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Based on analysis of documentation associated with the UN Food Systems Summit process, we identify three main ways in which the Summit failed to address the problem of corporate power in food systems in a meaningful way. First, the Summit was 'strategically silent' on the problem of corporate power, mentioning the problem only very infrequently and in a way that failed to identify corporations as holding disproportionate power in food systems. Second, it advanced technology and innovation-based solutions that benefit large agrifood companies rather than seeking structural transformation of food systems. Third, it gave corporations a priority seat at the table by engaging them in various settings in the lead up to the Summit.

Exhaust gas recirculation (EGR) cooler fouling occurs when particulate matter (PM) and hydrocarbons (HC) in diesel exhaust form a deposit on the walls of the EGR cooler through thermophoresis and condensation. To better understand the mechanisms controlling deposit formation and removal and how operating conditions can affect cooler performance, 20 identical tube-in-shell EGR coolers with sinusoidal fins were fouled using a 5-factor, 3-level experimental design. The deposit thickness was measured using two methods: (1) epoxy-mounting and polishing cooler cross-sections and comparing deposit thicknesses on the primary (outer tube) to the secondary (fins) heat transfer surfaces, and (2) milling tube sections such that the surface of a fin could be observed and measuring the deposit thickness across the fin using a 3D profilometer. Near the cooler inlet, high inlet gas temperatures reduced deposit thickness by promoting mud-cracking and spallation. Near the middle of the cooler, the flow rate had the largest impact on the deposit thickness through the effect on residence time of the PM. The HC concentration along with flow rate had the largest effects near the cooler outlet where the lower temperatures allows for more HC condensation. These insights into how engine operating conditions influence the development of fouling layers in EGR coolers learned through this study will aid in the development of more fouling resistant coolers in the future.

To meet the demand for greater fuel efficiency in passenger vehicles, various strategies are employed to increase the power density of light-duty SI engines, with attendant thermal or system efficiency increases. One approach is to incorporate higher-performance alloys for critical engine components. These alloys can have advantageous thermal or mechanical properties at higher temperatures, allowing for components constructed from these materials to meet more severe pressure and temperature demands, while maintaining durability. Advanced alloys could reduce the need for charge enrichment to protect certain gas-path components at high speed and load conditions, permit more selective cooling to reduce heat-transfer losses, and allow engine downsizing, while maintaining performance, by achieving higher cylinder temperatures and pressures. As a first step in investigating downsizing strategies made possible through high-performance alloys, a GT-Power model of a 4-cylinder 1.6L turbocharged direct-injection SI engine was developed. The model was tuned and validated against experimental dynamometer data collected from a corresponding engine. The model was then used to investigate various operating strategies for increasing power density. Results from these investigations will provide valuable insight into how new materials might be utilized to meet the needs of future light-duty engines and will serve as the basis for a more comprehensive investigation using more-detailed thermo-mechanical modeling.

Sierra “So there was this girl in my ward, Mariah, who I knew was an art student, so we decided to take ‘Drawing 2’ Together. So we’re taking Drawing 2 Together, they use nude models, it’s like whatever. Like the first couple times it’s weird and then it’s not weird anymore. So we get this email before class, from Ray, the Drawing professor and he’s like ‘Hey guys, just want to let you know…” cause we’ve used professional models up to this point. [Interjecting into his email quote] “…we’re having a student model come in today, so please be really cautious. When you come into class, please turn off your phone, and keep it in your backpack… just so there’s no…. like just to protect yourself, so that there’s no accusations that you’re like taking photos or anything, make sure to be really respectful, please be on time… blah blah blah” -- [Interrupted by waitress, the conversation side tracks to talking about the normal, professional models, includio Mario a frequent model for her class] -- Sierra: “so hE [Mario] was great to work with, so he [the professor] list’s off [that Mario would be coming] and the student’s name is like ‘whatever.’ And I’m just like skimming this email, and I’m like ‘whatever.’ And I’m like getting ready for class, and Mariah my next-door neighbor calls me and is like ‘Oh my Gosh Sierra, we can’t go to class today.’ And I’m like ‘Dude, we need to go to class, of course we need to go to class’ and she’s like ‘DID YOU NOT READ THE EMAIL?’ [said in a hushed yell voice] she’s freaking out at me, and I’m like ‘Mariah, I read the email, I don’t know why it’s such a big deal, like yeah, it’s a student model’ and she’s like ‘No did you read the name of who it is?’ and I’m like ‘yeah, but like I don’t know him’ she’s like ‘YES YOU DO! It’s Johnny in the ward, our home teacher!” [same hushed yell voice] and I was like ‘NNOOOOOOOOOOO’ and I’m like, ‘I’m not going, I can’t go to class, I can’t see my home teacher naked…’ Travis: “Did you GO?!” [Long pause] Sierra: “Well…” [Travis getting so excited to hear the end of this story, banging on the table] Sierra: “I made Mariah call him, I’m like ‘Call him and tell him: there are two girls in the ward in this class, and he will not show up, I guarantee it’ So she’s like ‘Okay.’ so she call’s him and tells him, and then she calls me back and says ‘he said he’s just going to stand it up, he’s not going to go’” Travis: “But doesn’t that effect like the whole class?” Me: “Stand it up”…”You get it?” [Me interjecting an inappropriate joke to laughter from Travis and rolled eyes from Sierra as she continues the story] Sierra: “So we just went to class, and like, he didn’t show up, and Ray was super mad, and was like ‘This guy called in sick at the last second’ and Mariah and i were like ‘well, too bad, lets get to work’…” Travis: “Come one why didn’t he just follow through with it, like he’s over at your house the next week, sharing some message from the Ensign [Mormon magazine] and you’re like ‘I’ve seen your penis’ that would just like hit you right then…” [story devolves into questions about nude models]

[one of the simplest forms of the design, and most common, as it is on a blue background, we know it’s Aggie based] [A fan wears the shirt in 2011] [A Red variant, found online, to be worn by a University of Utah Fan, the man in the photo also interestingly has a white undershirt, indicative of religious vestments (garments) and is likely a member of the Church of Jesus Christ of Latter-Day Saints, who owns BYU. The individual may not wear it if it explicitly said “FUCK BYU”] [A black version, available for purchase, likely to be interchangeable between different fan bases]

[The Chicago Bears use the limit to reference a Saturday Night Live Skit, in Humor] [I use the new limit to share a longer portion of a classic poem, more than I might have previously, as a proud English Major] [Student uses satire to mock the new limit, playing the part of an annoying internet user who abuses and overuses the limit] [a reference to both 420, the marijuana celebration, and a classic meme from It’s Always Sunny in Philidelphia, that explains confusing situations] [user shows the full limit of how bad this change could be] [TV Show Law And Order use the limit to show their entire intro dialogue, which, in itself, is a meme on the internet] [Nat Geo uses the new limit to post all the animal emoji’s and show they are happy with the new limit] [NBA Ref’s use 280 to mock people’s criticism of them] [Dictionary Company uses 280 to define “Extravagent”] [New York Yankees, known to be the winningest baseball team in MLB history, take the opportunity to post all of the years they have won the world-series, in one tweet. Bragging] [a play off of another viral post, this student mocks STEM (Science Technology Engineering Math) majors, referencing the 280 phenomenon, stating his tweet of 280 characters will have a better audience on twitter than they STEM Major’s 20 page research paper. The original tweet was STEM major’s mocking liberal arts students and how easy their work was]

pictures [The Most common design, surely the one printed the most time, uses the actual Block Letters, heavily vectored, with soft edges to justify not breaking copyright issues] [Here a student with an Anti-BYU sign wears the shirt, as does the man with blue hair, and two others in the photo] [A less common design, but more well done, this version could not be mass produced as it utilizes copyrighted trademarks of the universities, their logos. Also a variant of such]

The President’s Office, Currently President Michael Scott Peters, has a door. [yes and entire door.] IT is a door that used to lead to the adjacent office, but now, opening to a blank wall, serving as a micro-closet, is signed by the past Presidents. The Executive Vice President has a large vertical flag, signed back at least 15 years, that is currently displayed behind VP Blake Harm’s Desk prominently. Student Advocate Vice President has a small [child toy] gold colored bull. It is signed back a few years, but will soon be completely covered. It sits on a shelf of VP Baldwin. Student Alumni Vice President, a new position as of last year, already has one, a Gothic type banner, carrying a single signature, and is hung on the wall of VP Brendon Brady CHaSS Senator has a Felt V banner, hung above my desk, signed back 8 years. It bears the block A, not the athletic logos. Ag Senator has a small toy John Deere Tractor, held in a display case, the signatures are in the bed of the trailer, and only has sporadic signatures, as if some senators did not know or choose to sign. Heather Lieber, incumbent Senator has not signed yet. Admin Assistant has a painting, of Old Main, on display in that office. On the Back are signatures. Currently on display in Admin Assit. Dallin Johnson’s office. Athletics Vice President mentioned that they are done differently and many, many items are passed down year to year, and the original gifter usually signs their object only. Other officers did not respond, or were unaware of any objects.

Pictures [the account “@aggiestrife” mocking the fact that BYU Student, and Rapper, “James the Rapper” hates Aggies] [Parody account “@noellecockett, a profile who pretends to be USU President Noelle Cockett, mocks the parking situation] [I mocked a professor’s grading process, back in April] [School Newspaper, The Utah Statesman, uses it for a serious issue]

Me: “What is the worst date you’ve ever been on?” [Not skipping a beat] Ryker: “OH. Easy. Junior Ball. Her parents drove, we did not get dinner, I had to live off the winter mints they have on the table, and like the water…like you know at high school. You go to a high school dance and they have the little ‘Lifesaver Wintermint’ I had to live off of those and water, and a to-go box out of my friend’s trunk. [laughing] it was from his date, because of course THEY went to dinner.” [interjecting] ME: Wait why did you not go to dinner?” Ryker: “Because… I don’t know… we didn’t go to dinner. It was a girl’s choice dance, and I literally got asked two weeks before the dance, she moved in to the school from like Florida…” [interjecting roommate] Luke: “Well buddy you chose the. Wrong. Girl.” [Frustrated and annoyed] Ryker: “IT was a GIRLS. CHOICE. DANCE. Those are not an option. You cannot say no, or you will never go to a dance again.” Luke: “Is this true? I guess we didn’t have girls’ choice dances” Ryker: “Yeah we had girls’ choice dances, and if you said no, you were never getting asked again. You were an asshole who would never get asked to a girls’ choice dance again.” [Luke interjects with story about girl at his high school] Ryker: “Well I don’t know where that story came from, but anyways, she picks me up, and to her credit, she did clean up really quite nice, I was impressed, I was like ‘WOW.’ I mean she wasn’t like ugly, but she wasn’t like ‘wow, this girl is going to be damn good looking in a like a dress’, but then she showed up in this like black dress, and I was like ‘okay, well hello.’ So we start walking out to the car, and I was like ‘oh yeah, there’s people in the car’ and like, I figured so, cause I knew she didn’t drive. So I was like sittin there, and it’s like winter, and she’s from Florida, so she’s really not going to drive now, so I’m like ‘ oh it’s our group.’ And I hopped in the car and it’s Dad, Mom in the passenger seat, and little brother in the backseat In the middle with us. So I’m like ‘this is literally a movie, like I’m getting punked’ Like Ashton Kutcher was going to pop out of nowhere and be like… Anyways, so we start driving, I’m like, well her dad’s pissed, because I’m trying to give him directions. And he’s like “SNOW. FLORIDA. ‘F’ EVERYTHING IN THE WORLD’, ‘how dare you take my daughter on a date: Don’t look at her’” [said in quite the sarcastic angry voice] He’s being the usual dad, pissed off. And her mom’s doing the usual “So what do your parents do?... What do you like to do? …Where are you from?...” And then little Brother’s playing video games. And then like halfway through this drive, I have this conversation in my head that is like ‘OH SHIT, are they going to dinner with us?’ I’m like ‘are we going to have this family dinner, and me?’ and I’m like. NO they dropped us fifteen minutes off early, before the dance starts. It’s start’s at eight, I’m there at 7:45. Like the Vice Principal is still setting stuff up, the lights aren’t even off yet. And you can tell. And this is how great my Vice Principal was, She’s like, Sue Bayles, loved her to death, she was my homie. But you could just tell she was like strugglin’, like “OH YOU’RE HERE, AWWWESWOME” [shrill female surprised voice] Like they don’t have a table out for tickets yet or anything, so she’s like “okay, go right in, have a grand ole time’ she’s just like ‘SHIT what do I do, I don’t know, there is nothing set-up, but I am going to act like it is perfectly normal that you are here’” Spencer: “…On time...” [laughing] Ryker: “EARLY. We were there EARLY. I walk up stairs thinking ‘there is going to be no-one, but us. Like only us will be here. WRONG. There is like eight kids from the damn theatre group, Which, OF COURSE, SHE KNOWS, And is friends [with.] And at the same time I’m sitting there like ‘why the hell are we not with these kids, because these kids surely got dinner.” [laughing] “AND, their parent’s did not drive. I would rather sit awkwardly with nine people I did not enjoy, then have to ride alone, in a car with parents, and not-get-fed. Like…” Me: “Had your date already ate?” Ryker: “I don’t know.” [High voice, unsure, almost hoping] “I mean she didn’t text me and say “Hey, eat dinner before” and when she said “I’ll pick you up at seven” that didn’t sound weird because lt was like we’ll go to dinner, and then show up at the dance at like nine, so like nothing was out of the usual for a normal dance. Had no reason to raise a red flag.” Luke: [faintly] “That’s fuckin’ hilarious…” Ryker: “And like, it’s like when you played sports, when you stopped moving, or stopped running, your coach would make it worse?” Me: [referring to Luke] “Yeah he didn’t play sports…” [knowing he played sports, but mocking his weight] Luke: [pissed] “Who are you talk about? ME?” [Ryker laughing trying to keep his sotry on track] Ryker: “So it was like that though, with dancing, It was like that with dancing: Like if I stoped dancing, I would have to talk, and it would be worse, so I power-fisted, dance moved, three and half hours man. [lots of laughter] I was not stopping for anything. Like “unce unce unce” [making techno dance songs while dancing for us] -- [Conversation diverged to talking about grinding style dancing] -- Ryker: “So like then during the dance, she would come up to me and be like “We have an hour and fifteen minutes left.” in like five to ten minute intervals. Like, giving me this minute break down, so I’m like “we can go, if you’re just counting down the minutes… We don’t need to stay the whole time” So at this point, I’m finally having fun. I’ve finally got some sort of energy, and my friends are there so I can just like chill with them, and ya know, like she was around, I didn’t ditch her… Every slow dance I danced with her…” -- [Conversation diverged to talking about how this girl actually helped Ryker graduate in a class] -- Ryker: “So like the dance get’s over, and I think it’s like ‘oh I’ll head to the car and I can talk to her mom’ WRONG. It’s just dad. Who is pissed off again, because it’s snowing, and he’s not in florida, and this state is awful or something. So we’re driving home, and my driveway, you’ve seen it. [pointing to me] he’s like “I’m not pulling up that.” And I’m like “I understand” So I had to walk up in the snow, which is like no problem, but she was like “do you want me to walk you up?” and I’m like “Nah, you stay here” I gave her a fistbump and walked away. And I was like “MOM! Where’s food? I’m dying…” And that was the end, of my worst date.” [Conversation returns to how she helped him graduate]

[See photo's] [My Personal Usage of it recently] [A Ute Fan’s Instagram Post, used in conjunction with making fun of Max Hall, a Former BYU Quarterback who went into Rehab for Cocaine Use, something that would have got him kicked out of BYU] [General usage on Twitter] [Former USU Basketball User, at the time a Professional BB player, wishing his former teammates good luck against BYU]

[Had explained to us that both Lacrosse team’s, male and female shared the same practice space and crossed over on practice times] Sierra: “A lot of us, the girls, would come early, and run and warm up, and the guys would like stay after their practice and there was like a thirty minute window when we all play together, and we just mess around, shoot on the goal, and it was like fun, it was a good way to make friends, like between the teams, and we were all pretty close. Like when the girls’ choice dances, like MORP [Prom backwards, a Utah term for girls’ choice dances] like the Anti-prom came around, we would go with the guys team and we would make them wear our jersey’s and we would wear theirs, and it was so funny, because ours were like tank tops on them stretched out, and theirs drown us like dresses, and it was just…, we thought it was so funny. And stuff like that, we would just do all the time. But they had two team captains, on their varsity team, and one of their captains was a year older than me, he’s like a senior, and he’s talking to me, and everyone is like ‘Sean’s into you’ and I’m like ‘no, he’s not, because he’s like a Senior and the captain of the lacrosse team, and I’m an Honors student and a dweeb, like NO he’s not into me, that’s not how it works’ and there like ‘no he’s totally into you.’” [Distracted by roommates] Sierra: “So anyways, we’d been like hanging out as teams together, and then it got to like my close friends on my teams with him and his friends, and then pretty soon, it’s just like him and I who are hanging out. But I’m still just dense, ya know what I mean? I’m just like ‘no, this guy’s not into me, that’s not what’s happening’ Anyways so we have mutual friends, and girls’ choice formal is coming up, and Sean, Matt, and I are playing wall-ball one night, and it’s late, and I hear Matt talking to Sean, and he thinks I can’t hear because I have earbuds in and he’s like ‘It’s my senior year, and I didn’t get asked to Girls’ choice formal’ –I wasn’t planning on going- ‘and I’m not going to get asked…’ So it all kind of weird, because it’s kind of a vulnerable conversation for two guys to be having, and I was like ‘SHOOT’ cause I hadn’t asked anyone, and so I tell Sean ‘I think I have to ask Matt” [Conversation diverges, but come back to pick up Sierra while she is sick, to go ask Matt] Sierra: “So I go drop the thing off at his house, still in my pajamas, still so sick, and Sean is like ‘how about we hang out, do you want to watch a movie?’ I’m like ‘No, I really just want to go home, I don’t feel good’ and he’s like ‘No, let’s go back to my place, I want to watch a movie’ and I’m like ‘I really, just want to go to bed honestly…’ and he’s like ‘no, we can just watch a show, like a TV show, it will be quick, let’s hang out let’s do something.’ And I’m like ‘Sean, I’m really sick.’ And so somehow he talks me into this and I’m like ‘Alright, I’m just going to fall asleep on your couch’ and we pull up to his house, and it turns out that his parents had this rule that if they weren’t home, he couldn’t have girls over, right? And he’s like ‘o can we go to your house’ and I’m like ‘sure. Fine. I don’t care’ so we go back to my parent’s house, and my parents have this loft over their garage, and so we’re in my loft, watching TV, but he’s trying to pick something, but like I’m so sick, by this point I’ve already taken NyQuil, I’m dying. I’m at THAT point, I needed to take something, it was too late in the day to take Dayquil, I just felt so gross, I’m like ‘let’s watch somethings that’s like 30 minutes, and then you gotta go home, and I’m going to go to bed and we can like hang out another time’ he’s like ‘okay.’ So he’s trying to pick something, he’s like, he’s suggesting all these weird shows, and I’m like I don’t care we’re just going to watch something for twenty minutes, he’s flipping through channels, and I’m just like ‘I just am going to fall asleep here, Sean.’ And he’s like flipping through and he finally settles on like on Animal Hoarders.” [Distracted by talk of the next day’s basketball game against BYU] Sierra: “Anyway, I’m like exhausted, and feeling gross, and he’s flipping through channels, settles on Animal Hoarders, not cause we picked it, but just cause like he’s talking to me and the show’s on, right? It’s like the lease romantic show of all time, it’s about people who have too many animals, and their also hoarders.” [a bunch of questions about this horrifying show] “Anyways, this story is also horrifying, Sean is like 6’5” and I’m 5”9” so we’re like sitting there and we’re watching the show, and we’re on a catch that’s like this size [motioning to my three seater couch] and that’s all my parents have up there, so we’re on that, and I want to go to bed, so I throw a pillow on Sean’s lap and I’m just like laying down, sleeping. BUT his arm is like this [showing us that it’s under the pillow]which I didn’t realize, and we’re like watching animal hoarders, and by WE I mean, He is, and I’m trying to go to sleep cause I feel sick, and I’m just thinking I want him to go home.” [distracted about teenage awkwardness] “Anyways so he’s like watching the show, and he says something to me He’s like ‘uh, hey, Sierra?’ and I’m like ‘yeah?’ and I turn up, and like look at him, because he’s talking to me, so I’m like looking at him, right? And he like begins his descent. [She starts laughing hard at this point] So he has his arm under the pillow, with my head on it, and like pulls my head up to his face, but he’s like 6’5” and carries a lot of his height in his Torso, he’s like a large person, and he closes his eyes before he begins his lean, so he’s not aiming at this point, he’s flying blind, no directional control. So I’m sick, I’m seventeen, we’re watching Animal Hoarders, I’m in my pajamas, there’s no consent ha, and I don’t understand initially what’s going on, until it’s too late. And I like, I’m still convinced that this guy wasn’t into me, like I would’ve been into him, but I’m like ‘oh he’s not interested in me, we’re just friends’ and so he goes in for it, I just like panicked, I just didn’t know what was happening, and I was like help, this is not what I imagined my first kiss going like, he just like smashes his face into mine for maybe like, three seconds, and then just straight drops me onto his lap. And I’m just like ‘WHOA.’ And he’s literally says out loud, I’m not making this up ‘YESSSS’ [she’s making a downward fist pump, like Tiger Wood’s does] And I’m just laying there so confused and I’m like ‘okay, so can I go to bed now? Is this what we were going to do tonight?’ [Conversation diverged]

*Introducing it* Spencer: “want to get a reaction out of people?” “When’s the last time you sharted yourself?” *laughing* “It’s funny because everyone knows the last time they sharted themselves” Myself: “I honestly don’t know that I do” Other Roommate “aw, yeah you do man, yeah you do” Spencer: “Yeah I can tell you mine vividly” “I was working in a fucking flip house, kay, back in California. It was a beat up old ass house I was working in to restore it” *answering interjections* “So I was working in that shit all by myself doing demo, okay? I was fucking ripping out like sheetrock and bullshit like that. And then… Like I’m there all by myself, and I’m like ‘my stomach hurts’ *giggling trying to talk* “there was like no bathrooms in that place cause they were all just freakin’… We tore ‘em all out already. ‘N so I’m just like ‘Damn my stomach hurts a lot now’ like after twenty minutes I’m just like ‘okay this is uncomfortable.’ BUT THEN I’m like ‘okay, I gotta go!’ So I start driving to the nearest McDonald’s, okay, and I’m like halfway there, and...” *holding back laughs* “It’s bad, it, it all just let’s lose bro, so I like waddle my ass into this McDonald’s, and freakin’ try and clean out my shorts” *laughing stops it for some 10 seconds* “and then I just finish my day, just like stained, and it’s just like, it’s a McDonald’s, so they got that like one-ply freaking toilet paper, that you can’t clean shit up with, it just –Smears- “ Myself: “So did you like, throw your underwear away or…?” Spencer: “No so I’m like trying to clean off my underwear” *roommate gagging, dry heaving, trying not to laugh* Roommate: “So you just free-balled it…?” Spencer: I was at… So then I go to work, and I like work for another couple hours in freaking shitty ass underwear, and then I like go home” *interjecting* Roommate: “HOW DID NOBODY like ‘like what is that smell?!” Spencer: “WELL, like I was, working by myself, so It didn’t really matter. I’m pretty sure I was in like Stockton too, so it was like, it was like a forty-minute drive home” … “But anyways it was like bad bro”

Detection of low concentrations of bacteria in food samples is a challenging process. Key to this process is the separation of the target from the food matrix. We demonstrate magnetic beads and magnetic micro-cilia based microfluidic mixing and capture, which are particularly useful for pre-concentrating the target. The first method we demonstrate makes use of magnetic microbeads held on to NiFe discs on the surface of the substrate. These beads are rotated around the magnetic discs by rotating the external magnetic field. The second method we demonstrate shows the use of cilia which extends into the fluid and is manipulated by a rotating external field. Magnetic micro-features were fabricated by evaporating NiFe alloy at room temperature, on to patterned photoresist. The high magnetic permeability of NiFe allows for maximum magnetic force on the features. The magnetic features were actuated using an external rotating magnet up to frequencies of 50Hz. We demonstrate active mixing produced by the microbeads and the cilia in a microchannel. Also, we demonstrate the capture of target species in a sample using microbeads.

The fetal intestinal mucosa is characterized by elevated Toll-like receptor 4 (TLR4) expression, which can lead to the development of necrotizing enterocolitis (NEC)—a devastating inflammatory disease of the premature intestine—upon exposure to microbes. To define endogenous strategies that could reduce TLR4 signaling, we hypothesized that amniotic fluid can inhibit TLR4 signaling within the fetal intestine and attenuate experimental NEC, and we sought to determine the mechanisms involved. We show here that microinjection of amniotic fluid into the fetal (embryonic day 18.5) gastrointestinal tract reduced LPS-mediated signaling within the fetal intestinal mucosa. Amniotic fluid is abundant in EGF, which we show is required for its inhibitory effects on TLR4 signaling via peroxisome proliferator-activated receptor, because inhibition of EGF receptor (EGFR) with cetuximab or EGF-depleted amniotic fluid blocked the inhibitory effects of amniotic fluid on TLR4, whereas amniotic fluid did not prevent TLR4 signaling in EGFR- or peroxisome proliferator-activated receptor γ–deficient enterocytes or in mice deficient in intestinal epithelial EGFR, and purified EGF attenuated the exaggerated intestinal mucosal TLR4 signaling in wild-type mice. Moreover, amniotic fluid-mediated TLR4 inhibition reduced the severity of NEC in mice through EGFR activation. Strikingly, NEC development in both mice and humans was associated with reduced EGFR expression that was restored upon the administration of amniotic fluid in mice or recovery from NEC in humans, suggesting that a lack of amniotic fluid-mediated EGFR signaling could predispose to NEC. These findings may explain the unique susceptibility of premature infants to the development of NEC and offer therapeutic approaches to this devastating disease.

Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal-related mortality in premature infants, and it develops under conditions of exaggerated TLR4 signaling in the newborn intestinal epithelium. Because NEC does not develop spontaneously, despite the presence of seemingly tonic stimulation of intestinal TLR4, we hypothesized that mechanisms must exist to constrain TLR4 signaling that become diminished during NEC pathogenesis and focused on the intracellular stress response protein and chaperone heat shock protein-70 (Hsp70). We demonstrate that the induction of intracellular Hsp70 in enterocytes dramatically reduced TLR4 signaling, as assessed by LPS-induced NF-κB translocation, cytokine expression, and apoptosis. These findings were confirmed in vivo, using mice that either globally lacked Hsp70 or overexpressed Hsp70 within the intestinal epithelium. TLR4 activation itself significantly increased Hsp70 expression in enterocytes, which provided a mechanism of autoinhibition of TLR4 signaling in enterocytes. In seeking to define the mechanisms involved, intracellular Hsp70-mediated inhibition of TLR4 signaling required both its substrate-binding EEVD domain and association with the cochaperone CHIP, resulting in ubiquitination and proteasomal degradation of TLR4. The expression of Hsp70 in the intestinal epithelium was significantly decreased in murine and human NEC compared with healthy controls, suggesting that loss of Hsp70 protection from TLR4 could lead to NEC. In support of this, intestinal Hsp70 overexpression in mice and pharmacologic upregulation of Hsp70 reversed TLR4-induced cytokines and enterocyte apoptosis, as well as prevented and treated experimental NEC. Thus, a novel TLR4 regulatory pathway exists within the newborn gut involving Hsp70 that may be pharmacologically activated to limit NEC severity.

Background & Aims Necrotizing enterocolitis (NEC), the leading cause of gastrointestinal death from gastrointestinal disease in preterm infants, is characterized by exaggerated TLR4 signaling and decreased enterocyte proliferation through unknown mechanisms. Given the importance of β-catenin in regulating proliferation of many cell types, we hypothesize that TLR4 impairs enterocyte proliferation in NEC via impaired β-catenin signaling. Methods Enterocyte proliferation was detected in IEC-6 cells or in ileum or colon from wild-type, TLR4-mutant, or TLR4 −/− mice after induction of NEC or endotoxemia. β-Catenin signaling was assessed by cell fractionation or immunoconfocal microscopy to detect its nuclear translocation. Activation and inhibition of β-catenin were achieved via cDNA or small interfering RNA, respectively. TLR4 in the intestinal mucosa was inhibited with adenoviruses expressing dominant-negative TLR4. Results TLR4 activation significantly impaired enterocyte proliferation in the ileum but not colon in newborn but not adult mice and in IEC-6 enterocytes. β-Catenin activation reversed these effects in vitro. To determine the mechanisms involved, TLR4 activation phosphorylated the upstream inhibitory kinase GSK3β, causing β-catenin degradation. NEC in both mouse and humans was associated with decreased β-catenin and increased mucosal GSK3β expression. Strikingly, the inhibition of enterocyte β-catenin signaling in NEC could be reversed, and enterocyte proliferation restored, through adenoviral-mediated inhibition of TLR4 signaling in the small intestinal mucosa. Conclusion We now report a novel pathway linking TLR4 with inhibition of β-catenin signaling via GSK3β activation, leading to reduced enterocyte proliferation in vitro and in vivo. These data provide additional insights into the pathogenesis of diseases of intestinal inflammation such as NEC.

We used three dimensional computer simulations to examine heat transport in a microchannel that encompasses a periodic array of biomimetic synthetic cilia. We modeled two different configurations of tilted cilia. Both configurations consisted of a grid of evenly spaced cilia with length L and square cross-section 0.1L×0.1L. The cilia were spaced at a distance δx between cilium rows and the inter-cilia spacing in the rows was fixed at δz = 0.25L for one configuration and δz = 0.5L for the other. The channel was filled with a viscous fluid and its top and bottom walls were maintained at different temperatures. The cilia were attached to the bottom channel wall at a specific angle and were actuated by a periodic external force applied vertically to their free ends. The periodical beating of cilia induces fluid mixing inside the fluid that facilitates heat transport. To model this multi-component system, we employed a thermal lattice Boltzmann model coupled with the lattice spring model. In order to investigate how the active cilia affect the heat transfer between the channel walls we varied three parameters in the system. Specifically, we systematically changed the tilt of the cilia, the spacing between cilia and the oscillation frequency of the cilia. Our investigations have allowed us to determine the optimal conditions for using cilia to increase the heat flux from a heated surface. Our findings could be useful for developing new methods for temperature control in microscale devices.Copyright © 2012 by ASME

Factors regulating the proliferation and apoptosis of intestinal stem cells (ISCs) remain incompletely understood. Because ISCs exist among microbial ligands, immune receptors such as toll-like receptor 4 (TLR4) could play a role. We now hypothesize that ISCs express TLR4 and that the activation of TLR4 directly on the intestinal stem cells regulates their ability to proliferate or to undergo apoptosis. Using flow cytometry and fluorescent in situ hybridization for the intestinal stem cell marker Lgr5, we demonstrate that TLR4 is expressed on the Lgr5-positive intestinal stem cells. TLR4 activation reduced proliferation and increased apoptosis in ISCs both in vivo and in ISC organoids, a finding not observed in mice lacking TLR4 in the Lgr5-positive ISCs, confirming the in vivo significance of this effect. To define molecular mechanisms involved, TLR4 inhibited ISC proliferation and increased apoptosis via the p53-up-regulated modulator of apoptosis (PUMA), as TLR4 did not affect crypt proliferation or apoptosis in organoids or mice lacking PUMA. In vivo effects of TLR4 on ISCs required TIR-domain-containing adapter-inducing interferon-β (TRIF) but were independent of myeloid-differentiation primary response-gene 88 (MYD88) and TNFα. Physiological relevance was suggested, as TLR4 activation in necrotizing enterocolitis led to reduced proliferation and increased apoptosis of the intestinal crypts in a manner that could be reversed by inhibition of PUMA, both globally or restricted to the intestinal epithelium. These findings illustrate that TLR4 is expressed on ISCs where it regulates their proliferation and apoptosis through activation of PUMA and that TLR4 regulation of ISCs contributes to the pathogenesis of necrotizing enterocolitis.

In cold wet weather, mammals face hypothermia if they cannot dry themselves. By rapidly oscillating their bodies, through a process similar to shivering, furry mammals can dry themselves within seconds. We use high-speed videography and fur particle tracking to characterize the shakes of 33 animals (16 animals species and five dog breeds), ranging over four orders of magnitude in mass from mice to bears. We here report the power law relationship between shaking frequencyfand body massMto bef∼M−0.22, which is close to our prediction off∼M−0.19based upon the balance of centrifugal and capillary forces. We also observe a novel role for loose mammalian dermal tissue: by whipping around the body, it increases the speed of drops leaving the animal and the ensuing dryness relative to tight dermal tissue.

One of the emerging issues in the field of digital crime and digital forensics is corporate preparedness in dealing with attacks on computer network security. Security attacks and breaches of an organization’s computer network can result in the compromise of confidential data, loss of customer confidence, poor public relations, disruption of business, and severe financial loss. Furthermore, loss of organizational data can present a number of criminal threats, including extortion, blackmail, identity theft, technology theft, and even hazards to national security. This chapter first examines the preparedness and response of three southwestern companies to their own specific threats to corporate cyber-security. Secondly, this chapter suggests that by developing an effective security policy focusing on incident detection and response, a company can minimize the damage caused by these attacks, while simultaneously strengthening the existing system and forensic processes against future attacks. Advances in digital forensics and its supporting technology, including intrusion detection, intrusion prevention, and application control, will be imperative to maintain network security in the future.

One of the emerging issues in the field of digital crime and digital forensics is corporate preparedness in dealing with attacks on computer network security. Security attacks and breaches of an organization’s computer network can result in the compromise of confidential data, loss of customer confidence, poor public relations, disruption of business, and severe financial loss. Furthermore, loss of organizational data can present a number of criminal threats, including extortion, blackmail, identity theft, technology theft, and even hazards to national security. This chapter first examines the preparedness and response of three southwestern companies to their own specific threats to corporate cyber-security. Secondly, this chapter suggests that by developing an effective security policy focusing on incident detection and response, a company can minimize the damage caused by these attacks, while simultaneously strengthening the existing system and forensic processes against future attacks. Advances in digital forensics and its supporting technology, including intrusion detection, intrusion prevention, and application control, will be imperative to maintain network security in the future.

Using computational modeling, we examine the development of an unsteady laminar flow of a Newtonian fluid in a channel with sinusoidal walls. The flow is driven by a constant pressure gradient. The simulations reveal two types of unsteady flows occurring in sinusoidal channels. When the amplitude of the wavy walls is relatively small, vortices forming in the channel furrows are shed downstream. For larger wall wave amplitudes, vortices remain inside the furrows and exhibit periodic oscillations and topological changes. We present a phase diagram in terms of wall amplitude and driving pressure gradient separating different flow regimes. Our simulations establish the optimum wall amplitude and period leading to an unsteady flow at the minimum pressure gradient. The results are important for designing laminar heat/mass exchangers utilizing unsteady flows for enhancing transport processes.

Using computational modeling, we probed the utility of actuated synthetic cilia for enhancing heat transport in microfluidic channels. Cilia are elastic filaments that are attached to the bottom channel wall with a constant tilt and actuated by a periodical vertical force applied to their free ends. We show that periodical oscillations of elastic cilia mix the heated fluid and create secondary flows in the microchannel that facilitate heat transport between channel walls. The magnitude of the secondary flows and the cilium deformation pattern are controlled by the frequency and amplitude of the periodic driving force. Thus, by varying the force parameters one can effectively regulate the local heat transport in ciliated microchannels.