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DICK COUCH graduated at the top of BUD/S Class 45 in 1969. He commanded a SEAL platoon in Vietnam and led one of the only successful POW rescue operations of that conflict. Mr. Couch is the author of four novels and lives in Ketchum, Idaho. This is his first nonfiction book.CLIFF HOLLENBECK is an award-wining photographer and photojournalist. He served with Naval Special Warfare Units, including Underwater Demolition, and was a naval aviator. He has written numerous books on photography and has two novels in print. Mr. Hollenbeck lives in Seattle.From the Hardcover edition.
Given the updated release of Steve Mariotti's classic The Young Entrepreneur's Guide to Starting and Running a Business on Tuesday, we decided...... READ MORE
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subset: commoncrawl


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College Lecturer caught in unwillfulsexual assault of his student..He was only set free after
he signed a check to pay the people who caught him. This only happens to men that refuse to stay with their wife. What do you think about this? Please post your comments below.
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Why have we limited something as important as an interactive form of cultural expression to a term like "videogames"? Isn't it true that it's probably due to someone who a long time ago thought it would be fun to play games on a computer? They would play games. On a computer. They wouldn't play videogames, no, they would play games on a computer.
Some engineers and software developers thought about this for a while after entering the videogames industry and realised they wanted something more. I won't be naming them here since the name of their company isn't the important thing (I'm sure you can figure it out on your own with a little bit of research) but recently they held their first event with the purpose of gathering developers of similiar minds and presenting their results. What can be explored? How far can we go?
I personally also believe that we're restricted by the whole term "games" which is why I'd like to bash in the head of whoever said it first but even with such a limiting form we've been blessed with innovations like Fahrenheit and The Path. Two great examples of just how different games can be from one another rather than just having the exact same idea with their own twist.
I'd also like to say something in regard to the indie-developers out there. Don't mistake indie-developers for innovative developers or companies that produce material of a different kind than the major ones. There are a ton of rip-offs out there and only a few really stand out. Don't get me wrong, I love games. But I also love other things like taking a walk with friends, getting stressed out on facebook, breaking my Gameboy Advance SP in half when I get pissed off but when there is a whole other world… no, let me rephrase that, when there are billions of other possibilities that we haven't explored I want to explore them. There's nothing wrong with liking games the way they are, but the fact that we've become limited by them or rather that we are and always have been limited by them is a painful fact.
Here's an example of what can be done when you're not limited by the word "game" or the criterias for being one: http://blabla.nfb.ca/
So what I'd like to do is to create something entirely new, something that would serve as the creator for the category "games" on computers, and I'm not talking about "software". The actual content already exists, but we need something that's broader than just "videogames". Making up a word based on the criteria for it to have a foundation in an or several actual words is hard, but for now I'll settle with "interexperience". It may sound ambitious but this, or a simplified form of it, is what I will call everything that resides within interactive experiences such as games or interexperience like The Path. Do you have any better ideas for the name or can you come up with a simplified form that is easy to remember and pronounce?


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Word: subissare
Added on: 2011-02-05 Listened: 0 timesin: verbi infinito
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Healthsouth Rehabilitation Hospital
Geisinger Healthsouth Rehabilitation Hospital offers acute inpatient rehabilitation with an individualized plan of care incorporating three hours of therapy each day, including physical therapy, occupational therapy, speech therapy and therapeutic reaction. Geisinger Healthsouth Rehabilitation Hospital is a joint venture partnership between Geisinger Health System and the HEALTHSOUTH Corporation. This 40-bed, stand-alone facility is located on top of the hill behind Geisinger Medical Center in Danville, PA. Click for Rehabilitation Medicine at Geisinger.
2 Rehab LnT: 800-232-8260
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Danville, PA 17821
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PHP has various ways in which you can implement Web services, including NuSOAP, PHP-SOAP, and PEAR (PHP Extension and Application Repository). Some of these packages are more mature than others, but in essence they achieve the same goal, which is to deploy Web services in PHP. We will use PEAR, which is is not a standalone package for Web services but more of a framework for building PHP applications, and which includes a Web services module.
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Offline Support
Enable offline reading for all unread items +images in feeds
I catch up on my RSS reading in the metro (spotty at best cell service) and on flights (often no service even available) -- please enable offline reading of unread items, and sync unread/bookmark/etc. on the next connect. The workflow of the MobileRSS app does this very well currently, and allows per-folder caching and selection of whether to cache images or not, on wifi only or any connection. That is a bit overboard, but being able to add an offline cache is the main feature I'll miss moving from my current solution.
PS: Otherwise, great app!
Currently feedly does not work without network, making reading on the tube/metro/subway impossible. - would be great if feedly just displayed the latest downloaded content.
Like, if you're offering this as a chrome extension, why not make it work offline as in downloading the articles and then syncing with the web service when online? Sort of like how google has offline docs.
Create offline reading capability for iOS and Android. When on an airplane I'd like to read my feeds
To be able to have everything in cache of the Android phone for the offline reading of full articles not only an introduction. Like gReader does.
please enter a function on the app for smartphones that allows you to download, just connected to the internet, all feeds and then read them offline ... like greader
Someting caching last imported data and if possible possibility to define how many items and how often those available offline content would be updated.
Full offline support for not readed content everyday, and delete automatically cache of 1,2 or days you wants..!
And synchronize automatically whenever so often given a day.!
It's would be fantastic for all mobile apps, like Androis and iOS.!
Keeping my saved items available in offline mode and enable export my items stored in html, keeping the division by folder / tag.
I'm sure fellow chromebook/laptop users would rejoice if you made the chrome app work offline. By this I mean having the articles download to the cache and sync with feedly.com
It would be fantastic if you could support the offline and sync with mobile dispositovos.
This is the great sin of all existing applications. Many partially cover this functionality, the best is still the good old NewsRob Pro and gReader improving but still sin in UI and UX.
Congratulations to Feedly, you really have been too accommodating orphans in Google Reader. =]
"seria una gran idea un modo offline y no me declaro genio ya que basta con ver las demas sugerencias ahora que cierra google reader son mi 2 segunda opcion pero implementen el modo offline"
would be a great idea an offline mode and I declare genius because just look at the other suggestions now that google reader closes are my 2 second choice but implement offline mode
Ability to store articles locally and access them in locations lacking internet connection.
please provide a feature to cache content so that i can view in offline
Have offline support for saved articles and today section.
The current feedly apps (iOS and Android) do not offer offline article caching.
This is a feature we are looking into.
If you're looking for offline support, some feedly partner apps support it (eg.Reeder and Newsify on iOS, or Press on Android).
Those apps are powered by the feedly Cloud API and will seamlessly recreate your reading environment (all your feeds are sync'ed from feedly when you login).
To explore the feedly partner apps and their features, visit http://www.feedly.com/apps.html
234 comments
Anonymous commented
Why are the pictures in Feedly so often wrong?
Stefan Colmer commented
I would pay for pro as well if this was available.
Mypich Monoskochjet commented
please send my money work to me now
Anonymous commented
i would pay for pro if you make this available....
Tyler Smith commented
I would pay for pro if this happens.
Andy commented
Given this is the #3 requested feature this seems a lame response. Does 'Under Review' actually mean it's a possibility?
I moved to Feedly after Google Reader closed, offline reading and its simple UI were the two features that made reader. Feedly has a great UI but I really miss the offline capability. The alternative parter apps' UIs don't really work for me, I've grown used to the feedly one so I really don't want to be forced to stop using feedly.
John commented
Wish it was added to feedly pro, which I'm already a subscriber of.
Malik Peeler commented
Great for this article. Moreover, you can try with this PhoneClean, it can help you Remove Junk Files & Clear Private Data on iPhone. including App Caches/Cookies/Temp files/Crash Logs, Photo Caches, Safari Cookies/Caches/History, and so on.
Jeff Summers commented
This is a problem for people living in London too. Not good that there is two major cities who can't really use it because of no offline support!
Tomi Kel commented
Sorry Remi but this response is very sad and it sounds like a political problem. At the moment you are still my favorite reader but overtime feedly became a browsing tool through which i save to Pocket / Instapaper to view offline. If I were you I would get myself together and make this super important feature a reality, otherwise someone else will do it before you and everyone will abandon ship.
I really appreciate what you do but do not support a very important use case in which people go underground and still want to read stuff, not to mention the fact that if you were underground and read a few stories (without images) it won't sync and you then need to review these again.
Mark McGuire commented
With over 100K user on Android, I would imagine you can do better than your competition by enabling your users the power of using Feedly offline.
Peter commented
I'm wanting this feature too! It's essential for any RSS feed reader to read off line .. I recently switched from feedddlerPro to feedly.. Hope some updates arrive soon..
PatrickJSpears commented
People want offline features because we live and work in places where fast reliable access isn't always available.
Tony Izzo commented
I just voted for this, but want to add my personal request that content stored for offline viewing be stored (at least optionally) on the SD card.
Hubert commented
As many others have stated, this singular feature would convince me to stump up for a Pro subscription. I appreciate that there are other apps that will integrate but you've done a good job so far on the Android app and I don't want to have to use a 3rd party workaround as they're almost always a compromise.
Niko Lowry commented
I didn't see an edit button, and wanted to add: if any Android developers walk into this thread, please for the love of god make an XPOSED module that enables offline reading.
Niko Lowry commented
This feature is a must. Why would I ever want to use two apps?
I love the style, ui/ux of Feedly, but being a NYer I'll never even consider replacing Pulse for two apps.
Mickets BR commented
JustReader is still the best for Android, IMHO. Downloads content for offline, customized settings per feed (choose to download or not images, audio, full web view, etc.). Just works.
John Pappas commented
This one feature would create another Pro user. This feature is why pay a number of "freemium" services. As with others, I frequently do not have a reliable connection (Secure areas, heavy buildings, remote locations, Firewalls, etc), and rely on apps that overcome the requirement for constant and reliable internet connection.
Shane Burger commented
I'm coming back to this after initially voting on it in March, and find it amazing that this is the third highest voted request (an essential, in my book) yet it isn't even being considered by Feedly. Wow, guys. Wow. I wish I could give it all the votes I have left.
As a New Yorker who takes the subway, having access to articles in their full form (with images) is a BIG plus.
Yes - you are right - it has been done in other apps. Therefore, how hard can it be to do it in yours? Instead, we have to lessen our overall Feedly UX by using another app on our iOS devices.


text:
Proteins: Structure, Function, Bioinformatics
The solution structure of the forkhead box-O DNA binding domain of Brugia malayi DAF-16a
[Oct 2014]
Brugia malayi is a parasitic nematode that causes lymphatic filariasis in humans. Here the solution structure of the forkhead DNA binding domain of Brugia malayi DAF-16a, a putative ortholog of Caenorhabditis elegans DAF-16, is reported. It is believed to be the first structure of a forkhead or winged helix domain from an invertebrate. C. elegans DAF-16 is involved in the insulin/IGF-I signaling pathway and helps control metabolism, longevity, and development. Conservation of sequence and structure with human FOXO proteins suggest that B. malayi DAF-16a is a member of the FOXO family of forkhead proteins. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
TGP, an extremely stable, non-aggregating fluorescent protein created by structure-guided surface engineering
[Oct 2014]
In this paper we describe the engineering and X-ray crystal structure of Thermal Green Protein (TGP), an extremely stable, highly soluble, non-aggregating green fluorescent protein. TGP is a soluble variant of the fluorescent protein eCGP123, which despite being highly stable, has proven to be aggregation-prone. The X-ray crystal structure of eCGP123, also determined within the context of this paper, was used to carry out rational surface engineering to improve its solubility, leading to TGP. The approach involved simultaneously eliminating crystal lattice contacts while increasing the overall negative charge of the protein. Despite intentional disruption of lattice contacts and introduction of high entropy glutamate side chains, TGP crystallized readily in a number of different conditions and the X-ray crystal structure of TGP was determined to 1.9 Å resolution. The structural reasons for the enhanced stability of TGP and eCGP123 are discussed. We demonstrate the utility of using TGP as a fusion partner in various assays and significantly, in amyloid assays in which the standard fluorescent protein, EGFP, is undesirable because of aberrant oligomerization. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
Structure of human SNX10 reveals insights into its role in human autosomal recessive osteopetrosis
[Oct 2014]
Sorting nexin 10 (SNX10), the unique member of the SNX family having vacuolation activity in cells, was shown to be involved in the development of autosomal recessive osteopetrosis (ARO) in recent genetic studies. However, the molecular mechanism of the disease-related mutations affecting the biological function of SNX10 is unclear. Here, we report the crystal structure of human SNX10 to 2.6Å resolution. The structure reveals that SNX10 contains the extended phox-homology domain we previously proposed. Our study provides the structural details of those disease-related mutations. Combined with the vacuolation study of those mutations, we found that Tyr32 and Arg51 are important for the protein stability and both play a critical role in vacuolation activity, while Arg16Leu may affect the function of SNX10 in osteoclast through protein–protein interactions. Proteins 2014. © 2014 Wiley Periodicals, Inc.
Polyanion binding accelerates the formation of stable and low-toxic aggregates of ALS-linked SOD1 mutant A4V
[Oct 2014]
The toxic property thus far shared by both ALS-linked SOD1 variants and wild-type SOD1 is an increased propensity to aggregation. However, whether SOD1 oligomers or aggregates are toxic to cells remains to be well defined. Moreover, how the toxic SOD1 species are removed from intra- and extracellular environments also needs to be further explored. The DNA binding has been shown to be capable of accelerating the aggregatio\n of wild-type and oxidized SOD1 forms under acidic and neutral conditions. In this study, we explore the binding of DNA and heparin, two types of essential life polyanions, to A4V, an ALS-linked SOD1 mutant, under acidic conditions, and its consequences. The polyanion binding alters the A4V conformation, neutralizes its local positive charges, and increases its local concentrations along the polyanion chain, which are sufficient to lead to acceleration of the pH-dependent A4V aggregation. The accelerated aggregation, which is ascribed to the polyanion binding-mediated removal or shortening of the lag phase in aggregation, contributes to the formation of amorphous A4V nanoparticles. The prolonged incubation with polyanions not only results in the complete conversion of likely soluble toxic A4V oligomers into non- and low-toxic SDS-resistant aggregates, but also increases their stability. Although this is only an initial step toward reducing the toxicity of SOD1 mutants, the accelerating role of polyanions in protein aggregation might become one of the rapid pathways that remove toxic forms of SOD1 mutants from intra- and extracellular environments. Proteins 2014. © 2014 Wiley Periodicals, Inc.
Protein-spanning water networks and implications for prediction of protein–protein interactions mediated through hydrophobic effects
[Oct 2014]
Hydrophobic effects, often conflated with hydrophobic forces, are implicated as major determinants in biological association and self-assembly processes. Protein–protein interactions involved in signaling pathways in living systems are a prime example where hydrophobic effects have profound implications. In the context of protein–protein interactions, a priori knowledge of relevant binding interfaces (i.e., clusters of residues involved directly with binding interactions) is difficult. In the case of hydrophobically mediated interactions, use of hydropathy-based methods relying on single residue hydrophobicity properties are routinely and widely used to predict propensities for such residues to be present in hydrophobic interfaces. However, recent studies suggest that consideration of hydrophobicity for single residues on a protein surface require accounting of the local environment dictated by neighboring residues and local water. In this study, we use a method derived from percolation theory to evaluate spanning water networks in the first hydration shells of a series of small proteins. We use residue-based water density and single-linkage clustering methods to predict hydrophobic regions of proteins; these regions are putatively involved in binding interactions. We find that this simple method is able to predict with sufficient accuracy and coverage the binding interface residues of a series of proteins. The approach is competitive with automated servers. The results of this study highlight the importance of accounting of local environment in determining the hydrophobic nature of individual residues on protein surfaces.Proteins 2014. © 2014 Wiley Periodicals, Inc.
Molecular dynamic studies on the impact of mutations on the structure, stability, and N-terminal orientation of annexin A1: Implications for membrane aggregation
[Oct 2014]
Multiple MD simulations were performed for the full-length wild-type A1, the full length A1 mutations S27E and S27A, as well as the N-terminal peptide (AMVSEFLKQAWFIDNEEQEYIKTVKGS27KGGPGSAVSPYPTFN) of wild-type A1 and mutations S27E and S27A. The MD simulation trajectories of about 350 ns were generated and analyzed to examine the changes of core domain calcium binding affinity, core domain and N-terminal domain structures, and N-terminal domain orientation. Our results indicated that S27A and S27E mutations caused little changes on the calcium-binding affinity of the core domain of A1. However, the S27A mutation made the N-terminal domain of A1 less helical, and made the N-terminal domain migrate faster toward the core domain; these impacts on A1 are beneficial to the membrane aggregation process. On the contrary, the S27E mutation made the N-terminal domain of A1 more stable, and hindered the migration to the core domain; these changes on A1 are antagonistic for the membrane aggregation process. Our results using MD simulations provide an atomistic explanation for experimental observations that the S27E mutant showed a higher calcium concentration requirement and lower maximal extent of aggregation, while the wild-type and two mutants S27E and S27A required identical calcium concentrations for liposome binding. Proteins 2014. © 2014 Wiley Periodicals, Inc.
An Application of Information Theory to a Three-Body Coarse-Grained Representation of Proteins in the PDB: Insights into the Structural and Evolutionary Roles of Residues in Protein Structure
[Sep 2014]
Knowledge-based methods for analyzing protein structures, such as statistical potentials, primarily consider the distances between pairs of bodies (atoms or groups of atoms). Considerations of several bodies simultaneously are generally used to characterize bonded structural elements or those in close contact with each other, but historically do not consider atoms that are not in direct contact with each other. In this report, we introduce an information-theoretic method for detecting and quantifying distance-dependent through-space multibody relationships between the sidechains of three residues. The technique introduced is capable of producing convergent and consistent results when applied to a sufficiently large database of randomly chosen, experimentally solved protein structures. The results of our study can be shown to reproduce established physico-chemical properties of residues as well as more recently discovered properties and interactions. These results offer insight into the numerous roles that residues play in protein structure, as well as relationships between residue function, protein structure, and evolution. The techniques and insights presented in this work should be useful in the future development of novel knowledge-based tools for the evaluation of protein structure. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
Terminal sialic acids on CD44 N-glycans can block hyaluronan binding by forming competing intramolecular contacts with arginine sidechains
[Sep 2014]
Specific sugar residues and their linkages form the basis of molecular recognition for interactions of glycoproteins with other biomolecules. Seemingly small changes, like the addition of a single monosaccharide in the covalently attached glycan component of glycoproteins, can greatly affect these interactions. For instance, the sialic acid capping of glycans affects protein-ligand binding involved in cell–cell and cell–matrix interactions. CD44 is a single-pass transmembrane glycoprotein whose binding with its carbohydrate ligand hyaluronan (HA), an extracellular matrix component, mediates processes such as leukocyte homing, cell adhesion, and tumor metastasis. This binding is highly regulated by glycosylation of the N-terminal extracellular hyaluronan-binding domain (HABD); specifically, sialic acid capped N-glycans of HABD inhibit ligand binding. However, the molecular mechanism behind this sialic acid mediated regulation has remained unknown. Two of the five N-glycosyation sites of HABD have been previously identified as having the greatest inhibitory effect on HA binding, but only if the glycans contain terminal sialic acid residues. These two sites, Asn25 and Asn120, were chosen for in silico glycosylation in this study. Here, from extensive standard molecular dynamics simulations and biased simulations, we propose a molecular mechanism for this behavior based on spontaneously-formed charge-paired hydrogen bonding interactions between the negatively-charged sialic acid residues and positively-charged Arg sidechains known to be critically important for binding to HA, which itself is negatively charged. Such intramolecular hydrogen bonds would preclude associations critical to hyaluronan binding. This observation suggests how CD44 and related glycoprotein binding is regulated by sialylation as cellular environments fluctuate. Proteins 2014. © 2014 Wiley Periodicals, Inc.
Sequence and conformational preferences at termini of α-helices in membrane proteins: Role of the helix environment
[Sep 2014]
α-helices are amongst the most common secondary structural elements seen in membrane proteins and are packed in the form of helix bundles. These α-helices encounter varying external environments (hydrophobic, hydrophilic) that may influence the sequence preferences at their N and C-termini. The role of the external environment in stabilization of the helix termini in membrane proteins is still unknown. Here we analyze α-helices in a high-resolution dataset of integral α-helical membrane proteins and establish that their sequence and conformational preferences differ from those in globular proteins. We specifically examine these preferences at the N and C-termini in helices initiating/terminating inside the membrane core as well as in linkers connecting these transmembrane helices. We find that the sequence preferences and structural motifs at capping (Ncap and Ccap) and near-helical (N' and C') positions are influenced by a combination of features including the membrane environment and the innate helix initiation and termination property of residues forming structural motifs. We also find that a large number of helix termini which do not form any particular capping motif are stabilized by formation of hydrogen bonds and hydrophobic interactions contributed from the neighboring helices in the membrane protein. We further validate the sequence preferences obtained from our analysis with data from an ultradeep sequencing study that identifies evolutionarily conserved amino acids in the rat neurotensin receptor. The results from our analysis provide insights for the secondary structure prediction, modeling and design of membrane proteins. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
The crystal structure of archaeal serine hydroxymethyltransferase reveals idiosyncratic features likely required to withstand high temperatures
[Sep 2014]
Serine hydroxymethyltransferases (SHMTs) play an essential role in one-carbon unit metabolism and are employed in biomimetic reactions. We determined the crystal structure of free (apo) and PLP-bound (holo) SHMT from Methanocaldococcus jannaschii, the first from a hyperthermophile, from the archaea domain of life and that uses H4MPT as a cofactor, at 2.83 and 3.0 Å resolution, respectively. Idiosyncratic features were observed that are likely to contribute to structure stabilization. At the dimer interface, the C-terminal region folds in a unique fashion with respect to SHMTs from eubacteria and eukarya. At the active site, the conserved tyrosine does not make a cation-π interaction with an arginine like that observed in all other SHMT structures, but establishes an amide-aromatic interaction with Asn257, at a different sequence position. This asparagine residue is conserved and occurs almost exclusively in (hyper)thermophile SHMTs. This led us to formulate the hypothesis that removal of frustrated interactions (such as the Arg-Tyr cation-π interaction occurring in mesophile SHMTs) is an additional strategy of adaptation to high temperature. Both peculiar features may be tested by designing enzyme variants potentially endowed with improved stability for applications in biomimetic processes. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
Lipid-associated aggregate formation of superoxide dismutase-1 is initiated by membrane-targeting loops
[Sep 2014]
Copper-Zinc superoxide dismutase 1 (SOD1) is a homodimeric enzyme that protects cells from oxidative damage. Hereditary and sporadic amyotrophic lateral sclerosis may be linked to SOD1 when the enzyme is destabilized through mutation or environmental stress. The cytotoxicity of demetallated or apo-SOD1 aggregates may be due to their ability to cause defects within cell membranes by co-aggregating with phospholipids. SOD1 monomers may associate with the inner cell membrane to receive copper ions from membrane-bound copper chaperones. But how apo-SOD1 interacts with lipids is unclear. We have used atomistic molecular dynamics simulations to reveal that flexible electrostatic and zinc-binding loops in apo-SOD1 dimers play a critical role in the binding of 1-octanol clusters and phospholipid bilayer, without any significant unfolding of the protein. The apo-SOD1 monomer also associates with phospholipid bilayer via its zinc-binding loop rather than its exposed hydrophobic dimerization interface. Our observed orientation of the monomer on the bilayer would facilitate its association with a membrane-bound copper chaperone. The orientation also suggests how membrane-bound monomers could act as seeds for membrane-associated SOD1 aggregation. Proteins 2014. © 2014 Wiley Periodicals, Inc.
Backbone dependency further improves side chain prediction efficiency in the Energy-based Conformer Library (bEBL)
[Sep 2014]
Side chain optimization is an integral component of many protein modeling applications. In these applications, the conformational freedom of the side chains is often explored using libraries of discrete, frequently occurring conformations. Because side chain optimization can pose a computationally intensive combinatorial problem, the nature of these conformer libraries is important for ensuring efficiency and accuracy in side chain prediction. We have previously developed an innovative method to create a conformer library with enhanced performance. The Energy-based Library (EBL) was obtained by analyzing the energetic interactions between conformers and a large number of natural protein environments from crystal structures. This process guided the selection of conformers with the highest propensity to fit into spaces that should accommodate a side chain. Because the method requires a large crystallographic data-set, the EBL was created in a backbone-independent fashion. However, it is well established that side chain conformation is strongly dependent on the local backbone geometry, and that backbone-dependent libraries are more efficient in side chain optimization. Here we present the backbone-dependent EBL (bEBL), whose conformers are independently sorted for each populated region of Ramachandran space. The resulting library closely mirrors the local backbone-dependent distribution of side chain conformation. Compared to the EBL, we demonstrate that the bEBL uses fewer conformers to produce similar side chain prediction outcomes, thus further improving performance with respect to the already efficient backbone-independent version of the library. Proteins 2014. © 2014 Wiley Periodicals, Inc.
Accurate single-sequence prediction of solvent accessible surface area using local and global features
[Sep 2014]
We present a new approach for predicting the Accessible Surface Area (ASA) using a General Neural Network (GENN). The novelty of the new approach lies in not using residue mutation profiles generated by multiple sequence alignments as descriptive inputs. Instead we use solely sequential window information and global features such as single-residue and two-residue compositions of the chain. The resulting predictor is both highly more efficient than sequence alignment-based predictors and of comparable accuracy to them. Introduction of the global inputs significantly helps achieve this comparable accuracy. The predictor, termed ASAquick, is tested on predicting the ASA of globular proteins and found to perform similarly well for so-called easy and hard cases indicating generalizability and possible usability for de-novo protein structure prediction. The source code and a Linux executables for GENN and ASAquick are available from Research and Information Systems at http://mamiris.com, from the SPARKS Lab at http://sparks-lab.org, and from the Battelle Center for Mathematical Medicine at http://mathmed.org. Proteins 2014. © 2014 Wiley Periodicals, Inc.
General mean-field theory for mechanical hysteresis of network-like macromolecules
[Sep 2014]
In the framework of the mean-field theory for the order parameter, which characterizes the degree of deviating the structure of a network-like macromolecule from its natural state under the action of the external force, its mechanical hysteresis is considered. Elastic hysterical properties of a macromolecule are studied as a function of the applied force, temperature and some other parameters controlling the viscous-elastic behavior of network-like macromolecules. Proteins 2014. © 2014 Wiley Periodicals, Inc.
Talin-driven inside-out activation mechanism of platelet αIIbβ3 integrin probed by multimicrosecond, all-atom molecular dynamics simulations
[Sep 2014]
Platelet aggregation is the consequence of the binding of extracellular bivalent ligands such as fibrinogen and von Willebrand factor to the high affinity, active state of integrin αIIbβ3. This state is achieved through a so-called "inside-out" mechanism characterized by the membrane-assisted formation of a complex between the F2 and F3 subdomains of intracellular protein talin and the integrin β3 tail. Here, we present the results of multi-microsecond, all-atom molecular dynamics simulations carried on the complete transmembrane (TM) and C-terminal (CT) domains of αIIbβ3 integrin in an explicit lipid-water environment, and in the presence or absence of the talin-1 F2 and F3 subdomains. These large-scale simulations provide unprecedented molecular-level insights into the talin-driven inside-out activation of αIIbβ3 integrin. Specifically, they suggest a preferred conformation of the complete αIIbβ3 TM/CT domains in a lipid-water environment, and testable hypotheses of key intermolecular interactions between αIIbβ3 integrin and the F2/F3 domains of talin-1. Notably, not only do these simulations give support to a stable left-handed reverse turn conformation of the αIIb juxtamembrane motif rather than a helical turn, but they raise the question as to whether TM helix separation is required for talin-driven integrin activation. Proteins 2014. © 2014 Wiley Periodicals, Inc.
Specificity of a protein–protein interface: Local dynamics direct substrate recognition of effector caspases
[Sep 2014]
Computational and experimental investigation of constitutive behavior in AraC
[Sep 2014]
Many mutations in the N-terminal arm of AraC result in constitutive behavior in which transcription of the araBAD genes occurs even in the absence of arabinose. To begin to understand the mechanism underlying this class of mutations, we used molecular dynamics with self-guided Langevin dynamics to simulate (1) wild type AraC, (2) known constitutive mutants resulting from alterations in the regulatory arm, particularly alanine and glycine substitutions at residue eight because P8G is constitutive whereas P8A behaves like wild type, and (3) selected variant AraC proteins containing alterations in the dimerization core. In all of the constitutive arm mutants, but not the wild type protein, residues 37-42, which are located in the core of the dimerization domain, became restructured. This raised the question of whether or not these structural changes are an obligatory component of constitutivity. Using molecular dynamics, we identified alterations in the core that produced a similar restructuring. The corresponding mutants were constructed and their ara constitutivity status was determined experimentally. Because the core mutants were not found to be constitutive, we conclude that restructuring of core residues 37-42 does not, itself, lead to constitutivity of AraC. The available data lead to the hypothesis that the interaction of the N-terminal arm with something other than the front lip is the primary determinant of the inducing versus repressing state of AraC. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
Alanine and proline content modulate global sensitivity to discrete perturbations in disordered proteins
[Sep 2014]
Molecular transduction of biological signals is understood primarily in terms of the cooperative structural transitions of protein macromolecules, providing a mechanism through which discrete local structure perturbations affect global macromolecular properties. The recognition that proteins lacking tertiary stability, commonly referred to as intrinsically disordered proteins, mediate key signaling pathways suggests that protein structures without cooperative intramolecular interactions may also have the ability to couple local and global structure changes. Presented here are results from experiments that measured and tested the ability of disordered proteins to couple local changes in structure to global changes in structure. Using the intrinsically disordered N-terminal region of the p53 protein as an experimental model, a set of proline and alanine to glycine substitution variants were designed to modulate backbone conformational propensities without introducing non-native intramolecular interactions. The hydrodynamic radius (Rh) was used to monitor changes in global structure. Circular dichroism spectroscopy showed that the glycine substitutions decreased polyproline II (PPII) propensities relative to the wild type, as expected, and fluorescence methods indicated that substitution-induced changes in Rh were not associated with folding. The experiments showed that changes in local PPII structure cause changes in Rh that are variable and that depend on the intrinsic chain propensities of proline and alanine residues, demonstrating a mechanism for coupling local and global structure changes. Molecular simulations that model our results were used to extend the analysis to other proteins and illustrate the generality of the observed proline and alanine effects on the structures of intrinsically disordered proteins. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
Hamiltonian replica exchange combined with elastic network analysis to enhance global domain motions in atomistic molecular dynamics simulations
[Sep 2014]
Coarse-grained elastic network models (ENM) of proteins offer a low resolution representation of protein dynamics and directions of global mobility. A Hamiltonian-replica exchange molecular dynamics (H-REMD) approach has been developed that combines information extracted from an ENM analysis with atomistic explicit solvent MD simulations. Based on a set of centers representing rigid segments (centroids) of a protein a distance-dependent biasing potential is constructed by means of an ENM analysis to promote and guide centroid/domain rearrangements. The biasing potentials are added with different magnitude to the force field description of the MD simulation along the replicas with one reference replica under the control of the original force field. The magnitude and the form of the biasing potentials are adapted during the simulation based on the average sampled conformation to reach a near constant biasing in each replica after equilibration. This allows for canonical sampling of conformational states in each replica. The application of the methodology to a 2-domain segment of the glycoprotein 130 and to the protein cyanovirin-N indicates significantly enhanced global domain motions and improved conformational sampling compared to conventional MD simulations. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
Physics-Based Enzyme Design: Predicting Binding Affinity and Catalytic Activity
[Sep 2014]
Computational enzyme design is an emerging field that has yielded promising success stories, but where numerous challenges remain. Accurate methods to rapidly evaluate possible enzyme design variants could provide significant value when combined with experimental efforts by reducing the number of variants needed to be synthesized and speeding the time to reach the desired endpoint of the design. To that end, extending our computational methods to model the fundamental physical-chemical principles that regulate activity in a protocol that is automated and accessible to a broad population of enzyme design researchers is essential. Here, we apply a physics-based implicit solvent MM-GBSA scoring approach to enzyme design and benchmark the computational predictions against experimentally determined activities. Specifically, we evaluate the ability of MM-GBSA to predict changes in affinity for a steroid binder protein, catalytic turnover for a Kemp eliminase, and catalytic activity for α-Gliadin peptidase variants. Using the enzyme design framework developed here, we accurately rank the most experimentally active enzyme variants, suggesting that this approach could provide enrichment of active variants in real-world enzyme design applications. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.


text:
Though the Diamondbacks are tempted to bring up starting pitcher Kevin Jarvis
from Triple-A Tucson, there might be no immediate changes to Arizona's starting
rotation unless Orlando Hernandez still has issues with his back upon throwing a
bullpen session before Friday's game against the visiting Atlanta Braves.
Hernandez wrenched something in his back or his side while pitching in the
first inning Tuesday against the Padres and had to leave the game after walking
the first batter he faced in the third. He also had soreness in his right knee
and there was speculation he might be headed to the disabled list.
But "El Duque" had no problems running on Wednesday and after Thursday's day
off, the Diamondbacks are hoping he will be healthy enough to make his next
scheduled start. That could be on Sunday or Monday. Arizona has had a series of
early exits by most of its starters, other than ace Brandon Webb, which is
beginning to put a burden on a bullpen that ranked second in the National League
behind the Cardinals with a 3.22 ERA.
Last season, the Diamondbacks had the worst bullpen in the majors, as the
relievers had a 5.40 ERA.
If Hernandez isn't able to pitch, Jarvis would be the likeliest call-up,
although an adjacent move would have to be made to put him on the 40-man roster.
Other options include Tucson right-handers Enrique Gonzalez and Dustin Nippert,
both of whom are already on the 40-man.
--The Diamondbacks, who are 14-10 against the NL West and 8-8 against the NL
Central, face their first opponents from the NL East on Friday when Atlanta
comes to Phoenix for the first of three games at Chase Field.
--Arizona turned two more double plays on Wednesday, increasing its major
league-leading total to 58.
--Though the Diamondbacks' grasp of first place in the NL West was
short-lived, RHP Jason Grimsley said it bore significance, even in the middle of
"Hey, if you're 10 games below .500 and 11 games out, you've got a big hole
to dig yourselves out of," Grimsley said. "We're right in the mix. Who's to say
where we're going to be come Sept. 15, but I'd rather be where we are right now
and take my chances."
--1B Tony Clark has a clause in his contract that helps pay tribute to
firefighters and police officers in Arizona. The program, called Badge of Honor
Days, allowed firemen and cops to receive a complimentary ticket to a game for
every ticket they purchase. The first Badge of Honor Day is Friday against the
visiting Braves.
BY THE NUMBERS: 9 -- Double plays Chad Tracy had helped turn, the most among
National League third baseman as of May 12.
QUOTE TO NOTE: "He had a couple bad starts, but he's worked some things out
and ever since we've gotten him, he's been very good for us. Every now and then,
everybody's going to hit a little bump in the road. But he's been quite a pickup
for us, especially considering how we got him." -- Manager Bob Melvin on RHP
Claudio Vargas, who is 13-7 for the Diamondbacks dating to last season, when
they claimed him off waivers from the Nationals.
The D'Backs Inside Pitch
"I just had a bad day," Juan Cruz said after getting shelled for nine runs in just 2/3 of an inning.…


text: 000 ABNT20 KNHC 171144 TWOAT TROPICAL WEATHER OUTLOOK NWS NATIONAL HURRICANE CENTER MIAMI FL 800 AM EDT FRI OCT 17 2014 For the North Atlantic...Caribbean Sea and the Gulf of Mexico: The National Hurricane Center is issuing advisories on Hurricane Gonzalo, located a few hundred miles south-southwest of Bermuda. Tropical cyclone formation is not expected during the next five days. $$ Forecaster Landsea


text: Talk:J's Partner Edit this page History 5,545pages on this wiki Back to page Same? Ninja of the Kumo with Aoba early episode 256, he would not have this character?—This unsigned comment was made by Gok993 (talk • contribs) . It does look like him actually in the anime. Just to note that in the manga, however, it wasn't him.--Cerez365™(talk) 22:51, April 9, 2012 (UTC) Retrieved from "http://naruto.wikia.com/wiki/Talk:J%27s_Partner?oldid=624335" Facts about J's PartnerRDF feed


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We've sourced a top-notch, fairly-traded Italian-roasted coffee with a rich, aromatic flavour. Our tea is a proper English breakfast brew and our hot chocolate is 100% natural and super-chocotaley. We only use organic milk.
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served in milk bottles with a straw
Mango Lasi
Fresh mango & cardamon seeds pulsed with yogurt. It's fruity, sweet & creamy, like the topping of a cheesecake with added spice. £4.00
Peanut butter milkshake
Doesn't the name sell it enough? Heaped teaspoons of peanut butter whizzed with banana, splash of milk & honey. It's delicious & creamy, except for the lovely crunch of peanut butter. £3.00
Beat & squeeze
A classic combination of beetroot & our freshly squeezed orange juice, whizzed with banana & crushed ice to create a gorgeous bright red smoothie that's earthy & sweet. £3.00
Served over ice in jam jars
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Zippy lime. juicy blueberries, mint & warming ginger beer, all stirred with crushed ice. As refreshing as standing under a waterfall, but slightly more practical. £3.00
Green tea lemonade.
Fresh green tea, ginger syrup & lemon juice, topped with soda water. A refreshing homemade lemonade: not too sweet, not too bitter. £3.00
Strawberry tart.
Real strawberry purée is brought to life by lots of tangy lemon juice, then topped with soda water & shaken up. It's a little bit tart, a little bit sweet, & more than a little drinkable. £4.00
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Pisco sour
On Edwina Currie's advice we've removed the egg whites, but we've added pineapple juice to make it as silky smooth as ever. The rest is as the South Americans have it- lots of lime, pisco ABA and Angostura bitters. £6.50
Recipease gin
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If the pun hasn't sold you, how about the fresh espresso, Kahlua and sugar syrup, all shaken with ice. It's refreshing like an iced tea. But with coffee. And alcohol. £5.50
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Pale lemon in colour, crisp apple & a touch of citrus on the nose. Glass £4.95/ Carafe 250ml £6.95/ Carafe 500ml £11.99/ Bottle £16.99
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Pale lemon in colour with a youthful rim, fresh, crisp apple and a touch of citrus on the nose. On the palate, it has attractive weight, with a good balance of ripe, yellow plums and greengage fruit character and fresh lemon-lime acidity. Fresh and zippy on the finish. Glass £4.95/ Carafe 250ml £6.95/ Carafe 500ml £11.99/ Bottle £16.99
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Intense & concentrated, lovely pure fruit character, with flavours of peach & lime. Bottle £39.95


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Ty Vernon
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Koegel Autism Center at the University of California Santa Barbara
The Koegel Autism Center offers state-of-the-art intervention and assessment services for children and adults with autism spectrum disorders. We emphasis the use of motivational strategies, choice, and the use of natural learning environments. See Full Profile
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Autism In Wikipedia
Autism is a neurodevelopmental disorder characterized by impaired social interaction, verbal and non-verbal communication, and by restricted and repetitive behavior. Learn more >>
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Autism Speaks
Autism Speaks is an autism advocacy organization in the United States that sponsors autism research and conducts awareness and outreach activities aimed at families, governments, and the public. Learn more >>


text:
+ - Console gaming is dead? How about $14,600 for a launch-day PS4->
Submitted by aussersterne
aussersterne (212916) writes "Seven years after the release of the PS3, Sony released the PS4 on Friday to North American audiences. Research group Terapeak, who have direct access to eBay data, finds that despite claims to the contrary, console gaming still opens wallets. Millions of dollars in PS4 consoles were sold on eBay before the launch even occurred, with prices for single consoles reaching as high as $14,600 on Friday. Would you be willing to pay this much to get a PS4 before Christmas? Or are you more likely to have been the seller, using your pre-orders to turn a tidy profit?"
Link to Original Source
Link to Original Source


text:
Job Mocked By His Wife - Georges de la Tour, 1630s
Giusto de' Menabuoi, Paradiso. 1375-76. The dome of Padua's Baptistry. Fresco.
(via cavetocanvas)
Dyad - Barbara Hepworth, 1949
From the National Galleries of Scotland:
'Dyad' is one of Hepworth's most overtly figurative sculptures. On one side there is the incised profile of a man's head and on the other there is a smaller, female profile. The form suggests that the two figures are embracing. There is no front or back view: both sides are equal. 'Dyad' is a mathematical term meaning 'two'. Hepworth wrote that she 'used it in this sense of the two forms and the two entities,' combined in one figure. Hepworth made her first pierced sculpture in 1931. Here, she uses holes as a way of uniting the two sides of the work.
— Oscar Wilde (via fine-and-bold)
(via mazamitla)
(via mazamitla)
Homage to Hermann Hesse by the akirA project on Flickr.
Charlotte Salomon - "The Embrace"
Fishermen on the Beach at Skagen - Peder Severin Krøyer, 1891
(via cavetocanvas)
(Quelle: inverse-square)
Work Interrupted - William Bouguereau, 1891
(via cavetocanvas)
(Quelle: lushcollective, via wanweird-of-an-argonaut)
(Quelle: lushcollective, via wanweird-of-an-argonaut)
Ancient Sound - Paul Klee, 1925
(via cavetocanvas)
Cat and Bird - Paul Klee, 1928
(Quelle: cavetocanvas)


text:
Key Cybersecurity, Inc.
Key Cybersecurity, Inc.
Key Cybersecurity, Inc. is the developer of CyberMerlin, a deep hash algorithm and vision technology forensics solution that is designed to pro-actively identify illicit files and the associated activity of "bad actors" on commercial, federal and K-12 enterprise networks. The solution searches for unknown and known files not typically addressed by existing safeguards and countermeasures. CyberMerlin automatically monitors, detects and provides alerts as well as compiles forensics reports for investigators and law enforcement entities.
17959 Dumfries Shopping Plaza Suite B
Dumfries, VA 22026-2490


text:
There have been home runs in baseball history bigger than Raul Ibanez's 9th inning, game-tying shot last night or even his 12th inning game-winning swat. Bobby Thomson's, after all, won a pennant; Bill Mazeroski's won a World Series. But I don't think any pair of home runs turned so many careers o ... More >>
Clip Job: an excerpt every day from the Voice archives. June 14, 1973, Vol. XVIII, No. 24 A horse for all seasons by Joe Flaherty A group of us, accompanied by the baggage of New York blase, gathered early at Penn Station Saturday for an odyssey to Belmont Park. The onus lay with the horse ... More >>
Bing Crosby didn't know it, but when he took off for Paris on October 12, 1960, he left us all with a wonderful Christmas present. Bing was part owner of the Pittsburgh Pirates and fearful that his National League champions were no match for the Mickey Mantle-Roger Maris-Whitey Ford Yankees. ... More >>
And proud of it
On October 3, 1951, the Giants' Bobby Thomson - who died yesterday at age 86 - did more than hit the most famous home run in baseball history. He also inspired one of baseball's most famous sayings. The Yankees had clinched the American League pennant just a couple of days before the Giant ... More >>
A Guide to the Scandals and Issues That Could Stall Her Senate Run


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Meeting Facilities Hotels in Harrison
See Harrison Meeting Facilities hotels on a map
Explore Harrison
Popular with travellers from India
Meeting Facilities hotels in Harrison
Hotel Seville, an Ascend Collection Hotel
Excellent 4.4 / 5 ( 66 reviews )
50 people looked at this hotel in the last hour
Most recent review
"Just went for a little getaway with the wife. Hotel was nice,good customer service. Would definatly recommend to a friend. Only downfall was we could'nt get the wifi to work in our room.."
A Traveller, Oct 2014, US
Hampton Inn Harrison
Outstanding 4.8 / 5 ( 29 reviews )
37 people looked at this hotel in the last hour
Most recent review
"Fair price for a clean decent hotel room on a Saturday night approx 20 minutes from table rock lake. Not much around the hotel."
A Traveller, Sep 2014, US
Meeting Facilities hotels within 40 kilometers of Harrison
Bluegreen Vacations Paradise Point, Ascend Resort Collection
Excellent 4.5 / 5 ( 11 reviews )
53 people looked at this hotel in the last hour
Most recent review
"It was a great place to stay. These appear to be owner-rented condos, but it was very nice. Ten minute drive into Branson, less than that to Big Cedar Lodge. Rates were very good, especially for the newness of the room."
A Traveller, Jul 2014, US