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Social media provides a rich source of data that reflects current trends on a multitude of topics. The data can be harvested from Twitter, Facebook, blogs, and other social applications. The high rate of adoption of social media has created a domain that is difficult to analyze, due to the ever-expanding volume of data. Information visualization is key in drawing out features of interest in social media. The Scalable Reasoning System is an application that couples a back-end server equipped with analysis algorithms and an intuitive visual in- terface to allow for investigation. We provide a componentized system that can be rapidly adapted to user needs. The in- formation in which they are most interested is featured prominently in the application. As an example, we have developed a weather and traffic monitoring application for use by emergency operators in the city of Seattle.

After translational stalls, colliding eukaryotic ribosomes are cleared through dissociation into subunits by the ribosome quality control trigger complex, RQT, by an unknown mechanism. Here we show that RQT requires accessible mRNA and the presence of a neighboring ribosome. Cryo-EM of several RQT-ribosome complexes revealed the structural basis of splitting: RQT engages the 40S subunit of the lead ribosome and can switch between two conformations. We propose a mechanistic model in which the Slh1 helicase subunit of RQT applies a pulling force on the mRNA, causing destabilizing conformational changes of the 40S subunit. The collided ribosome functions as a ram or giant wedge, ultimately resulting in subunit dissociation. Our findings provide a first conceptual framework for a helicase driven ribosomal splitting mechanism.One-Sentence SummaryRQT clears collided ribosomes by pulling mRNA to trigger destabilizing conformational transitions for subunit dissociation.

Abstract. Relevance of emotional information varies with self-involvement. The current study was undertaken to test whether subtle facial self-resemblance is sufficient to affect attentional and affective processing of complex socio-emotional pictures. Faces digitally manipulated to resemble the participants’ (final sample: N = 21) own versus unfamiliar control faces (form and color morphs) were presented in pictures of emotionally evocative social interactions, that is, threat versus sex scenes. At stimulus onset asynchronies (SOAs) of either 300 ms or 3,000 ms after picture onset, startle responses were elicited by acoustic white noise bursts (50 ms, 105 dB), and recorded at the orbicularis oculi via electromyography (EMG). The majority of participants remained unaware of the morphing manipulation, and awareness did not affect the principal results. As indexed by inhibition of startle at short lead intervals and by picture-evoked heart rate deceleration, facial self-resemblance modulates effects of motivational salience in a context-sensitive way, increasing prepulse inhibition with threat-related, but not erotic cues. Overall, the present study suggests that visual cues of general motivational significance and of self-relevance are integrated in a fast, presumably automatic manner.

International audience; Proceeding our effort to study protein-protein interaction between the death receptor CD95 and phospholipase PLCγ1, we present in the current work chameleon-like traits of peptidomimetic inhibitors. Minute analysis of the interaction suggests that most of the binding energy relies on van der Waals contacts rather than more specific features, such as hydrogen bonds or salt bridges. The two most important positions of the peptoid for its interaction with PLCγ1 (Arg184 and Arg187) were modified to test this hypothesis. While Arg184 proves to be exchangeable for Trp, with no alteration in affinity, the nature of the amino acid replacing Arg187 is more dependent on its positive charge. However, affinity can be partially recovered by increasing van der Waals interactions. Overall, this study shows that for both positions, a subtle balance exists between hydrophobicity, surface contacts and affinity for CD95/PLCγ1, and provides information for the generation of new therapeutic compounds toward this druggable target.

The death receptor CD95 (also known as Fas) induces apoptosis through protein/protein association and the formation of the death-inducing signaling complex. On the other hand, in certain biological conditions, this receptor recruits different proteins and triggers the formation of another complex designated motility-inducing signaling complex, which promotes cell migration and inflammation. This pathway relies on a short sequence of CD95, called calcium-inducing domain (CID), which interacts with the phospholipase PLCγ1. To better understand how CID/PLCγ1 interaction occurs, we synthesized different α-AA peptides mimicking CID. Some of these peptidomimetics are as potent as the natural peptide to disrupt the CID/PLCγ1 interaction and cell migration, and showed improved pharmacokinetic properties. We also generated biotinyl- and palmitoyl-labelled peptidomimetics, useful chemico-biological tools to further explore the pro-inflammatory signal of CD95, which plays an important role in the pathogenesis of lupus and other autoimmune diseases.

International audience; CD95L is a transmembrane ligand (m-CD95L) that is cleaved by metalloproteases to release a soluble ligand (s-CD95L). Unlike m-CD95L, interaction between s-CD95L and CD95 fails to recruit caspase-8 and FADD to trigger apoptosis and instead induces a Ca2+ response via docking of PLC gamma 1 to the calcium-inducing domain (CID) within CD95. This signaling pathway induces accumulation of inflammatory Th17 cells in damaged organs of lupus patients, thereby aggravating disease pathology. A large-scale screen revealed that the HIV protease inhibitor ritonavir is a potent disruptor of the CD95-PLC gamma 1 interaction. A structure-activity relationship approach highlighted that ritonavir is a peptidomimetic that shares structural characteristics with CID with respect to docking to PLC gamma 1. Thus, we synthesized CID peptidomimetics abrogating both the CD95-driven Ca2+ response and transmigration of Th17 cells. Injection of ritonavir and the CID peptidomimetic into lupus mice alleviated clinical symptoms, opening a new avenue for the generation of drugs for lupus patients.

Market forecasting works well when markets are stable: small consumer segments can be sampled and the results statistically applied to large national consumer segments. In this column, Best argues that today's consumer food market is far too fast changing, fragmented, and fungible to effectively accommodate traditional market analyses. As reality checks against developing traditional and potentially fatal market research assumptions, Best proposes the use of three additional simple and relatively low-cost market research techniques, framing these techniques in the context of bread industry futures. 1) Attend new retail food product shows: attend and walk the relevant trade shows to get a taste of new trends. 2) Track Internet traffic: Internet chatter data mining can provide indicators of and insights into new product and venue trends. 3) Walk retail outlets: walk through retail stores, ethnic markets, boutiques and shops, and farmers' markets and note their traffic patterns, product facings, and SKU tren...

International audience; One-pot formation of arylacetic acid esters, thioesters, and amides via Rh(II)-catalyzed arylation of a Meldrum's acid-derived diazo reagent with electron-rich arenes is described. The methodology was used to efficiently synthesize an anticancer compound. © 2016 American Chemical Society.

CD95L is a transmembrane ligand (m-CD95L) that is cleaved by metalloproteases to release a soluble ligand (s-CD95L). Unlike m-CD95L, interaction between s-CD95L and CD95 fails to recruit caspase-8 and FADD to trigger apoptosis and instead induces a Ca

1,3-Enynes containing allylic hydrogens cis to the alkyne function as three-carbon components in rhodium(III)-catalyzed, all-carbon [3+3] oxidative annulations to produce spirodialins. The proposed mechanism of these reactions involves the alkenyl-to-allyl 1,4-rhodium(III) migration.

Internet chatter is a large and valuable data source that can be mined for real-time trend tracking and reaction to market changes. To be effective Internet data mining requires tools that can be used to enhance signal-to-noise ratios and quantify, organize, and qualify collected data. This has very significant implications for the cereal foods industry, because it can provide cereal food companies with early detection of and analysis mechanisms for emergent consumer trends, identify causal relationships between consumer trends to help optimize marketing and communication narratives, and assist in avoiding or mitigating the negative effects of black swan events. As such, real-time Internet chatter analysis can improve the flexibility of companies in reacting to changing circumstances. The tools developed by the financial industry to evaluate equity markets offer the potential to significantly amplify the power of Internet chatter analysis for the benefit of the cereal foods industry, as well as other indu...

Today's food and beverage industries are once again undergoing the stress and turmoil of what Austrian-school economist Joseph Schumpeter referred to as a process of “creative destruction.” Although part of the stress and turmoil is technological and informational, another big part is generational. Today's market is dominated and driven by two consumer groups: the relatively wealthy Baby Boomer generation and their Millennial offspring. Although change is stressful and stress forces change, Best argues that, in whatever form the industry emerges, it will prove to be very good for those who adapt and persevere and that the industry is readying itself for the next golden era of food and beverage manufacturing and innovation. However, adaptation requires a clear-eyed appreciation of what needs to be changed in all aspects of the industry—including, and especially, its professional organizations. Best contends there is a very large intangible asset gap waiting to be filled by professional organizations, such ...

Pulses are perfectly positioned to profit handsomely in today's emerging food landscape. This column explores how and why. Consumers today live in an age in which they can obtain and exchange ideas, discuss issues, and purchase products using the Internet. Thus, the Internet represents the world's largest consumer and customer database. Data-mining information from the Internet enables consumer trends to be tracked on a nearly real-time basis: when interest in an issue rises, Internet chatter rises; if interest falls off, Internet chatter declines. The challenge is to separate the relevant signals from the background “noise.” Internet chatter velocity and a VIC TrendAlert™ volatility index are nearly real-time indicators of trend stability versus impending change. These tools are applied to the analysis of leading consumer dietary trends to reveal how well aligned these trends are with the benefits provided by pulse ingredients.

The relative configuration of the title compound, C8H 12O5, was unequivocally established by X-ray crystallographic analysis; the absolute configuration was determined by the use of D-ribose as a starting material. © 2007 International Union of Crystallography All rights reserved.

2-Deoxy- d -glucitol and 2-deoxy- d -allitol, both prepared as crystalline polyols from d -erythronolactone, are oxidized by Gluconobacter thailandicus NBRC 3254 to 5-deoxy- d - threo -hexulose [5-deoxy- d -fructose = 5-deoxy- l -sorbose] and 5-deoxy- d - erythro -hexulose [5-deoxy- l -psicose = 5-deoxy- d -tagatose], respectively. d -Tagatose-3-epimerase (DTE) equilibrates 5-deoxy- d -fructose to 5-deoxy- d -psicose and 5-deoxy- l -psicose to 5-deoxy- l -fructose, providing substrates for the preparation of all eight d - and l -5-deoxy aldohexoses by aldose isomerases. This combination of chemical and biotechnological methods allows a concise approach to the synthesis of all twelve 5-deoxy hexoses and further demonstrates the range of deoxy sugar substrates on which DTE is active. NMR studies show that 5-deoxy- d -fructose exists solely as the β-pyranose form whereas both pyranoses of 5-deoxy- d -fructose [α:β. 22:78] are observed. [For the sake of clarity, all ketoses in this Letter are shown in blue, alditols in red and aldoses in purple.]

2-Acetamido-1,2-dideoxy- d -galacto-nojirimycin [DGJNAc], prepared in 20% overall yield from d -glucuronolactone, is the first potent competitive sub-micromolar inhibitor of α-N-acetyl-galactosaminidases (Ki 0.081 μM from chicken liver, Ki 0.136 μM from Charonia lampas). DGJNAc is a good competitive—whereas the enantiomer l -DGJNAc is a very weak but non-competitive—inhibitor of β-hexosaminidases.

The stereochemistry of crystalline 1-de-oxy-4-C-hydroxy-methyl-3,4-O- isopropyl-idene-Β-l-ribulofuran-ose, C9H16O5, was unequivocally established by X-ray crystallographic analysis to be the Β-anomer; the absolute configuration was determined by the use of d-ribose as a starting material. © 2007 International Union of Crystallography. All rights reserved.

Azaarene-containing, Boc-protected aminoalcohols are prepared by three-component coupling of vinylazaarenes, dipinacolyl hypodiborate, and N-Boc imines followed by oxidation of initially formed boronates.

Cu-catalyzed three-component couplings of vinylazaarenes, B2(pin)2, and N-Boc imines are described. Oxidation of the initially formed boronate gives azaarene-containing, Boc-protected amino alcohols with reasonable to good diastereoselectivities.

Dynemicin A 2-1 was first isolated in the mid-1980s from Micromonospora chersina, a soil microorganism collected in the state of Gujarat in India. From a 200 L culture broth, it was possible to obtain 5.7 mg of 2-1 as a violet amorphous solid after extraction and purification. The production of 2-1 was later improved by the addition of sodium iodide to the culture medium, which allowed isolation of up to 2 g of 2-1 from a 10 000 L fermentation broth. The presence of ionexchanging resins in the neutral culture medium also improved the efficiency. The spectroscopic characterization was facilitated by converting dynemicin A into the triacetate derivative 2-2, which is soluble in most organic solvents, and allowed unequivocal structural determination by single-crystal X-ray diffraction. Although the structure obtained by X-ray diffraction revealed the relative configurations of stereogenic centers, the absolute configuration of 2-1 was not firmly established until the first total asymmetric synthesis described by Myers in 1995 and 1997.

1,3-Enynes containing allylic hydrogens cis to the alkyne function as three-carbon components in rhodium(III)-catalyzed, all-carbon [3+3] oxidative annulations to produce spirodialins. The proposed mechanism of these reactions involves the alkenyl-to-allyl 1,4-rhodium(III) migration.

Food companies continually strive to discern the minds of consumers in their search to get ahead of trend curves and be the first to market with products that will meet consumer needs. In this column, Best discusses what narratives can tell us about what is resonating with consumers in the cereal foods marketplace, shaping views on diets, foods, beverages, and nutrition. To examine narratives and evaluate the market, the first question is, “What are people talking about?” Monitoring Internet activity through search engine patterns can reveal where the action is, where it isn't, and where attention needs to be focused. The nutrition, food science, and cereal science communities must monitor whether consumers are getting the messages they are sending and be prepared to confront counter-messages from other sources, such as popular books and diet trends. An Internet background-chatter analysis should be step one in any marketing research or strategic planning program. Inexpensive and readily available, it pro...

Price and cost relationships are probably the most important and most difficult factors to address when developing and marketing new products and technologies but are often overlooked. In this column Best discusses new product economics as a marketing discipline. The food industry relies on continuous innovation for its success. Innovation entails product and technology development, commercialization, and market entry. The right price is that which maximizes the benefits to both the supplier and customer. Establishing the right product price requires properly capturing product costs: fixed, variable, and semivariable. As a basic rule, it is best to break down and allocate as many costs as possible to specific products and their related activities as variable, rather than fixed, costs. Cost reallocation should be done before a product or technology is introduced to the market, because miscalculated cost structures inevitably lead to poor pricing strategies and to sometimes fatal mistakes. The financial or ...

A convenient large-scale synthesis of 1-deoxynojirimyin (DNJ) from d -glucuronolactone involves introduction of azide at C-5 with retention of configuration to give 5-azido-5-deoxy-1,2- O -isopropylidene-α- d -glucofuranose as a key intermediate in an overall yield of up to 72%; the same intermediate can be transformed into DMDP [(2 R, 3 R, 4 R, 5 R )-2,5-bis(hydroxymethyl)pyrrolidine-3,4-diol] and (3 R )-3-hydroxy- l -bulgecinine [(2 S, 3 R, 4 R, 5 R )-3,4-dihydroxy-5-hydroxymethyl- l -proline]. l -Glucuronolactone, a readily available l -sugar chiron, may similarly be used to access the enantiomers l -DNJ, l -DMDP, and (3 S )-3-hydroxy- d -bulgecinine. A comparison of glycosidase inhibition by DMDP (an inhibitor of β-glucosidases and β-galactosidases) and l -DMDP (a potent and specific α-glucosidase inhibitor) with the corresponding enantiomeric hydroxybulgecinines is reported; DMDP and (3 R )-3-hydroxy- l -bulgecinine show weak inhibition of glycogen phosphorylase.

1,2-O-Isopropylidene-α-l-glucurono-3,6-lactone may be synthesized on a 100-200 g scale from cheaply available d-glucoheptonolactone in an overall yield of 94% in four steps via l-glucuronolactone. Subsequent elaboration to l-glucose, diacetone-l-glucose (1,2:5,6-di-O-isopropylidene-α-l-glucofuranose), and monoacetone-l-glucose (1,2-O-isopropylidene-α-l-glucofuranose) allows easy access to a range of l-sugar chirons. © 2009 Elsevier Ltd. All rights reserved.

A protecting group that can be introduced efficiently without the need for any acid or base catalysis and which is not prone to acid or base catalysed migration is a significant advantage for many syntheses. Benzhydryl [diphenylmethyl] ethers of sugar lactones are formed in high yield under neutral conditions when the corresponding alcohol is heated with diphenyldiazomethane in an inert solvent such as acetonitrile or toluene; this allows the easy protection of base sensitive and highly hindered tertiary alcohols in the absence of any other reagents. © 2008 Elsevier Ltd. All rights reserved.

A commercially available rhodium(II) complex catalyzes the direct arylation of 5-diazobarbituric acids with arenes, allowing straightforward access to 5-aryl barbituric acids. Free N—H groups are tolerated on the barbituric acid, with no complications arising from N—H insertion processes. This method was applied to the concise synthesis of a potent matrix metalloproteinase (MMP) inhibitor.

A commercially available rhodium(II) complex catalyzes the direct arylation of 5-diazobarbituric acids with arenes, allowing straightforward access to 5-aryl barbituric acids. Free N—H groups are tolerated on the barbituric acid, with no complications arising from N—H insertion processes. This method was applied to the concise synthesis of a potent matrix metalloproteinase (MMP) inhibitor.

The dearomatizing oxidative annulation of 2-alkenylphenols with alkynes and enynes proceeds with high yields and regioselectivities under Rh(III) catalysis. These reactions are successful using Cu(OAc)2 or air as the stoichiometric oxidant, and provide spirocyclic enones, the basic ring system of which appears in several natural products. Application of this process to the preparation of a highly functionalized tetracycle is also demonstrated.

In the more developed Western economies, foods that have historically been thought of as “poor people's foods,” such as pulses, sorghum, quinoa, and even potatoes, have recently gained in popularity. However, pulse product development remains underexplored, and there are a number of challenges and opportunities related to pulses to be considered. Pulses are superb rotational crops because they contribute nitrogen to the soil and grow well in areas where weed pressure is low, making them highly sustainable. Global production of edible pulses has increased to nearly 60 million tonnes. Two important nutritional drivers behind consumption of pulses are their roles as primary sources of dietary protein and high-value nutrients. Pulses can also function as substitutes for common allergenic food ingredients (e.g., wheat and soybeans). There are technical obstacles to future pulse development, however, that will require significant R&D investment. In addition, although some individual regional organizations have ...

The dearomatizing oxidative annulation of 2-alkenylphenols with alkynes and enynes proceeds with high yields and regioselectivities under Rh(III) catalysis. These reactions are successful using Cu(OAc)2 or air as the stoichiometric oxidant, and provide spirocyclic enones, the basic ring system of which appears in several natural products. Application of this process to the preparation of a highly functionalized tetracycle is also demonstrated.

Nitrogen-containing aromatic heterocycles (azaarenes) are of widespread chemical significance, and chiral compounds containing azaarenes feature prominently in pharmaceuticals, agrochemicals, and natural products. This Perspective highlights the use of a relatively underdeveloped strategy to prepare chiral azaarene-containing compounds: exploitation of the C═N bond embedded within certain azaarenes to activate adjacent functionality in catalytic asymmetric reactions. Work in this area has resulted in the development of several different types of catalytic enantioselective processes, including reductions, nucleophilic additions, and reductive couplings. It is hoped that this Perspective will encourage more researchers to work in this promising area.

Motivational states may be induced by affective foreground stimulation or via proprioceptive feedback by certain postures or body movements. In the present study, we addressed the question of an interaction between basic motor actions and the valence of visual stimuli in an affective modulation of startle paradigm: is the potentiation for aversive and the attenuation for pleasant stimuli more pronounced when the muscles for a congruent approach or avoidance action are activated? Thirty-four volunteers (20 female) watched emotional pictures on a computer screen while simultaneously contracting the flexor vs. extensor muscles of the upper arm. After 3–4 s, an acoustic startle stimulus (105 dB, binaural, instantaneous rise time) was presented via headphones. Arm movement interacted with picture valence: flexion, compared to extension, increased affective startle modulation (F = 4.32, p < 0.05). This result suggests integration and not simple summation of postural and body movement effects on startle reflexivity.

Nitrogen-containing aromatic heterocycles (azaarenes) are of widespread chemical significance, and chi-ral compounds containing azaarenes feature prominently in pharmaceuticals, agrochemicals, and natural products. This Perspective highlights the use of a relatively underdeveloped strategy to prepare chiral azaarene-containing compounds: exploitation of the C=N bond embedded within certain azaarenes to activate adjacent functionality in catalytic asym-metric reactions. Work in this area has resulted in the development of several different types of catalytic enantioselec-tive processes, including reductions, nucleophilic additions, and reductive couplings. It is hoped that this Perspective will encourage more researchers to work in this promising area.