5 Aug 31 • iPhone XR vs. iPhone 8 Plus: Which iPhone should you buy? Sarah Tew/CNET The end came quietly, slipped in with a series of back-to-school announcements about better screens and lower prices for the MacBook Air, and, uh, more Touch Bars for the MacBook Pro. No formal announcement was made in the jargon-filled press release letting us know that the entry-level Pro now features “Touch Bar and Touch ID, a True Tone Retina display and the Apple T2 Security Chip,” but a quick check online confirmed that the 12-inch MacBook had been removed from Apple’s website. And the 12-inch MacBook wasn’t alone in going to the big upstate farm where old computers allegedly roam, with free Wi-Fi and plenty of power outlets. The “classic” MacBook Air and the Touch-Bar-less MacBook Pro also exited active duty. But those are easier to let go of. The former was so outdated as to be hard to recommend, the latter is getting the higher-end features of its more-expensive cousin while keeping the same price. I’ll come right out and say it. The 12-inch MacBook was an unfairly maligned, misunderstood product. In fact, at several points since its 2015 debut, it’s been my favorite laptop. Insanely portable, very light, great 12-inch display, and a sharp look that turned coffee shop heads back when smaller-screen laptops were mostly low-end junk. In 2016, I proudly declared it “my favorite laptop” and “my top go-to machine.” I even wrote most of a 75,000-word book on its super-shallow keyboard. But I also acknowledged why a lot of people just didn’t “get” the 12-inch MacBook. “The knocks against this system — an odd-man-out, not part of either the Air or Pro MacBook lines — were numerous. Its screen was too small; the keyboard too shallow; not enough ports; no MagSafe power connection; underpowered, even compared to the base MacBook Air; and battery life that didn’t measure up to the MacBook standard.”I also said, “The 12-inch MacBook won’t do everything and isn’t for everyone. But its strictly enforced minimalism will make this laptop the model that industrial designers will strive to copy for the next several years.” And that has certainly come to pass. USB-C as the go-to standard? Check. Butterfly keyboard on every MacBook? Check (although who knows for how much longer). Higher-res, Retina-style screens as table stakes for premium laptops? Check.I recall people tearing their hair out over the single USB-C port in the first 12-inch MacBook. No USB-A, no HDMI — how could anyone use a laptop like that? Now, many super-premium 13-inch laptops have at best a couple of USB-C ports and little else. Just one port. Sarah Tew/CNET It reminds me of when Apple led the way dropping things like Ethernet jacks and optical drives from computers. The company was just a little ahead of the curve about what features were on their way out. The 12-inch MacBook didn’t physically connect to anything because many modern laptops don’t need to physically connect to anything. Between Bluetooth, Wi-Fi and cloud-connected services, I can’t recall the last time I had to plug something into a travel laptop. I was excited to get a USB memory key with dual USB-A and USB-C ports several months ago. Still haven’t taken it out of the package. If it was so great, then what killed the 12-inch MacBook? The culprit was the very system the it was originally supposed to replace. The 13-inch MacBook Air, for many years the single most universally useful laptop you could buy (and a staple for students and office workers alike), had fallen into the phantom zone where Apple sticks products that stagnate with minimal, if any, updates for years on end. But last year, the Air finally got the top-to-bottom makeover it needed and became a sales leader, leaving few reasons beyond slightly better portability to choose the 12-inch model instead. Call it natural selection or survival of the fittest, but it’s the law of the gadget jungle. And before I get too morose over the death of the 12-inch MacBook, I should remember that I’m writing this on — you guessed it — an excellent new 13-inch MacBook Air. Aug 31 • Verizon vs AT&T vs T-Mobile vs Sprint: Choose the best 5G carrier Share your voice Aug 31 • Your phone screen is gross. Here’s how to clean it Apple • Apple Tags Computers Laptops Comments See All reading • RIP 12-inch Apple MacBook, my misunderstood friend Aug 31 • iPhone 11, Apple Watch 5 and more: The final rumors
Donald Trump. File photoUS president Donald Trump is in full campaign mode five months before pivotal mid-term elections, employing a mix of anti-immigration rhetoric, Democrat-bashing and off-script improvisation in a bid to help Republicans hold their congressional majority.Democrats, riding a swell of grass-roots activism and buoyed by Trump’s poor approval numbers and an ongoing investigation into possible coordination between Russia and Trump’s campaign, are seeking to flip the US House and Senate.Trump is pushing back, hitting the road-including at a fiery Tuesday night rally in Tennessee-as he seeks to energize his base to come out and vote in November for Republican Senate candidates in states where he can have a major impact.But the strategy apparently seeks to minimize his exposure in states where Republicans in close House races might feel the divisive president’s presence would be more of a hindrance, motivating Democrats and independents instead of helping moderate GOP candidates.Despite the risks of an unrestrained Trump addressing large crowds at campaign-style events, it is a strategy aimed at firing up his loyal supporters in red states where vulnerable Senate Democrats are running for re-election, or challenging for open seats.Such was the case Tuesday when Trump rallied in Nashville in support of congresswoman Marsha Blackburn’s bid to succeed retiring Senator Bob Corker.“We need more Republicans,” Trump boomed.“If you want your country to be safe, then you must go out and get the Democrats the hell out of office.”A sitting president’s party often loses seats during mid-term elections.While analysts say Democrats have a decent shot at flipping the 24 seats needed to reclaim the House, the opposition party is up against an extraordinarily tough Senate election map.Of the 35 Senate races, Democrats are defending a whopping 26 seats — 10 of them in states that Trump won in 2016.And Democrats are seeing their overall mid-term advantage shrink.In December, according to a RealClearPolitics polling average, Democrats enjoyed a 13-point advantage among voters who were asked which party they would support in the 2018 congressional election.That figure this week stood at just four points.Trump ‘coming after’ vulnerable DemocratsThe president has grown increasingly annoyed at his party’s 51-49 Senate majority as he seeks to push through his policy agenda, including a dramatic curtailing of illegal and legal immigration.Highlighting his rigid stance during his Nashville rally, he recalled the term he used recently to describe undocumented immigrants, including members of transnational gang MS-13, targeted for deportation.“What was the name?” Trump goaded the crowd. “Animals!” they shouted.Trump also savaged the Democratic candidate, former Tennessee governor Phil Bredesen, insisting he would be in the pocket of the Senate and House Democratic leaders.“He’s an absolute total tool of Chuck Schumer and of course the MS-13 lover, Nancy Pelosi,” Trump said.Over the past month Trump has held campaign-style rallies or speeches in Michigan, Ohio, Indiana and Tennessee-all states he carried in 2016, and where Republicans are facing tough Senate races. On Thursday he heads to Texas.Trump is also expected to travel in the coming weeks to North Dakota, Montana, Missouri, and West Virginia, the New York Times reported, citing White House officials familiar with the president’s summer strategy.They are states that Trump won easily, and where Senate Democrats face tough re-elections.Several other states may be added to the itinerary later, including Florida, where outgoing Governor Rick Scott is spending millions of dollars of his own personal fortune in a bid to oust a Senate Democratic incumbent.Trump on Tuesday night “had a message for 2018 red state Dems – he’s coming after them too,” said Katie Martin, communications director for the National Republican Senatorial Committee, the party’s Senate campaign arm.He relished his opportunity before the cheering crowd to tout his economic successes including major tax cuts that he signed into law.But Trump also eagerly returned to one of the tropes of his 2016 campaign, by declaring that Mexico would pay for a wall that he intends to build on the southern US border.“They’re going to pay for the wall and they’re going to enjoy it,” Trump said.
Explore further This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. More information: Single-molecule resolution of protein structure and interfacial dynamics on biomaterial surfaces, PNAS November 26, 2013 vol. 110 no. 48 19396-19401, doi:10.1073/pnas.1311761110 Moreover, Kaar continues, monitoring molecule-by-molecule structure changes in organophosphorus hydrolase had its own challenges related to eliminating mislabeled protein molecules – that is, molecules with other than one donor and one acceptor fluorophore – from analysis. “We met this challenge by creating and implementing filters during data analysis that separated signals from properly labeled and mislabeled species.”Kaar points out that using SM-FRET tracking had its own issue. For one, it required high-throughput tracking algorithms (developed by co-authors Kastantin and Schwartz) critical to monitor changes in FRET signals for large numbers of molecules, which in turn was essential to identifying protein structure changes accurately (that is, with high statistical confidence). He points out that SM-FRET also required prior knowledge of the crystal structure of OPH, which was needed to make the FRET signal indicative of quantitative changes in protein conformation.The study’s results suggest that surfaces may act as a source of unfolded (that is, aggregation-prone) protein back into solution – but validating this implication faces the challenge of identifying the conformation of protein molecules immediately before desorption from the surface. “The question of whether the unfolded proteins induced aggregation in solution after desorption remains to be fully understood,” Kaar explains. “Fully understanding if this is actually the case requires further analysis of protein in solution in the presence of the surface.”The team leveraged two key innovations to address these research challenges – the implementation of site-specific labeling methods, and high-throughput tracking algorithms with SM-FRET. “Combining these methods enabled the decoupling of surface-induced conformational changes from protein adsorption and desorption events,” Kaar notes. “By decoupling such phenomenon, this approach allowed us to overcome the limitations of conventional surface characterization methods.”The research also shows that SM-FRET permits a unique level of understanding of the ways in which surface chemistry influences molecular conformation and, in turn, function. “By observing molecular-level changes in protein structure in isolation from competing surface dynamics, it’s easier to make a direct connection between surface chemistry and conformation,” Kaar points out. “Therefore, it is more straightforward to see the effects of surface chemistry and can lead to new ideas for how to improve chemistry for a given application.Another important finding is that the new method will enable the creation of surfaces and modifications with improved biocompatibility by uncovering the connection between surface properties and protein unfolding. “This connection is critical to inspiring and developing surfaces and modifications that meld with the biological world,” Kaar explains. “For example, with this understanding, we can begin to design surfaces that promote protein folding and therefore favorable responses from cells present in the surrounding milieu. In this example, the folded state of the protein may display certain biological signals to cells that thwart unwanted inflammatory or harmful reactions while instructing cells to respond in ways that may facilitate proliferation, differentiation or even wound healing in vivo.”Kaar tells Phys.org that future experiments are aimed at determining if the observed effects of fused silica on organophosphorus hydrolase are general or specific to this combination of surface and protein. “We plan to address this question by probing how fused silica and surfaces with other properties impact the folding of other proteins. We’re also interested in expanding our methods to understand how surface effects on conformation impact the binding of a third protein species. Understanding this impact is critical to, for example, enumerating how cells respond to biological cues on surfaces in physiological environments.” Other innovations that the researchers may develop, Kaar adds, include more sophisticated labeling to minimize SM-FRET protein mislabeling on surfaces, as well as labeling and detection schemes to enable multiple molecular events, including unfolding and binding, to be monitored simultaneously.”Given that the interaction of proteins and surfaces are relevant in virtually all areas of biotechnology,” Kaar notes, “many other areas of research – for example, tissue engineering and regenerative medicine, biosensing, biocatalysis, and pharmaceutical protein formulation – may benefit from exploiting our approach.” (Phys.org) —Proteins accomplish something rather amazing: A protein can have many functions, with a given function being determined by the way they fold into a specific three-dimensional geometry, or conformations. Moreover, the structural transitions form one conformation to another is reversible. However, while these dynamics affect protein conformation and therefore function, and so are critical to a wide range of areas, methods for understanding how proteins behave near surfaces, which is complicated by protein and surface heterogeneities, has remained elusive. Recently, however, scientists at University of Colorado utilized a method known as Single-Molecule Förster Resonance Energy Transfer (SM-FRET) tracking to monitor dynamic changes in protein structure and interfacial behavior on surfaces by single-molecule Förster resonance energy transfer, allowing them to explicate changes in protein structure at the single-molecule level. (SM-FRET describes energy transfer between two chromophores – molecular components that determine its color.) In addition, the researchers state that their approach is suitable for studying virtually any protein, thereby providing a framework for developing surfaces and surface modifications with improved biocompatibility. Journal information: Proceedings of the National Academy of Sciences © 2013 Phys.org. All rights reserved. Citation: Two for the price of one: Single-molecule microscopy simultaneously monitors protein structure and function (2013, December 4) retrieved 18 August 2019 from https://phys.org/news/2013-12-price-single-molecule-microscopy-simultaneously-protein.html Protein surfaces defects act as drug targets Structure of OPH showing the position of site-specific donor and acceptor labeling. OPH is a homodimer (C2 symmetry) that consists of two (α/β)8 monomers. The position K175, which was replaced with AzF in monomers A and B of OPH, is highlighted (yellow). Credit: Copyright © PNAS, doi:10.1073/pnas.1311761110 Prof. Joel L. Kaar discussed the paper he and his co-authors, Dr. Sean Yu McLoughlin, Prof. Mark Kastantin and Prof. Daniel K. Schwartz, recently published in Proceedings of the National Academy of Sciences. “The primary challenges in devising our approach to characterizing changes in protein structure were implementing a site-specific labeling method, which enabled single-molecule resolution, as well as a method to only image molecules at the solution-surface interface,” Kaar tells Phys.org. The scientists overcame the former challenge by incorporating unnatural amino acids – that is, those not among the 20 so-called standard amino acids – with unique functional groups for labeling with fluorophores (chemical compounds that can re-emit light upon light excitation); the latter, by using total internal reflection fluorescence microscopy, which only excites molecules in the near-surface environment, thereby minimizing the background fluorescence of molecules free in solution. “Although site-specific labeling methods have been used to monitor changes in protein conformation mainly in bulk solution, such techniques have not previously been exploited to study freely diffusible protein molecules at interfaces,” Kaar adds. As such, the researchers are the first to apply site-specific labeling methods to study protein-surface interactions,”The major challenge associated with incorporating unnatural amino acids for labeling was related to the optimization of protein expression,” Kaar continues. Specifically, he explains, the expression of the enzyme organophosphorus hydrolase (OPH) – which is notoriously difficult to make in large quantities due to inclusion body formation – with the unnatural amino acid p-azido-L-Phe (AzF) had to be optimized to efficiently incorporate p-azido-L-Phe. (Inclusion body formation refers to the intracellular aggregation of partially folded expressed proteins,) “This process required modification of expression conditions,” he adds, “in which bacteria with modified genetic machinery were grown to enable production of soluble enzyme for single-molecule experiments.”