ライフサイエンスコーパス: dengue virus

1 ethylation (m7Gpppm6A in mammals, m7GpppA in dengue virus).

2 helium, subsequently inhibiting infection by dengue virus.

3 penic) mice exhibited a higher prevalence of dengue virus.

4 n of robust correlates of protection against dengue virus.

5 esponses seen in humans naturally exposed to dengue virus.

6 se during a subsequent exposure to wild-type dengue virus.

7 accines designed to protect against the four dengue viruses.

8 reduction neutralisation assays for Zika and dengue viruses.

9 For dengue viruses 1 to 4 (DENV1-4), a specific range of ant

10 l inoculation of embryonic mouse brains with dengue virus 2 (DENV2), and found that DENV2 is sufficie

11 Nile virus, Japanese encephalitis virus, and dengue virus 2.

12 st dependency factors required for efficient dengue virus-2 (DENV2) infection of human cells.

13 l Host & Microbe, Young et al. shed light on dengue virus 3-specific epitopes.

14 IMPORTANCE Dengue virus, a member of the family Flaviviridae, can r

15 sideropenic status of hosts largely reduced dengue virus acquisition and infection by mosquitoes.

16 Dengue virus acquisition by Aedes aegypti was inversely

17 rt that serum iron in human blood influences dengue virus acquisition by mosquitoes.

18 Because of the similarity of Zika and dengue viruses, an analogous unwanted outcome might occu

19 increases the competence of this species for dengue virus and chikungunya virus as well as Aedes albo

20 ible to ZIKV compared to the closely related dengue virus and induced the expression of alpha interfe

21 es are the limited assessment of the role of dengue virus and other possible cofactors, the small num

22 nge of different viral infections, including dengue virus and SARS-CoV, and consider ADE in the conte

23 gs support possible cross-reactivity between dengue virus and SARS-CoV-2, which can lead to false-pos

24 In contrast, both the flavivirus dengue virus and the alphavirus Sindbis virus replicated

25 ng the last 70 years, including epidemics of dengue virus and West Nile virus, and the most recent ex

26 ed by Ae. aegypti include the 2 flaviviruses dengue virus and yellow fever virus and the alphavirus c

27 ctious particle production of HCV as well as dengue virus and Zika virus revealing a conserved requir

28 Structures of flavivirus (dengue virus and Zika virus) particles are known to near

29 Flaviviruses, including dengue virus and Zika virus, contain a single-stranded p

30 Flaviviruses, including dengue virus and Zika virus, extensively remodel the cel

31 iruses, including hepatitis A and C viruses, dengue virus and Zika virus.

32 several human pathogenic viruses, including dengue virus and Zika virus.

33 erging mosquito-borne flavivirus, related to dengue virus and Zika virus.

34 flaviviruses and neutralize a broad range of dengue virus and ZIKV isolates.

35 Three targets, zika virus, dengue virus, and chikungunya virus, in human serum were

36 he within-host evolution of influenza virus, dengue virus, and cytomegalovirus.

37 rus, Hepatitis A-E Virus, Chikungunya virus, dengue virus, and West Nile virus, as well the human pol

38 Detection of dengue virus antibodies is important for understanding f

39 vaccination.IMPORTANCE The four serotypes of dengue virus are the causative agents of dengue fever an

40 Infections with dengue virus are usually self-limiting, and chronic deng

41 Dengue viruses are endemic in most tropical and subtropi

42 Dengue virus assembly requires cleavage of viral C-prM-E

43 pounds demonstrate improved activity against dengue virus both in vitro and in human primary dendriti

44 o endemic mosquito-borne infections, such as dengue virus, both for routine management involving vect

45 nfer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue

46 f children with suspected ZIKV infection for dengue virus coinfection should be considered in dengue-

47 Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and m

48 gue disease despite the global prevalence of dengue virus (DENV) and its mosquito vectors.

49 pping geographical distribution of ZIKV with dengue virus (DENV) and other flaviviruses, possibly res

50 g that often shows cross-reactivity with the Dengue virus (DENV) and other flaviviruses.

51 are exquisitely required for replication of dengue virus (DENV) and other mosquito-borne flaviviruse

52 ritical prerequisite for vaccination against dengue virus (DENV) and other viral diseases.

53 Infection with flaviviruses, such as dengue virus (DENV) and the recently re-emerging Zika vi

54 the world where other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), are endem

55 of global public health importance, such as dengue virus (DENV) and yellow fever virus (YFV), origin

56 minant target of neutralizing antibodies for dengue virus (DENV) and yellow fever virus (YFV).

57 embers of the Flaviviridae family, including dengue virus (DENV) and yellow fever virus, cause seriou

58 Infections with dengue virus (DENV) and Zika virus (ZIKV) can induce cro

59 Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), cause severe

60 Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), rely heavily

61 vaccines for pathogenic flaviviruses such as dengue virus (DENV) and Zika virus.

62 Because dengue virus (DENV) and ZIKV co-circulate, understanding

63 Anti-Dengue virus (DENV) antibodies can be either protective

64 Although dengue virus (DENV) antibodies can neutralize or enhance

65 Low preexisting anti-dengue virus (DENV) antibody levels are associated with

66 Zika virus (ZIKV) and dengue virus (DENV) are antigenically related flavivirus

67 Zika virus (ZIKV) and dengue virus (DENV) are co-endemic in many parts of the

68 ow fever virus (YFV), Zika virus (ZIKV), and dengue virus (DENV) are important human pathogens.

69 pearance was not observable with a different dengue virus (DENV) as our control.

70 Dengue virus (DENV) can cause life-threatening disease c

71 Dengue virus (DENV) causes 400 million infections annual

72 Dengue virus (DENV) causes a range of illness, including

73 Dengue virus (DENV) causes frequent epidemics infecting

74 T cells contribute to protection from severe dengue virus (DENV) disease and vaccine efficacy.

75 15 and 2016, Zika virus (ZIKV) swept through dengue virus (DENV) endemic areas of Latin America.

76 emerging virus that has recently spread into dengue virus (DENV) endemic regions and cross-reactive a

77 ) and associated birth defects in regions of dengue virus (DENV) endemicity emphasize the need for se

78 Dengue virus (DENV) exists as four genetically distinct

79 ut the complex effects of age and sequential dengue virus (DENV) exposures on these correlations.

80 in the host immune response directed against dengue virus (DENV) has demonstrated the need to underst

81 he last few decades, the global incidence of dengue virus (DENV) has increased dramatically, and it i

82 antigenic glycoprotein for the detection of dengue virus (DENV) IgG antibodies.

83 cas, a major question that has arisen is how dengue virus (DENV) immunity impacts Zika virus infectio

84 (DEP) chip was conducted to rapidly detect a dengue virus (DENV) in vitro based on the fluorescence i

85 inuing studies of vaccine approaches against dengue virus (DENV) infection are warranted, particularl

86 Diagnostic testing for Zika virus (ZIKV) or dengue virus (DENV) infection can be accomplished by a n

87 Dengue virus (DENV) infection causes a characteristic pa

88 Dengue virus (DENV) infection causes dengue fever in hum

89 Dengue virus (DENV) infection disrupts host innate immun

90 The increased prevalence of dengue virus (DENV) infection has had a significant soci

91 results in areas with various levels of past dengue virus (DENV) infection incidence.

92 cell-associated viral reservoir during acute dengue virus (DENV) infection remains unclear.

93 Dengue virus (DENV) infection requires cholesterol as a

94 sma leakage are immune-pathologies of severe dengue virus (DENV) infection, but the mechanisms underl

95 increased disease severity during secondary dengue virus (DENV) infection.

96 skin and draining lymph nodes (DLNs) during dengue virus (DENV) infection.

97 ated with susceptibility to DHF in secondary dengue virus (DENV) infections (odds ratio [OR], 3.22; [

98 We sought to characterize dengue virus (DENV) infections among febrile children en

99 approaches to differentially detect ZIKV and dengue virus (DENV) infections, accentuating the urgent

100 from patients during clinical influenza and dengue virus (DENV) infections.

101 Dengue virus (DENV) is a global health threat, causing r

102 Dengue virus (DENV) is a member of the genus Flavivirus

103 nd inflammation in DENV infection.IMPORTANCE Dengue virus (DENV) is a mosquito-borne pathogen that th

104 Dengue virus (DENV) is a mosquito-borne virus that infec

105 Dengue virus (DENV) is responsible for growing numbers o

106 Dengue virus (DENV) is responsible for the most prevalen

107 Dengue virus (DENV) is the causative agent of dengue fev

108 Dengue virus (DENV) is the most prevalent vector-borne v

109 Preexisting immunity to Zika virus (ZIKV) or dengue virus (DENV) may alter the course of their infect

110 rove a sdAb-based assay for the detection of dengue virus (DENV) nonstructural protein 1 (NS1) in ser

111 re dengue disease, are directly triggered by dengue virus (DENV) nonstructural protein 1 (NS1).

112 Dengue virus (DENV) NS5 RNA-dependent RNA polymerase (Rd

113 spite replicating in the cytoplasm, ZIKV and Dengue virus (DENV) polymerases, NS5 proteins, are predo

114 velop antivirals that can effectively reduce dengue virus (DENV) replication and decrease viral load.

115 Robust dengue virus (DENV) replication requires lipophagy, a se

116 Transmission of dengue virus (DENV) requires successful completion of th

117 tralizing antibodies to distinguish ZIKV and dengue virus (DENV) responses, which we found were commo

118 A deletion variant of the dengue virus (DENV) serotype 2 (DENV2) Tonga/74 strain l

119 public health problem and is caused by four dengue virus (DENV) serotypes (DENV1-4).

120 of immunological interactions among the four dengue virus (DENV) serotypes and their epidemiological

121 The four dengue virus (DENV) serotypes are mosquito-borne flavivi

122 The four dengue virus (DENV) serotypes are mosquito-borne flavivi

123 The 4 antigenically distinct serotypes of dengue virus (DENV) share extensive homology with each o

124 Dengue virus (DENV) subdues cell membranes for its cellu

125 count for the many forms of heterogeneity in dengue virus (DENV) transmission, which could have impli

126 d for detection of consensus DNA sequence of Dengue virus (DENV) using methylene blue (MB) as an inte

127 The rational design of dengue virus (DENV) vaccines requires a detailed underst

128 Dengue virus (DENV) was designated as a top 10 public he

129 The cross-reactivity of ZIKV epitopes to dengue virus (DENV) was tested using IFN-gamma-ELISPOT a

130 ly related to other human pathogens, such as dengue virus (DENV)(1).

131 Dengue virus (DENV), a common and widely spread arboviru

132 sting target sites for inhibition.IMPORTANCE Dengue virus (DENV), an important arthropod-transmitted

133 e of neutralizing antibodies (NAbs) to ZIKV, dengue virus (DENV), and West Nile virus (WNV).

134 irus genus, including West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV), but had no s

135 aviviruses, including West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV).

136 athogens including yellow fever virus (YFV), dengue virus (DENV), and Zika virus (ZKV), all of which

137 V) and Zika (ZIKV) viruses co-circulate with dengue virus (DENV), hampering clinical diagnosis.

138 Brazil, which is hyperendemic for dengue virus (DENV), has had recent Zika (ZIKV) and (CHI

139 We demonstrate that ZIKV, but not dengue virus (DENV), induces DNA double-strand breaks (D

140 ral protein 5 (NS5) of Zika virus (ZIKV) and dengue virus (DENV), revealing two-pronged interactions

141 egree of sequence and structural homology to Dengue virus (DENV), the role of immunological cross-rea

142 antibodies that cross-react with the related dengue virus (DENV), we designed modified prM-E RNA enco

143 Infections with dengue virus (DENV), West Nile virus (WNV) and Zika viru

144 une responses protect against infection with dengue virus (DENV), yet cross-reactivity with distinct

145 eport that like the NS5 proteins of ZIKV and dengue virus (DENV), YFV NS5 protein is able to bind hST

146 es many medically important viruses, such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever

147 oss the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus

148 ic tests, particularly for pregnant women in dengue virus (DENV)-endemic regions.

149 urified inactivated vaccine (ZPIV)(4-7) in a dengue virus (DENV)-experienced human elicited potent cr

150 identified and were not cross-recognized by dengue virus (DENV)-infected patients' antibodies.

151 While it is widely accepted that dengue virus (DENV)-neutralizing antibody (nAb) titers a

152 e show that expression of ZIKV-NS2A, but not Dengue virus (DENV)-NS2A, leads to reduced proliferation

153 Although some cross-reactive dengue virus (DENV)-specific antibodies can enhance ZIKV

154 0, 1 or >1 prior infections with the related dengue virus (DENV).

155 opulations that have been largely exposed to dengue virus (DENV).

156 er of viruses pathogenic to humans including dengue virus (DENV).

157 n acute febrile infectious disease caused by dengue virus (DENV).

158 ated individuals to infection by the related Dengue virus (DENV).

159 rotective immunity against pathogens such as dengue virus (DENV).

160 ZIKV viral RNA replication when compared to dengue virus (DENV).

161 squito borne viruses including flaviviruses (dengue virus (DENV; nine isolates analyzed), Japanese en

162 Dengue virus (DENV; serotypes 1 to 4), a member of the F

163 Dengue viruses (DENV) are the most common cause of mosqu

164 ZIKV and Dengue viruses (DENV) entry to the host cell takes place

165 is study defined the genetic epidemiology of dengue viruses (DENV) in two pivotal phase III trials of

166 cal attributes of ADE disease exemplified by dengue viruses (DENV).

167 uated vaccines to each of the 4 serotypes of dengue virus (DENV1-4).

168 travalent DLAV vaccine (TV005) with pools of dengue virus-derived predicted major histocompatibility

169 lectrochemical DNA hybridization sensors for Dengue virus detection, spanning both labeled and label-

170 West Nile, Japanese encephalitis, Zika, and dengue viruses did not affect recall responses.

171 a long-term reduction in risk of symptomatic dengue virus disease in vaccinees.

172 ine-related serious adverse events or severe dengue virus disease were reported.

173 ains for safe and effective vaccines against dengue virus disease, particularly for individuals who a

174 emonstrate that infection with ZIKV, but not dengue virus, disrupts the cell cycle of hNPCs by haltin

175 OCK), to detect specific strains of Zika and Dengue virus, distinguish pathogenic bacteria, genotype

176 opt a protein fold remarkably similar to the dengue virus E glycoprotein and related class II viral f

177 Dengue virus elicits robust type-specific and cross-reac

178 ic antibody responses in mice immunized with dengue virus envelope domain III protein (DENVrEDIII), a

179 ee chemically distinct vaccine components, a dengue virus Envelope protein Domain III (EDIII) subunit

180 d functional homologies between the Zika and Dengue viruses' envelope proteins raise the possibility

181 Applying CapQuant to RNA from purified dengue virus, Escherichia coli, yeast, mouse tissues, an

182 ordering effect of influenza virus, HIV, and Dengue virus FPs has been consistently observed.

183 ework to estimate transmission intensity for dengue virus from age-specific incidence data, and apply

184 y used with 5 clinical specimens of zika and dengue virus from real patients.

185 e designed based on analysis of the zika and dengue virus genomes.

186 ed sequences present in all the serotypes of Dengue virus has been employed for fabrication of a geno

187 Dengue virus has been shown to be particularly sensitive

188 immunodeficiency virus, influenza virus, and dengue virus have evolved a multitude of mechanisms to e

189 ntibody to correlate with protection against dengue virus have highlighted the need for a human DENV

190 egypti mosquitoes that transmit the Zika and Dengue virus in a one choice landing rate inhibition ass

191 What was once blurred and confused with dengue virus in both diagnosis and name has since become

192 d Raman scattering (SERS) based diagnosis of dengue virus in clinical blood samples collected from to

193 nal fluid, but postmortem analysis confirmed dengue virus in the brain by immunohistochemistry, in si

194 quencing of the virus demonstrated wild-type dengue virus in the central nervous system.

195 the infectivity of bovine viral diarrhea and dengue viruses in cellular models.

196 ble to suppress replication of West Nile and dengue viruses in infected cells in the micromolar range

197 ransplantation carried out in a patient with dengue virus induced acute liver failure (ALF).((1)) The

198 eover, AAK1 is overexpressed specifically in dengue virus-infected but not bystander cells.

199 profile in monocytes isolated from ZIKV- and dengue virus-infected patients was comparable, except fo

200 rature on this association in the context of dengue virus infection (DENV).

201 Dengue virus infection also induced cross-reactive MBC r

202 cating its therapeutic potential against the dengue virus infection as a drug candidate for further p

203 Inhibition of dengue virus infection by 1-stearoyl-2-arachidonoyl-phos

204 eas neutralization of serum iron facilitated dengue virus infection in A. aegypti mosquitoes.

205 hat can provide long-term protection against dengue virus infection is needed.

206 Previously it was shown that Dengue virus infection of the mosquito led to an in incr

207 ve for S. marcescens were more permissive to dengue virus infection than those free of S. marcescens.

208 Dengue virus infection typically causes mild dengue feve

209 ellular host factors are required to support dengue virus infection, but their identity and roles are

210 Despite the clear medical importance of dengue virus infection, the mechanism of viral replicati

211 ractome is profoundly reprogrammed following dengue virus infection.

212 potent innate immune response that restricts dengue virus infection.

213 g of NK cells in a patient cohort with acute dengue virus infection.

214 increased with age, irrespective of previous dengue virus infection.

215 nd one sample each was confirmed for ZIKV or dengue virus infection.

216 derstanding of the innate immune response to dengue virus infection.

217 body titers in cases were unrelated to prior dengue virus infection.

218 tions such as tuberculosis, melioidosis, and dengue virus infection.

219 tion campaign were seropositive for previous dengue virus infection.

220 2676 (89.3%) were seropositive for previous dengue virus infection.

221 s for achieving long-term protection against dengue virus infection.IMPORTANCE Continuing studies of

222 Because dengue virus infections are ubiquitous in residents and

223 Our findings suggest that dengue virus infections may persist in the central nervo

224 Secondary dengue virus infections were also shown to influence dis

225 ues were synthesized and evaluated as potent dengue virus inhibitors.

226 The effect of adding excess defective dengue virus interfering particles to patients as a ther

227 ue virus cell invasion and receptor-mediated Dengue virus invasion.

228 ccination coverage, pre-existing immunity to dengue virus is abundant in the human population, and se

229 Dengue virus is an arthropod-borne virus transmitted pri

230 Dengue virus is an emerging mosquito-borne flavivirus re

231 A as well as specific nucleotides.IMPORTANCE Dengue virus is an important human pathogen responsible

232 The process of RNA replication by dengue virus is still not completely understood despite

233 the search for an efficient vaccine against dengue virus is the immunodominance of the fusion loop e

234 ent of vaccines against ZIKV and the related dengue virus is the induction of cross-reactive poorly n

235 Dengue virus is the most common arbovirus worldwide and

236 and the cross-reactivity with West Nile and dengue viruses is minimal (0%-4%).

237 utics that target this essential step of the dengue virus life cycle.

238 d Bartonella), and 13 viruses (parechovirus, dengue virus, Nipah virus, varicella-zoster virus, mumps

239 g of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease.

240 Dengue virus NS5 also binds SLAs from different serotype

241 We show that dengue virus NS5 binds SLA with a 1:1 stoichiometry and

242 Quantitatively characterizing dengue virus NS5-SLA interactions will facilitate the de

243 ross-react with the E protein of the related dengue virus on account of the high level of similarity

244 ory-confirmed Zika (three co-infections with dengue virus, one missing complete blood count data) and

245 ed microcephaly, 336 patients with suspected dengue virus or chikungunya virus infection, and 349 sam

246 logous epitope located at the surface of the dengue virus particle.

247 ive analysis of the interactions between the dengue virus polymerase NS5 and SLA in solution has not

248 Influenza and dengue viruses present a growing global threat to public

249 uisition model, iron supplementation reduced dengue virus prevalence and viral load, whereas neutrali

250 th sides of the active site as inhibitors of dengue virus protease.

251 th P bodies in uninfected cells and with the dengue virus replication complex after infection.

252 ion (UTR), is critical for the initiation of dengue virus replication, but quantitative analysis of t

253 bodies is important for understanding future dengue virus risk and for prevaccination screening.

254 accines against respiratory syncytial virus, dengue virus, SARS-CoV and Middle East respiratory syndr

255 116 also binds to and cross-neutralizes some dengue virus serotype 1 (DENV1) strains, with genotype-d

256 CHIKV and dengue virus serotype 1 infections were more common in o

257 Using a dengue virus serotype 2 (DENV-2) vaccine strain (PDK53),

258 ibody activity against Zika virus (ZIKV) and dengue virus serotype 2 (DENV2).

259 n infected cells, antiviral activity against Dengue virus serotype 2 using prodrugs of the inhibitors

260 Zika virus and dengue virus serotype 2 were isolated from a patient wit

261 s of the DENV3-specific 5J7 mAb epitope into dengue virus serotype 4 (DENV4).

262 rs and recipients, we assess the dynamics of dengue virus serotype 4 during the 2012 outbreak in Rio

263 operties of human antibodies that neutralize dengue virus serotype 4.

264 Based on dengue virus serotype-specific neutralizing antibody (NA

265 virologically confirmed dengue caused by any dengue virus serotype.

266 1%) among children with immunity to just one dengue virus serotype.

267 Dengue, caused by four dengue virus serotypes (DENV-1 to DENV-4), is a highly p

268 that is safe and effective against all four dengue virus serotypes (DENV-1-4) in recipients of all a

269 The four dengue virus serotypes (DENV1-4) cause major public heal

270 ralizing antibodies (bNAbs) against the four dengue virus serotypes (DENV1-4) that are spreading into

271 re found to incorporate smaller outbreaks of dengue virus serotypes 1 and 4 and Zika virus, with iden

272 nterest in whether immune interactions among dengue virus serotypes 1 to 4 (DENV1 to -4) extend to th

273 Unexpectedly, dengue virus serotypes 1 to 4 (DENV1 to DENV4) and the y

274 However, other related flaviviruses, dengue virus serotypes 1 to 4 and the yellow fever 17D v

275 es on the envelope (E) protein of viruses of dengue virus serotypes 1, 2, and 3 targeted by human neu

276 rm protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determ

277 nation of ZIKV from West Nile virus and four dengue virus serotypes.

278 the infection kinetics for each of the four dengue virus serotypes.

279 These targets include dengue virus specific consensus primer (DENVCP) and four

280 to provide protection against four different dengue virus stereotypes.

281 Despite antigenic similarities with dengue viruses, structural studies have suggested the ex

282 Norovirus submissions since May 2018 and for Dengue virus submissions since January 2019.

283 ntibody titres against ZIKV, but not against dengue viruses that circulated during the same period.

284 ontribute to the vectorial permissiveness to dengue virus, thereby facilitating its spread by mosquit

285 We used an agent-based model of dengue virus transmission calibrated to data from Iquito

286 uction of Wolbachia endosymbionts that block dengue virus transmission into populations of the primar

287 ith a non-natural Wolbachia strain to reduce dengue virus transmission.

288 laviviruses yellow fever virus 17D (YFV) and dengue virus type 2 (DENV2).

289 include Lassa pseudovirus, influenza virus, dengue virus type 2, herpes simplex virus 1, and nonenve

290 The leading dengue virus vaccine candidates in clinical testing are

291 antigens than E protein monomers.IMPORTANCE Dengue virus vaccine development is particularly challen

292 Previous respiratory syncytial virus and dengue virus vaccine studies revealed human clinical saf

293 The first dengue virus vaccine, Dengvaxia, now licensed in 20 ende

294 be the structure and attributes of two other dengue virus vaccines.

295 es aegypti, the latter an important Zika and Dengue virus vector insensitive to Ls Bin.

296 Dengue virus was also detectable by polymerase chain rea

297 Preexisting high antibody titers to dengue virus were associated with reduced risk of ZIKV i

298 A virus, HIV-1, Rift Valley fever virus, and dengue virus, were unaffected by TRIM69.

299 at share a similar envelope protein, such as dengue virus, West Nile virus, and yellow fever virus.

300 Global arboviruses, including dengue virus, Zika virus, and chikungunya virus, have al