ライフサイエンスコーパス: multifunctional

1 codes relatively few proteins that are often multifunctional.

2 strate, making the 2D-Xene systems promising multifunctional 2D materials for nanotechnology.

3 ature provides the feasibility for designing multifunctional 2D optoelectronic devices.

4 Here, a multimaterial, multiscale, and multifunctional 3D printing approach is employed to fabr

5 Gelsolin, a multifunctional actin-binding protein, mediates cell dea

6 "smart" is used here to refer to switchable, multifunctional, adaptable, or tunable ligands and, in g

7 ted signaling but also signaling through the multifunctional adapter protein beta-arrestin.

8 p62/sequestosome-1 (SQSTM1) is a multifunctional adaptor protein and autophagic substrate

9 oubiquitination, and by association with the multifunctional adaptor protein beta-arrestin2.

10 amily of intracellular proteins are dimeric, multifunctional adaptor proteins that bind to and regula

11 Poly(rC)-binding proteins are multifunctional adaptors that serve as iron ion chaperon

12 polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellul

13 of promiscuity result from sharing a common multifunctional ancestor.

14 identified open reading frame 52 (ORF52), a multifunctional and abundant tegument protein, as being

15 cidic auxiliary groups, the complexes become multifunctional and catalyze the cis-selective hydrogena

16 ys a key role in the emerging AM of advanced multifunctional and multimaterial systems including livi

17 s an emerging and powerful method to develop multifunctional and tissue responsive nanomedicines for

18 ies provides a feasible approach to generate multifunctional antibodies for therapeutic applications.

19 will certainly open a new era of structural-multifunctional application for the conventional 2D coll

20 fness, are reviewed, and their potential for multifunctional applications beyond mechanics is examine

21 s recently discovered and ideal for advanced multifunctional applications.

22 Multifunctional autoprocessing repeats-in toxin (MARTX)

23 tifs (SLiMs), and protein processing promote multifunctional behaviour.

24 Multifunctional beta-catenin, with critical roles in bot

25 Sphingosine 1-phosphate (S1P) is a multifunctional bioactive sphingolipid involved in the d

26 tions with opioid receptors, and result in a multifunctional biochemical phenotype that exerts potent

27 irected immobilization (DDI) of two distinct multifunctional biohybrid gold nanoparticles.

28 ional and three-dimensional architectures as multifunctional biological platforms.

29 characterization of ruthenium complexes with multifunctional bipyridyl diphosphonate ligands as well

30 f aversive tastes, and that are sourced in a multifunctional brainstem central pattern generator.

31 models to demonstrate that expression of the multifunctional BRCT (BRCA1 C-terminal) domain-containin

32 We have developed a novel multifunctional C2-symmetric biphenyl-based diamine-teth

33 The multifunctional Ca(2+)/calmodulin-dependent protein kina

34 tory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced in muri

35 antify changes in secondary structure of the multifunctional calcium-binding messenger protein Calmod

36 these inherent properties of GMs enable its multifunctional capabilities as a bioactive interface.

37 Here, we provide a detailed analysis of the multifunctional carriers designed for different types of

38 work (MOF), UiO-66-NH2 (Pt@UiO-66-NH2 ) as a multifunctional catalyst in the one-pot tandem synthesis

39 nal modeling led to the rational design of a multifunctional catalyst that enables stereoselectivity

40 The heterogeneous synthesis of nitrones with multifunctional catalysts is extremely attractive but ra

41 ion and conversion of CO2 can be achieved on multifunctional catalytic sites available at the metal/o

42 Pleiotrophin (PTN) is a multifunctional, cationic, glycosaminoglycan-binding cyt

43 d interleukin 17 splenic responses, and more multifunctional CD4(+) T cells.

44 The interferon gamma+ (IFN-gamma+) and multifunctional CD4+ T-cell responses were maintained in

45 idual production of IFN-gamma or IL-2, and a multifunctional CD8(+) T cell profile of up to four func

46 is, a wealth of newer data demonstrated that multifunctional CD8(+) T cell responses are instrumental

47 High frequencies of multifunctional CD8(+) T cells directed against three ep

48 have significant potential as an autologous, multifunctional cell therapy for stroke, which is the pr

49 Eosinophils are multifunctional cells of the innate immune system linked

50 Macrophages are multifunctional cells that perform diverse roles in heal

51 fied by serological screening are targets of multifunctional cellular immune responses that correlate

52 new ways to scalable fabrication of advanced multifunctional ceramic composites with controllable des

53 al devices, also enabling the realization of multifunctional chemical sensors, in which multiple tran

54 the metal's selectivity for hydrogenation of multifunctional chemicals.

55 reospecific transformations of the resulting multifunctional chiral building blocks highlight the pot

56 Both are multisubstrate and multifunctional clade III enzymes, which catalyze consec

57 The resulting multifunctional classification describing the severity,

58 Multifunctional composite materials are currently highly

59 This emerging class of soft multifunctional composites have potential applications i

60 Natural products comprise a palette of multifunctional compounds with which to address this que

61 Herein, we report a scalable synthesis of multifunctional conducting polyacrylic acid (PAA) hydrog

62 etamaterial as a transformative platform for multifunctional control.

63 A multifunctional core-satellite nanoconstruct is designed

64 TGF-beta is a multifunctional cytokine affecting many cell types and i

65 The nature of this multifunctional cytokine has limited the development of

66 IL-27, a multifunctional cytokine produced by APCs, antagonizes i

67 ss this challenge with an organic electronic multifunctional device that is capable of chemical stimu

68 n-pairing compounds through the miniaturized multifunctional device, the single-probe, for reactive M

69 evelopment of methods for the 3D printing of multifunctional devices could impact areas ranging from

70 al-time manipulation of light and serving as multifunctional devices in near-infrared frequency regim

71 A key requirement in realising multifunctional devices is the need to understand and co

72 ir potential in constructing next-generation multifunctional devices.

73 -related modifier) ligase ZATT (ZNF451) is a multifunctional DNA repair factor that controls cellular

74 the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO,

75 On the other hand, development of multifunctional drug carriers at the 'nano'-scale is pro

76 e have developed a folate receptor-targeting multifunctional dual drug-loaded nanoparticle (MDNP) con

77 A multifunctional dual-channel scanning probe nanopipet th

78 nd delivered to the oral cavity by a complex multifunctional ductal system.

79 a simple and rapid approach for fabricating multifunctional e-textiles by integrating conductive two

80 nd mu receptors and yield very high affinity multifunctional (e.g. 12) or highly selective (e.g. 16)

81 ropic activities of a ubiquitously expressed multifunctional E3 ubiquitin ligase.

82 romising approach towards rational design of multifunctional, elastic SEIs that overcome the most ser

83 The development of a multifunctional electrocatalyst composed of nitrogen, ph

84 Au@NC is a multifunctional electrocatalyst, which demonstrates high

85 l recovery of precious Au and fabrication of multifunctional electrocatalysts in an environmentally b

86 The multifunctional electrocatalytic activities originate fr

87 The key component is a multifunctional electrode; light passes through this ele

88 mitochondrial respiratory chain can act as a multifunctional electron sink for reductant from cytosol

89 -dependent quantum-confinement properties in multifunctional electronic and optoelectronic devices.

90 Stretchable and flexible multifunctional electronic components, including sensors

91 Development of multifunctional electronic textiles (e-textiles) with th

92 ectronics has nourished progress in building multifunctional energy-storage systems that can be bent,

93 oaded in a nanoparticle with siRNA (YSK12-C4 multifunctional envelope type nano device [YSK12-MEND]),

94 To address this need, a multifunctional enzymatic amplification reactor that com

95 1 or sterol 27-hydroxylase) is a ubiquitous, multifunctional enzyme catalyzing regio- and stereospeci

96 ridoxal 5'-phosphate (PLP) is a fundamental, multifunctional enzyme cofactor used to catalyze a wide

97 trates the evolutionary conservation of this multifunctional enzyme family.

98 RecBCD is a multifunctional enzyme that possesses both helicase and

99 Human tissue transglutaminase (hTG2) is a multifunctional enzyme.

100 somerase (hPDI), is an essential four-domain multifunctional enzyme.

101 t the comparatively weak activities of these multifunctional enzymes are each physiologically relevan

102 e-diphosphate-kinases (NDKs) are leaderless, multifunctional enzymes.

103 ding protein 2 (MECP2) gene, which encodes a multifunctional epigenetic regulator with known links to

104 Therefore, multifunctional exosomes with combined diagnostic and th

105 The multifunctional Eya1 protein plays important roles durin

106 onstrated great potential as a multimaterial multifunctional fabrication method in areas as diverse a

107 a striking cupped ring structure containing multifunctional FHV RNA replication protein A.

108 The multifunctional fibrillar adhesin CshA, which mediates b

109 realised potential for management to promote multifunctional forests.

110 l (3), a new nitronyl nitroxide containing a multifunctional framework of strong electron-withdrawing

111 novation, future autonomous, intelligent and multifunctional fuel-free micro-/nanomachines are expect

112 MeaB is a multifunctional G-protein chaperone, which gates loading

113 ne receptor alpha 1 and alpha 2 subunit, the multifunctional gene vitellogenin, immune system genes a

114 We show that heavily annotated ('multifunctional') genes are likely to appear in genomics

115 The usefulness and value of a multifunctional global laboratory database is far reachi

116 The key to the chemistry is multifunctional guanidinylated peptide-based ligands tha

117 omain 2 of NS5A (NS5A-D2), another essential multifunctional HCV protein that is required for RNA rep

118 e-pot synthesis of nitrones using recyclable multifunctional heterogeneous catalysts.

119 Therapeutic and diagnostic multifunctional HNPs conjugated with anti-MG1 monoclonal

120 ect a highly promising strategy to designing multifunctional hybrid materials/systems is to combine b

121 The LuPc2 was then doped to form multifunctional hydrogel (PAA-rGO/VS-PANI/LuPc2-MFH).

122 The protein NUPR1 is a multifunctional IDP involved in chromatin remodeling and

123 h dsDNA was prevented by expressing the HCMV multifunctional IE1 transactivator.

124 c)-chain cytokine interleukin 15 (IL15) is a multifunctional immune-modulator which impacts the gener

125 g potential as a strategy for development of multifunctional ingredients targeting metabolic syndrome

126 Macrophages are multifunctional innate immune cells that seed all tissue

127 ed 3D structure, enabling the fabrication of multifunctional inorganic-carbon-polymer hybrid 3D mater

128 ttice film can find applications as a robust multifunctional insulating film that can be applied in i

129 e surfaces evolutionarily modified to act as multifunctional interfaces that must contend with a host

130 1.1-dicyanomethylene-3-indanone (IDIC), as a multifunctional interlayer, which combines efficient tra

131 cleotidyltransferase (PRNTase) domain of the multifunctional L protein of rhabdoviruses, such as vesi

132 e that has been studied as a transformative, multifunctional land-use solution.

133 d composition control is vital for designing multifunctional lanthanide-doped core/shell nanocrystals

134 Eosinophils are now recognized as multifunctional leukocytes that provide critical homeost

135 We designed and synthesized multifunctional ligands characterized in vitro as high-a

136 ew class of guanidine-containing peptides as multifunctional ligands for transition-metal catalysis a

137 Here we introduce multifunctional lipid derivatives to study lipid metabol

138 FcepsilonRII is a multifunctional low-affinity IgER that is involved in th

139 ehavior opens new possibilities for creating multifunctional magnetic and spintronic devices which ca

140 irpin probe (HP) with 3'-phosphoryl, forming multifunctional magnetic probes (HP-MBs).

141 ion of T4 PNK activity has been developed by multifunctional magnetic probes and polymerization nicki

142 Multifunctional materials and devices may lead to a para

143 In solid state science, multifunctional materials and especially multiferroics h

144 Multifunctional materials composed of ultrathin magnetic

145 In recent years, multifunctional materials contained simultaneous ferroel

146 applications in polymer science, geophysics, multifunctional materials, and other areas.

147 provide access to a new generation of smart, multifunctional materials, coatings, and surfaces.

148 ersatile platform for the rational design of multifunctional materials, combining large specific surf

149 Despite remarkable progress in developing multifunctional materials, spin-driven ferroelectrics fe

150 of CNT and graphene, for developing advanced multifunctional materials.

151 ets enables a range of new opportunities for multifunctional materials.

152 hese findings define DEK as an important and multifunctional mediator of HR, and establish a syntheti

153 erived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase inhibito

154 We propose that mammalian retromer forms a multifunctional membrane coat that supports shared cargo

155 contrary to predictions, recently discovered multifunctional metal/metal oxide catalysts (e.g., Rh/Re

156 ant needs to develop renewable, scalable and multifunctional methods for the fabrication of 3D carbon

157 Pentraxin 3 (PTX3) is a multifunctional molecule that plays a nonredundant role

158 In photopolymerization reactions, mostly multifunctional monomers are employed, as they ensure fa

159 that this approach could allow manufacturing multifunctional multimodal LSPR chips for multiplexed an

160 onomical" strategy in the rational design of multifunctional nano-theranostic systems for real-time s

161 ugated gold nanorod (GNR) was developed as a multifunctional nanocarrier for targeted, pH-and near in

162 A 2D multifunctional nanocomposite system of gold nanorods (A

163 As a result, this new DNA-GNR based multifunctional nanomedicine exerted greatly increased p

164 surface to complete the construction of the multifunctional nanomedicine.

165 This multifunctional nanoparticle retains its strong near-IR

166 Multifunctional nanoparticles for biomedical application

167 We have developed multifunctional nanoparticles for codelivery of bortezom

168 ultaneous detection of two proteins by using multifunctional nanoparticles with a magnetic immunoassa

169 Top-down lithographic methods can produce multifunctional nanoparticles with precise size and shap

170 Here, we demonstrate that multifunctional, nanoscale catalysts that enable high-pe

171 lid tumors either through the engineering of multifunctional nanosystems or through manipulation of b

172 OF NPs in a self-assembly process generating multifunctional nanosystems.

173 et) of ATXR5 up to 58-fold, highlighting the multifunctional nature of ATXR5 PHD domain.

174 mproves, we will undoubtedly uncover how the multifunctional nature of these HIV-1 regulatory and acc

175 ssibility that HIV-1 proteins leverage their multifunctional nature to alter host transcriptional net

176 Despite the recent development of multifunctional neural probes, integration of these moda

177 Herpes simplex virus 1 (HSV-1) encodes the multifunctional neurovirulence protein ICP34.5.

178 novel mechanism of generating specificity in multifunctional NGF signaling.

179 is result shows the possibility of obtaining multifunctional nitronyl nitroxides via the interaction

180 The multifunctional nonstructural protein 1 (NS1) is the mai

181 n an interaction of capsid proteins with the multifunctional nonstructural protein 2C(ATPase) In this

182 Previous studies have suggested that multifunctional nonstructural proteins encoded by flaviv

183 self-assembly approach for the generation of multifunctional NPs and future biological applications.

184 at flexibility for the targeted synthesis of multifunctional NPs for specific purposes.

185 Although multifunctional NPs theoretically have many desirable pr

186 Here, we describe the first example of a multifunctional nucleoside probe, containing a conformat

187 ic reward circuitry and pain pathways with a multifunctional opioid agonist-NK1R antagonist may be an

188 duction, make these materials attractive for multifunctional optoelectronic, electron transfer sensin

189 binding selectivity, enabling the design of multifunctional or selective opioid ligands from such sc

190 ration of multiple nanoscale components into multifunctional ordered nanostructures are extensively e

191 Highly oxygenated multifunctional organic compounds (HOMs) originating fro

192 elds of highly oxidized compounds, including multifunctional organosulfates (OSs) and hydroperoxides,

193 mesoscale quantum phenomena and engineering multifunctional oxide devices.The properties of complex

194 The excavation data document a multifunctional palace complex covering a maximum estima

195 palace complex at El Palenque is the oldest multifunctional palace excavated thus far in the Valley

196 atory syndrome coronavirus (MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have t

197 Each MFC was fabricated by sandwiching multifunctional paper layers for two-chambered fuel cell

198 e to their interesting physics and promising multifunctional performance.

199 pens up a new method for using DNA to create multifunctional periodic biomaterials with tunable optic

200 The contemporary growth of state-of-the-art multifunctional perovskites in the field of light-signal

201 Taken together, this multifunctional platform is expected to enable seamless

202 thin film technologies in order to develop a multifunctional platform suitable for on-chip thermal tr

203 methodology used here is built upon a highly multifunctional platform that offers numerous advantages

204 , this novel class of potentially widespread multifunctional polarity regulators is deeply embedded i

205 ppressor of Hairy-wing [Su(Hw)], an exemplar multifunctional polydactyl ZF protein.

206 diated cascade reaction for the synthesis of multifunctional polyheterocyclic systems is developed by

207 ld nanorods (GNRs) are being investigated as multifunctional probes for a range of biomedical applica

208 due to their intrinsic few-nanometre width, multifunctional properties and field-controlled topology

209 or favorable delivery, while maintaining the multifunctional properties of the siRNAs for combined th

210 ic (NAC), the GCM demonstrates a sequence of multifunctional properties simultaneously that have not

211 des are well known for their nutritional and multifunctional properties.

212 As PGE2 is a multifunctional prostanoid with diverse roles in respira

213 en well studied is aminopeptidase N (APN), a multifunctional protease known to cleave biologically ac

214 hosphatase nonreceptor type 12 (PTPN12) is a multifunctional protein and has elicited much research a

215 We sought to determine whether Apc, a multifunctional protein and key negative regulator of th

216 The multifunctional protein arginine methyltransferase 8 (PR

217 known as annexin II light chain, S100A10), a multifunctional protein binding to 5-HT receptors, in la

218 The multifunctional protein cytochrome c (cyt c) plays key r

219 tency-associated nuclear antigen (LANA) is a multifunctional protein encoded by members of the Rhadin

220 low levels of survival motor neuron (SMN), a multifunctional protein essential for higher eukaryotes.

221 SHARPIN is a widely expressed multifunctional protein implicated in cancer, inflammati

222 Here we show that in LHb neurons, p11, a multifunctional protein implicated in depression, is sig

223 p62/Sqstm1 is a multifunctional protein involved in cell survival, growt

224 d to encapsulate viral RNA, and it is also a multifunctional protein involved in the regulation of ho

225 Our findings show that FXR1 is a multifunctional protein involved in translational regula

226 It is an evolutionary conserved multifunctional protein localized primarily in the mitoc

227 Recently, the 54-kDa multifunctional protein NONO was found to be involved in

228 The multifunctional protein p62 is associated with neuropath

229 t GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNFalpha signaling an

230 our data establish novel roles for SNX9 as a multifunctional protein scaffold that regulates, and pot

231 Both viruses produce a multifunctional protein termed VP35, which acts as a pol

232 luenza virus NS1 protein is a nonstructural, multifunctional protein that counteracts host innate imm

233 a A virus nucleoprotein (NP) is an essential multifunctional protein that encapsidates the viral geno

234 High-mobility group box 1 (HMGB1) is a multifunctional protein that exerts proinflammatory acti

235 r (NSF) attachment protein (alpha-SNAP) is a multifunctional protein that participates in SNARE-media

236 HMGB1 is a ubiquitous redox-sensitive multifunctional protein that serves as both a DNA regula

237 suppressed), we hypothesize that Tic40 is a multifunctional protein that, in addition to its origina

238 However, since Srs2 is a multifunctional protein with helicase activity and the a

239 (CoV) nonstructural protein 14 (nsp14) is a multifunctional protein with N7-methyltransferase (N7-MT

240 GRP78, a multifunctional protein with potent cytoprotective prope

241 RAD51, a multifunctional protein, plays a central role in DNA rep

242 colysis enzyme but actually a quintessential multifunctional protein, translocates to the unique cort

243 Thus, CrPV-1A is a multifunctional protein.

244 lls (GCs) in ovarian physiology, the role of multifunctional proteins able to simultaneously coordina

245 These multifunctional proteins are involved in the formation o

246 A motif function in the context of the large multifunctional proteins in which they are embedded.

247 Members of the DEAD-box family are often multifunctional proteins involved in several RNA transac

248 Multifunctional proteins play a variety of roles in meta

249 izosaccharomyces pomberepresents a family of multifunctional proteins that bind to specific terminato

250 es with limited genetic content often encode multifunctional proteins that function at multiple stage

251 uccessful infection, viruses usually produce multifunctional proteins to coordinate the counteraction

252 kanes with mass yields up to 28.1 wt% over a multifunctional Pt/NbOPO4 catalyst in cyclohexane.

253 and DNA maintenance, establishing Nol12 as a multifunctional RBP essential for genome integrity.

254 Here, we describe Nol12 as a multifunctional RBP with roles in RNA metabolism and gen

255 y available terpenoid scaffolds as efficient multifunctional reagents for the direct primary aminatio

256 oles for the MET receptor tyrosine kinase, a multifunctional receptor that mediates distinct biologic

257 n (LDL) Receptor-related Protein-1 (LRP1), a multifunctional receptor which mediates trafficking of c

258 e adaptor protein Bicaudal-D2 (BicD2) or the multifunctional regulator Lissencephaly-1 (Lis1).

259 Gle1 is a multifunctional regulator of DBPs with roles in mRNA exp

260 nclusion, the tandem WH2 domains of SALS are multifunctional regulators of actin dynamics.

261 polymerases, most eukaryotic cells contain a multifunctional replicative enzyme called primase-polyme

262 identified vigilin, a ubiquitously expressed multifunctional RNA-binding protein.

263 n's syndrome antigen B [SSB]) is an abundant multifunctional RNA-binding protein.

264 We conclude that alpha-4-1BB has a multifunctional role for enhancing CAR T-cell responses

265 In the current study, we identify the multifunctional scaffolding protein spinophilin as a nov

266 , as a simple one-step approach, to generate multifunctional scaffolds with previously unattainable b

267 This work provides a new direction for multifunctional self-powered textiles with potential app

268 Hybrid perovskites, as emerging multifunctional semiconductors, have demonstrated dual e

269 Long, multifunctional sequence-defined oligomers were obtained

270 Activated protein C (APC) is a multifunctional serine protease with anticoagulant, cyto

271 ily of phosphatases, PP2A, PP4, and PP6, are multifunctional serine/threonine protein phosphatases in

272 The conserved multifunctional shelterin complex associates with telome

273 This suggests that STIM1 is a multifunctional signaling effector that participates in

274 vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which

275 ssues and organs with amazing resilience and multifunctional smart properties.

276 Here, we report the fabrication of multifunctional, smart nanoparticle systems by combining

277 Multifunctional smHSSs integrated with proteins, fluores

278 Nanoscale protein ionic liquids represent multifunctional solvent systems that are well suited to

279 NQO1 is a FAD-dependent, two-domain multifunctional stress protein acting as a Phase II enzy

280 The centriole is a multifunctional structure that organizes centrosomes and

281 Flap endonuclease-1 (FEN1) is a multifunctional, structure-specific nuclease that has a

282 and ultrafast approach for the synthesis of multifunctional submicrometer hollow silica spheres (smH

283 To take first steps towards such a multifunctional surface we propose merging topographical

284 h a dual physicochemical approach to achieve multifunctional surfaces represents a first step in the

285 production of diverse nutrients and viable, multifunctional, sustainable landscapes.

286 idelines for the development of bioinspired, multifunctional systems whose hierarchical structure imp

287 novel findings highlight SYK as a potential multifunctional target in the treatment of alcoholic ste

288 Our findings open a path for multifunctional technologies combing transparent electro

289 PMCS thus represent a novel multifunctional theranostic platform for improved treatm

290 eparation system, these surfaces can be made multifunctional to work simultaneously for oil-water sep

291 transcription factor TFIID that serves as a multifunctional transcriptional regulator.

292 The multifunctional, transmembrane glycoprotein human CD38 c

293 was highly correlated with the induction of multifunctional triple-positive T cells expressing high

294 In this work, we employ a recently developed multifunctional trityl paramagnetic probe and electron p

295 capable of forming monodisperse, stable, and multifunctional unilamellar and multilamellar onion-like

296 Although multifunctional upconversion imaging probes have recentl

297 ults support the further development of this multifunctional vaccine approach for the treatment of sy

298 We propose that CrPV-1A is a multifunctional, versatile protein that creates a cellul

299 with embedded catalytic metals can serve as multifunctional windows for biofilm diagnostic microchip

300 ersatility of this technique in formation of multifunctional wood hybrids can inspire both research a