functional METHOD FOR PRODUCING FUNCTIONAL FILM, APPARATUS FOR PRODUCING FUNCTIONAL FILM, AND METHOD FOR PRODUCING FILM By www.freepatentsonline.com Published On :: Thu, 22 Jun 2017 08:00:00 EDT A method for producing a functional film is provided. In the method, a film is sequentially transferred through processing devices including a film inspection device. At least one expander roll is used for film transfer from a processing device to the film inspection device next to the processing device. Full Article
functional Computerized Identification of App Search Functionality for Search Engine Access By www.freepatentsonline.com Published On :: Thu, 29 Jun 2017 08:00:00 EDT A search system includes a device controller that provisions a device to execute a copy of a selected mobile application. A crawler extracts content and metadata from states of the selected mobile application. A search input state classifier identifies search input states within the states based on a first set of heuristics, including recognition of user-visible search indicia and recognition of metadata that correlates with search functionality. A parameter identifier identifies, for each of the search input states, necessary input parameters. A search function data store stores a record for each identified search function. Each record includes a path to reach a corresponding search input state, an indication of required input parameters, and a mapping of the input parameters to user interface widgets. A query processing system uses the stored search functions to scrape content from the selected mobile application in response to a query. Full Article
functional Computerized Identification Of App Search Functionality For Search Engine Access By www.freepatentsonline.com Published On :: Thu, 29 Jun 2017 08:00:00 EDT A search system includes a device controller that provisions a device to execute a copy of a selected mobile application. A crawler extracts content and metadata from states of the selected mobile application. A search input state classifier identifies search input states within the states based on a first set of heuristics, including recognition of user-visible search indicia and recognition of metadata that correlates with search functionality. A parameter identifier identifies, for each of the search input states, necessary input parameters. A search function data store stores a record for each identified search function. Each record includes a path to reach a corresponding search input state, an indication of required input parameters, and a mapping of the input parameters to user interface widgets. A query processing system uses the stored search functions to scrape content from the selected mobile application in response to a query. Full Article
functional Multi-functional furniture-accessory system By www.freepatentsonline.com Published On :: Tue, 14 Apr 2015 08:00:00 EDT A central housing in a generally rectilinear configuration. The central housing has a horizontal open top, a horizontal open bottom and side walls. A horizontal lower divider panel is between the top and the bottom. Lateral openings in the housing are located in the lower section of the upstanding side walls adjacent to the bottom extent. A plurality of interchangeable upper components is chosen from the class including a cover having seat and table top on the top and bottom of the planar surfaces, an ice chest a large planter, an upper horizontal divider panel and an ice chest. The upper components are adapted to be selectively positioned on the open top and depend into the upper component. A plurality of lower components is chosen from the class including doors and casters. A lateral opening is formed in the housing adjacent to the bottom. Full Article
functional Multifunctional tool for automotive air conditioning system testing and maintenance By www.freepatentsonline.com Published On :: Tue, 28 Oct 2014 08:00:00 EDT An automotive tool for servicing air-conditioning (AC) systems equipped with quick-connect adaptors. May be used to service modern refrigerant R132A-compatible systems or retrofitted older systems. The tool is adapted for attaching, detaching, opening, and closing valved T-adaptors used to attach gas lines and pressure gauges such as required for adjusting pressure in AC systems at full operational pressure and temperature, and particularly finds use when the “hi-tap” and “lo-tap” fittings are in hard to reach places around the engine block or chassis. The tool includes swappable extension arms so that length and angular geometry may be adjusted as needed. The tool aids in avoiding injury on dangerously hot surfaces and moving fan blades or belts. Surprisingly, using two such tools, one for the high tap and one for the low tap, a mechanic may work each tool singlehandedly to complete any necessary pressure adjustments. Full Article
functional FUNCTIONAL COATINGS ENHANCING CONDENSER PERFORMANCE By www.freepatentsonline.com Published On :: Thu, 22 Jun 2017 08:00:00 EDT Coatings for enhancing performance of materials surfaces, methods of producing the coating and coated substrates, and coated condensers are disclosed herein. More particularly, exemplary embodiments provide chemical coating materials useful for coating condenser components. Full Article
functional METHOD FOR REMOVING GLYPHOSATE FROM A SOLUTION USING FUNCTIONALIZED POLYMERIC NANOPARTICLES By www.freepatentsonline.com Published On :: Thu, 22 Jun 2017 08:00:00 EDT A method for removing glyphosate from a solution by contacting the solution with a polymeric particle including a moiety selected from the group consisting of ammonium, amine and combinations thereof, wherein the moiety is positively charged in the solution. Full Article
functional SYSTEMS AND METHODS FOR MULTIFUNCTIONAL VOLUMETRIC FLUID CONTROL By www.freepatentsonline.com Published On :: Thu, 29 Jun 2017 08:00:00 EDT Systems and methods for controlling fluid movement and volumes of fluid between a subject and a controlled compliant flow path. The controlled compliant flow path has a means for selectively metering in and metering out fluid from the controlled compliant flow path. An extracorporeal flow path is in fluid communication with the controlled compliant flow path across a semi-permeable membrane where the extracorporeal flow path has a first terminal end and a second terminal end. Full Article
functional MONOFUNCTIONAL AMINES AS ADHESION PRIMERS FOR CONDUCTIVE POLYMERS By www.freepatentsonline.com Published On :: Thu, 29 Jun 2017 08:00:00 EDT The present invention relates to a process for producing an electrolytic capacitor, the process comprising process steps i) ii): i) providing a capacitor body (1) that comprises an electrode body (2) of an electrode material,a dielectric (3) which at least partially covers the surface of this electrode material, anda solid electrolyte (4) at least comprising an electrically conductive material which at least partially covers the dielectric surface; ii) applying a primer solution e) to the capacitor body (1), followed by an application of a solution or dispersion a) comprising a conjugated polymer b) and a solvent or dispersant d), followed by an at least partial removal of the solvent or dispersant d) for the formation of the polymeric outer layer (5) that is formed onto the capacitor body (1); wherein the primer solution e) comprises at least one monofunctional amine and at least one carboxylic acid. Full Article
functional How can I get the functionality of Twitter's Legacy Version? By ask.metafilter.com Published On :: Sat, 09 May 2020 15:40:03 GMT Twitter has announced it is shutting down its "Legacy Version" on June 1, 2020. I use the legacy version to get the functionality of Legacy Twitter that allows you to have a window open with a Twitter page up, and when a new Tweet happens, a "(1)" shows in the browser tab. How can I get that functionality? The solution needs to work in Chrome & Firefox, and whether I have a twitter account or not. I want to be able to open 3 or 4 or however many tabs with twitter accounts I'm waiting for an update from, and see a notification in the tab header that there's a new tweet. Full Article Browser Chrome Firefox LegacyVersion Twitter
functional City of Perth inquiry reveals the dying final days of a dysfunctional council By www.abc.net.au Published On :: Thu, 19 Sep 2019 09:41:00 +1000 The culture within the Perth City Council reached its "zenith" in the lead-up to its suspension, breeding an environment unlike anything one of its councillors had experienced previously, an inquiry hears. Full Article ABC Radio Perth perth Australia:WA:All Australia:WA:Perth 6000
functional Ecologist warns of dingo 'functional extinction' north of dog fence ahead of new controls By www.abc.net.au Published On :: Fri, 24 Apr 2020 09:53:40 +1000 The SA Government is proposing new incentives for landholders to kill wild dogs on their properties, as well as allowing aerial baiting, but an ecologist says the new policy will inevitably target native dingoes. Full Article Animals and Nature Agriculture Rural Dog Environment Environmental Management Government and Politics Human Interest Animals Animal Welfare Livestock Animal Behaviour
functional Could functional fitness trends like CrossFit and F45 become an Olympic sport? By www.abc.net.au Published On :: Sat, 03 Aug 2019 08:54:00 +1000 Paying money to see other people work out might not sound like everyone's idea of fun, but it is fast becoming a part of the international sporting calendar, and there's hope it will become part of a future Olympic Games. Full Article ABC Capricornia sydney capricornia southeastsa Arts and Entertainment:Kids Games and Links:Extreme Sports Health:Exercise and Fitness:All Health:Women's Health:All Lifestyle and Leisure:Clubs and Associations:All Sport:All:All Sport:Olympics (Summer):All Sport:Other Sports:All Sport:Sports Organisations:All Australia:All:All Australia:NSW:All Australia:NSW:Sydney 2000 Australia:QLD:All Australia:QLD:Gladstone 4680 Australia:SA:All Australia:SA:Mount Gambier 5290 Sweden:All:All United States:All:All
functional Dysfunctional Families: Growing Wings By nielsenhayden.com Published On :: 2019-04-07T16:53:46-05:00 It's been a long time since I've posted a new entry to this community, and I know the comments on... Full Article
functional Dysfunctional polycomb transcriptional repression contributes to lamin A/C–dependent muscular dystrophy By www.jci.org Published On :: Lamin A is a component of the inner nuclear membrane that, together with epigenetic factors, organizes the genome in higher order structures required for transcriptional control. Mutations in the lamin A/C gene cause several diseases belonging to the class of laminopathies, including muscular dystrophies. Nevertheless, molecular mechanisms involved in the pathogenesis of lamin A–dependent dystrophies are still largely unknown. The polycomb group (PcG) of proteins are epigenetic repressors and lamin A interactors, primarily involved in the maintenance of cell identity. Using a murine model of Emery-Dreifuss muscular dystrophy (EDMD), we show here that lamin A loss deregulated PcG positioning in muscle satellite stem cells, leading to derepression of non–muscle-specific genes and p16INK4a, a senescence driver encoded in the Cdkn2a locus. This aberrant transcriptional program caused impairment in self-renewal, loss of cell identity, and premature exhaustion of the quiescent satellite cell pool. Genetic ablation of the Cdkn2a locus restored muscle stem cell properties in lamin A/C–null dystrophic mice. Our findings establish a direct link between lamin A and PcG epigenetic silencing and indicate that lamin A–dependent muscular dystrophy can be ascribed to intrinsic epigenetic dysfunctions of muscle stem cells. Full Article
functional Google Chatback: New functionality added to this blog By rss.blogontravel.com Published On :: Wed, 02 Apr 2008 10:39:10 +0000 Those who want to add this Chatback feature to their own blog (or website!), need to register to Google Talk and then they need to create a Google Talk chatback badge. Copy the script and paste it to the page of your choice. You're done. Enjoy. Full Article Blogs Google Google related blackberry chat chatback google chatback google-talk gtalk
functional Important Functionalities for an E-Commerce Theme By spyrestudios.com Published On :: Thu, 23 Apr 2020 00:43:34 PDT As web designers/developers, finding the right theme for a client’s website can be a complicated process. There are several factors to consider – preference, needs, functionality, and even budget. When you first look at themes, aesthetics is often what captures the eye, looks are important and will play an essential role in creating the right […] The post Important Functionalities for an E-Commerce Theme appeared first on SpyreStudios. Full Article Ecommerce ecommerce themes
functional oscon: Mobile UX Design & Development for Apps - learn to craft an app that’s functional and fun to use http://t.co/L8kTLaxbYH #oscon #tutorial By twitter.com Published On :: Thu, 23 May 2013 16:11:21 +0000 oscon: Mobile UX Design & Development for Apps - learn to craft an app that’s functional and fun to use http://t.co/L8kTLaxbYH #oscon #tutorial Full Article
functional velocityconf: Help your dev + ops teams be cross-functional and more successful. http://t.co/1mqGK3zh0U Free webcast 5/22 w/ @lnxchk By feedproxy.google.com Published On :: Mon, 20 May 2013 16:58:59 +0000 velocityconf: Help your dev + ops teams be cross-functional and more successful. http://t.co/1mqGK3zh0U Free webcast 5/22 w/ @lnxchk Full Article
functional Lebanon Is Paying the Cost of Its Dysfunctional Politics By feedproxy.google.com Published On :: Wed, 26 Feb 2020 05:27:10 +0000 26 February 2020 Nadim Shehadi Associate Fellow, Middle East and North Africa Programme @Confusezeus A series of fights to political stalemate have led its economy to the brink and cut it off from its natural economic partners in the Gulf. 2020-02-25-Leb1.jpg Protests against economic conditions and government inaction turned violent in January. Photo: Getty Images. To understand Lebanon’s financial collapse, look to its politics.The country has been deeply damaged by an increasingly dysfunctional political system. A series of compromises have alienated it from its main markets in the Gulf and strangled its economy; anyone that has glanced at fluctuations in Lebanese bank deposits over the last 10 years can see the correlation.Imagine if Boris Johnson or Donald Trump were obliged to form joint governments with Jeremy Corbyn or Bernie Sanders. The result would be paralysis and lack of accountability as each party pulls the country in opposite directions and blames the other for the state of limbo. This has been the state of affairs in Lebanon since the Doha agreement of 2008. That agreement followed an 18-month siege that paralyzed Beirut and an attack on the city by Hezbollah’s ‘black shirts’. The Doha formula imposed governments of national unity between Prime Minister Saad Hariri’s pro-Saudi camp and Hezbollah’s pro-Iran camp and their respective internal allies.The pattern was set: each period of subsequent paralysis was followed by further compromise as the tug of war pulled the country away from its principal economic partners, the Arab Gulf states, with the regional balance of power tilting towards Hezbollah. It was not supposed to be like this. The Baabda Declaration in June 2012, reached after a process of national dialogue, was meant to secure Lebanon’s neutrality in regional conflicts, with both sides promising to hold back on external alliances and coexist despite difference over major regional issues like the war in Syria, the standoff between the US and Iran or relations with Israel or the Gulf states.This has worn away. The Baabda declaration itself became a sham when Hezbollah inserted itself into the war in Syria in support of the Assad regime and overtly got involved in Iraq and Yemen as an Iranian proxy. This was followed by Saudi opposition to concessions by Hariri that led to the election of General Michel Aoun, an ally of Hezbollah, as president in October 2016; again, after a political paralysis that lasted 29 months with no active government and no head of state. The Saudis were also furious when President Aoun’s son-in-law, Foreign Minister Gebran Bassil, abstained from condemning the burning of the Saudi embassy in Tehran at an Arab League meeting in Cairo in January 2016, citing the need to preserve national unity.Fearing that he was simply providing Hezbollah with protection in the guise of compromise, the Saudis pressured Hariri to resign in November 2017 during a trip to Riyadh, but he later challenged that by retracting on his resignation when back in Beirut. Lebanon was caught between two sides, and as the regional conflict intensified from tension to open confrontation, neutrality was no longer an option.Gulf connectionsAn estimated 350,000 Lebanese expats live and work in Saudi Arabia, the UAE, Qatar and Kuwait. These countries are also the main clients for Lebanese contractors, consultants and advertising companies, some of which have offices there. The domestic tourism industry relies heavily on Arab Gulf visitors and they are a principal source of foreign investments especially in the real estate sector.Lebanon also enjoyed a certain degree of political and economic protection from the US and the Gulf, and Hezbollah benefited indirectly from that protection, as it also shielded it to a certain degree from sanctions.The deterioration of relations meant that the country was cut off by its Gulf partners. This was manifested in travel bans for Gulf Cooperation Council (GCC) nationals to Lebanon and a decrease in investments and bank deposits, as well as a decrease in remittances from Lebanese expats, partly because of economic crisis in the Gulf countries themselves.Saudi Arabia withdrew $4 billion of aid to the Lebanese army and internal security forces, and no aid or deposits were forthcoming as the economic and financial situation deteriorated. The costs to the Lebanese economy include the opportunity cost created by the annual threat of war with Israel, after which trips are cancelled and projects postponed. Hezbollah also controls a section of Beirut port where it pays no duty or taxes. Add to that the economic fallout from the war in Syria, such as the impact on exports, the inflow of refugees and the cost of Hezbollah’s involvement.The burden of these political factors is difficult to estimate but it constitutes the ransom that the Lebanese economy bears as a cost of the compromise. This is not to absolve Lebanese politicians from corruption or bankers of mismanagement but to add that political factors cannot be ignored.The cumulative cost and economic impact of being cut off from its main economic partner eventually bankrupted the country. The fiscal and financial aspects, with Lebanon’s inability to service its debt, are but a reflection of these political factors. In the long run, the key to avoiding complete collapse is to restore relations with the GCC and free Lebanon from that very costly grip. Full Article
functional High Resolution Clear Native Electrophoresis for In-gel Functional Assays and Fluorescence Studies of Membrane Protein Complexes By feedproxy.google.com Published On :: 2007-07-01 Ilka WittigJul 1, 2007; 6:1215-1225Research Full Article
functional A Versatile Nanotrap for Biochemical and Functional Studies with Fluorescent Fusion Proteins By feedproxy.google.com Published On :: 2008-02-01 Ulrich RothbauerFeb 1, 2008; 7:282-289Research Full Article
functional Structural and mutational analyses of the bifunctional arginine dihydrolase and ornithine cyclodeaminase AgrE from the cyanobacterium Anabaena [Enzymology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena. Full Article
functional Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase By feedproxy.google.com Published On :: 2000-02-01 Jorge H. CapdevilaFeb 1, 2000; 41:163-181Reviews Full Article
functional Lipid rafts and neurodegeneration: structural and functional roles in physiologic aging and neurodegenerative diseases [Thematic Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Lipid rafts are small, dynamic membrane areas characterized by the clustering of selected membrane lipids as the result of the spontaneous separation of glycolipids, sphingolipids, and cholesterol in a liquid-ordered phase. The exact dynamics underlying phase separation of membrane lipids in the complex biological membranes are still not fully understood. Nevertheless, alterations in the membrane lipid composition affect the lateral organization of molecules belonging to lipid rafts. Neural lipid rafts are found in brain cells, including neurons, astrocytes, and microglia, and are characterized by a high enrichment of specific lipids depending on the cell type. These lipid rafts seem to organize and determine the function of multiprotein complexes involved in several aspects of signal transduction, thus regulating the homeostasis of the brain. The progressive decline of brain performance along with physiological aging is at least in part associated with alterations in the composition and structure of neural lipid rafts. In addition, neurodegenerative conditions, such as lysosomal storage disorders, multiple sclerosis, and Parkinson’s, Huntington’s, and Alzheimer’s diseases, are frequently characterized by dysregulated lipid metabolism, which in turn affects the structure of lipid rafts. Several events underlying the pathogenesis of these diseases appear to depend on the altered composition of lipid rafts. Thus, the structure and function of lipid rafts play a central role in the pathogenesis of many common neurodegenerative diseases. Full Article
functional Evaluation of extreme values of entropy functionals By www.ams.org Published On :: Mon, 02 Mar 2020 06:58 EST Yu. S. Mishura and H. S. Zhelezniak Theor. Probability and Math. Statist. 99 (2020), 199-210. Abstract, references and article information Full Article
functional On the lack of memory for distributions of overshoot functionals in the case of upper almost semicontinuous processes defined on a Markov chain By www.ams.org Published On :: Mon, 02 Mar 2020 06:58 EST D. V. Gusak and E. V. Karnaukh Theor. Probability and Math. Statist. 99 (2020), 77-89. Abstract, references and article information Full Article
functional The Ricci pinching functional on solvmanifolds II By www.ams.org Published On :: Thu, 02 Apr 2020 13:59 EDT Jorge Lauret and Cynthia E. Will Proc. Amer. Math. Soc. 148 (2020), 2601-2607. Abstract, references and article information Full Article
functional Large Deviations for Additive Functionals of Markov Chains By www.ams.org Published On :: Alejandro D. de Acosta and Peter Ney - AMS, 2014, 108 pp., Softcover, ISBN-13: 978-0-8218-9089-9, List: US$76, All AMS Members: US$60.80, MEMO/228/1070 For a Markov chain ({X_j}) with general state space (S) and ({f:S ightarrowmathbf{R}^d}), the large deviation principle for... Full Article
functional Research found a new way to make functional materials based on polymers of metal clusters By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (University of Jyväskylä - Jyväskylän yliopisto) Researchers at the universities of Jyvaskyla and Xiamen discovered a novel way to make functional macroscopic crystalline materials out of nanometer-size 34-atom silver-gold intermetallic clusters. The cluster material has a highly anisotropic electrical conductivity, being a semiconductor in one direction and an electrical insulator in other directions. The research was published in Nature Communications on May 6, 2020. Full Article
functional Development of a novel {beta}-1,6-glucan-specific detection system using functionally-modified recombinant endo-{beta}-1,6-glucanase [Methods and Resources] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 β-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring β-1,6-glucan, another primary β-glucan structure of fungal polysaccharides. Herein, we describe the development of an economical and highly-sensitive and specific assay for β-1,6-glucan using a modified recombinant endo-β-1,6-glucanase having diminished glucan hydrolase activity. The purified β-1,6-glucanase derivative bound to the β-1,6-glucan pustulan with a KD of 16.4 nm. We validated the specificity of this β-1,6-glucan probe by demonstrating its ability to detect cell wall β-1,6-glucan from both yeast and hyphal forms of the opportunistic fungal pathogen Candida albicans, without any detectable binding to glucan lacking the long β-1,6-glucan branch. We developed a sandwich ELISA-like assay with a low limit of quantification for pustulan (1.5 pg/ml), and we successfully employed this assay in the quantification of extracellular β-1,6-glucan released by >250 patient-derived strains of different Candida species (including Candida auris) in culture supernatant in vitro. We also used this assay to measure β-1,6-glucan in vivo in the serum and in several organs in a mouse model of systemic candidiasis. Our work describes a reliable method for β-1,6-glucan detection, which may prove useful for the diagnosis of invasive fungal infections. Full Article
functional Structural and mutational analyses of the bifunctional arginine dihydrolase and ornithine cyclodeaminase AgrE from the cyanobacterium Anabaena [Enzymology] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena. Full Article
functional Genetic Profile and Functional Proteomics of Anal Squamous Cell Carcinoma: Proposal for a Molecular Classification By feedproxy.google.com Published On :: 2020-04-01 Lucía Trilla-FuertesApr 1, 2020; 19:690-700Research Full Article
functional Developments and Applications of Functional Protein Microarrays By feedproxy.google.com Published On :: 2020-04-17 Guan-Da SyuApr 17, 2020; 0:R120.001936v1-mcp.R120.001936Review Full Article
functional Lebanon Is Paying the Cost of Its Dysfunctional Politics By feedproxy.google.com Published On :: Wed, 26 Feb 2020 05:27:10 +0000 26 February 2020 Nadim Shehadi Associate Fellow, Middle East and North Africa Programme @Confusezeus A series of fights to political stalemate have led its economy to the brink and cut it off from its natural economic partners in the Gulf. 2020-02-25-Leb1.jpg Protests against economic conditions and government inaction turned violent in January. Photo: Getty Images. To understand Lebanon’s financial collapse, look to its politics.The country has been deeply damaged by an increasingly dysfunctional political system. A series of compromises have alienated it from its main markets in the Gulf and strangled its economy; anyone that has glanced at fluctuations in Lebanese bank deposits over the last 10 years can see the correlation.Imagine if Boris Johnson or Donald Trump were obliged to form joint governments with Jeremy Corbyn or Bernie Sanders. The result would be paralysis and lack of accountability as each party pulls the country in opposite directions and blames the other for the state of limbo. This has been the state of affairs in Lebanon since the Doha agreement of 2008. That agreement followed an 18-month siege that paralyzed Beirut and an attack on the city by Hezbollah’s ‘black shirts’. The Doha formula imposed governments of national unity between Prime Minister Saad Hariri’s pro-Saudi camp and Hezbollah’s pro-Iran camp and their respective internal allies.The pattern was set: each period of subsequent paralysis was followed by further compromise as the tug of war pulled the country away from its principal economic partners, the Arab Gulf states, with the regional balance of power tilting towards Hezbollah. It was not supposed to be like this. The Baabda Declaration in June 2012, reached after a process of national dialogue, was meant to secure Lebanon’s neutrality in regional conflicts, with both sides promising to hold back on external alliances and coexist despite difference over major regional issues like the war in Syria, the standoff between the US and Iran or relations with Israel or the Gulf states.This has worn away. The Baabda declaration itself became a sham when Hezbollah inserted itself into the war in Syria in support of the Assad regime and overtly got involved in Iraq and Yemen as an Iranian proxy. This was followed by Saudi opposition to concessions by Hariri that led to the election of General Michel Aoun, an ally of Hezbollah, as president in October 2016; again, after a political paralysis that lasted 29 months with no active government and no head of state. The Saudis were also furious when President Aoun’s son-in-law, Foreign Minister Gebran Bassil, abstained from condemning the burning of the Saudi embassy in Tehran at an Arab League meeting in Cairo in January 2016, citing the need to preserve national unity.Fearing that he was simply providing Hezbollah with protection in the guise of compromise, the Saudis pressured Hariri to resign in November 2017 during a trip to Riyadh, but he later challenged that by retracting on his resignation when back in Beirut. Lebanon was caught between two sides, and as the regional conflict intensified from tension to open confrontation, neutrality was no longer an option.Gulf connectionsAn estimated 350,000 Lebanese expats live and work in Saudi Arabia, the UAE, Qatar and Kuwait. These countries are also the main clients for Lebanese contractors, consultants and advertising companies, some of which have offices there. The domestic tourism industry relies heavily on Arab Gulf visitors and they are a principal source of foreign investments especially in the real estate sector.Lebanon also enjoyed a certain degree of political and economic protection from the US and the Gulf, and Hezbollah benefited indirectly from that protection, as it also shielded it to a certain degree from sanctions.The deterioration of relations meant that the country was cut off by its Gulf partners. This was manifested in travel bans for Gulf Cooperation Council (GCC) nationals to Lebanon and a decrease in investments and bank deposits, as well as a decrease in remittances from Lebanese expats, partly because of economic crisis in the Gulf countries themselves.Saudi Arabia withdrew $4 billion of aid to the Lebanese army and internal security forces, and no aid or deposits were forthcoming as the economic and financial situation deteriorated. The costs to the Lebanese economy include the opportunity cost created by the annual threat of war with Israel, after which trips are cancelled and projects postponed. Hezbollah also controls a section of Beirut port where it pays no duty or taxes. Add to that the economic fallout from the war in Syria, such as the impact on exports, the inflow of refugees and the cost of Hezbollah’s involvement.The burden of these political factors is difficult to estimate but it constitutes the ransom that the Lebanese economy bears as a cost of the compromise. This is not to absolve Lebanese politicians from corruption or bankers of mismanagement but to add that political factors cannot be ignored.The cumulative cost and economic impact of being cut off from its main economic partner eventually bankrupted the country. The fiscal and financial aspects, with Lebanon’s inability to service its debt, are but a reflection of these political factors. In the long run, the key to avoiding complete collapse is to restore relations with the GCC and free Lebanon from that very costly grip. Full Article
functional 11C-PABA as a Novel PET Radiotracer for Functional Renal Imaging: Preclinical and First-in-Human Studies By jnm.snmjournals.org Published On :: 2020-03-20T13:59:23-07:00 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. Full Article
functional Genetic Profile and Functional Proteomics of Anal Squamous Cell Carcinoma: Proposal for a Molecular Classification [Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 Anal squamous cell carcinoma is a rare tumor. Chemo-radiotherapy yields a 50% 3-year relapse-free survival rate in advanced anal cancer, so improved predictive markers and therapeutic options are needed. High-throughput proteomics and whole-exome sequencing were performed in 46 paraffin samples from anal squamous cell carcinoma patients. Hierarchical clustering was used to establish groups de novo. Then, probabilistic graphical models were used to study the differences between groups of patients at the biological process level. A molecular classification into two groups of patients was established, one group with increased expression of proteins related to adhesion, T lymphocytes and glycolysis; and the other group with increased expression of proteins related to translation and ribosomes. The functional analysis by the probabilistic graphical model showed that these two groups presented differences in metabolism, mitochondria, translation, splicing and adhesion processes. Additionally, these groups showed different frequencies of genetic variants in some genes, such as ATM, SLFN11 and DST. Finally, genetic and proteomic characteristics of these groups suggested the use of some possible targeted therapies, such as PARP inhibitors or immunotherapy. Full Article
functional Developments and Applications of Functional Protein Microarrays [Review] By feedproxy.google.com Published On :: 2020-04-17T09:38:19-07:00 Protein microarrays are crucial tools in the study of proteins in an unbiased, high-throughput manner, as they allow for characterization of up to thousands of individually purified proteins in parallel. The adaptability of this technology has enabled its use in a wide variety of applications, including the study of proteome-wide molecular interactions, analysis of post-translational modifications, identification of novel drug targets, and examination of pathogen-host interactions. In addition, the technology has also been shown to be useful in profiling antibody specificity, as well as in the discovery of novel biomarkers, especially for autoimmune diseases and cancers. In this review, we will summarize the developments that have been made in protein microarray technology in both in basic and translational research over the past decade. We will also introduce a novel membrane protein array, the GPCR-VirD array, and discuss the future directions of functional protein microarrays. Full Article
functional Functional recombinant apolipoprotein A5 that is stable at high concentrations at physiological pH [Methods] By feedproxy.google.com Published On :: 2020-02-01T00:05:23-08:00 APOA5 is a low-abundance exchangeable apolipoprotein that plays critical roles in human triglyceride (TG) metabolism. Indeed, aberrations in the plasma concentration or structure of APOA5 are linked to hypertriglyceridemia, hyperchylomicronemia, myocardial infarction risk, obesity, and coronary artery disease. While it has been successfully produced at low yield in bacteria, the resulting protein had limitations for structure-function studies due to its low solubility under physiological buffer conditions. We hypothesized that the yield and solubility of recombinant APOA5 could be increased by: i) engineering a fusion protein construct in a codon optimized expression vector, ii) optimizing an efficient refolding protocol, and iii) screening buffer systems at physiological pH. The result was a high-yield (25 mg/l) bacterial expression system that produces lipid-free APOA5 soluble at concentrations of up to 10 mg/ml at a pH of 7.8 in bicarbonate buffers. Physical characterization of lipid-free APOA5 indicated that it exists as an array of multimers in solution, and far UV circular dichroism analyses show differences in total α-helicity between acidic and neutral pH buffering conditions. The protein was functional in that it bound and emulsified multilamellar dimyristoyl-phosphatidylcholine vesicles and could inhibit postprandial plasma TG accumulation when injected into C57BL/6J mice orally gavaged with Intralipid. Full Article
functional Composition-function analysis of HDL subpopulations: influence of lipid composition on particle functionality [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 The composition-function relationship of HDL particles and its effects on the mechanisms driving coronary heart disease (CHD) is poorly understood. We tested the hypothesis that the functionality of HDL particles is significantly influenced by their lipid composition. Using a novel 3D-separation method, we isolated five different-sized HDL subpopulations from CHD patients who had low preβ-1 functionality (low-F) (ABCA1-dependent cholesterol-efflux normalized for preβ-1 concentration) and controls who had either low-F or high preβ-1 functionality (high-F). Molecular numbers of apoA-I, apoA-II, and eight major lipid classes were determined in each subpopulation by LC-MS. The average number of lipid molecules decreased from 422 in the large spherical α-1 particles to 57 in the small discoid preβ-1 particles. With decreasing particle size, the relative concentration of free cholesterol (FC) decreased in α-mobility but not in preβ-1 particles. Preβ-1 particles contained more lipids than predicted; 30% of which were neutral lipids (cholesteryl ester and triglyceride), indicating that these particles were mainly remodeled from larger particles not newly synthesized. There were significant correlations between HDL-particle functionality and the concentrations of several lipids. Unexpectedly, the phospholipid:FC ratio was significantly correlated with large-HDL-particle functionality but not with preβ-1 functionality. There was significant positive correlation between particle functionality and total lipids in high-F controls, indicating that the lipid-binding capacity of apoA-I plays a major role in the cholesterol efflux capacity of HDL particles. Functionality and lipid composition of HDL particles are significantly correlated and probably both are influenced by the lipid-binding capacity of apoA-I. Full Article
functional Lipid rafts and neurodegeneration: structural and functional roles in physiologic aging and neurodegenerative diseases [Thematic Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Lipid rafts are small, dynamic membrane areas characterized by the clustering of selected membrane lipids as the result of the spontaneous separation of glycolipids, sphingolipids, and cholesterol in a liquid-ordered phase. The exact dynamics underlying phase separation of membrane lipids in the complex biological membranes are still not fully understood. Nevertheless, alterations in the membrane lipid composition affect the lateral organization of molecules belonging to lipid rafts. Neural lipid rafts are found in brain cells, including neurons, astrocytes, and microglia, and are characterized by a high enrichment of specific lipids depending on the cell type. These lipid rafts seem to organize and determine the function of multiprotein complexes involved in several aspects of signal transduction, thus regulating the homeostasis of the brain. The progressive decline of brain performance along with physiological aging is at least in part associated with alterations in the composition and structure of neural lipid rafts. In addition, neurodegenerative conditions, such as lysosomal storage disorders, multiple sclerosis, and Parkinson’s, Huntington’s, and Alzheimer’s diseases, are frequently characterized by dysregulated lipid metabolism, which in turn affects the structure of lipid rafts. Several events underlying the pathogenesis of these diseases appear to depend on the altered composition of lipid rafts. Thus, the structure and function of lipid rafts play a central role in the pathogenesis of many common neurodegenerative diseases. Full Article
functional Structural and mutational analyses of the bifunctional arginine dihydrolase and ornithine cyclodeaminase AgrE from the cyanobacterium Anabaena [Enzymology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena. Full Article
functional Time Course of Normalization of Functional {beta}-Cell Capacity in the Diabetes Remission Clinical Trial After Weight Loss in Type 2 Diabetes By care.diabetesjournals.org Published On :: 2020-03-20T11:50:34-07:00 OBJECTIVE To assess functional β-cell capacity in type 2 diabetes during 2 years of remission induced by dietary weight loss. RESEARCH DESIGN AND METHODS A Stepped Insulin Secretion Test with Arginine was used to quantify functional β-cell capacity by hyperglycemia and arginine stimulation. Thirty-nine of 57 participants initially achieved remission (HbA1c <6.5% [<48 mmol/mol] and fasting plasma glucose <7 mmol/L on no antidiabetic drug therapy) with a 16.4 ± 7.7 kg weight loss and were followed up with supportive advice on avoidance of weight regain. At 2 years, 20 participants remained in remission in the study. A nondiabetic control (NDC) group, matched for age, sex, and weight after weight loss with the intervention group, was studied once. RESULTS During remission, median (interquartile range) maximal rate of insulin secretion increased from 581 (480–811) pmol/min/m2 at baseline to 736 (542–998) pmol/min/m2 at 5 months, 942 (565–1,240) pmol/min/m2 at 12 months (P = 0.028 from baseline), and 936 (635–1,435) pmol/min/m2 at 24 months (P = 0.023 from baseline; n = 20 of 39 of those initially in remission). This was comparable to the NDC group (1,016 [857–1,507] pmol/min/m2) by 12 (P = 0.064) and 24 (P = 0.244) months. Median first-phase insulin response increased from baseline to 5 months (42 [4–67] to 107 [59–163] pmol/min/m2; P < 0.0001) and then remained stable at 12 and 24 months (110 [59–201] and 125 [65–166] pmol/min/m2, respectively; P < 0.0001 vs. baseline) but lower than that of the NDC group (250 [226–429] pmol/min/m2; P < 0.0001). CONCLUSIONS A gradual increase in assessed functional β-cell capacity occurred after weight loss, becoming similar to that of NDC group participants by 12 months. This result was unchanged at 2 years with continuing remission of type 2 diabetes. Full Article
functional Sparsely observed functional time series: estimation and prediction By projecteuclid.org Published On :: Thu, 27 Feb 2020 22:04 EST Tomáš Rubín, Victor M. Panaretos. Source: Electronic Journal of Statistics, Volume 14, Number 1, 1137--1210.Abstract: Functional time series analysis, whether based on time or frequency domain methodology, has traditionally been carried out under the assumption of complete observation of the constituent series of curves, assumed stationary. Nevertheless, as is often the case with independent functional data, it may well happen that the data available to the analyst are not the actual sequence of curves, but relatively few and noisy measurements per curve, potentially at different locations in each curve’s domain. Under this sparse sampling regime, neither the established estimators of the time series’ dynamics nor their corresponding theoretical analysis will apply. The subject of this paper is to tackle the problem of estimating the dynamics and of recovering the latent process of smooth curves in the sparse regime. Assuming smoothness of the latent curves, we construct a consistent nonparametric estimator of the series’ spectral density operator and use it to develop a frequency-domain recovery approach, that predicts the latent curve at a given time by borrowing strength from the (estimated) dynamic correlations in the series across time. This new methodology is seen to comprehensively outperform a naive recovery approach that would ignore temporal dependence and use only methodology employed in the i.i.d. setting and hinging on the lag zero covariance. Further to predicting the latent curves from their noisy point samples, the method fills in gaps in the sequence (curves nowhere sampled), denoises the data, and serves as a basis for forecasting. Means of providing corresponding confidence bands are also investigated. A simulation study interestingly suggests that sparse observation for a longer time period may provide better performance than dense observation for a shorter period, in the presence of smoothness. The methodology is further illustrated by application to an environmental data set on fair-weather atmospheric electricity, which naturally leads to a sparse functional time series. Full Article
functional On Mahalanobis Distance in Functional Settings By Published On :: 2020 Mahalanobis distance is a classical tool in multivariate analysis. We suggest here an extension of this concept to the case of functional data. More precisely, the proposed definition concerns those statistical problems where the sample data are real functions defined on a compact interval of the real line. The obvious difficulty for such a functional extension is the non-invertibility of the covariance operator in infinite-dimensional cases. Unlike other recent proposals, our definition is suggested and motivated in terms of the Reproducing Kernel Hilbert Space (RKHS) associated with the stochastic process that generates the data. The proposed distance is a true metric; it depends on a unique real smoothing parameter which is fully motivated in RKHS terms. Moreover, it shares some properties of its finite dimensional counterpart: it is invariant under isometries, it can be consistently estimated from the data and its sampling distribution is known under Gaussian models. An empirical study for two statistical applications, outliers detection and binary classification, is included. The results are quite competitive when compared to other recent proposals in the literature. Full Article
functional Recent developments in complex and spatially correlated functional data By projecteuclid.org Published On :: Mon, 04 May 2020 04:00 EDT Israel Martínez-Hernández, Marc G. Genton. Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 2, 204--229.Abstract: As high-dimensional and high-frequency data are being collected on a large scale, the development of new statistical models is being pushed forward. Functional data analysis provides the required statistical methods to deal with large-scale and complex data by assuming that data are continuous functions, for example, realizations of a continuous process (curves) or continuous random field (surfaces), and that each curve or surface is considered as a single observation. Here, we provide an overview of functional data analysis when data are complex and spatially correlated. We provide definitions and estimators of the first and second moments of the corresponding functional random variable. We present two main approaches: The first assumes that data are realizations of a functional random field, that is, each observation is a curve with a spatial component. We call them spatial functional data . The second approach assumes that data are continuous deterministic fields observed over time. In this case, one observation is a surface or manifold, and we call them surface time series . For these two approaches, we describe software available for the statistical analysis. We also present a data illustration, using a high-resolution wind speed simulated dataset, as an example of the two approaches. The functional data approach offers a new paradigm of data analysis, where the continuous processes or random fields are considered as a single entity. We consider this approach to be very valuable in the context of big data. Full Article
functional Nonparametric discrimination of areal functional data By projecteuclid.org Published On :: Mon, 03 Feb 2020 04:00 EST Ahmad Younso. Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 1, 112--126.Abstract: We consider a new nonparametric rule of classification, inspired from the classical moving window rule, that allows for the classification of spatially dependent functional data containing some completely missing curves. We investigate the consistency of this classifier under mild conditions. The practical use of the classifier will be illustrated through simulation studies. Full Article
functional $M$-functionals of multivariate scatter By projecteuclid.org Published On :: Fri, 20 Mar 2015 09:11 EDT Lutz Dümbgen, Markus Pauly, Thomas Schweizer. Source: Statistics Surveys, Volume 9, 32--105.Abstract: This survey provides a self-contained account of $M$-estimation of multivariate scatter. In particular, we present new proofs for existence of the underlying $M$-functionals and discuss their weak continuity and differentiability. This is done in a rather general framework with matrix-valued random variables. By doing so we reveal a connection between Tyler’s (1987a) $M$-functional of scatter and the estimation of proportional covariance matrices. Moreover, this general framework allows us to treat a new class of scatter estimators, based on symmetrizations of arbitrary order. Finally these results are applied to $M$-estimation of multivariate location and scatter via multivariate $t$-distributions. Full Article
functional Analyzing complex functional brain networks: Fusing statistics and network science to understand the brain By projecteuclid.org Published On :: Mon, 28 Oct 2013 09:06 EDT Sean L. Simpson, F. DuBois Bowman, Paul J. LaurientiSource: Statist. Surv., Volume 7, 1--36.Abstract: Complex functional brain network analyses have exploded over the last decade, gaining traction due to their profound clinical implications. The application of network science (an interdisciplinary offshoot of graph theory) has facilitated these analyses and enabled examining the brain as an integrated system that produces complex behaviors. While the field of statistics has been integral in advancing activation analyses and some connectivity analyses in functional neuroimaging research, it has yet to play a commensurate role in complex network analyses. Fusing novel statistical methods with network-based functional neuroimage analysis will engender powerful analytical tools that will aid in our understanding of normal brain function as well as alterations due to various brain disorders. Here we survey widely used statistical and network science tools for analyzing fMRI network data and discuss the challenges faced in filling some of the remaining methodological gaps. When applied and interpreted correctly, the fusion of network scientific and statistical methods has a chance to revolutionize the understanding of brain function. Full Article
functional Curse of dimensionality and related issues in nonparametric functional regression By projecteuclid.org Published On :: Thu, 14 Apr 2011 08:17 EDT Gery GeenensSource: Statist. Surv., Volume 5, 30--43.Abstract: Recently, some nonparametric regression ideas have been extended to the case of functional regression. Within that framework, the main concern arises from the infinite dimensional nature of the explanatory objects. Specifically, in the classical multivariate regression context, it is well-known that any nonparametric method is affected by the so-called “curse of dimensionality”, caused by the sparsity of data in high-dimensional spaces, resulting in a decrease in fastest achievable rates of convergence of regression function estimators toward their target curve as the dimension of the regressor vector increases. Therefore, it is not surprising to find dramatically bad theoretical properties for the nonparametric functional regression estimators, leading many authors to condemn the methodology. Nevertheless, a closer look at the meaning of the functional data under study and on the conclusions that the statistician would like to draw from it allows to consider the problem from another point-of-view, and to justify the use of slightly modified estimators. In most cases, it can be entirely legitimate to measure the proximity between two elements of the infinite dimensional functional space via a semi-metric, which could prevent those estimators suffering from what we will call the “curse of infinite dimensionality”. References:[1] Ait-Saïdi, A., Ferraty, F., Kassa, K. and Vieu, P. (2008). Cross-validated estimations in the single-functional index model, Statistics, 42, 475–494.[2] Aneiros-Perez, G. and Vieu, P. (2008). Nonparametric time series prediction: A semi-functional partial linear modeling, J. Multivariate Anal., 99, 834–857.[3] Baillo, A. and Grané, A. (2009). Local linear regression for functional predictor and scalar response, J. Multivariate Anal., 100, 102–111.[4] Burba, F., Ferraty, F. and Vieu, P. (2009). k-Nearest Neighbour method in functional nonparametric regression, J. Nonparam. Stat., 21, 453–469.[5] Cardot, H., Ferraty, F. and Sarda, P. (1999). Functional linear model, Stat. Probabil. Lett., 45, 11–22.[6] Crambes, C., Kneip, A. and Sarda, P. (2009). Smoothing splines estimators for functional linear regression, Ann. Statist., 37, 35–72.[7] Delsol, L. (2009). Advances on asymptotic normality in nonparametric functional time series analysis, Statistics, 43, 13–33.[8] Fan, J. and Gijbels, I. (1996). Local Polynomial Modelling and Its Applications, Chapman and Hall, London.[9] Fan, J. and Zhang, J.-T. (2000). Two-step estimation of functional linear models with application to longitudinal data, J. Roy. Stat. Soc. B, 62, 303–322.[10] Ferraty, F. and Vieu, P. (2006). Nonparametric Functional Data Analysis, Springer-Verlag, New York.[11] Ferraty, F., Laksaci, A. and Vieu, P. (2006). Estimating Some Characteristics of the Conditional Distribution in Nonparametric Functional Models, Statist. Inf. Stoch. Proc., 9, 47–76.[12] Ferraty, F., Mas, A. and Vieu, P. (2007). Nonparametric regression on functional data: inference and practical aspects, Aust. NZ. J. Stat., 49, 267–286.[13] Ferraty, F., Van Keilegom, I. and Vieu, P. (2010). On the validity of the bootstrap in nonparametric functional regression, Scand. J. Stat., 37, 286–306.[14] Ferraty, F., Laksaci, A., Tadj, A. and Vieu, P. (2010). Rate of uniform consistency for nonparametric estimates with functional variables, J. Stat. Plan. Inf., 140, 335–352.[15] Ferraty, F. and Romain, Y. (2011). Oxford handbook on functional data analysis (Eds), Oxford University Press.[16] Gasser, T., Hall, P. and Presnell, B. (1998). Nonparametric estimation of the mode of a distribution of random curves, J. Roy. Stat. Soc. B, 60, 681–691.[17] Geenens, G. (2011). A nonparametric functional method for signature recognition, Manuscript.[18] Härdle, W., Müller, M., Sperlich, S. and Werwatz, A. (2004). Nonparametric and semiparametric models, Springer-Verlag, Berlin.[19] James, G.M. (2002). Generalized linear models with functional predictors, J. Roy. Stat. Soc. B, 64, 411–432.[20] Masry, E. (2005). Nonparametric regression estimation for dependent functional data: asymptotic normality, Stochastic Process. Appl., 115, 155–177.[21] Nadaraya, E.A. (1964). On estimating regression, Theory Probab. Applic., 9, 141–142.[22] Quintela-Del-Rio, A. (2008). Hazard function given a functional variable: nonparametric estimation under strong mixing conditions, J. Nonparam. Stat., 20, 413–430.[23] Rachdi, M. and Vieu, P. (2007). Nonparametric regression for functional data: automatic smoothing parameter selection, J. Stat. Plan. Inf., 137, 2784–2801.[24] Ramsay, J. and Silverman, B.W. (1997). Functional Data Analysis, Springer-Verlag, New York.[25] Ramsay, J. and Silverman, B.W. (2002). Applied functional data analysis; methods and case study, Springer-Verlag, New York.[26] Ramsay, J. and Silverman, B.W. (2005). Functional Data Analysis, 2nd Edition, Springer-Verlag, New York.[27] Stone, C.J. (1982). Optimal global rates of convergence for nonparametric regression, Ann. Stat., 10, 1040–1053.[28] Watson, G.S. (1964). Smooth regression analysis, Sankhya A, 26, 359–372.[29] Yeung, D.T., Chang, H., Xiong, Y., George, S., Kashi, R., Matsumoto, T. and Rigoll, G. (2004). SVC2004: First International Signature Verification Competition, Proceedings of the International Conference on Biometric Authentication (ICBA), Hong Kong, July 2004. Full Article