para-Aminobenzoic acid (PABA) has been previously used as an exogenous marker to verify completion of 24-hour urine sampling. Therefore, we hypothesized that radiolabeled PABA with ¹¹C could allow high-quality dynamic PET of the kidneys while reducing the radiation exposure due to its short biological and physical half-lives. We evaluated if ¹¹C-PABA could visualize renal anatomy and quantify function in healthy rats, rabbits, and first-in-human studies in healthy volunteers. Methods: Healthy rats and rabbits were injected with ¹¹C-PABA intravenously. Subsequently, a dynamic PET was performed, followed by post-mortem tissue biodistribution studies. 11C-PABA PET was directly compared with the current standard, ^99mTc-MAG3 in rats. Three healthy human subjects also underwent dynamic PET after intravenous injection of ¹¹C-PABA. Results: In healthy rats and rabbits, dynamic PET demonstrated a rapid accumulation of ¹¹C-PABA in the renal cortex, followed by rapid excretion through the pelvicalyceal system. In humans, ¹¹C-PABA PET was safe and well tolerated. There were no adverse or clinically detectable pharmacologic effects in any subject. The cortex was delineated on PET, and the activity gradually transited to the medulla and then renal pelvis with high spatiotemporal resolution. Conclusion: ¹¹C-PABA demonstrated fast renal excretion with very low background signal in animals and humans. These results suggest that ¹¹C-PABA could be used as a novel radiotracer for functional renal imaging, providing high-quality spatiotemporal images with low radiation exposure.

The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [¹⁸F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [¹⁸F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

The study of protein subcellular distribution, their assembly into complexes and the set of proteins with which they interact with is essential to our understanding of fundamental biological processes. Complementary to traditional assays, proximity-dependent biotinylation (PDB) approaches coupled with mass spectrometry (such as BioID or APEX) have emerged as powerful techniques to study proximal protein interactions and the subcellular proteome in the context of living cells and organisms. Since their introduction in 2012, PDB approaches have been used in an increasing number of studies and the enzymes themselves have been subjected to intensive optimization. How these enzymes have been optimized and considerations for their use in proteomics experiments are important questions. Here, we review the structural diversity and mechanisms of the two main classes of PDB enzymes: the biotin protein ligases (BioID) and the peroxidases (APEX). We describe the engineering of these enzymes for PDB and review emerging applications, including the development of PDB for coincidence detection (split-PDB). Lastly, we briefly review enzyme selection and experimental design guidelines and reflect on the labeling chemistries and their implication for data interpretation.

Lee Call
Apr 29, 2020; 0:jlr.RA120000652v1-jlr.RA120000652
Research Articles

Producer Chris dives in this week to discuss the HTC 10 release, and why it's difficult to get excited about good mobile phones. Then Techworld.com editor Charlotte Jee chats Facebook chatbots and other F8 news (12:30). Finally, editor at Digitalartsonline.co.uk Neil Bennett jumps in to discuss the new Amazon e-reader (31:00) Kindle Oasis and why everyone is kicking off about the price.  

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For the second week running hosting duties are taken by Henry Burrell, who is joined by Techworld.com editor Charlotte Jee to discuss the impact of Brexit on the UK's startups. Producer Chris then jumps in to discuss the Pokemon Go launch in the UK and a debate breaks out over whether it is for adults (13:00) Finally, online editor at Computerworld UK Scott Carey brings the latest news around driverless cars, from Tesla's recent struggles and how it may affect the industry in general (25:00)  

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Host Matt Egan is in a sombre mood this week as the tech industry comes to terms with a Donald Trump US presidency. Staff writer at Macworld UK dives into what this could mean for Silicon Valley, Apple products and wether social media is at fault. Then producer Chris comes on to discuss the latest addition to the VR headset market with Google's Daydream. Will it be held back by a lack of applications though? (14:45) Finally, online editor at Computerworld UK talks about the biggest data breach at a UK bank, as Tesco Bank suffers a £2.5 million cyber theft and what this means for the banking industry as a whole (25:00).  

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Host Matt Egan clips us round the ear and tells us to listen up as we chat yet more tech and then some other stuff about tech. Consumer tech editor at PC Advisor Chris Martin lays down his definitive opinion after he went hands on with the Nintendo Switch this week, and why the company really should have had their star plumber ready in time for launch. Tamlin Magee, Online Editor at Computerworld UK then takes us through the odd goings on at Davos, and whether or not the elite can identify with what tech actually means to real working people. To round us up, Acting Macworld UK Editor David Price explains why app prices are going up in the UK for iOS users, and why it might - might - not be UKIP's fault. Sort of.  

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This week we dive into the new Surface Pro with Digital Arts' Neil Bennett. Who is it for and is it that different to the last one? And are 2 in 1 devices really the future of computing? Then Techworld's Scott Carey, fresh back from Cannes, discusses why the French film industry booed at a Netflix film - why was it there in the first place? Is the film industry being that affected by tech giants like Amazon? Tech Advisor's Dom Preston chimes in to let us know. Finally, we all quickly nerded out about Alien: Covenant. Mild spoiler alert!  

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Scott Carey necessarily tries to get his pronunciation game on fleek to deliver the latest Uber news - there's a new CEO in town, and it isn't a woman. Should it have been? He tells Henry Burrell what's next for the company. Then roles are reversed as Henry updates Scott on the Galaxy Note 8, LG V30 and September 12's very own iPhone 8 - will it be called that? Will anyone spend £1,000 on it?  

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We finally get the IoT acronym the pod has been waiting for as we discuss Bitcoin and 17th century Dutch finance. Charlotte Jee informs Henry Burrell, David Price and Scott Carey.

Scott then leads us down the winding road of the so-called platform wars, in a week when Google blocked the Amazon Echo Show from streaming YouTube. Is this a bump in the road or will services be cut from rival hardware?

And finally, led by David, the pod discusses its favourite tech of the year and what you might consider buying for friends and family for Christmas.

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Once more for 2017 as Henry Burrell, Karen Khan and Scott Carey bid farewell to this wonderful year (ahem) with musings on Apple's sexy new iMac Pro. Who is it for, how much is it and does this mean there is no Mac Pro in 2018?

We then tackle Netflix's Twitter shaming of its users and why Spotify got away with it earlier in the year. How comfortable are we all when we realise how much data companies really have on us?

In light of this, Apple bought Shazam - most likely for the data sets as much as the tech and the talent. What form will it take in Apple as another UK tech company is acquired?

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World Cup fever is upon us, and this time round is tech-heavy. The VAR (video assistant referee) makes its (their? know know) debut at a major international football tournament. Is it for the good of the sport?

We’re already used to Hawkeye and goal-line technology, so what makes it different in football? Henry Burrell resides as David Price, Christina Mercer and Sean Bradley set the record straight. NB: David loves cricket a lot.

And of course, the most tech sport of all, Formula One. Is there a balance the sport misses when it comes to safety and competition? We discuss some of the finer points in a lively debate.

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This week on the UK Tech Weekly Podcast our host Scott Carey talks to Macworld editor David Price about the ever-controversial Alex Jones and why the big tech companies are finally stepping up their efforts to ban him from their platforms. Editors note: we recorded this on Thursday before Twitter finally started to take some measures against Jones, without outright banning him.

Next our resident phone nerd and consumer tech editor at Tech Advisor Henry Burrell talks about the upcoming Samsung Galaxy Note 9, the latest iPhone X rumours and how Apple and Google are trying to make you use your phone less.

Lastly Techworld editor Charlotte Jee takes us on a trip down memory lane to talk about the utopian vision of the Millennium Experience, how it reflected the values of a New Labour government and its legacy.

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A quick-fire reaction Apple special, recorded the morning after new iPhones and an Apple Watch were announced at an event in California.

Henry Burrell joins David Price, Ashleigh Macro and Scott Carey to discuss which products we'll be buying, avoiding and coveting over the Christmas period.

Is the new iPhone named terribly? Is it an upgrade at all? What wasn't announced? And does Scott give the new Apple Watch any praise at all? It's all here.

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Two’s a crowd for this week’s games and Christmas pod with Consumer Tech Editor Henry Burrell and Games Editor Lewis Painter. Lewis lines up reviews of the awful Fallout 76 and the excellent online mode of Red Dead Redemption 2 – two polar opposites in how to make a decent online multiplayer game.

We also discuss smartwatches we’ve recently reviewed that left us feeling cold and why Apple is still king of the hill.

And to get into the festive vibe, interspersed throughout as we enter December are our top tech Christmas gift picks, both cheap and indulgent.

Everything we recommend is linked below:

Google Home Hub

Tile Bluetooth tracker

Red Dead Redemption 2 (PS4)

Super Smash Bros – Ultimate (Switch)

Pokémon: Let’s Go, Pikachu! (Switch)

Turtle Beach Elite Pro 2 + Superamp

Amazon Kindle Paperwhite

PlayStation Classic

PlayStation VR Starter Pack

The best budget smartphones

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Scott Carey is in the hosting chair this week as we have a rotating cast of staffers from across Macworld, Tech Advisor, Techworld and Computerworld to discuss our two favourite techie things of the year, from the best games and films, to our favourite devices and even, microchips.

Thank you for listening this year and for your continued support for the UK Tech Weekly Podcast and we will see you in the new year.

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Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite profiles in premature, parenterally fed pigs given a soy-oil lipid emulsion, Intralipid (IL); a multi component lipid emulsion, SMOFlipid (SMOF); a novel emulsion with a modified fatty-acid composition (EXP); or a control enteral diet (ENT) for 22 days. We assayed serum cholestasis markers; measured total bile acid levels in plasma, liver, and gut contents; and analyzed colonic bacterial 16S rRNA gene sequences and metabolomic profiles. Serum cholestasis markers (i.e. bilirubin, bile acids, and g-glutamyl transferase) were highest in IL-fed pigs and normalized in those given SMOF, EXP, or ENT. Gut bile acid pools were lowest in the IL treatment and were increased in the SMOF and EXP treatments and comparable to ENT. Multiple bile acids, especially their conjugated forms, were higher in the colon contents of SMOF and EXP than in IL pigs. Colonic microbial communities of SMOF and EXP pigs had lower relative abundance of several Gram-positive anaerobes, including Clostridrium XIVa, and higher abundance of Enterobacteriaceae than those of IL and ENT pigs. Differences in lipid and microbial-derived compounds were also observed in colon metabolite profiles. These results indicate that multi-component lipid emulsions prevent cholestasis and restore enterohepatic bile flow in association with gut microbial and metabolomic changes. We conclude that sustained bile flow induced by multi-component lipid emulsions likely exerts a dominant effect in reducing bile acid–sensitive, Gram-positive bacteria.

Patrice D. Cani
Jun 1, 2008; 57:1470-1481
Metabolism

BASSETERRE, St Kitts (CMC): ST KITTS AND Nevis Patriots have made some significant changes to their line-up for the upcoming Caribbean Premier League (CPL) season. Captain Carlos Brathwaite has gone to the Jamaica Tallawahs, while the Patriots have...

Portmore United captain Rosario Harriott says the Premier League Clubs Association shouldn’t rush to call off this season of the Red Stripe Premier League (RSPL) because of the COVID-19 pandemic. The league was stopped indefinitely in mid-March...

Winners of the Darwin Award must eliminate themselves from the gene pool in such an idiotic manner that their action ensures one less idiot will survive. Ben and Dennis Lendrem, and colleagues, have reviewed the data on winners of the Darwin Award over a 20 year period and they join us to discuss why men are idiots, and why their team is not the...

Doctors and the farming industry are often blamed for overuse of antibiotics that spurs the growing problem of antimicrobial resistance - but the professions are using different methods to combat resistance and reduce overuse. In this roundtable, we bring medics and vets together to discuss the problem - where antibiotic resistance arises, how...

Patrice D. Cani
Jun 1, 2008; 57:1470-1481
Metabolism

21 July 2014

Two of the authors of the American Dental Association's antibiotics guideline will discuss C. diff infections and antibiotic stewardship in dentistry April 21 as part of a free, online conference organized by the Peggy Lillis Foundation.

The American College of Emergency Physicians has endorsed the American Dental Association's clinical practice guideline on the use of antibiotics for the management of pulpal- and periapical-related pain and swelling.

OBJECTIVE

Recent studies have highlighted the significance of the microbiome in human health and disease. Changes in the metabolites produced by microbiota have been implicated in several diseases. Our objective was to identify microbiome metabolites that are associated with type 2 diabetes.

In Eliot Spitzer's sex scandal and tragicomic downfall, the question that bugged many people did not have to do with ethics or politics, but whether Spitzer got a raw deal.

Before the coronavirus pandemic, bioengineer Jim Collins and his team combined the power of AI with synthetic biology in an effort to combat a different looming crisis: antibiotic-resistant superbugs. Collins explains how they pivoted their efforts to begin developing a series of tools and antiviral compounds to help fight COVID-19 -- and shares their plan to discover seven new classes of antibiotics over the next seven years. (This ambitious plan is a part of The Audacious Project, TED's initiative to inspire and fund global change.)

The Patriots didn't draft a quarterback, but they signed two who went undrafted. Michigan State quarterback Brian Lewerke's agent revealed a week ago that Lewerke had signed with the Patriots. Patriots coach Bill Belichick wouldn't confirm the team had signed Louisiana Tech quarterback J'mar Smith as well. But Tuesday's official transactions report brought confirmation of [more]

Caterpillars -- Australia, Southern -- Identification -- Pictorial works.

Organized crime -- New South Wales -- Sydney -- History -- 20th century.

Punk rock music -- History and criticism.

Lawyers -- Fiction.

Internet -- Social aspects.

Londres : J.-B. Baillière, 1878.

Paris (rue de la Vannerie a l'image St. Michel) : Dupuis graveur du Roy, [1721]

London (in Cheapside) : Published according to Act of Parliament, by J. Boydell engraver, Sept.r 3rd, 1763.

Dani Gamerman.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 4, 686--705.

Abstract:
Point processes are one of the most commonly encountered observation processes in Spatial Statistics. Model-based inference for them depends on the likelihood function. In the most standard setting of Poisson processes, the likelihood depends on the intensity function, and can not be computed analytically. A number of approximating techniques have been proposed to handle this difficulty. In this paper, we review recent work on exact solutions that solve this problem without resorting to approximations. The presentation concentrates more heavily on discrete time but also considers continuous time. The solutions are based on model specifications that impose smoothness constraints on the intensity function. We also review approaches to include a regression component and different ways to accommodate it while accounting for additional heterogeneity. Applications are provided to illustrate the results. Finally, we discuss possible extensions to account for discontinuities and/or jumps in the intensity function.

Seth Flaxman, Michael Chirico, Pau Pereira, Charles Loeffler.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2564--2585.

Abstract:
We propose a generic spatiotemporal event forecasting method which we developed for the National Institute of Justice’s (NIJ) Real-Time Crime Forecasting Challenge (National Institute of Justice (2017)). Our method is a spatiotemporal forecasting model combining scalable randomized Reproducing Kernel Hilbert Space (RKHS) methods for approximating Gaussian processes with autoregressive smoothing kernels in a regularized supervised learning framework. While the smoothing kernels capture the two main approaches in current use in the field of crime forecasting, kernel density estimation (KDE) and self-exciting point process (SEPP) models, the RKHS component of the model can be understood as an approximation to the popular log-Gaussian Cox Process model. For inference, we discretize the spatiotemporal point pattern and learn a log-intensity function using the Poisson likelihood and highly efficient gradient-based optimization methods. Model hyperparameters including quality of RKHS approximation, spatial and temporal kernel lengthscales, number of autoregressive lags and bandwidths for smoothing kernels as well as cell shape, size and rotation, were learned using cross validation. Resulting predictions significantly exceeded baseline KDE estimates and SEPP models for sparse events.