Thorne QC maintains SIPT Trial is political vendetta

first_imgFacebook Twitter Google+LinkedInPinterestWhatsAppProvidenciales, 15 Feb 2016 – Every intrusive and erratic remark and statement made by the Special Prosecutor for the Crown must be proved to be true; it was the overarching theme of the statement today from Ralph Thorne, the Queen’s Counsel representing former premier Michael Misick. Thorne was revved up in his presentation and called the opening statement by Andrew Mitchell, QC nothing more than a political vendetta aimed at ‘getting Mike’. He said, when proceedings resumed this morning at the Myrtle Rigby Health complex that, “An expedition in character assassination…” is what Mitchell led in his abnormal opening, which seemed to draw conclusions instead of the traditional method of promising, then proving allegations. Thorne promises to prove that the charges are politically motivated and he will aim to defend the character of his client. Thorne has a problem with the absence of any civilian witnesses, he has an issue with government witnesses who are coming in their official capacity and he rejects that the former Governor was bullied by Michael Misick during his tenure and Thorne takes exception to the fact that Developers in the debacle, are missing from the trial. Thorne said, the mountain of apparent evidence by the SIPT will turn into a mouse of proof, and that it will not be enough to satisfy the court. Karen Delancy, former Cabinet Minister in Michael Misick regime takes the witness stand in SIPT trials Facebook Twitter Google+LinkedInPinterestWhatsApp Recommended for you BOYCE FIRES HER ATTORNEY, as SIPT Trial continues Delancy challenged on leadership style, calls Floyd Hall, ‘man of integrity’ Related Items:andrew mitchell, michael misick, queen’s counsel, ralph thorne, sipt triallast_img read more

San Diego Police increasing traffic safety enforcement

first_img Updated: 6:48 PM , SAN DIEGO (KUSI) — The San Diego Police Department is conducting an increased traffic safety enforcement operation Saturday.Officers were on the lookout for “collision causing factors” throughout the city from 10 a.m. to 6 p.m.“Routine traffic patrols will focus efforts in trouble spots while special targeted patrols will also be deployed to crack down on drivers and pedestrians who violate traffic laws meant to protect all roadway users,” SDPD Officer Mark McCullough said. “Officers will be looking for traffic offenses made by drivers, bicyclists and pedestrians alike that can lead to life changing injuries.”McCullough said attention will be directed toward drivers speeding, making illegal turns, failing to stop for signs and signals and failing to yield to pedestrians in crosswalks.Police also are looking for pedestrians who cross illegally or fail to yield to drivers who have the right-of-way.Funding for the program was provided by a grant from the California Office of Traffic Safety through the National Highway Traffic Safety Administration, McCullough said. January 20, 2018 Posted: January 20, 2018 Categories: Local San Diego News FacebookTwitter San Diego Police increasing traffic safety enforcementlast_img read more

Survey Digital Magazines Still Not a BreakOut Platform

first_imgDigital publishing consultancy Mequoda Group has released the results of its third Digital Magazine Market Study. This year, the firm tripled its sample size to 3,642 U.S. adults and backed off the tablet-specific demo they used for the previous studies, which negates year-over-year comparisons, but there are still more than a few highlights. Interestingly, that metric almost flips when Mequoda asked about print magazine readership. About 70 percent of respondents said they read an average of 2.91 print issues in the last 30 days while 30 percent did not read a print magazine at all. Either publishers are de-emphasizing monetization of subscriptions and single copy sales or most consumers simply aren’t buying. The study notes that 58 percent of respondents spent no money on digital magazine single copies or subscriptions in the last 12 months, and of those that did, they averaged $17.20. General advertising was a tick worse: Six percent said very important, 9 percent thought it was important, 21 percent said slightly important and 45 percent deemed it not important. Meanwhile, digital magazines don’t stand out as a singular preference when readers consider how they prefer to access magazine content. Yet, they’re holding their own against the print edition and web edition. Each format captured about a third of responses. Even so, advertising may not be viewed by readers as being part of a digital magazine’s functionality, but those low numbers indicate that readers are not seeing the value of advertising as part of a digital magazine experience.    Those may be harder to deliver, if at all, in basic PDF versions of a magazine, but beyond those two, responses on other more dynamic content features become more fractured. Only 10 percent of respondents say embedded video is very important and 22 percent say it’s not important, for example.center_img As for functionality, 79 percent of respondents say readable text is very important, while 56 percent say scrollable text is very important. Nevertheless, Mequoda notes that readable and scrollable text are features common in native and responsive web versions of digital magazines, which point to a reader preference for those formats. Advertising is way down on the functionality list, unfortunately. Nine percent said relevant advertising is ‘”very important” and 12 percent said it’s “important.” Thirty-seven percent said it’s “not important” and 17 percent said “slightly important.” Respondents are fairly active readers of digital magazines, but not overly so. According to the survey, about 63 percent had not read a digital magazine in the last 30 days. The remaining 37 percent read an average of 2.37 issues during that period, however. For the full study, including digital magazine best practices, click here.last_img read more

NOW HIRING 60 New Job Openings In Wilmington Week of July 14 2019

first_imgWILMINGTON, MA — Below are job listings previously published on Wilmington Apple during the week of July 14, 2019:Full-Time Class D Delivery Driver at J. Polep Distribution ServicesFull-Time Production Technician at CutisPharmaPart-Time Medical Assistant at AllOne HealthFull-Time Credit Analyst at Standard ElectricFull-Time Human Resources Manager at Northland Industrial Truck CompanyFull-Time Line Cook at Red Heat TavernFull-Time Drivers & Movers at Two Men And A TruckFull-Time/Part-Time Cooks & Servers at 99 RestaurantPart-Time Afternoon Route Delivery Driver at OptimaPart-Time Cargo Van Delivery Driver at OptimaPart-Time C.A.R.E.S. Group Leaders at Wilmington Public SchoolsFull-Time Speech & Language Pathologist Assistant at Wilmington Public SchoolsFull-Time Preschool Teacher at Abundant LifeFull-Time Food Safety Sanitor (3rd Shift) at Packer Sanitation Full-Time Payroll Auditor at New England Carpenters Benefit FundsFull-Time & Part-Time Delivery Driver at Optima CourierPart-Time Catering Coordinator at Panera BreadFull-Time Senior Quality Engineer at AmetekFull-Time Sr. Analyst at Charles River LabsFull-Time Technician at Xenon CorporationFull-Time Buyer at TextronFull-Time Buyer (Manufacturing) at Monogram FoodsFull-Time Service Technician at Cochrane VentilationPart-Time Customer Service at Anton’s CleanersPart-Time Dishwashers at 99 RestaurantFull-Time Healthcare Revenue Cycle Trainer at Casamba LLCFull-Time/Part-Time Infant/Toddler & Preschool Teacher at Tendre Learning CenterFull-Time Project Executive at Limbach Facility ServicesFull-Time Independent Life Coach at NuPath Inc.Full-Time Manager In Training at Nouria EnergyFull-Time/Part-Time Member Services Representative at Planet FitnessFull-Time/Part-Time Overnight Closer at Planet FitnessFull-Time/Part-Time Fitness Trainer at Planet FitnessFull-Time Sanitation Worker at Stuffed FoodsFull-Time Manufacturing Technician (Inspector) at AMETEK, Inc.Part-Time Warehouse Package Handler at FedExFull-Time Rx Authorization Specialist at AmetrosFull-Time Onboarding Coordinator at AmetrosFull-Time Food & Beverage Team Leader at TargetPart-Time Cashier at Panera BreadFull-Time Corporate Program Sales Executive at UniFirstPart-Time Retail Sales Associate at UPS StoreFull-Time Scrum Master at SOVOS CompliancePart-Time Housekeeper For Wilmington HomePart-Time Overnight Team Leader at Dunkin’ DonutsFull-Time Software Engineer at SymboticFull-Time Deployment Engineer at Locus RoboticsFull-Time Reset Specialist at Pepsi BeveragesFull-Time Business Unit Controller at MKS InstrumentsPart-Time Server For Glendale Dining ServicesFull-Time Educational Assistant (Grades 1-3) at Shawsheen Elementary SchoolFull-Time Grade 4 Teacher (1-Year Interim Position) at West Intermediate SchoolFull-Time Long-Term Substitute Reading Specialist (for 1 Year) at North Intermediate School & West Intermediate SchoolFull-Time Long-Term Substitute Special Education Teacher at Wilmington High SchoolPart-Time Substitute Teachers, Educational Assistants, LPNs and Nurses at Wilmington Public SchoolsFull-Time Custodial Worker at Wilmington High School(NOTE: Wilmington businesses — Feel free to send me your job postings at wilmingtonapple@gmail.com.)Like Wilmington Apple on Facebook. Follow Wilmington Apple on Twitter. Follow Wilmington Apple on Instagram. Subscribe to Wilmington Apple’s daily email newsletter HERE. Got a comment, question, photo, press release, or news tip? Email wilmingtonapple@gmail.com.Share this:TwitterFacebookLike this:Like Loading… RelatedNOW HIRING: 50 New Job Openings In Wilmington (Week of August 18, 2019)In “Business”NOW HIRING: 60 New Job Openings In Wilmington (Week of July 28, 2019)In “Business”NOW HIRING: 60 New Job Openings In Wilmington (Week of July 7, 2019)In “Business”last_img read more

Facebook is creating a cryptocurrency to use on WhatsApp says report

first_img 0 See how much time you’re wasting on Facebook In May, news site Cheddar reported that Facebook was “very serious” about the possibility of building its own digital currency for secure online payments. Facebook said at the time it had a small team looking into applications for blockchain — the encryption technology behind cryptocurrencies like bitcoin — but didn’t offer specifics.Facebook still has a ways to go before its cryptocurrency is ready, according to Bloomberg. The company plans to develop a stablecoin that’s pegged to the US dollar, unnamed sources told Bloomberg, but is still working on strategy and ways to protect the value of its coin.Facebook bought encrypted messaging app WhatsApp back in 2014 for $22 billion. Bitcoin Facebook Cryptocurrency WhatsApp Post a comment Share your voice Now playing: Watch this: 1:31 Tags Facebook may be getting into the cryptocurrency game.The social network is reportedly developing a digital currency that will let users transfer money on its WhatsApp messaging service, according to a report Friday from Bloomberg. The effort will focus first on the remittances market in India, according to Bloomberg.Facebook didn’t immediately respond to a request for comment. Mobile Mobile Appslast_img read more

IBM earns record patents in 2018 India 2nd highest contributor

first_img[Representational Image]ReutersIBM investors from India earned over 800 patents — the second highest contributor to the company’s global record of 9,100 patents in the US in 2018 — with nearly half in the fields of Artificial Intelligence (AI), Cloud computing, cybersecurity, Blockchain and Quantum Computing.One of the patents filed from India went to IBM inventors Shivali Agarwal, Gaargi B Dasgupta, Shripad J Nadgowda and Tapan K Nayak, the company said in a statement on Tuesday.They developed an AI-based approach for structured representation and classification of noisy and unstructured data in tickets used in service delivery.Ticket analysis helps create problem diagnostics, prediction of outages and prevention of issues in service delivery, for example for help desks.”IBM is committed to leading the way on the technologies that change the way the world works – and solving problems many people have not even thought of yet,” said Ginni Rometty, IBM Chairman, President and CEO.Among more than 1,600 AI patents included “Project Debater” that, with the use of Machine Learning, can debate humans on complex topics — identifying evidence such as relevant text segments in unstructured text data, which supports or opposes a claim or topic under consideration.IBM inventors received more than 2,000 Cloud computing and over 1,600 AI patents.The new patents were granted to a diverse group of more than 8,500 IBM inventors in 47 US states and 48 countries.last_img read more

Yogi govt to cancel arms licences of mafia criminals

first_imgThe state Home Department is drawing up the list of criminal-turned-politicians on the instructions of the Chief Minister.IANSThe Yogi Adityanath government in Uttar Pradesh has decided to cancel the arms licenses of mafia and criminal-turned-politicians and is preparing a list of such names.According to highly placed sources, the state Home Department is drawing up the list of such persons on the instructions of the Chief Minister.”We are checking the track records of prominent persons with criminal antecedents and the number of arm licences issued to them. We are also making a list of the licenses issued to their family and gang members and supporters. It has been seen that though arms licenses are issued to family members, they are used in gang wars,” said a senior official.On the list are names of mafia-turned-politicians such as Mukhtar Ansari, Ateeq Ahmad, Dhananjay Singh, Abhay Singh and Raja Bhaiyya. All these leaders, sources said, have multiple licenses.The state government believes that disarming persons with criminal antecedents would go a long way in improving the law and order situation in the state. This would also curb public display of firearms, which is aimed at intimidating the public.last_img read more

BNPs street campaign over should prepare for polls Quader

first_imgAwami League general secretary Obaidul Quader. File photoRuling Bangladesh Awami League (AL) general secretary Obaidul Quader said on Saturday opposition Bangladesh Nationalist Party’s (BNP) anti-government campaign is over.Also the road transport and bridges minister, Quader suggested that BNP should rather prepare for the next general elections now.Speaking to newsmen while inspecting the repair work of the Dhaka-Tangail four-lane highway in Chandra of Gazipur, the AL leader also claimed that the ruling party has no desire to keep BNP out of the next polls slated to be held at the year end.“As a registered political party, BNP reserves the right to take part in the polls. The issue of Khaleda Zia’s release is not in our hands. We’ve no objection if Khaleda Zia is freed through legal battle,” said Quader.The road transport and bridges minister said as much as 70 per cent work of Dhaka-Tangail four-lane highway is complete so far, hoping the home-goers would not need to suffer during the next Eid journey.last_img read more

ACC bans foreign trip of 7 bankers

first_imgLogo of Anti Corruption Commission. File photoThe Anti-Corruption Commission (ACC) has imposed a ban on the foreign travel of seven officials of The Farmers Bank Ltd over approving Tk 40 million loan against fake documents and depositing the money into former chief justice SK Sinha’s account, reports UNB.ACC public relations officer Pranab Kumar Bhattacharya on Wednesday told UNB that a notice was sent to superintendent of police (Immigration) of special branch of police in this regard.The officials are former managing director and chief executive officer AKM Shameem, first vice-president Swapan Kumar Roy, senior executive vice-president Gazi Salauddin, vice-president M Lutful Haque, assistant vice-president Shafiuddin Askaree Ahmed, former SVP Ziauddin and executive officer Umme Salma Sultana.Meanwhile, six of the seven officials were quizzed on Wednesday in this connection.Earlier on 6 May, ACC grilled two businessmen named — Md Shahjahan and Niranjan Chadra Saha — for allegedly taking Tk 40 million in loan from The Farmers Bank Ltd using fake documents and depositing the money in the bank account of a VVIP.last_img read more

India confirms 5 nationals killed in NZ shootings

first_imgMohsin Vora, the brother of Asif, told AFP that they were initially told his brother and nephew were injured in the attack, before a family member identified their bodies when they flew to New Zealand. “I and (the) parents of Ramiz’s wife have been granted visas. We will be leaving for New Zealand soon,” Vora said. Three of the dead from the mass shooting at Al Noor mosque were from Gujarat state. They were father and son victims Asif and Ramiz Vora, and 65-year-old retiree Mahboob Khokhar, who was visiting his son in Christchurch. Desperate families in India have been trying to confirm the safety of their relatives after 28-year-old Australian white supremacist Brenton Tarrant allegedly launched his murderous rampage. An Indian foreign ministry official in New Delhi told AFP that they are “in process of ascertaining information about all Indians affected by the terror attack”. The fifth victim, Ozair Kadir, was an aspiring commercial pilot from Hyderabad city. Five Indian nationals were among the 50 worshippers killed in the Christchurch mosque attacks, with at least two others reported to be injured, officials said Sunday. The official denied Indian media reports that claimed seven people were killed in the attack. Ansi Karippakulam Alibava — a 23-year-old from Kerala, who had lived with her husband in Christchurch since last year as she studied for a masters — was also confirmed dead. India’s embassy in New Zealand confirmed the deaths in a tweet, following the devastating shootings at twin mosques in the normally peaceful city. Vora said his 56-year-old brother had gone to meet his new grandchild a month ago.last_img read more

Android apps are full of potential leaks finds study

first_imgCredit: Sascha Fahl, et al. (Phys.org)—Many Android apps are capable of falling victim to Man in the Middle (MITM) attacks. How many? Far too many. Thousands of apps in the Google Play mobile market present vulnerabilities because of the way that protocols are implemented—namely, the Secure Sockets Layer (SSL) and Transport Layer Security (TLS). That Android apps are open to malware by now is a yawn-evoking statement if there ever was one, but a new paper provides findings that are making this week’s headlines. Computer science researchers from Philipps University of Marburg and Leibniz University of Hannover in Germany showed that Android apps that are used by over 180 million people can expose banking, social networking and email information. Citation: Android apps are full of potential leaks, finds study (2012, October 22) retrieved 18 August 2019 from https://phys.org/news/2012-10-android-apps-full-potential-leaks.html 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. Android users get malware with their apps More information: Research paper: www2.dcsec.uni-hannover.de/fil … android/p50-fahl.pdfVia Arstechnica © 2012 Phys.org They identified 41 apps available on the Google Play mart that leak sensitive information in traveling between smartphones and servers. The researchers used a smartphone with Android 4.0 Ice Cream Sandwich in their investigations. They installed potentially vulnerable apps on the phone and set up a WiFi access point with a Man in the Middle (MITM) SSL proxy. They equipped the SSL proxy with a self-signed certificate or with one that was signed by a trusted CA, but for an unrelated host name. Of the 100 apps selected for manual audit, 41 apps proved to have exploitable vulnerabilities. They captured credentials for numerous major services. “Furthermore, Facebook, email and cloud storage credentials and messages were leaked, access to IP cameras was gained and control channels for apps and remote servers could be subverted.”Their paper, testily called “Why Eve and Mallory Love Android: An Analysis of Android SSL (In)Security,” discovered the apps that have SSL code that either accepts all certificates or all hostnames for a certificate and thus are potentially vulnerable to MITM attacks.What also troubled the authors was the inability of many people in their survey to even recognize security threats attached to applications. “The results of our online survey with 754 participants showed that there is some confusion among Android users as to which security indicators are indicative of a secure connection, and about half of the participants could not judge the security state of a browser session correctly,” they said.Regarding secure connections, the researchers found that 47.5% of non-IT experts believed to be using a secure connection while the survey was served over HTTP. In addition, 34.7% of participants with prior IT education thought that they were using a secure channel when they were not. Only 58.9% of experts and 44.3% of non-experts correctly identified that they were using a secure or insecure connection when prompted.In summing up, the authors pointed to a need for more education and easier tools that can enable the secure development of Android apps. They also called attention to the need for research to identify which countermeasures can ensure the right mix of usability, security benefits and economic incentives for large-scale deployment.Android by the numbers merits that kind of care. Android is the most used smartphone operating system in the world. Building on the contributions of the open-source Linux community and more than 300 hardware, software, and carrier partners, Android has become the fastest-growing mobile operating system. The numbers keep shifting, but Android’s market share currently stays over 50 percent. Android users download more than 1.5 billion apps and games from Google Play each month, and the number is growing.last_img read more

Managing complexity Novel protein folding tool vastly simplifies understanding how sequence encodes

first_img Citation: Managing complexity: Novel protein folding tool vastly simplifies understanding how sequence encodes structure (2016, November 29) retrieved 18 August 2019 from https://phys.org/news/2016-11-complexity-protein-tool-vastly-sequence.html (Phys.org)—Protein folding is the process by which a polypeptide (a linear organic polymer chain consisting of many amino acid residues, or monomers) transforms from a random coil into the 3D conformation in which it can perform its biological function. Since different proteins fold into a range of very different shapes, the Protein Data Bank (PDB) – a database archive comprising experimentally-determined three-dimensional structures of large biological molecules, including numerous protein conformations – can be disarmingly complex. This is problematic because that space is fundamental to understanding how sequence encodes structure. Recently, however, scientists at Dartmouth College deconstructed the universe of known protein structures into reusable building blocks that they term tertiary structural motifs, or TERMs. (Structural motifs are compact blocks of a 3D protein structure.) They found that 50% of PDB protein conformations were described – at sub-Angstrom resolution – by a surprisingly small group of roughly 600 TERMs. Moreover, TERMs allowed them to discern sequence–structure relationships. The researchers state that these results can be used for protein structure prediction, protein design and other applications. In addition, some 600 TERMs describe 50% of the known protein structural universe at sub-Angstrom resolution. “This refers to the level of degeneracy we discovered in the protein structure space.” That only ~600 TERMs are required to describe half of all residues and inter-residue contacts in known protein structures suggests that at the local structural level, there just are not that many structural patterns that naturally emerge. There are, of course, a large number of more rare geometries, and full coverage of the protein structural universe requires tens or even hundreds of thousands of TERMs – but nevertheless, the majority of protein structure does appear to be quite degenerate at the local level.”As to the specific implications of their study for protein structure prediction, protein design, and other applications, Grigoryan points out that the major implication for protein design and structure prediction is the novel means of mining for sequence-structure relationships. “Statistical potentials, derived from known protein structures, have been employed for decades in both of these applications. However, such potentials typically describe the statistics associated with isolated simplistic structural features, like dihedral angles, individual interatomic or interresidue distances, or burial environments. However, TERMs offer the potential to describe sequence statistics in the context of holistic structural environments, which would be much more useful for both design and prediction.” Specifically, he explains, in design, this would allow for a better understanding of what sequences would or would not form the target structure; for prediction, it would help drive structural sampling towards structures whose TERMs are most consistent with the modeled structure. “A potential limitation is the amount of available data, because not all TERMs have sufficient known instances to synthesize accurate sequence models,” he acknowledges. “However, the early results shown in our paper, as well as some unpublished results in our lab, point to the fact that TERM-based statistics are already providing non-trivial insights that in many cases, other methods are unable to easily capture – and this is only going to get better as the amount of structural data continues to accumulate.”When asked about the implications of their work for synthetic genomics and synthetic proteomics, Grigoryan said “It’s a good question. I can certainly see a future in which a truly robust method for computational protein design serves as a key element in synthetic genomics and proteomics applications. I’d say that in terms of our current design techniques, we’re not quite there today – but our goal with TERM-based and other developments – as well as the general goal of our field – is certainly to keep improving the robustness of our methods, so that one day, we can offer them as black-box solutions to folks in other disciplines, whether that be materials science, biomedicine, or synthetic biology.”Moving forward, Grigoryan says that the team is focused on extending the capabilities of their TERM-based techniques to both protein design and structure prediction. “We’re also very interested in introducing ensemble-based modeling approaches into protein design: Since protein structural states are really conformational ensembles, the language of statistical mechanics is most appropriate for describing their behavior. Therefore, we’re pursuing methods for introducing statistical mechanics-based calculations towards improving the accuracy and robustness of protein design methods.”In addition to protein design and structure prediction, Grigoryan sees their study as having strong implications for our fundamental understanding of protein structure in general. “I think the new look at the protein structural universe our study offers can help not only with modeling and designing proteins, but it can also help with teaching about protein structure. The ideas of modularity and representation of standard motifs,” he concludes, “have already made their way into my own teaching here at Dartmouth.” Fig. 1. Discovering TERMs that optimally describe the protein structural universe. (A) A candidate motif is defined around each residue in the database, structural matches (from within the database) to each motif are identified using MASTER (58), and these matches are used in defining the coverage of every motif. Next, the set cover problem is solved to find the minimal set of motifs that jointly cover the structural universe. (B) Coverage of the universe as a function of the number of TERMs, in the order discovered by the greedy algorithm (inset uses logarithmic scale along the x axis). Mackenzie CO, Zhou J, Grigoryan G (2016} Tertiary alphabet for the observable protein structural universe. Proc Natl Acad Sci USA 113(47):E7438-E7447. Fig. 2. Universal TERMs. (A) Top 24 TERMs ranked by the number of elements covered in the set cover procedure; jointly these cover roughly a third of the universe elements. (B) A diverse selection of high-priority TERMs that span from one- to five-segment motifs, shown in the first to fifth columns, respectively. Shown in each column are representatives from the three most common secondary-structure classes for the given number of segments (SI Appendix, SI Methods). In both A and B, each TERM is represented with ten randomly chosen matches along with its centroid. The text underneath each TERM is formatted as follows: r; n (s/c) where r is the rank of the TERM in the set cover (lower rank corresponds to higher priority), n is the number of unique matches, s is the total fraction of universe elements covered by the TERM, and c is the marginal fraction of the universe elements covered by the TERM (i.e., fractional coverage of those elements not already covered by preceding TERMs in the set cover). Mackenzie CO, Zhou J, Grigoryan G (2016} Tertiary alphabet for the observable protein structural universe. Proc Natl Acad Sci USA 113(47):E7438-E7447. Grigoryan adds that by using residues and contacts rather than an a priori structural alphabet, defining the motif candidates was much easier. “It seemed particularly natural to define one candidate motif for every residue in the structural database,” he notes, “such that the motif would capture the residue and all of its contacts – that is, the motif would describe that residue’s local structural environment.” More information: Tertiary alphabet for the observable protein structural universe, PNAS November 3, 2016, Published online before print, doi:10.1073/pnas.1607178113 Researchers find possible universal code of protein structure A key finding discussed in the paper was that universal TERMs provide an effective mapping between sequence and structure. “Because universal TERMs recur many times in unrelated proteins,” Grigoryan tells Phys.org, “compiling the list of occurrences of each TERM allows us to start gleaning sequence rules that may underlie each of these structural motifs. The question was whether these sequence rules reflected fundamental determinants of structure, or simply noise from a limited structural database potentially biased by arbitrary evolutionary choices or the selection of proteins whose structures have been solved.” The team resolved this through a series of experiments in which they demonstrated that a significant component of the sequence statistics emerging from TERM matches does likely emerge from fundamental sequence-structure relationships.In effect, the natural utilization of TERMs provides a means of uncovering sequence–structure relationships. “Let’s say a given TERM is consistent of a two-strand beta sheet interacting with an alpha helix at a particular characteristic crossing angle and distance,” Grigoryan illustrates. “If we happen to have, for example, 600 instances of this motif from unrelated proteins, we essentially have 600 different examples of nature having made this structure with different amino-acid sequences. We can then use these 600 sequences to begin to understand what sequence features may be required or preferred to form such a structure – and we can do this for any TERM with sufficiently high usage in nature.”It turns out that by using this approach systematically for all TERMs contained in a given protein backbone structure, sequence variability predicted from TERM data agrees closely with evolutionary variation. “We can deduce a statistical model of what sorts of sequences would be likely to fold to that structure,” he explains. “If we then ask this model to produce a whole bunch of such sequences, we find that the emergent sequence variability is often in close agreement to the evolutionary variability observe for the corresponding protein.” © 2016 Phys.org 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. Prof. Gevorg Grigoryan discussed the paper that he and his co-authors published in Proceedings of the National Academy of Science of the United States of America. One of the primary challenges in their study was decomposing the set of known protein structures into standard reusable tertiary structural motifs. “The main challenge here was probably knowing where to begin,” Grigoryan tells Phys.org. “Our overarching goal was to describe, in his words, an alphabet of protein structure.” However, he points out that – unlike with text – the researchers were not able to visually determine where one structural unit (metaphorically a letter) began and another ended. “The number of ways in which we can potentially partition protein structure is extremely large, and so the task of finding a good decomposition seemed overwhelming.”The scientists addressed this problem by not defining a priori what the letters of the structural alphabet should be, but rather defining the task that these letters should accomplish – that is, describing the set of all residues and residue pair contacts observed in known protein structures. Next, they selected the smallest set of reusable building blocks they’re named tertiary structural motifs, or TERMs, that would achieve this goal.Another hurdle in determining the set of universal TERMs that capture all structure in the PDB was the difficult task of sifting through 13 million candidate TERMs, and describing which residues and contacts in known protein structures they individually explained. “Our previously-developed, efficient structure search algorithm MASTER helped us resolve this – but the total amount of computational time involved was still quite large, so we had to make use of a computer cluster.” A computer cluster is a single logical unit comprising multiple networked-linked computers. Explore further Fig. 5. An EF-hand TERM. (A) The 31 nonredundant EF hand-containing instances of the TERM (gray) with adjacent structure (green). Calcium atoms from TERM instances are shown as yellow spheres. (B) TERM instances alone with calcium-contacting side chains shown with sticks. (C) Variability among TERM instances. Four instances are shown in gray: two EF-hand examples with varying loop geometries (surrounding structure in green) and two non–EF-hand instances (from PDB ID codes 3HNO and 1CB7, surrounding structure in cyan), including one with TERM segments belonging to different chains. (D) Sequence logo of nonredundant EF hand-containing matches of the TERM. Position 18 corresponds to the canonical EF hand loop position 1 (61). Mackenzie CO, Zhou J, Grigoryan G (2016} Tertiary alphabet for the observable protein structural universe. Proc Natl Acad Sci USA 113(47):E7438-E7447. Journal information: Proceedings of the National Academy of Scienceslast_img read more