%PDF-1.4 % 8 0 obj <> endobj 68 0 obj <>stream /Artifact <>BDC q 1 i 0 841.89 595.276 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n 0 0 0 0 k /GS1 gs 0 373.04 595.2 469 re f EMC /Figure <>BDC Q q 1 i -8.504 850.394 603.78 -477.354 re W* n 0 841.89 595.276 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n /GS1 gs q -646.67 0 0 484.662 603.445 369.632 cm /Im1 Do Q EMC /P <>BDC Q q 1 i 0 841.89 595.276 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n /GS2 gs BT /F3 1 Tf 8 0 0 8 42.5196 331.3702 Tm 0 0 0 1 k 0 Tc 0 Tw (The Milking extracellular vesicles for improved infant formula)Tj ET EMC /P <>BDC BT 8 0 0 8 262.6717 331.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5196 319.3702 Tm [(\(MilkEV\) project is a new collaboration between T)71.8(eagasc Moorepark)]TJ ET EMC /P <>BDC BT 8 0 0 8 282.3375 319.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5196 307.3702 Tm [(and T)75.9(rinity College Dublin, which aims to quantify and characterise)]TJ ET EMC /P <>BDC BT 8 0 0 8 280.3363 307.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5196 295.3702 Tm [(extracellular vesicles in Irish cow)54.9(s milk.)]TJ ET EMC /P <>BDC BT 8 0 0 8 180.4482 295.3702 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 42.5196 283.3702 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F4 1 Tf 9 0 0 9 42.5196 271.3702 Tm 0 .68 .9 0 k [(Extr)23.9(acellular v)17.8(esicles)]TJ ET EMC /P <>BDC BT 9 0 0 9 136.185 271.3702 Tm ( )Tj ET EMC /P <>BDC /GS2 gs BT /F3 1 Tf 8 0 0 8 42.5196 259.3702 Tm 0 0 0 1 k (Extracellular vesicles \(EVs\) are small cellular particles composed of a)Tj ET EMC /P <>BDC BT 8 0 0 8 280.0477 259.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5196 247.3702 Tm (lipid membrane encasing proteins and nucleic acids. They are)Tj ET EMC /P <>BDC BT 8 0 0 8 260.6237 247.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5196 235.3702 Tm (released from cells and can be found in all body fluids \(blood, milk,)Tj ET EMC /P <>BDC BT 8 0 0 8 280.1037 235.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5196 223.3702 Tm (sperm\). Initially scientists viewed them as cell debris or as playing a)Tj ET EMC /P <>BDC BT 8 0 0 8 279.3917 223.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5196 211.3702 Tm [(sinister role in cancer)74(. W)39.8(e)0( now know that EVs are secreted in ever)-12(y)]TJ ET EMC /P <>BDC BT 8 0 0 8 276.9373 211.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5196 199.3702 Tm (physiological condition and are a form of cell-to-cell)Tj ET EMC /P <>BDC BT 8 0 0 8 226.4318 199.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5196 187.3702 Tm (communication. This communication can be a health benefit; for)Tj ET EMC /P <>BDC BT 8 0 0 8 272.6957 187.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5196 175.3702 Tm [(example, milk EVs carr)-12(y immune signals from mother to baby)74(.)]TJ ET EMC /P <>BDC BT 8 0 0 8 262.0716 175.3702 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 42.5196 163.3702 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F4 1 Tf 9 0 0 9 42.5196 151.3702 Tm 0 .68 .9 0 k [(Researc)17.8(h question)]TJ ET EMC /P <>BDC BT 9 0 0 9 124.0612 151.3702 Tm ( )Tj ET EMC /P <>BDC /GS2 gs BT /F3 1 Tf 8 0 0 8 42.5196 139.3702 Tm 0 0 0 1 k [(W)39.8(e)0( will track EVs during milk processing and the production of)]TJ ET EMC /P <>BDC BT 8 0 0 8 264.6013 139.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5196 127.3702 Tm (infant milk formula. The project will also seek to answer the)Tj ET EMC /P <>BDC BT 8 0 0 8 252.4877 127.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5196 115.3702 Tm (following questions:)Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 113.5837 115.3702 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F5 1 Tf 8 0 0 8 42.5196 103.3702 Tm 0 .68 .9 0 k ()Tj ET EMC /P <>BDC /GS2 gs BT /F3 1 Tf 8 0 0 8 48.6095 103.3702 Tm 0 0 0 1 k ( what is the composition of milk EVs?;)Tj ET EMC /P <>BDC BT 8 0 0 8 182.3135 103.3702 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F5 1 Tf 8 0 0 8 42.5196 91.3702 Tm 0 .68 .9 0 k ()Tj ET EMC /P <>BDC /GS2 gs BT /F3 1 Tf 8 0 0 8 48.6095 91.3702 Tm 0 0 0 1 k [( can EVs sur)-12(vive processing?;)]TJ ET EMC /P <>BDC BT 8 0 0 8 150.1293 91.3702 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F5 1 Tf 8 0 0 8 42.5196 79.3702 Tm 0 .68 .9 0 k ()Tj ET EMC /P <>BDC /GS2 gs BT /F3 1 Tf 8 0 0 8 48.6095 79.3702 Tm 0 0 0 1 k [( can EVs sur)-12(vive digestion?; and,)]TJ ET EMC /P <>BDC BT 8 0 0 8 163.0652 79.3702 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F5 1 Tf 8 0 0 8 42.5196 67.3702 Tm 0 .68 .9 0 k ()Tj ET EMC /P <>BDC /GS2 gs BT /F3 1 Tf 8 0 0 8 48.6095 67.3702 Tm 0 0 0 1 k ( are they transported across the gut barrier?)Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 203.8335 67.3702 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F2 1 Tf 14 0 0 14 308.9764 333.2127 Tm 0 .68 .9 0 k [(T)110.8(o)0( understand the effect of)]TJ ET EMC /P <>BDC BT 14 0 0 14 491.7626 333.2127 Tm ( )Tj ET EMC /P <>BDC BT 14 0 0 14 308.9764 311.2126 Tm [(pr)12(ocessing on EVs)23.9(,)36.9( commer)17.8(cial)]TJ ET EMC /P <>BDC BT 14 0 0 14 516.6443 311.2126 Tm ( )Tj ET EMC /P <>BDC BT 14 0 0 14 308.9764 289.2126 Tm [(first-sta)12(ge infant milk form)12(ula has)]TJ ET EMC /P <>BDC BT 14 0 0 14 541.9233 289.2126 Tm ( )Tj ET EMC /P <>BDC BT 14 0 0 14 308.9764 267.2127 Tm [(been pr)12(oduced at pilot plant scale)23.9(.)]TJ ET EMC /P <>BDC BT 14 0 0 14 541.35 267.2127 Tm ( )Tj ET EMC /P <>BDC /GS2 gs BT /F3 1 Tf 8 0 0 8 308.9764 247.3702 Tm 0 0 0 1 k ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 235.3702 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F4 1 Tf 9 0 0 9 308.9764 223.3702 Tm 0 .68 .9 0 k [(Studies in )74(T)91.8(e)0(a)12(gasc and )74(T)91.8(rinity College Dublin)]TJ ET EMC /P <>BDC BT 9 0 0 9 509.7709 223.3702 Tm ( )Tj ET EMC /P <>BDC /GS2 gs BT /F3 1 Tf 8 0 0 8 308.9764 211.3702 Tm 0 0 0 1 k [(Bulk milk from the current Irish dair)-12(y herd, as well as colostrum, first)]TJ ET EMC /P <>BDC BT 8 0 0 8 549.5681 211.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 199.3702 Tm (milk and mature milk from individual cows \(representing the next-)Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 187.3702 Tm [(generation dair)-12(y herd\) was collected from T)71.8(eagasc dair)-12(y farms from)]TJ ET EMC /P <>BDC BT 8 0 0 8 547.9135 187.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 175.3702 Tm [(Februar)-12(y to December 2019. In total, 159 milk samples have been)]TJ ET EMC /P <>BDC BT 8 0 0 8 543.3761 175.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 163.3702 Tm [(collected and EV extraction is currently under)-12(way using)]TJ ET EMC /P <>BDC BT 8 0 0 8 504.976 163.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 151.3702 Tm (ultracentrifugation density gradients. In short, EVs are purified and)Tj ET EMC /P <>BDC BT 8 0 0 8 543.6083 151.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 139.3702 Tm (collected from milk according to their density \(1.1-1.2 g/mlL\),)Tj ET EMC /P <>BDC BT 8 0 0 8 528.9843 139.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 127.3702 Tm [(following the International Society of Extracellular V)54.9(esicles guidelines)]TJ ET EMC /P <>BDC BT 8 0 0 8 551.241 127.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 115.3702 Tm [(\(Thr)-12(y )]TJ ET EMC /P <>BDC BT /F6 1 Tf 8 0 0 8 334.1121 115.3702 Tm (et al)Tj ET EMC /P <>BDC BT /F3 1 Tf 8 0 0 8 348.816 115.3702 Tm (., 2018\).)Tj ET EMC /P <>BDC BT 8 0 0 8 379.1841 115.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 103.3702 Tm [(T)71.8(o)0( understand the effect of processing, commer)17.8(cial first-stage infant)]TJ ET EMC /P <>BDC BT 8 0 0 8 549.5395 103.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 91.3702 Tm (milk formula has been produced at pilot plant scale )Tj ET EMC /P <>BDC BT 8 0 0 8 492.9843 91.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 79.3702 Tm (using two different processing methods: standard thermal)Tj ET EMC /P <>BDC BT 8 0 0 8 514.2963 79.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.9764 67.3702 Tm (processing; and, membrane cascade processing. The membrane)Tj ET EMC /P <>BDC BT 8 0 0 8 536.4004 67.3702 Tm ( )Tj ET EMC /Artifact <>BDC .06 .07 .09 .15 K 0 J 0 j .5 w 10 M [] 0 d /GS1 gs q 1 0 0 1 297.637 343.965 cm 0 0 m 0 -275.933 l S Q EMC /P <>BDC /GS2 gs BT /F2 1 Tf 7 0 0 7 68.0315 28.6398 Tm (TRESEARCH)Tj ET EMC /P <>BDC /GS1 gs BT /F4 1 Tf 7 0 0 7 109.1284 28.6398 Tm .78 .02 .98 .09 k ( | )Tj ET EMC /P <>BDC /GS2 gs BT /F2 1 Tf 7 0 0 7 114.8265 28.6398 Tm 0 0 0 1 k (SUMMER 2020)Tj ET EMC /P <>BDC /GS1 gs BT /F4 1 Tf 7 0 0 7 162.9305 28.6398 Tm .78 .02 .98 .09 k ( | )Tj ET EMC /P <>BDC /GS2 gs BT /F2 1 Tf 7 0 0 7 168.6285 28.6398 Tm 0 0 0 1 k [(V)36.9(OLUME 15 : NUMBER 2)]TJ ET EMC /P <>BDC /GS1 gs BT 16 0 0 16 42.5294 784.3701 Tm 0 0 0 0 k -.015 Tc (FOOD)Tj ET EMC /P <>BDC BT /F7 1 Tf 20 0 0 20 86.8654 784.3701 Tm .06 .07 .09 .15 k 0 Tc ( )Tj ET EMC /Artifact <>BDC 0 .68 .9 0 k 42.52 777.161 42.519 1.418 re f EMC /Artifact <>BDC 0 368.205 595.2 5.669 re f EMC /P <>BDC /GS2 gs BT /F4 1 Tf 7 0 0 7 42.5196 28.6398 Tm 0 0 0 1 k (24)Tj ET EMC /P <>BDC BT /F2 1 Tf 7 0 0 7 50.8077 28.6398 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F8 1 Tf 35 0 0 35 42.5196 487.3701 Tm 0 .68 .9 0 k (MilkEV)Tj ET EMC /P <>BDC BT 35 0 0 35 163.0247 487.3701 Tm ( )Tj ET EMC /P <>BDC BT /F3 1 Tf 8.5 0 0 8.5 42.5196 470.3701 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 42.5196 453.3701 Tm ( )Tj ET EMC /P <>BDC BT /F8 1 Tf 13 0 0 13 42.5196 439.37 Tm [(TEA)36.9(GASC)]TJ ET EMC /P <>BDC BT /F6 1 Tf 8.5 0 0 8.5 103.4524 439.3701 Tm 0 0 0 0 k ( )Tj ET EMC /P <>BDC BT /F8 1 Tf 13 0 0 13 105.8154 439.37 Tm [(r)12(esear)17.8(c)17.8(h)0( is e)5.9(xamining e)5.9(xtr)17.8(acellular)]TJ ET EMC /P <>BDC BT 13 0 0 13 329.9204 439.37 Tm ( )Tj ET EMC /P <>BDC BT 13 0 0 13 42.5196 422.37 Tm [(v)12(esicles in milk and ho)23.9(w the)29.8(y can be)]TJ ET EMC /P <>BDC BT 13 0 0 13 276.6799 422.37 Tm ( )Tj ET EMC /P <>BDC BT 13 0 0 13 42.5196 405.37 Tm [(incorpor)17.8(ated into infant form)12(ula.)]TJ ET EMC Q endstream endobj 69 0 obj <>/XObject<>/ExtGState<>>> endobj 151 0 obj <> endobj 155 0 obj <> endobj 163 0 obj <> endobj 167 0 obj <> endobj 171 0 obj <> endobj 179 0 obj <>stream /P <>BDC q 1 i 0 841.89 595.275 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n /GS2 gs BT /F3 1 Tf 8 0 0 8 42.5193 355.3702 Tm 0 0 0 1 k 0 Tc 0 Tw (cascade process incorporates low heat, so we will be able to)Tj ET EMC /P <>BDC BT 8 0 0 8 254.5672 355.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 343.3702 Tm (understand if reducing the thermal load during processing )Tj ET EMC /P <>BDC BT 8 0 0 8 251.8311 343.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 331.3702 Tm (protects EVs, and ensures the presence of intact, bioactive EVs )Tj ET EMC /P <>BDC BT 8 0 0 8 263.7273 331.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 319.3702 Tm (in the final product.)Tj ET EMC /P <>BDC BT 8 0 0 8 112.7193 319.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 307.3702 Tm [(T)71.8(eagasc scientists are global leaders in modelling food digestion )]TJ ET EMC /P <>BDC BT 8 0 0 8 270.609 307.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 295.3702 Tm [(in the laborator)-12(y)74(.)0( Using the INFOGEST protocol, infant milk formula)]TJ ET EMC /P <>BDC BT 8 0 0 8 282.3832 295.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 283.3702 Tm (has been subjected to semi-dynamic gastrointestinal digestion. )Tj ET EMC /P <>BDC BT 8 0 0 8 266.8712 283.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 271.3702 Tm [(W)39.8(e)0( are currently attempting to extract EVs from )]TJ ET EMC /P <>BDC BT 8 0 0 8 214.2568 271.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 259.3702 Tm (both gastric and intestinal samples. The effect of EVs on the )Tj ET EMC /P <>BDC BT 8 0 0 8 255.5193 259.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 247.3702 Tm (health of the intestinal barrier is estimated by monitoring)Tj ET EMC /P <>BDC BT 8 0 0 8 244.3351 247.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 235.3702 Tm (transepithelial electrical resistance, and quantifying tight junction)Tj ET EMC /P <>BDC BT 8 0 0 8 272.8392 235.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 223.3702 Tm (proteins \(i.e., occludin and claudin-1\) in 21-day-old Caco2-)Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 211.3702 Tm (HT29MTX cell monolayers. Cellular bioassays have been )Tj ET EMC /P <>BDC BT 8 0 0 8 243.0553 211.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 199.3702 Tm (developed in house to test the benefits of consumed EVs for )Tj ET EMC /P <>BDC BT 8 0 0 8 256.7352 199.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 187.3702 Tm (immune cells based on THP-1 macrophages treated with)Tj ET EMC /P <>BDC BT 8 0 0 8 243.0152 187.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 175.3702 Tm (bioavailable milk digesta.)Tj ET EMC /P <>BDC BT 8 0 0 8 131.2312 175.3702 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 42.5193 163.3702 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F4 1 Tf 9 0 0 9 42.5193 151.3702 Tm 0 .68 .9 0 k (Benefits of milk EVs)Tj ET EMC /P <>BDC BT 9 0 0 9 131.5473 151.3702 Tm ( )Tj ET EMC /P <>BDC /GS2 gs BT /F3 1 Tf 8 0 0 8 42.5193 139.3702 Tm 0 0 0 1 k [(This project will be of benefit to the Irish dair)-12(y industr)-12(y as it)]TJ ET EMC /P <>BDC BT 8 0 0 8 252.5666 139.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 127.3702 Tm (determines the quantity and composition of EVs present in )Tj ET EMC /P <>BDC BT 8 0 0 8 252.3272 127.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 115.3702 Tm [(Irish milk over the lactation cur)-12(ve. It will help infant formula)]TJ ET EMC /P <>BDC BT 8 0 0 8 253.6949 115.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 103.3702 Tm (manufacturers by tracking the fate of EVs during processing.)Tj ET EMC /P <>BDC BT 8 0 0 8 255.6712 103.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 91.3702 Tm (Whether or not bovine EVs can play a positive role in maturing )Tj ET EMC /P <>BDC BT 8 0 0 8 266.3353 91.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 79.3702 Tm (the gut barrier and boosting the immune system will also )Tj ET EMC /P <>BDC BT 8 0 0 8 247.4232 79.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 42.5193 67.3702 Tm (be investigated.)Tj ET EMC /P <>BDC BT 8 0 0 8 98.5992 67.3702 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F4 1 Tf 9 0 0 9 308.976 595.3701 Tm 0 .68 .9 0 k [(Ne)23.9(w kno)23.9(wledge gained)]TJ ET EMC /P <>BDC BT 9 0 0 9 412.5763 595.3701 Tm ( )Tj ET EMC /P <>BDC /GS2 gs BT /F3 1 Tf 8 0 0 8 308.976 583.3701 Tm 0 0 0 1 k (This collaboration brings together experts in EVs, )Tj ET EMC /P <>BDC BT 8 0 0 8 484.3359 583.3701 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 571.3701 Tm [(gastrointestinal digestion and dair)-12(y processing. Ultimately this)]TJ ET EMC /P <>BDC BT 8 0 0 8 528.2637 571.3701 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 559.3701 Tm [(resear)17.8(ch activity aims to create a next-generation infant formula)]TJ ET EMC /P <>BDC BT 8 0 0 8 534.9213 559.3701 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 547.3701 Tm (enriched with EVs.)Tj ET EMC /P <>BDC BT 8 0 0 8 374.0399 547.3701 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 308.976 535.3701 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F4 1 Tf 9 0 0 9 308.976 523.3701 Tm 0 .68 .9 0 k (Reference)Tj ET EMC /P <>BDC BT 9 0 0 9 352.3289 523.3701 Tm ( )Tj ET EMC /P <>BDC /GS2 gs BT /F3 1 Tf 8 0 0 8 308.976 511.3701 Tm 0 0 0 1 k [(Thr)-12(y)74(,)0( C., W)23.9(itwer)49.8(, K., Aikawa, A., )]TJ ET EMC /P <>BDC BT /F6 1 Tf 8 0 0 8 427.3701 511.3701 Tm (et al)Tj ET EMC /P <>BDC BT /F3 1 Tf 8 0 0 8 442.074 511.3701 Tm (. \(2018\). )Tj ET EMC /P <>BDC BT 8 0 0 8 475.258 511.3701 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 499.3701 Tm (Minimal information for studies of extracellular vesicles 2018)Tj ET EMC /P <>BDC BT 8 0 0 8 525.5999 499.3701 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 487.3701 Tm (\(MISEV2018\): a position statement of the International Society )Tj ET EMC /P <>BDC BT 8 0 0 8 532.3359 487.3701 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 475.3701 Tm [(for Extracellular V)54.9(esicles and update of the MISEV2014 guidelines.)]TJ ET EMC /P <>BDC BT 8 0 0 8 543.8405 475.3701 Tm ( )Tj ET EMC /P <>BDC BT /F6 1 Tf 8 0 0 8 308.976 463.3701 Tm [(Journal of Extracellular V)54.9(esicles)]TJ ET EMC /P <>BDC BT /F3 1 Tf 8 0 0 8 411.4964 463.3701 Tm (, 7: 1.)Tj ET EMC /P <>BDC BT 8 0 0 8 432.1605 463.3701 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 451.3701 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F4 1 Tf 9 0 0 9 308.976 439.3701 Tm 0 .68 .9 0 k [(Ac)17.8(kno)23.9(wledgements:)]TJ ET EMC /P <>BDC BT 9 0 0 9 399.1221 439.3701 Tm ( )Tj ET EMC /P <>BDC /GS2 gs BT /F3 1 Tf 8 0 0 8 308.976 427.3701 Tm 0 0 0 1 k (MilkEV is funded by the Department of Agriculture, Food and the)Tj ET EMC /P <>BDC BT 8 0 0 8 539.8318 427.3701 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 415.3701 Tm [(Marine, through the Food Institutional Resear)17.8(ch Measure \(FIRM\),)]TJ ET EMC /P <>BDC BT 8 0 0 8 538.6253 415.3701 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 403.3701 Tm (Project 17 F 234 MilkEV Milking extracellular vesicles for improved)Tj ET EMC /P <>BDC BT 8 0 0 8 551.6641 403.3701 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 391.3701 Tm [(infant milk formula. Charlotte Oliver is in receipt of a T)71.8(eagasc )]TJ ET EMC /P <>BDC BT 8 0 0 8 529.6017 391.3701 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 379.3701 Tm [(W)39.8(alsh Scholarship.)]TJ ET EMC /P <>BDC BT 8 0 0 8 374.7935 379.3701 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 308.976 367.3701 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 308.976 355.3702 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 308.976 343.3702 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 308.976 331.3702 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 308.976 319.3702 Tm ( )Tj ET EMC /P <>BDC /GS1 gs BT /F4 1 Tf 9 0 0 9 308.976 307.3702 Tm 0 .68 .9 0 k [(A)29.8(uthors:)]TJ ET EMC /P <>BDC BT 9 0 0 9 347.3809 307.3702 Tm ( )Tj ET EMC /P <>BDC /GS2 gs BT /F9 1 Tf 8.5 0 0 8.5 308.976 295.3702 Tm 0 0 0 1 k (Charlotte Oliver)Tj ET EMC /P <>BDC BT /F3 1 Tf 8.5 0 0 8.5 372.7855 295.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 283.3702 Tm [(T)71.8(eagasc Food Resear)17.8(ch Centre, Moorepark, Fermoy)74(, Co. Cork)]TJ ET EMC /P <>BDC BT 8 0 0 8 525.6194 283.3702 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 308.976 271.3702 Tm ( )Tj ET EMC /P <>BDC BT /F9 1 Tf 8.5 0 0 8.5 308.976 259.3702 Tm (Linda Giblin)Tj ET EMC /P <>BDC BT /F3 1 Tf 8.5 0 0 8.5 357.1454 259.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 247.3702 Tm [(T)71.8(eagasc Food Resear)17.8(ch Centre, Moorepark, Fermoy)74(, Co. Cork)]TJ ET EMC /P <>BDC BT 8 0 0 8 525.6194 247.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 235.3702 Tm (Correspondence: linda.giblin@teagasc.ie)Tj ET EMC /P <>BDC BT 8 0 0 8 452.416 235.3702 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 308.976 223.3702 Tm ( )Tj ET EMC /P <>BDC BT /F9 1 Tf 8.5 0 0 8.5 308.976 211.3702 Tm (Andre Brodkorb)Tj ET EMC /P <>BDC BT /F3 1 Tf 8.5 0 0 8.5 373.0744 211.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 199.3702 Tm [(T)71.8(eagasc Food Resear)17.8(ch Centre, Moorepark, Fermoy)74(, Co. Cork)]TJ ET EMC /P <>BDC BT 8 0 0 8 525.6194 199.3702 Tm ( )Tj ET EMC /P <>BDC BT 8.5 0 0 8.5 308.976 187.3702 Tm ( )Tj ET EMC /P <>BDC BT /F9 1 Tf 8.5 0 0 8.5 308.976 175.3702 Tm (Lorraine ODriscoll)Tj ET EMC /P <>BDC BT /F3 1 Tf 8.5 0 0 8.5 383.1045 175.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 163.3702 Tm (School of Pharmacy and Pharmaceutical Sciences, )Tj ET EMC /P <>BDC BT 8 0 0 8 487.384 163.3702 Tm ( )Tj ET EMC /P <>BDC BT 8 0 0 8 308.976 151.3702 Tm [(T)75.9(rinity College Dublin)]TJ ET EMC /P <>BDC BT 8 0 0 8 385.8405 151.3702 Tm ( )Tj ET EMC /Artifact <>BDC .06 .07 .09 .15 K 0 J 0 j .5 w 10 M [] 0 d /GS1 gs q 1 0 0 1 297.566 603.804 cm 0 0 m 0 -535.748 l S Q EMC /P <>BDC BT /F2 1 Tf 16 0 0 16 508.206 787.0821 Tm .06 .07 .09 .15 k -.015 Tc (FOOD)Tj ET EMC /P <>BDC /GS2 gs BT 7 0 0 7 344.877 28.6398 Tm 0 0 0 1 k 0 Tc (TRESEARCH)Tj ET EMC /P <>BDC /GS1 gs BT /F4 1 Tf 7 0 0 7 385.9739 28.6398 Tm .78 .02 .98 .09 k ( | )Tj ET EMC /P <>BDC /GS2 gs BT /F2 1 Tf 7 0 0 7 391.6719 28.6398 Tm 0 0 0 1 k (SUMMER 2020)Tj ET EMC /P <>BDC /GS1 gs BT /F4 1 Tf 7 0 0 7 439.776 28.6398 Tm .78 .02 .98 .09 k ( | )Tj ET EMC /P <>BDC /GS2 gs BT /F2 1 Tf 7 0 0 7 445.474 28.6398 Tm 0 0 0 1 k [(V)36.9(OLUME 15 : NUMBER 2)]TJ ET EMC /Artifact <>BDC 0 .68 .9 0 k /GS1 gs 510.244 777.161 42.519 1.418 re f EMC /Artifact <>BDC 0 0 0 0 k 308.976 68.032 51.024 62.362 re f EMC /Figure <>BDC Q q 1 i 308.976 130.394 51.024 -62.362 re W* n 0 841.89 595.275 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n /GS1 gs q 54.207 0 0 65.507 307.384 66.367 cm /Im3 Do Q EMC /Artifact <>BDC Q q 1 i 0 841.89 595.275 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n 0 0 0 0 k /GS1 gs 365.257 68.032 51.024 62.362 re f EMC /Figure <>BDC Q q 1 i 365.257 130.394 51.024 -62.362 re W* n 0 841.89 595.275 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n /GS1 gs q 54.266 0 0 65.122 363.836 66.545 cm /Im5 Do Q EMC /P <>BDC Q q 1 i 0 841.89 595.275 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n /GS2 gs BT /F2 1 Tf 7 0 0 7 542.5214 28.6398 Tm 0 0 0 1 k 0 Tc 0 Tw ( )Tj ET EMC /P <>BDC BT /F4 1 Tf 7 0 0 7 544.4675 28.6398 Tm (25)Tj ET EMC /Artifact <>BDC 0 0 0 0 k /GS1 gs 421.257 68.032 51.024 62.362 re f EMC /Figure <>BDC Q q 1 i 421.257 130.394 51.024 -62.362 re W* n 0 841.89 595.275 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n /GS1 gs q 53.757 0 0 65.123 419.963 66.565 cm /Im7 Do Q EMC /Artifact <>BDC Q q 1 i 0 841.89 595.275 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n 0 0 0 0 k /GS1 gs 477.257 68.032 51.024 62.362 re f EMC /Figure <>BDC Q q 1 i 477.257 130.394 51.024 -62.362 re W* n 0 841.89 595.275 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n /GS1 gs q 53.806 0 0 65.306 476.505 66.506 cm /Im9 Do Q EMC /Artifact <>BDC Q q 1 i 0 841.89 595.275 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n 0 0 0 0 k /GS1 gs 42.519 399.685 243.78 204.095 re f EMC /Figure <>BDC Q q 1 i 42.519 603.78 243.78 -204.095 re W* n 0 841.89 595.275 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n /GS1 gs q 246.718 0 0 206.957 41.226 398.224 cm /Im11 Do Q EMC /P <>BDC Q q 1 i 0 841.89 595.275 -841.89 re 297.6 421.08 m W n 0 842.04 595.2 -841.92 re W n /GS2 gs BT /F1 1 Tf 7 0 0 7 42.5193 388.6713 Tm 0 0 0 1 k -.015 Tc 0 Tw [(T)17.8(his r)17.8(esear)23.9(c)23.9(h)0( aims to cr)17.8(eate a next-gener)29.8(ation inf)17.8(ant f)17.8(orm)12(ula enric)23.9(hed with EVs)17.8(.)]TJ ET EMC Q endstream endobj 180 0 obj <>/XObject<>/ExtGState<>>> endobj 6 0 obj <> endobj 5 0 obj <> endobj 78 0 obj <>stream Adobed   !!!!!!'''''''''''''''  !!'!!'''''''''''''''''''''''''''''B""  s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjzm!1AQa"q2#BRbr3$4CS%cs5DT &6E'dtU7()󄔤euFVfvGWgw8HXhx9IYiy*:JZjz?52zJz21A Lf:t´r/2jcKH?G/2c)f4sz87L513zxf>- GzyoGpL}2- }ގoGpʦ>HDxez#y^2U12<6jcKH@cL6T+Z@_W4ǕLfƑH/_pLeZA_/_jci ހoOLS513}\`O+*f4|zxee^B _W;1ƹ|1L|qJf<,i-61b|rclxQIq6bc=2 b3a$G0Ł/L Q#FR(u(#x渕֯{QsGwpbET:Pv{hwocxJ+pwM6!ŊG>8|OQ-&QOa#Iڔw9-Ppa{N1?v_(Glzp(jc2ꃨ"UlKKs'<Ưa>e-gw嵝ֱ۹ϼ=k}4b;#s/O˜G G9l:R"1y7)LmΥgil׳Lnj?ln2+[i3PeoJ#:=UO[,Ww X8"Sjjc,;Jx%Ŗ_Γv14%r#V6ٽfqw,W.{bI&EO뚹ab3SLfj͊jcf5sfV51٩.m2Lف͊ 8bʦ?675peqUiOWWU3f͛)qjf͛6*7}3S6lٱU>9\͛l6QAOW V6t R#+6]2Sjf͛6>9隙f͊9隙f͊ҟ83S6lٱE)S(ٳfTq)L2͉ҝ2fU2͎ LRӔ10aĬ#+>Lp9`TJ÷r֝riS+^EqJWq]rraB\i\V1܎`+0 iLXaֹo`TJxv͚ƕNӛlFVlR#*F(X=,}sO ^q?lr{nF̞3&إK7iXtcЧ _uƻW#< g +־]]0+yyTh8@~! 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