Consociationalism and the evolution of political cleavages in Northern Ireland, 1989-2004

Political cleavages are often understood as deriving from either deep-rooted social divisions or institutional incentives. Contemporary Northern Ireland provides a test of the mutability of apparently entrenched cleavages to institutional change. Research undertaken before the ceasefire in the 1990s found noticeable asymmetries in the patterns of cleavage within the unionist and nationalist blocs. Within the unionist bloc, economic 'left-right' issues formed the main ideological division between the two major unionist parties. This contrasted with an ethno-national source of ideological division between the two nationalist parties. The emergence of a consociational form of government structure since then has demonstrated the ability of institutional incentives to swiftly reform some aspects of party competition however. As evidence of this, we show that between 1989 and 2004 there was little change in the sources of support for Sinn F�©in relative to the SDLP, but the influence of left-right ideology within the unionist bloc was negated as the influence of ethno-nationalism dramatically increased.

Parties, cleavages, and issue evolution: The case of the religious-secular cleavage in Chile

Several recent articles have reached different conclusions regarding the impact of the religious–secular cleavage in Chile. The resolution of this debate has important consequences for the understanding of cleavages. Studies subscribing to the view that parties have considerable agency in the maintenance of cleavages have found that religiosity no longer affects vote choice, while studies rooted in a sociological perspective argue that religiosity still matters. We show that the reason for the discrepant results is because a partisan realignment is underway, whereby religious voters are gradually shifting their loyalties from the parties of the left to the parties of the right, matching a division that has taken place at the elite level. These results are consistent with an issue evolution perspective, which provides a clearer articulation of how cleavages form than either the agency or the sociological approaches.

The organizational ecology of ethnic cleavages: The nonlinear effects of ethnic diversity on party system fragmentation

The conventional wisdom regarding party system fragmentation assumes that the effects of electoral systems and social cleavages are linear. However, recent work applying organizational ecology theories to the study of party systems has challenged the degree to which electoral system effects are linear. This paper applies such concepts to the study of social cleavages. Drawing from theories of organizational ecology and the experience of many ethnically diverse African party systems, I argue that the effects of ethnic diversity are nonlinear, with party system fragmentation increasing until reaching moderate levels of diversity before declining as diversity reaches extreme values. Examining this argument cross-nationally, the results show that accounting for nonlinearity in ethnic diversity effects significantly improves model fit.

Electoral Systems, Ethnic Cleavages, and Experience with Democracy

Recent studies show the effects of electoral systems and ethnic cleavages on the number of parties in emerging democracies differ from those effects observed in more established democracies. Building on recent arguments maintaining the quality of democracy improves with experience, we argue the reason for the differences in the findings between established and emerging democracies is that the effects of these variables on the number of parties differ according to a country’s experience with elections. To test this argument, we analyse party system fragmentation in 89 established and emerging democracies and the conditioning effects experience with elections have on the effects of district magnitude, ethnic cleavages, and variables relating to the presidential party system. The results show the effects of institutional and social cleavage variables differ substantially between emerging and established democracies, but these effects begin to approximate those seen in more established democracies with additional experience with elections.

Not all social cleavages are the same: On the relationship between religious diversity and party system fragmentation

Most studies examining the relationship between social cleavages and party system fragmentation maintain that higher levels of social diversity lead to greater party system fragmentation. However, most aggregate-level studies focus on one type of social cleavage:ethnic diversity. In order to develop a better understanding of how different cleavages impact electoral competition, this paper considers another type of social cleavage: religious diversity.Contrary to previous literature, higher levels of religious diversity provide incentives for cross-religious cooperation, which in turn reduces party system fragmentation. Using a cross national data set of elections from 1946-2011, the results show that, in contrast to most studies examining the effects of social cleavage diversity on the number of parties, higher religious diversity is associated with lower levels of party system fragmentation.

Societal cleavages and institutional change in Canada : retention, reform and removal of nominee councils

En concevant que toute société a deux clivages dominants, l’un social et l’autre partisan, cette thèse développe une théorie sur le changement institutionnel. L’hypothèse initiale, selon laquelle les groupes sociaux créés par le premier clivage agiront pour restreindre le changement institutionnel et que le changement aura lieu lors de l’émergence d’un groupe partisan capable de croiser le clivage social, fut testée par les processus traçant les changements qui furent proposés et qui ont eu lieu au sein des conseils nominés en Amérique du Nord britannique. Ces conseils furent modifiés un bon nombre de fois, devenant les chambres secondaires de législatures provinciales avant d’être éventuellement abolies. La preuve supporte l’hypothèse, bien qu’il ne soit pas suffisant d’avoir un groupe partisan qui puisse croiser le clivage qui mène le changement : un débat partisan sur le changement est nécessaire. Ceci remet aussi en cause la théorie prédominante selon laquelle les clivages sociaux mènent à la formation de partis politiques, suggérant qu’il est plus bénéfique d’utiliser ces deux clivages pour l’étude des institutions.

Social cleavages and electoral support in Turkey -- toward convergence?

Studies on Western democracies have shown that deep-seated social cleavages stabilize the electoral behavior and thus reduce electoral volatility. But how do social cleavages affect a party system that is undergoing democratic consolidation, such as in Turkey? In this study, investigations were carried out on long- and short-term relationships between social cleavages (religiosity, ethnicity, and sectarism) and electoral volatility in Turkey during the 1961-2002 period. Cross-sectional multiple regressions were applied to electoral and demographic data at the provincial level. The results showed that in the long-term, social cleavages on the whole have increased volatility rather than reduced it. The cleavage-volatility relationship, however, has changed over time. Repeated elections have mitigated the volatile effect of social cleavages on the voting behavior, as political parties have become more representative of the existent social cleavages.

The two single-strand cleavages at each end of Tn10 occur in a specific order during transposition.

During Tn10 transposition, the element is excised from the donor site by double-strand cleavages at the two transposon ends. Double-strand cleavage is a central step in the nonreplicative transposition reaction of many transposons in both prokaryotes and eukaryotes. Evidence is presented to show that the Tn10 double-strand cut is made by an ordered, sequential cleavage of the two strands. The transferred strand is cut first, and then the nontransferred strand is cleaved. The single-strand nicked intermediate is seen to accumulate when Mn2+ is substituted for Mg2+ in the reaction or when certain mutant transposases are used. The fact that the transferred strand is cleaved before the non-transferred strand implies that the order of strand cleavages is not the determining factor that precludes a replicative mechanism of transposition.

Regulated Cleavages at the West Nile Virus NS4A-2K-NS4B Junctions Play a Major Role in Rearranging Cytoplasmic Membranes and Golgi Trafficking of the NS4A Protein

A common feature associated with the replication of most RNA viruses is the formation of a unique membrane environment encapsulating the viral replication complex. For their part, flaviviruses are no exception, whereupon infection causes a dramatic rearrangement and induction of unique membrane structures within the cytoplasm of infected cells. These virus-induced membranes, termed paracrystalline arrays, convoluted membranes, and vesicle packets, all appear to have specific functions during replication and are derived from different organelles within the host cell. The aim of this study was to identify which protein(s) specified by the Australian strain of West Nile virus, Kunjin virus (KUNV), are responsible for the dramatic membrane alterations observed during infection. Thus, we have shown using immunolabeling of ultrathin cryosections of transfected cells that expression of the KUNV polyprotein intermediates NS4A-4B and NS213-34A, as well as that of individual NS4A proteins with and without the C-terminal transmembrane domain 2K, resulted in different degrees of rearrangement of cytoplasmic membranes. The formation of the membrane structures characteristic for virus infection required coexpression of an NS4A-NS4B cassette with the viral protease NS2B-3pro which was shown to be essential for the release of the individual NS4A and NS4B proteins. Individual expression of NS4A protein retaining the C-terminal transmembrane domain 2K resulted in the induction of membrane rearrangements most resembling virus-induced structures, while removal of the 2K domain led to a less profound membrane rearrangement but resulted in the redistribution of the NS4A protein to the Golgi apparatus. The results show that cleavage of the KUNV polyprotein NS4A-4B by the viral protease is the key initiation event in the induction of membrane rearrangement and that the NS4A protein intermediate containing the uncleaved C-terminal transmembrane domain plays an essential role in these membrane rearrangements.

Cholesterol enhances phospholipid-dependent activated protein C anticoagulant activity

The influence of cholesterol on activated protein C (APC) anticoagulant activity in plasma and on factor Va inactivation was investigated. Anticoagulant and procoagulant activities of phosphatidylcholine/phosphatidylserine (PC/PS) vesicles containing cholesterol were assessed in the presence and absence of APC using factor Xa-1-stage clotting and factor Va inactivation assays. Cholesterol at approximate physiological membrane levels (30%) in PC/PS (60%/10% w/w) vesicles prolonged the factor Xa-1-stage clotting time dose-dependently in the presence of APC but not in the absence of APC. APC-mediated cleavage of purified recombinant factor Va variants that were modified at specific APC cleavage sites (Q306/Q679-factor Va; Q506/Q679-factor Va) was studied to define the effects of cholesterol on APC cleavage at R506 and R306. When compared to control PC/PS vesicles, cholesterol in PC/PS vesicles enhanced factor Va inactivation and the rate of APC cleavage at both R506 and R306. Cholesterol also enhanced APC cleavage rates at R306 in the presence of the APC cofactor, protein S. In summary, APC anticoagulant activity in plasma and factor Va inactivation as a result of cleavages at R506 and R306 by APC is markedly enhanced by cholesterol in phospholipid vesicles. These results suggest that cholesterol in a membrane surface may selectively enhance APC activities. © 2005 International Society on Thrombosis and Haemostasis.

Rational design of serine protease inhibitors

Proteases regulate a spectrum of diverse physiological processes, and dysregulation of proteolytic activity drives a plethora of pathological conditions. Understanding protease function is essential to appreciating many aspects of normal physiology and progression of disease. Consequently, development of potent and specific inhibitors of proteolytic enzymes is vital to provide tools for the dissection of protease function in biological systems and for the treatment of diseases linked to aberrant proteolytic activity. The studies in this thesis describe the rational design of potent inhibitors of three proteases that are implicated in disease development. Additionally, key features of the interaction of proteases and their cognate inhibitors or substrates are analysed and a series of rational inhibitor design principles are expounded and tested. Rational design of protease inhibitors relies on a comprehensive understanding of protease structure and biochemistry. Analysis of known protease cleavage sites in proteins and peptides is a commonly used source of such information. However, model peptide substrate and protein sequences have widely differing levels of backbone constraint and hence can adopt highly divergent structures when binding to a protease’s active site. This may result in identical sequences in peptides and proteins having different conformations and diverse spatial distribution of amino acid functionalities. Regardless of this, protein and peptide cleavage sites are often regarded as being equivalent. One of the key findings in the following studies is a definitive demonstration of the lack of equivalence between these two classes of substrate and invalidation of the common practice of using the sequences of model peptide substrates to predict cleavage of proteins in vivo. Another important feature for protease substrate recognition is subsite cooperativity. This type of cooperativity is commonly referred to as protease or substrate binding subsite cooperativity and is distinct from allosteric cooperativity, where binding of a molecule distant from the protease active site affects the binding affinity of a substrate. Subsite cooperativity may be intramolecular where neighbouring residues in substrates are interacting, affecting the scissile bond’s susceptibility to protease cleavage. Subsite cooperativity can also be intermolecular where a particular residue’s contribution to binding affinity changes depending on the identity of neighbouring amino acids. Although numerous studies have identified subsite cooperativity effects, these findings are frequently ignored in investigations probing subsite selectivity by screening against diverse combinatorial libraries of peptides (positional scanning synthetic combinatorial library; PS-SCL). This strategy for determining cleavage specificity relies on the averaged rates of hydrolysis for an uncharacterised ensemble of peptide sequences, as opposed to the defined rate of hydrolysis of a known specific substrate. Further, since PS-SCL screens probe the preference of the various protease subsites independently, this method is inherently unable to detect subsite cooperativity. However, mean hydrolysis rates from PS-SCL screens are often interpreted as being comparable to those produced by single peptide cleavages. Before this study no large systematic evaluation had been made to determine the level of correlation between protease selectivity as predicted by screening against a library of combinatorial peptides and cleavage of individual peptides. This subject is specifically explored in the studies described here. In order to establish whether PS-SCL screens could accurately determine the substrate preferences of proteases, a systematic comparison of data from PS-SCLs with libraries containing individually synthesised peptides (sparse matrix library; SML) was carried out. These SML libraries were designed to include all possible sequence combinations of the residues that were suggested to be preferred by a protease using the PS-SCL method. SML screening against the three serine proteases kallikrein 4 (KLK4), kallikrein 14 (KLK14) and plasmin revealed highly preferred peptide substrates that could not have been deduced by PS-SCL screening alone. Comparing protease subsite preference profiles from screens of the two types of peptide libraries showed that the most preferred substrates were not detected by PS SCL screening as a consequence of intermolecular cooperativity being negated by the very nature of PS SCL screening. Sequences that are highly favoured as result of intermolecular cooperativity achieve optimal protease subsite occupancy, and thereby interact with very specific determinants of the protease. Identifying these substrate sequences is important since they may be used to produce potent and selective inhibitors of protolytic enzymes. This study found that highly favoured substrate sequences that relied on intermolecular cooperativity allowed for the production of potent inhibitors of KLK4, KLK14 and plasmin. Peptide aldehydes based on preferred plasmin sequences produced high affinity transition state analogue inhibitors for this protease. The most potent of these maintained specificity over plasma kallikrein (known to have a very similar substrate preference to plasmin). Furthermore, the efficiency of this inhibitor in blocking fibrinolysis in vitro was comparable to aprotinin, which previously saw clinical use to reduce perioperative bleeding. One substrate sequence particularly favoured by KLK4 was substituted into the 14 amino acid, circular sunflower trypsin inhibitor (SFTI). This resulted in a highly potent and selective inhibitor (SFTI-FCQR) which attenuated protease activated receptor signalling by KLK4 in vitro. Moreover, SFTI-FCQR and paclitaxel synergistically reduced growth of ovarian cancer cells in vitro, making this inhibitor a lead compound for further therapeutic development. Similar incorporation of a preferred KLK14 amino acid sequence into the SFTI scaffold produced a potent inhibitor for this protease. However, the conformationally constrained SFTI backbone enforced a different intramolecular cooperativity, which masked a KLK14 specific determinant. As a consequence, the level of selectivity achievable was lower than that found for the KLK4 inhibitor. Standard mechanism inhibitors such as SFTI rely on a stable acyl-enzyme intermediate for high affinity binding. This is achieved by a conformationally constrained canonical binding loop that allows for reformation of the scissile peptide bond after cleavage. Amino acid substitutions within the inhibitor to target a particular protease may compromise structural determinants that support the rigidity of the binding loop and thereby prevent the engineered inhibitor reaching its full potential. An in silico analysis was carried out to examine the potential for further improvements to the potency and selectivity of the SFTI-based KLK4 and KLK14 inhibitors. Molecular dynamics simulations suggested that the substitutions within SFTI required to target KLK4 and KLK14 had compromised the intramolecular hydrogen bond network of the inhibitor and caused a concomitant loss of binding loop stability. Furthermore in silico amino acid substitution revealed a consistent correlation between a higher frequency of formation and the number of internal hydrogen bonds of SFTI-variants and lower inhibition constants. These predictions allowed for the production of second generation inhibitors with enhanced binding affinity toward both targets and highlight the importance of considering intramolecular cooperativity effects when engineering proteins or circular peptides to target proteases. The findings from this study show that although PS-SCLs are a useful tool for high throughput screening of approximate protease preference, later refinement by SML screening is needed to reveal optimal subsite occupancy due to cooperativity in substrate recognition. This investigation has also demonstrated the importance of maintaining structural determinants of backbone constraint and conformation when engineering standard mechanism inhibitors for new targets. Combined these results show that backbone conformation and amino acid cooperativity have more prominent roles than previously appreciated in determining substrate/inhibitor specificity and binding affinity. The three key inhibitors designed during this investigation are now being developed as lead compounds for cancer chemotherapy, control of fibrinolysis and cosmeceutical applications. These compounds form the basis of a portfolio of intellectual property which will be further developed in the coming years.

Schooling elsewhere: Rurality, inclusion and education

Over its history, the International Journal of Inclusive Education has had a strong record of naming, critiquing and redressing the ways in which particular social locations shape experiences of inclusion and exclusion in education. In this special issue, we continue this tradition taking as our focus those who live outside the metropolitan mainstream. To date, rural schools and the communities of which they are part have often been overlooked by researchers of inclusive education. This is not to suggest that the rural has been ignored entirely in research on inclusivity and schooling. For example, a number of studies have included rural case studies as part of broader research on subjects such as educational disadvantage and experiences of poverty (Horgan 2009), inclusivity and early childhood services (Penn 1997), constraints to inclusive educational practice (Shevlin, Winter, and Flynn 2013) and the efficacy of inclusivity training programmes for teachers (Strieker, Logan, and Kuhel 2012). Such work provides a critical reference point for this special issue as it has demon- strated that the educational landscape may be very differently experienced in the rural compared to the urban. Illustrative is Wikeley et al.’s (2009, 381) assertion that working class Irish youth living outside the urban sphere are ‘doubly disadvantaged’ in terms of accessing out-of-school activities and Milovanovic et al.’s (2014, 47) claim that for young children in the Western Balkans, there is a ‘dearth of pre-school provision in rural areas’. As well as highlighting cleavages of disadvantage as they exist between urban and rural schools, work in this journal has also revealed disadvantage that exists within rural schools. This scholarship has explored how particular social locations, such as disability, ethnicity, sexuality, gender and class intersect with rurality to produce very different educational biographies. For example, it may be class, as Holt (2012) found in her study of young rural women’s transition to a city university, or it may be gender, as Tuwor and Sossou (2008) posited in their work on the schooling of girls in West Africa.

Commercial Law in East Asia

The shift of economic gravity towards East Asia requires a critical examination of law's role in the Asian Century. This volume explores the diverse scholarly perspectives on law's role in the economic rise of East Asia and moves from general debates, such as whether law enjoys primacy over culture, state intervention or free markets in East Asian capitalism, to specific case studies looking at the nature of law in East Asian negotiations, contracts, trade policy and corporate governance. The collection of articles exposes the clefts and cleavages in the scholarly literature explaining law's form, function and future in the Asian Century.

Political transition and structural politicisation : The long shadow of Taiwan's one-party legacy

Väitöskirjatutkimuksessa tarkastellaan Taiwanin politiikkaa ensimmäisen vaalien kautta tapahtuneen vallanvaihdon jälkeen (2000) yhteiskunnan rakenteellisen politisoitumisen näkökulmasta. Koska Taiwanilla siirryttiin verettömästi autoritaarisesta yksipuoluejärjestelmästä monipuoluejärjestelmään sitä on pidetty poliittisen muodonmuutoksen mallioppilaana. Aiempi optimismi Taiwanin demokratisoitumisen suhteen on sittemmin vaihtunut pessimismiin, pitkälti yhteiskunnan voimakkaasta politisoitumisesta johtuen. Tutkimuksessa haetaan selitystä tälle politisoitumiselle. Yhteiskunnan rakenteellisella politisoitumisella tarkoitetaan tilannetta, jossa ”poliittisen” alue kasvaa varsinaisia poliittisia instituutioita laajemmaksi. Rakenteellinen politisoituminen muuttuu helposti yhteiskunnalliseksi ongelmaksi, koska siitä usein seuraa normaalin poliittisen toiminnan (esim. lainsäädännän) jähmettyminen, yhteiskunnan jyrkkä jakautuminen, alhainen kynnys poliittisille konflikteille ja yleisen yhteiskunnallisen luottamuksen alentuminen. Toisin kuin esimerkiksi Itä-Euroopassa, Taiwanissa entinen valtapuolue ei romahtanut poliittisen avautumisen myötä vaan säilytti vahvan rakenteellisen asemansa. Kun valta vaihtui ensimmäisen kerran vaalien kautta, vanha valtapuolue ei ollut valmis luovuttamaan poliittisen järjestelmän ohjaksia käsistään. Alkoi vuosia kestänyt taistelu järjestelmän hallinnasta vanhan ja uuden valtapuolueen välillä, jossa yhteiskunta politisoitui voimakkaasti. Tutkimuksessa Taiwanin yhteiskunnan politisoituminen selitetään useiden rakenteellisten piirteiden yhteisvaikutuksen tuloksena. Tällaisia politisoitumista edistäviä rakentellisia piirteitä ovat hidas poliittinen muutos, joka säilytti vanhat poliittiset jakolinjat ja niihin liittyvät vahvat edut ja intressit; sopimaton perustuslaki; Taiwanin epäselvä kansainvälinen asema ja jakautunut identiteetti; sekä sosiaalinen rakenne, joka helpottaa ihmisten nopeaa mobilisointia poliittiisiin mielenilmauksiin. Tutkimuksessa kiinnitetään huomiota toistaiseksi vähän tutkittuun poliittiseen ilmiöön, joidenkin demokratisoituvien yhteiskuntien voimakkaaseen rakenteelliseen politisoitumiseen. Tutkimuksen pääasiallinen havainto on, että yksipuoluejärjestelmän demokratisoituminen kantaa sisällään rakenteellisen politisoitumisen siemenen, jos entinen valtapuolue ei romahda demokratisoitumisen myötä.

Mechanisms for alphavirus nonstructural polyprotein processing

Replication and transcription of the RNA genome of alphaviruses relies on a set of virus-encoded nonstructural proteins. They are synthesized as a long polyprotein precursor, P1234, which is cleaved at three processing sites to yield nonstructural proteins nsP1, nsP2, nsP3 and nsP4. All the four proteins function as constitutive components of the membrane-associated viral replicase. Proteolytic processing of P1234 polyprotein is precisely orchestrated and coordinates the replicase assembly and maturation. The specificity of the replicase is also controlled by proteolytic cleavages. The early replicase is composed of P123 polyprotein intermediate and nsP4. It copies the positive sense RNA genome to complementary minus-strand. Production of new plus-strands requires complete processing of the replicase. The papain-like protease residing in nsP2 is responsible for all three cleavages in P1234. This study addressed the mechanisms of proteolytic processing of the replicase polyprotein in two alphaviruses Semliki Forest virus (SFV) and Sindbis virus (SIN) representing different branches of the genus. The survey highlighted the functional relation of the alphavirus nsP2 protease to the papain-like enzymes. A new structural motif the Cys-His catalytic dyad accompanied with an aromatic residue following the catalytic His was described for nsP2 and a subset of other thiol proteases. Such an architecture of the catalytic center was named the glycine specificity motif since it was implicated in recognition of a specific Gly residue in the substrate. In particular, the presence of the motif in nsP2 makes the appearance of this amino acid at the second position upstream of the scissile bond a necessary condition for the cleavage. On top of that, there were four distinct mechanisms identified, which provide affinity for the protease and specifically direct the enzyme to different sites in the P1234 polyprotein. Three factors RNA, the central domain of nsP3 and the N-terminus of nsP2 were demonstrated to be external modulators of the nsP2 protease. Here I suggest that the basal nsP2 protease specificity is inherited from the ancestral papain-like enzyme and employs the recognition of the upstream amino acid signature in the immediate vicinity of the scissile bond. This mechanism is responsible for the efficient processing of the SFV nsP3/nsP4 junction. I propose that the same mechanism is involved in the cleavage of the nsP1/nsP2 junction of both viruses as well. However, in this case it rather serves to position the substrate, whereas the efficiency of the processing is ensured by the capability of nsP2 to cut its own N-terminus in cis. Both types of cleavages are demonstrated here to be inhibited by RNA, which is interpreted as impairing the basal papain-like recognition of the substrate. In contrast, processing of the SIN nsP3/nsP4 junction was found to be activated by RNA and additionally potentiated by the presence of the central region of nsP3 in the protease. The processing of the nsP2/nsP3 junction in both viruses occurred via another mechanism, requiring the exactly processed N-terminus of nsP2 in the protease and insensitive to RNA addition. Therefore, the three processing events in the replicase polyprotein maturation are performed via three distinct mechanisms in each of two studied alphaviruses. Distinct sets of conditions required for each cleavage ensure sequential maturation of P1234 polyprotein: nsP4 is released first, then the nsP1/nsP2 site is cut in cis, and liberation of the nsP2 N-terminus activates the cleavage of the nsP2/nsP3 junction at last. The first processing event occurs differently in SFV and SIN, whereas the subsequent cleavages are found to be similar in the two viruses and therefore, their mechanisms are suggested to be conserved in the genus. The RNA modulation of the alphavirus nonstructural protease activity, discovered here, implies bidirectional functional interplay between the alphavirus RNA metabolism and protease regulation. The nsP2 protease emerges as a signal transmitting moiety, which senses the replication stage and responds with proteolytic cleavages. A detailed hypothetical model of the alphavirus replicase core was inferred from the data obtained in the study. Similar principles in replicase organization and protease functioning are expected to be employed by other RNA viruses.