scalable and creates tremendous processing burden on the server, since significant volumes of products flood through the supply chain's nodes. In addition, centralized supply chains require substantial data storage to store authentication records for all products. Moreover, as with centralized systems, traditional supply chains inherently have the problem of a single-point of failure. The thesis of this dissertation is that a robust, scalable, counterfeiting-resistant supply chain that addresses the above drawbacks and can be simultaneously achieved by (i) using a combination of NFC tags on products and a distributed ledger such as blockchain for reapplication-proof, decentralized, and transparent product authentication (ii) a novel game-theoretical consensus protocol for enforcing true decentralization, and enhancing the protocol's security and performance. In this dissertation, we first propose a new Tag Reapplication Detection (TRD) system to detect reapplication attacks using low-cost NFC tags and public key cryptography. To detect reapplication attacks, TRD tracks the number of times a tag has been read in the supply chain using a 'central' authentication server. Second, leveraging the blockchain technology, we propose the Block-Supply Chain, a transformation of TRD into a decentralized supply chain. In this chain, each node maintains a blockchain (distributed public ledger) per product. This blockchain comprises chained blocks, where each is an authentication event. The Block-Supply Chain can detect tag reapplication attacks and can replace the centralized supply chain design, thus overcoming the centralization issues. One of the fundamental characteristics of blockchain technology is the consensus protocol. Consensus protocols ensure that all nodes in the blockchain network agree on the validity of a
The studies collected in this chapter are emblematic of the wider universe of non-binding instruments, illustrating the flexibility in substantive content and procedural context that is a principal hallmark of non-binding undertakings.Taken as a group, the studies reveal cleavages characteristic of the legal and policy dynamics surrounding non-binding instruments, as they vary in: (l) choice of non-binding rather than binding format; (2) institutional setting; (3) relationship to binding international law; (4) identity of norm-creating entities; (5) identity of parties addressed; (6) processes for adoption and implementation; (7) impact on domestic policy and law: and (8) the role of the public in norm formulation, implementation, and compliance.Beth Simmons' analysis highlights many attributes of a 'classical' or 'traditional' non-binding vehicle, to the extent such a model can be identified among the extraordinarily diverse examples assembled in this volume.Her study consequently is useful as a benchmark, providing a reference point against which the others can be compared.The Forty Recommendations of the Financial Action Task Force (FATF) are a policy response to an archetypal collective action problem: how to overcome the incentives inherent in the decentralized and consent-based international system, which often rewards holdouts, scofflaws, free riders, and laggards.As described by Professor Simmons, the efforts of the United States to encourage or, indeed, leverage higher standards of performance on the part of other states-to 'harmonize up' -was a principal motivating factor explaining the nature of the FATF's activities generally and the Forty Recommendations in particular.Professor Simmons identifies characteristics frequently cited as benefits of a non-binding approach, which might be described as the 'choice of instrument' question.The commitment of states other than the United States is described as tentative or equivocal.In such a context, states might commit to binding obligations only of a modest character, if at all, while a non-binding 'soft' instrument can allow them to gain experience with more ambitious, aspirational goals in a less risky milieu.non-binding instruments also may be appropriate for circumstances in which consensus is elusive or illusory.Thus, they may be attractive alternatives to an inertial downward spiral towards the 'least common denominator' characteristic of many multilateral efforts.For these reasons, among others, non-binding instruments are often phrased, as
Abengourou, with a population of 444,000 \n inhabitants, is one of the ten regions in Cote \n d'Ivoire. In this region, the fight against HIV/AIDS is \n enforced by a Regional Coordination Committee. What is \n special compared to other regional initiatives in the fight \n against HIV/AIDS is the organizational and community \n approach as well as the system established for financing activities.
This short note provides a framework for looking at public sector governance and productivity improvements. It argues that the role of government in enhancing productivity growth is two-fold. First, government should provide an environment that is conducive in improving total factor productivity in private sector production. Second, government should work to increase the productivity of the public sector itself. In terms of providing the appropriate economic setting that is favorable to private-sector-led development, government needs (1) to provide the macroeconomic and the microeconomic environment that will establish incentives for firms/individuals to act in accordance with the invisible hand had there been no market imperfection, (2) to provide the institutional infrastructure (i.e., property rights, law and order, rules and even application and enforcement of the same) that markets need to work efficiently; and (3) to ensure the financing/provision of adequate basic health care and education, and basic physical infrastructure (World Bank 1992). In particular, the instruments that government may use in this regard are include (1) direct government interventions in the product markets as defined by the regulatory structure in strategic sectors, and (2) economy-wide policies like financial liberalization, trade liberalization, and foreign investments liberalization. On the other hand, (1) budget reform (2) the installation of a system of performance measurement and incentive in the public sector, (3) the re-engineering of the bureaucracy, (4) the combating of corruption, and (5) decentralization are the key features of a program that will increase the productivity of government operations.
espanolEn ausencia de un margen significativo para la descentralizacion plena de los principales tributos en Venezuela, la consecucion de los beneficios esperados de la descentralizacion amerita discutir que tipo de diseno institucional deben tener sus mecanismos de financiamiento. En mi entender, el reto fundamental para los responsables de ese diseno consiste en incorporar en esos mecanismos los incentivos apropiados para que los distintos actores coordinen sus acciones y promuevan la participacion de la sociedad civil en la toma de decisiones colectivas. Esto exige desarrollar una cultura intergubernamental cooperativa. La viabilidad de una cultura intergubernamental cooperativa solo sera sostenible cuando se internalice la nocion de que los recursos generados por los tributos de administracion centralizada no pertenecen exclusivamente al gobierno nacional, sino que deben ser derramados en toda la extension del territorio venezolano, de acuerdo con una mezcla de criterios redistributivos, de eficiencia asignativa y respetando el desarrollo socioeconomico balanceado. Esto es mas probable si prevalece la perspectiva de que figuras como el situado, las asignaciones economicas especiales y el Fides representan mecanismos de coparticipacion en los ingresos fiscales del pais y no simples transferencias desde el gobieno central. Asi, al interpretar los mecanismos intergubernamentales de financiamiento como modalidades de coparticipacion sobre unos recursos fiscales generados en todo el territorio, las relaciones intergubernamentales se hacen mas horizontales, aun cuando se siga reconociendo al gobierno central como un primu inter pares. EnglishGiven the fact that there is not a significant margin for full decentralization of the main taxes in Venezuela, achieving the expected benefits of decentralization requires to discuss what kind of institutional design should have its financing mechanisms. In my view, the fundamental challenge for the policy-makers is to built-in these mechanisms with the appropriate incentives for different levels of government coordination and civil society participation in the process of collective decisions making. This requirement implies to develop an intergovernmental cooperative culture. The viability of an intergovernmental cooperative culture will be sustainable to the extent the venezuelan society internalize the notion that central administered taxes do not belong exclusively to the national government. On the contrary, these resources must be spread through the whole national territory, according to a blend of redistributive, assignative and economic equilibrium criteria. This is more likely if there is a prevalent perspective that policy instruments such as the situado, the special economic assignments and Fides represent revenue-sharing mechanisms, and not just transfers from the central government. In such a way, interpreting the ingovernmental financial mechanisms as co-sharing devises over the fiscal resources produced in the whole territory, the intergovernmental relations become more horizontal, although we recognize the central government as a primu inter pares.
The “region”, sub-national entity in Europe, plays some more important roles in a place of Nation-States in a context of European integration. However, “island regions” around European Continent have a risk to be more marginalised by the economic integration advanced by the central regions. The island region in Europe has a special socio-economic backwardness caused by its remoteness from the Continent and this special character is called “insularity”.Political autonomy is, I think, one of the best choices that activate an island region without delete its insularity. Thus European insular regions have a special status that is different from the regions in the Continent, that rules their political autonomy. However, there are many cases that island regions have a heterogeneous historic-cultural fact and a strong identity that could appeal to nationalism or separatism from the mainland country. So that autonomous status of island region in Europe is not homogeneous.Corsica, Mediterranean island region that belongs to France, has not been autonomous for a long time because of its special socio-political situations, Corsican nationalism and “clan”, one of patriarchal formations typically observed in some Mediterranean insular regions.In 1982, by the decentralization policies of socialist President Mitterrand, France was reorganized into 22 more autonomous “regions” from the “prefecture” whose prefect has been nominated by the Ministry of Interior, French administrative. Corsica was ruled by an act as a region with a special status. The Regional Assembly of Corsica consisted of 61 representatives elected by the islanders was created in this year and could vote projects of program on mainly Corsican linguistic and cultural education of a supplemental course in a school, regional transportation and development of new energy. The regional administration of Corsica could exert these programs.However, instability in the Regional Assembly because of lack of a strong core party and frequent elections, shortage of competence or finance of the Region of Corsica caused their dysfunction and discredit from the islanders.And in 1991, Corsican act was revised and Corsica changed a Territorial Collectivity, original local entity, from a region, common local entity. Though this renewal act defined Corsica as a “people”, Constitutional Council judged that this definition would be against the French Constitution that rules French national unity and its equality, and deleted Article 1 that contains this definition.However, Corsica was authorized to be more autonomous with an original competence. In addition to education and broadcasting of regional language and culture, special taxation and some economic development program are ceded to Corsica. And Corsican regional organization also was changed. Regional Assembly was divided into Corsican Territorial Assembly and Corsican Executive Council. The president and 6 members of Executive Council exert Corsican regional administrative and vote projects of budget and cultural and economic programs, and these members are elected from the representatives in the Territorial Assembly by election. Executive Councilors are obliged to make some annual reports on the executive situation and their results in the Assembly and to be credited by it. Thus after 1991, Corsica establishes its collegiality and responsibility for the smooth practice of the larger competence.It is doubtful whether Corsica has a political autonomy by the status reform in 1991. Because there is not any articles on Corsican status in the French Constitution though those of TOMs' status, French Overseas Islands, are in it, and those of Sicilian and Sardinian status are in the Italian Constitution. And Corsican Territorial Assembly can vote only motions, some taxation and programs of local cultural and economic development, but not any
Alexander Gerschenkron argued that banks facilitate growth in “backward” countries, and modern theorists sometimes similarly claim that banks can promote growth by reducing informational asymmetries and improving the allocation of funds. Japan has played a part in these debates. In early twentieth‐century Japan, firms relied heavily on bank debt, observers argue. Those firms with preferential access to debt outperformed the others, and those that were part of the zaibatsu corporate groups obtained that access through their affiliated banks. In fact, Japanese banks did not play the role attributed to them. Japan was not a bank‐centered economy; instead, firms relied on equity finance. It was not an economy where firms with access to banks outperformed their rivals; instead, such firms earned no advantage. And it was not a world in which the zaibatsu manipulated their banks to favor affiliated firms; instead, zaibatsu banks loaned affiliated firms little more than the deposits those firms had made with the banks. During the first half of the last century, Japanese firms obtained almost all their funds through decentralized, competitive capital markets.
Localism and regionalism are normally seen as conflicting, conceptions of metropolitan area governance. Localism is the belief that the existing system of a large number of relatively small governments wielding power over such critical matters as land use regulation, local taxation, and the financing of local public services ought to be preserved. Regionalism would move some power to institutions, organizations or procedures with a larger territorial scope and more population than existing local governments. Regionalism appears to be a step towards centralization, and the antithesis of the decentralization represented by localism. Yet, in the metropolitan areas that dominate America at the end of the twentieth century, regionalism is not just the enemy of localism: It is also localism's logical extension. Localism is based on a set of arguments concerning the role of local governments in promoting governmental efficiency, democracy, and community. But in contemporary metropolitan areas, the economically, socially, and ecologically relevant local area is often the region. In these areas, concerns about efficiency, democracy, and community ought to lead to a shift in power from existing localities to new processes, structures, or organizations that can promote decision-making on behalf of the region. Regionalism is, thus, localism for metropolitan areas. Localists, however, do not become regionalists when they live in metropolitan areas. Indeed, resistance to regionalism is intense in many metropolitan areas. Localism is not simply a theory intended to advance certain normative goals. It is also a means of protecting the interests of those who receive advantages from the existing governance structure. Local self-interest, rather than the political values localism is said to advance, plays a central role in the opposition to regionalism. This essay explores the relationship between localism and regionalism. It considers the meaning of regionalism in contemporary urban policy debates and the reasons why regionalism currently enjoys so much attention from academics, urbanists and policy analysts. It reviews the arguments for localism, and explains how, despite the asserted conflict between localism and regionalism, the theories underlying localism actually make a case for regionalism in contemporary metropolitan areas. Finally, it examines the role of local self-interest in the resistance to regionalism, and the efforts of regionalists to respond by making the case for regionalism in terms of local self-interest as well.
K. Kwiatkowski, Patrícia Flatley Brennan, David L. DeMets, Karen Dahlen · 5 authors
The University of Wisconsin-Madison Health Sciences Schools are currently in the planning stage of developing an Integrated Advanced Information Management System (IAIMS). The planning phase of this project attends to the unique opportunities that are found at the flagship campus of a large state university system. Statewide teaching and research initiatives and accelerated campus-level capital development challenge the planners to create an IAIMS plan that anticipates an emerging health science environment. Additionally, UW-Madison has an organizational culture with a strong tradition of faculty governance, which provides a very desirable and flexible decision-making environment for a cross-discipline collaborative information management initiative. Development of a shared IAIMS vision conflicts with a governance model that most directly supports intradepartmental decision-making. The challenge presented here for an IAIMS initiative has less to do with hard wiring a technical infrastructure and more to do with increased stakeholder cooperation in a highly decentralized organization with autonomous information systems.
With an introduction to the overall underdevelopment of higher education in China compared with the American counterpart, this article briefly examines the main trends of over two decades of development of the governance and financing systems of China's higher education sector. This article analyzes the resource allocation from governments and revenue generation in institutions under the reform policies of administrative decentralization and financing diversification. ...