ライフサイエンスコーパス: instigate

1 unknown, and often no specific treatment is instigated.

2 tive causes, including malignancy, should be instigated.

3 object decision making in the human brain is instigated.

4 have not yet been sufficiently compelling to instigate a clinical trial testing this hypothesis, nor

5 ely in a complex liquid solution and in turn instigate a controlled chemical reaction.

6 2s interact with antigen-specific T cells to instigate a dialog in which IL-2 production from T cells

7 The cells instigate a fast transcriptome and proteome response, in

8 tro to examine the molecular events that can instigate a genetic load.

9 ility influence motility mode plasticity and instigate a mode termed stable bleb migration in embryon

10 lieu in a rapidly proliferating tissue might instigate a proinflammatory response.

11 Cortical infarcts also instigate a prolonged period of dendritic spine turnover

12 ed mitogen-activated protein kinase cascades instigate a range of changes to enable eukaryotic cells

13 ment should be present to disrupt anergy and instigate a response that might cause disease.

14 terior cruciate ligament (except for 6N) and instigated a cascade of temporal and topographical featu

15 onavirus disease 2019 (COVID-19) has rapidly instigated a global pandemic.

16 We suggest that the quest for silver instigated a long, exploratory phase, first in Anatolia

17 Further reduction of the leaf RWC to 60% instigated a metabolic shift in S. stapfianus toward the

18 of antibiotic-resistant lung infections has instigated a much-needed search for new therapeutic stra

19 habilitative training in vivo Focal ischemia instigated a period of synapse turnover in peri-infarct

20 Inactivation of this pathway instigated a rapid onset of anoxia induced death in infe

21 disease (AD) has proven challenging and has instigated a shift in AD research focus toward the earli

22 This proposal has instigated a wider discussion about the use of patient-r

23 ines to their cognate receptors on monocytes instigates a cascade of events that directs these cells

24 n underlying cause of cardiac senescence and instigates a decline in cardiac function.

25 I think Just's life story instigates a discussion on diversity in science, as well

26 By increasing GATA2 expression, the enhancer instigates a fate-promoting mechanism while abrogating a

27 ions, we propose that the force transduction instigates a partial unfolding of the pore-occluding lum

28 Preceding apoptosis, RES instigates a rapid dissipation of mitochondrial membrane

29 Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cell

30 Interaction of PRRs with viral compounds instigates a signaling pathway(s), resulting in the acti

31 ed to the polyoxovanadate, and when reduced, instigates a spin transition at iron.

32 1 to activate nuclear factor-kappaB, thereby instigating a vicious circle to persistently promote ath

33 We conclude that smoking (through nicotine) instigates AAA through AMPK-alpha2-mediated AP-2alpha-de

34 rtebral disc alters the microenvironment and instigates aberrant tissue remodelling and the adoption

35 for the need to mitigate climate change and instigate actions to reduce marine heatwaves.

36 an important role and that supercoiling can instigate additional ligand-DNA contacts that would not

37 ificant source of carbon in these sites, and instigate additional research into the nature and origin

38 temporary exposure to developmental signals instigates adipocyte differentiation are unknown.

39 The instigating agent typically triggers an inflammatory res

40 ical properties affect protein stability and instigate aggregation is essential for the engineering o

41 uggested that oxidation of methionine 46 may instigate aggregation.

42 d a highly amyloidogenic sequence motif that instigates aggregation and forms the core of the growing

43 n asthma, but the environmental factors that instigate allergic airway disease remain poorly understo

44 To identify IFN-stimulated genes (ISGs) that instigate an antiviral state against two medically impor

45 r position to observe a predator and, hence, instigate an evasion manoeuvre.

46 Phosphor-residues at the amino-terminus instigate an intra-molecular interaction that enlists bo

47 es was taken forward to an in vivo model and instigated an increase in tumor cell necrosis.

48 d acting as incentive stimuli, such cues can instigate and invigorate drug-seeking behavior.

49 hosphorylated MRLC are essential for PDGF to instigate and maintain control over the actin-myosin-bas

50 hese cues can evoke motivational states that instigate and maintain drug-seeking behavior.

51 sychological and related social factors that instigate and sustain violent extremism and polarizing g

52 e (IBD) is a complex genetic disease that is instigated and amplified by the confluence of multiple g

53 search for the location of the ODD locus was instigated and linkage to polymorphic markers located on

54 vational state ("wanting" or "craving") that instigates and/or invigorates drug-seeking behavior.

55 Checkpoint inhibitors (CI) instigate anticancer immunity in many neoplastic disease

56 alk with BrCa cells by utilizing exosomes to instigate antiviral signaling.

57 Although most of these introductions did not instigate any detected onward transmission, a small mino

58 esponses as well as the molecular mechanisms instigating apoptosis via IRE1 and PERK signaling.

59 The gene regulation mechanisms they instigate are largely mediated through the CCR4-NOT dead

60 s suggest that astrogliosis, physiologically instigated as a brain tissue damage response, is hijacke

61 educe short-term risk of death, and hence DR instigated at any age could generate a full reversal of

62 ow circulating LDL enters the artery wall to instigate atherosclerosis.

63 Such ACC signals may instigate attentionally demanding and difficult processe

64 We also present evidence that USP13 instigates Aurora B deubiquitination and/or protect it f

65 tylase SIRT1 displaces chromatin-bound BRD4, instigating autophagy gene activation and cell survival.

66 However, the signal in dACC that instigates behavioral change need not itself be a confli

67 Subsequent DNA packaging instigates bending of MCP A domain loops outwards, closi

68 e two eyes, a stimulation condition known to instigate binocular rivalry, during which one image is s

69 d surfaces of most multicellular species and instigate both beneficial and harmful infections.

70 elanocyte death in vitiligo is thought to be instigated by a highly pro-oxidant state in the epidermi

71 Instead it appears to be instigated by a substantial drop in cellular NADPH, whic

72 Reduction in ChAT activity instigated by AbetaOs may thus be a relevant event in ea

73 Allograft rejection can thus be instigated by activated platelets through CD154.

74 ich MMR proteins convert single-strand nicks instigated by activation-induced cytidine deaminase (AID

75 Class switch recombination (CSR) is instigated by activation-induced cytidine deaminase, whi

76 series of events that we demonstrate can be instigated by an LPS-negative pathogen in the absence of

77 , BrxU undergoes a multi-step reaction cycle instigated by an unexpected ATP-dependent shift from an

78 revealed that augmentation of renal fibrosis instigated by AT1 receptor-deficient macrophages is medi

79 es a nexus between TLR ligation and fibrosis instigated by binding of anti-Ro Abs to the target prote

80 athway requires Syk activity and Ca(2+) flux instigated by CD14/TLR4-mediated LPS internalization.

81 While continuing its meteoric rise instigated by constant technological refinements and con

82 conductive pathway to remove chips possibly instigated by excess Ca(2+) at the boring site.

83 the ALS-like phenotype of SOD1(G93A) mice is instigated by expression of the mutant SOD1, we show the

84 gation, the misfolding process is frequently instigated by flanking domains.

85 by skill, fast behavior in novices is likely instigated by high stress levels, at the expense of accu

86 ifying that auto-inhibition is paradoxically instigated by incipient auto-phosphorylation.

87 Unlike circuits instigated by individual factors, efforts to identify ge

88 rception of entire visual scenes that can be instigated by interocular conflict.

89 s mechanistic insights into the cytotoxicity instigated by KP372-1 and lays an essential foundation t

90 the core of chronic vascular disease that is instigated by leukocytes and can be targeted therapeutic

91 al processes, and such networks are commonly instigated by master regulators for development.

92 Such networks are commonly instigated by master regulators of development.

93 s an aberrant epithelial barrier that can be instigated by microbial toxins, environmental insults, o

94 the interleukin-2 (IL-2) and IL-6 production instigated by ODN D19 exposure was blocked.

95 osis is a proinflammatory form of cell death instigated by pore-forming toxins such as S. pneumoniae

96 AN(et)) mitigates photoreceptor degeneration instigated by protein misfolding in a mouse model of ret

97 murine tumours exhibit PTEN loss of function instigated by reduced PTEN mRNA, and increased phosphory

98 id increases in sediment flux and discharge, instigated by regional vegetation overturn and enhanced

99 allow the RPE to integrate multiple signals instigated by shed POS at different stages of the phagoc

100 is likely that this sustained activation is instigated by signal transduction occurring specifically

101 te under a general base catalysis mechanism, instigated by the beta-phosphonium enoate alpha-vinyl an

102 of Col108 in which the axial periodicity is instigated by the built-in sequence periodicity and stab

103 pulations declined between 1492 and 1900 CE, instigated by the European colonization of the Americas.

104 Melioidosis, instigated by the Gram-negative bacterium Burkholderia p

105 DNTF can be instigated by the insertion of a telomere repeat array (

106 major changes to the clinical trial process instigated by the pandemic and suggest ways to make thes

107 V(D)J recombination is instigated by the recombination-activating proteins RAG1

108 y within the H3K36me3-containing nucleosome, instigated by the Tudor binding to H3K36me3, is dramatic

109 Surface nucleation appears to be instigated by these [Cdx (CH3 CO2 )y (C5 H7 N2 /C5 H8 N2

110 Furthermore, the G1 arrest instigated by these DP-1 mutants could be rescued by coe

111 s disease (AD) is increasingly thought to be instigated by toxic oligomers of the amyloid beta peptid

112 omises the initiation and maintenance of EMT instigated by various signaling pathways, including Snai

113 Either guided and instigated by, or independent of, the results of gene in

114 -induced IL-12p70, whereas the same pathogen-instigated C5aR-TLR2 crosstalk upregulates other inflamm

115 ortunities for exploration and learning that instigate cascades of development across diverse psychol

116 breaching of a rock dam at the Dover Strait instigated catastrophic drainage of a large pro-glacial

117 However, the upstream signaling events that instigate CCF formation remain unknown.

118 development establishes a genetic network to instigate cell-type-specific autophagy.

119 erturbation of chloride homeostasis in cells instigates cell death by inducing the caspase-mediated i

120 This hitherto unknown trigger for instigating cellular differentiation in a distinctive ma

121 ible individuals, the type I IFN pathway can instigate certain features of SS.

122 evel cultural systems, with the potential to instigate change in these systems over time.

123 Concurrently, p53 loss instigated chromosomal rearrangements linked to LINE seq

124 nd harboring proteobacteria can drive and/or instigate chronic colitis.

125 Some lipids are involved in instigating chronic inflammatory diseases, and new studi

126 brin clot, which could explain how protamine instigates clot lysis and increases bleeding after surge

127 loud activity generated planetary waves that instigated cloud activity at other latitudes across Tita

128 ng 3 (NLRP3) and caspase-1 with caspase-8 in instigating cmo However, the signaling components upstre

129 Our data indicate that STING instigates cytoplasmic DNA-mediated cellular defense gen

130 ial and behavioral factors are also known to instigate depression.

131 fic role for IL-1beta, but not IL-1alpha, in instigating dermatitis in Sharpin(cpdm) mice.

132 ory response in vitro and in vivo, which can instigate development of pulmonary hypertension.

133 The specific IL-1 cytokine instigating development of FMF and the enzymatic caspase

134 el system, the pathobiont Helicobacter bilis instigates disease following sub-pathological dextran su

135 the core affect of threat, disgust and fear instigate distinct response profiles, providing novel in

136 the RPC has fast exchange of the bitterness-instigating diterpene of Reb A into the binding sites of

137 However, how ribonucleotides instigate DNA damage is poorly understood.

138 not exclusive to immunoglobulin loci; it can instigate DNA lesions in non-immunoglobulin genes and th

139 activation-induced cytidine deaminase (AID)-instigated DNA double-strand breaks into the IgH loci.

140 During CSR, AID instigates DNA double-strand break (DSB) formation in sw

141 Activation of PKR by hPNPase(old-35) also instigates down-regulation of the antiapoptotic protein

142 Ca(2+)(o) also instigates E-cadherin-mediated cell-cell adhesion, which

143 diet accelerates endothelial senescence and instigates endothelial inflammation.

144 To identify the true instigating event of GAPDH misfolding, we mapped the pos

145 Signals that instigate Eya1 oncogenic activities remain to be determi

146 "Spontaneous" perforation in CC, in which no instigating factor is identified, is even less common, w

147 monocyte-derived tissue factor are important instigating factors driving the thrombotic, inflammatory

148 ered germline mutations in single genes that instigate familial MDS/AML.

149 ent-stimulation also has drive-like effects, instigating feeding, copulation, predation, and other mo

150 This observation instigated further genetic screening for prostacyclin re

151 We propose that GATA-1 instigates GATA-2 repression by means of disruption of p

152 -of-function strategies to define the GATA-2-instigated genetic network in human endothelial cells.

153 Spontaneous DNA breaks instigate genomic changes that fuel cancer and evolution

154 This can instigate genomic instability resulting from a gain or l

155 t single-stranded nicks, producing ends that instigate genomic instability.

156 lly accumulate, but subsequently resolve, L1-instigated genotoxic threats independent of piRNAs and d

157 pro-inflammatory cytokines such as TNF-alpha instigate gradual suppression of MITF expression through

158 rated by nitric oxide and superoxide anions, instigates GTPCH1 ubiquitination and degradation.

159 Mutational sensitization to stress that instigates hematopoietic failure constitutes a paradigm

160 g389 variant predisposes to heart failure by instigating hyperactive signaling programs leading to de

161 such as anti-dsDNA and anti-histone Abs, can instigate I/R injury and suggest that they are involved

162 -13Ralpha1) expressed on dendritic cells and instigates IL-12 downregulation.

163 another mechanism by which MPK4 may rapidly instigate immune responses.

164 suggests a novel function of p30, which may instigate immune tolerance by reducing activation of ada

165 terns (PAMPs) are known to be fundamental in instigating immune responses, but their role in influenc

166 urther decontamination procedures need to be instigated in sterile-service departments (SSDs) to redu

167 A community annotation project has been instigated in which acknowledged experts are invited to

168 meres represent genomic hazards, as they can instigate inappropriate repair reactions.

169 he infection process takes 1-2 days, the PFP-instigated infection process is irreversibly established

170 he ability to infiltrate various tissues and instigate inflammation.

171 , our findings demonstrate that a pathobiont instigates inflammation without being the primary target

172 indicate that IKKbeta is an IRF5 kinase that instigates inflammation.

173 e receptor 5 (TLR5) recognition of flagellin instigates inflammatory signalling.

174 study was to test whether higher 5-HT levels instigate inhibition specifically in the face of errors,

175 social pressures and societal developments, instigated initial eastward exploration, resulting in SC

176 ns of macrophage Nrp1 in high-fat diet (HFD)-instigated insulin resistance in vivo.

177 ndicating that Nrp1 reduction in macrophages instigates insulin resistance by increasing macrophage N

178 Moreover, angiotensin II infusion instigated interferon-gamma, which induced the expressio

179 areas, such that the accumulation process is instigated, is not well understood.

180 ell death(1,2); however, how inflammation is instigated, its cellular and molecular mediators, and it

181 ring CSR or inhibited from accessing the AID-instigated lesions, or whether the numerous AID-initiate

182 y several factors, including an inability to instigate long-term effective functional antitumor immun

183 ment of C. elegans with Cry5B PFP is able to instigate many other Bacillus species, including B. anth

184 entanglement convolutes understanding of the instigating mechanism.

185 now thought that early-stage biomarkers that instigate memory loss are composed of Abeta oligomers.

186 ways activated by extracellular signals that instigate migration are mostly undefined in smooth muscl

187 osine triphosphate (GTP)-Rab7 effectors that instigate minus end-directed microtubule transport.

188 The discovery of instigating molecular toxicities or disease progression

189 adenine nucleotides and phosphorylation may instigate movement of lipoyl domain-held kinase to a new

190 ergo significant conformational changes that instigate movement of the EF helix-loop region and make

191 stablish a conserved mechanism in which NK-B instigates multiple activities that collectively oppose

192 Activation-induced cytidine deaminase (AID) instigates mutations and DNA breaks in Ig genes that und

193 The resulting mTOR activation instigates MZ B-cell proliferation, immunoglobulin G (Ig

194 k regulation of tissue inflammation that may instigate NAFLD severity.

195 blood supply through end plate changes could instigate NC disappearance.

196 have been shown to have an important role in instigating neuronal degeneration.

197 d alone did not disrupt barrier integrity or instigate neutrophil trans-epithelial migration without

198 ells and sera of patients with breast cancer instigate nontumorigenic epithelial cells to form tumors

199 Nitroalkenes react with Keap1 to instigate Nrf2 signaling, activate heat shock response g

200 We conclude that the HFD-instigated Nrp1 reduction in macrophages exacerbates ins

201 blastoma cells increased ATM phosphorylation instigating nuclear translocation and increased gamma-H2

202 studies have shown a mechanism for HTRA1 to instigate ocular tissue abnormalities.

203 nhancer elements, including super-enhancers, instigating oncogenic activity.

204 Ca(2+) binding instigates opening of the neck through allosteric means

205 cts of avoidance, but their contributions to instigating or suppressing actions remains to be clarifi

206 lite to control tolerance and immunity or to instigate pathology.

207 anisms and biological pathways by which TLR9 instigates periodontal inflammation are yet to be identi

208 o determine whether this microbial imbalance instigates perturbation of the host intestinal mucosal i

209 short-term PEMF treatment was sufficient to instigate PGC-1alpha-associated transcriptional cascades

210 o be used as weapons of mass destruction and instigate population-based fear.

211 These results indicate that both models instigated post-ischemic vascular structural changes.

212 ensing role of the vascular endothelium that instigates postprandial VAT inflammation.

213 ssociated neurocognitive disorders (HAND) by instigating primary dysfunction and subsequent death of

214 low to the high-carbohydrate diet, which if instigated prior to the development of HCC, resulted in

215 ation permitted IP(3)RII levels to increase, instigating pro-hypertrophic calcium signaling and conco

216 production trigger marrow vessel leakiness, instigating pro-leukemic function.

217 ed that the process of meiotic recombination instigates programmed activation of p53 in the germ line

218 a disease is diagnosed, the first step is to instigate protective measures to prevent further degener

219 in the bone microenvironment necessitate and instigate rapid and temporal changes in gene expression

220 lready developed efficient networks that can instigate rapid response and consensus when key elements

221 t reduced Smn levels induce SMA pathology by instigating rapidly progressive neurodegenerative pathwa

222 Although mechanisms that instigate rDNA recombination have been identified, none

223 merase backtracking promotes break repair by instigating RecA loading by RecBCD, without the influenc

224 heterotypic fibroblasts, which subsequently instigate reciprocal signaling in the tumor cells.

225 Both warming and acidification instigate reduced calcification in tropical and temperat

226 genic rewiring by transduction of (V12)HaRas instigates regulation of RhoA-ROCK signalling through an

227 armacological agents that target CK2 and PKA instigated relocalization of endogenous APC.

228 fetal trophoblast invading from the placenta instigate remodeling by triggering cell death in vascula

229 Although immune parameters that instigate renal damage have been characterized, their li

230 Whereas ER-GATA-1-instigated repression abolished the -1.8-kb HS, the -3.9

231 nserved C-4 type ZF family of viral proteins instigate reprogramming of plant development by mimickin

232 The advent of autonomous self-propulsion has instigated research towards making colloidal machines th

233 o protein-coding genes and could potentially instigate RNA interference (RNAi) responses.

234 ide pervasive transcription is sufficient to instigate RNAi, and propose that pervasive transcription

235 tudy, we report that model RNA, but not DNA, instigated robust cytokine and chemokine production from

236 ate Ub-Rheb, and blockade of its degradation instigates robust lysosomal mTORC1 localization and its

237 est that protein carbonylation plays a major instigating role in cytokine-dependent mitochondrial dys

238 s faithful repair, it is unclear how the AID-instigated S region lesions are converted into DSBs rath

239 anulin (GRN) as the most upregulated gene in instigating Sca1+ cKit- BMCs relative to counterpart con

240 inistration of trichloroethylene for 6 weeks instigated selective complex 1 mitochondrial impairment

241 athways and sensors that are responsible for instigating self-DNA triggered autoinflammatory events i

242 atrix (ECM) and the ECM bound growth factors instigate several signal transducing events that ultimat

243 e glands become infiltrated with lymphocytes instigating severe damage to the salivary and lacrimal g

244 he largest family of membrane receptors that instigate signalling through nucleotide exchange on hete

245 preventing responsiveness to erythropoietin-instigated signals that promote differentiation.

246 preparations for human health should also be instigated, since they can suppress hyperglycemia and in

247 e possibility of a recent progenitor of WPV1 instigating single-source transmission across the countr

248 -1beta, both of which signals through IL-1R, instigates skin inflammation and systemic disease is not

249 le or unwilling to stop smoking, they should instigate smoke-free homes.

250 The findings newly implicate ischemia-instigated spine turnover as a mediator of cortical syna

251 lts indicate that RT interacts with ischemia-instigated spine turnover to promote preferential stabil

252 reflect, in part, interactions with ischemia-instigated spine turnover.

253 tated into negatively charged glutamic acids instigates spontaneous bona fide receptor activator of N

254 al state of the track does not automatically instigate stepping in the absence of an additional stimu

255 tify a mechanism in which climate change can instigate surges of Arctic tidewater glaciers.

256 ad receded into a deepening proglacial lake, instigating sustained calving losses and more rapid ice

257 t accumulate in AD brains and are thought to instigate synapse damage and memory loss, induce depress

258 of subunit vaccine history as it pertains to instigating T cell responses.

259 otein-coupled receptor (GPCR) kinases (GRKs) instigate the desensitization of activated GPCRs via pho

260 ment, in the form of brain somatic mutations instigate the disease.

261 that in RAW macrophages TLR2 is essential to instigate the early immune response to OmpA via NF-kappa

262 tunity for the active enhancer to locate and instigate the expression of Shh.

263 Here, we find that human breast carcinomas instigate the growth of otherwise-indolent tumor cells,

264 through which stressed and dead hepatocytes instigate the profibrogenic crosstalk with HSC and macro

265 The rods may instigate the vascular abnormalities that are the clinic

266 These limitations instigated the development of supramolecular platforms t

267 mosphere of Titan; this observation likewise instigated the study of fundamental chemical processes i

268 Tissue factor (TF) instigates the extrinsic pathway of blood coagulation.

269 rotein pathology in the medial temporal lobe instigates the loss of episodic memory in Alzheimer's di

270 actor but, instead, colocalizes with Bim and instigates the mitochondrial, or intrinsic, death pathwa

271 alculations suggest that a B...F interaction instigates the reaction chemistry, the magnitude of whic

272 These data suggest that CLA instigates the release of inflammatory signals from adip

273 eceptors to novel downstream molecules or by instigating their degradation.

274 to resolve conflicts of interest, as well as instigate them.

275 certain whether metabolic derangements might instigate this arrhythmia.

276 The binding of ATP provides the signal to instigate this change, while release of phosphate post-A

277 nto nonphagocytic cells; however, the events instigating this process are incompletely understood.

278 icion, particularly in the acute setting, to instigate timely coordination of appropriate care and ma

279 ptional high mortality of lung cancer can be instigated to a high degree by late diagnosis.

280 Consequently, these studies were instigated to identify sequences within the primary RNA

281 mperative to ensure appropriate measures are instigated to reduce associated morbidity and mortality.

282 -bound ePAB also interacts with eIF4G, which instigates translation initiation of CPEB-bound mRNAs.

283 d binding promotes receptor dimerization and instigates transmembrane signaling and receptor kinase a

284 o initiate appropriate investigations and to instigate treatments that could dramatically improve pat

285 Furthermore, instigating tumor infiltration by T cells sensitized tum

286 Aneuploidy can instigate tumorigenesis.

287 We find that BMCs of hosts bearing instigating tumors are functionally activated prior to t

288 Secretion of osteopontin by instigating tumors is necessary for BMC activation and t

289 t- hematopoietic BMCs of mouse hosts bearing instigating tumors promote the growth of responding tumo

290 vel by endocrine factors released by certain instigating tumors, and hold important experimental and

291 BMCs mimic the systemic effects imparted by instigating tumors.

292 Also, we instigate two different directions of utilizing the carb

293 Upregulation of IL33 instigated type 2 inflammation in the metastatic microen

294 , autoimmunity and transplant rejection, DCs instigate unwanted responses that cause disease, but, ag

295 eeking, but their respective contribution in instigating versus suppressing actions in aversive conte

296 , rather than all cells within a tumour, may instigate VM, supplant host-derived endothelium, and for

297 the propensity for surface-reaching holes to instigate water-splitting chemistry by serially applying

298 pecific CD8(+) T cell populations, which may instigate ways to augment therapies depending on fit CD8

299 d destabilize TCP transcription factors, but instigated weaker changes in leaf morphogenesis than wil

300 infection of neurons, but, as a consequence, instigates ZIKV-associated paralysis.