пятница, 24 мая 2013 г.

Games

Games


SQLEditor 2.1.3 - Create SQL databases graphically.

Posted: 24 May 2013 03:14 AM PDT



SQLEditor is a SQL database design and entity relationship diagram (ERD) tool for OS X.

SQLEditor replaces typing SQL by hand with dragging, dropping, and clicking. It makes creating databases faster and easier.

If you already have a database then SQLEditor can help you see what it looks like by reverse engineering a diagram.

SQLEditor supports exporting database designs to MySQL, Postgres, Oracle, and others. Plus it also imports and exports Ruby On Rails Migration files.

Site license: $349, Single Copy $79. Discounts for qualified educational orders

Discounted upgrades from SQLEditor 1.x and free upgrades for copies bought on or after August 1st 2010



Version 2.1.3:
  • Revised java handling, changed requirement to an installed JDK (not JRE) - either Oracle 7 or Apple 6
  • Added new commands to table context menu for adding indexes, constraints, and table-level foreign key
  • Fix for schemaView canDelete crash
  • Fix for exception when setting labels using context menu
  • Fix for Table Type not enabling and disabling with Dialect change
  • Fix for performance issue with object inspection
  • Fix for color exception with comments
  • Fix to ensure indexes appear before foreign keys in SQLServer/Sybase dialect
  • Fix for odd bug where double-clicking an object after changing a label color could change the label color to black
  • Fix for bug where choosing a label color affected other color settings unexpectedly
  • Fix for canvas-area title not displaying when first added
  • Fix for comment name in labels panel not being trimmed
  • Fix for canvas-area objects being described as comments in labels panel
  • Fix for field inspector not updating
  • Fix for exception with label handling


OS X 10.6.8 or later


More information

StockXloader 4.1 - Automated downloading of market quotes.

Posted: 24 May 2013 03:09 AM PDT



StockXloader is a native OS X application for fully automated downloading of stock market quotes and indexes from Yahoo! Finance to the technical analysis program ProTA or ProTA Gold from BeeSoft (http://beesoft.net), or to MS Excel or iWork Numbers, or you can drag-and-drop a file onto some other application.

Get historical quotes, or "snapshots," of the latest price values for today (delayed intraday values). This way you can build your own database of ticker symbols containing historical quotes for the open/high/low/close of each day, plus current-day snapshots. You can get data for any stock exchange in the world that Yahoo! Finance carries quotes for.

StockXloader keeps track of the last date you got quote values, and it does that individually for every ticker symbol, so the next time you download, it will fetch quotes starting after that date. So if a particular symbol lags, StockXloader will pick up where it was left last time. You can also see in your ticker list the last date, individually for each symbol. For snapshots, you can even see the last trading time for the given price data, displayed according to your local time zone and in your language's format.

Fully optimized for the new Retina Macs with high-resolution graphics and text. Compatible with OS X 10.8 Mountain Lion, 10.7 Lion and 10.6 Snow Leopard.

A full and completely uncrippled version of StockXloader can be tried out for evaluation up to 60 days!

Security: StockXloader is signed with an Apple Developer ID certificate, so the Gatekeeper in Mountain Lion will check this cryptographic signature and find that this software comes from an identified developer, and has not been modified on the way to you.

Version 4.1:

  • A separate button Snapshots Only in the Download Controller: This is a convenience button which does the same as the button Download, with the exception that it will skip download of historical quotes. This is useful in situations where you have a tick mark for both Historical and Snapshot and you have done a first download of these, but then you want to quickly update your data during the day with the latest snapshots. It saves you the trouble of deselecting Historical for all ticker lists. There is also a corresponding menu item, along with a shortcut equivalent.
  • There are now two new choices of what to do with the downloaded and converted data:
    1. Default Text App, which will open the final resulting file in the application you have set as the default for text files.
    2. Show File in Finder, which will open the folder where the final resulting text file resides, and the file is then selected (highlighted). This will make it easy for you to drag & drop the file onto an application for import of its data.
  • Date conversions: For import of data to other applications than ProTA, it will now convert all dates to the localized form according to your Language & Text settings in System Preferences. Earlier versions only converted the date and time stamps from Snapshots, whereas it used the ISO date format for Historical quotes. In addition, the text encoding is now UTF-8 for non-ProTA apps. The new all-localized policy for all dates, and the UTF-8 encoding, will expand the number of applications that can successfully import data from StockXloader without problems.
  • A "secret" feature to remove the dates completely: If you change the Last Date of a ticker symbol (Set/Adjust Date, or double click the Last Date), and set the year to 0001, both the historical Last Date and the snapshot date/time will be removed completely. Most users will never have any use for this feature, but it has been useful when creating templates of ticker lists where it has been desirable to remove all dates, leaving those fields empty.
  • Bug fix: The Oldest Snapshot, as shown in the Download Controller, displayed the oldest snapshot date of all symbols in the ticker list, whereas it should have looked at only the enabled symbols in the list. That issue is now fixed!


  • OS X 10.6.8 or later



More information

BuzzBundle 2.2 - Social-media marketing management tool.

Posted: 23 May 2013 09:00 PM PDT



BuzzBundle is a social media management tool that comes in handy here creating the entire buzz you need by means of one tool. An important part of making your brand/product popular on the net is creating buzz about it on social networks. You can do this manually but there's definitely a limit to how much of it a person can create.

Here's exactly what it does. BuzzBundle creates multiple profiles of different personas across almost all social networks out there. You can then create threads, spread announcements, reply to conversations on behalf of different people and create the impression your product/company is the hottest topic on the net. You can send post threads/announcements in real time or use time scheduler and have them posted on a time you choose.

BuzzBundle also works from behind proxies, so that all personas you create come out with a different IP address and the buzz you create looks totally natural.

BuzzBundle is a software product of Link-Assistant.Com, the company behind the famous SEO PowerSuite, the number one SEO software on the web. It has already become one of the hottest cakes of Link-Assistant.Com and definitely for a reason - this is the first software that works like a huge group of people would creating positive impression about your product/company by spreading the word in most of the social networks, collecting what has already been said and a lot more. You can even track all conversations about the brand/company of your competitor and join those if you feel like on behalf of different personas each behind a unique IP address. The great news is you can start using it now and get the world really talk about you.



Version 2.2:
  • A number of performance improvements and bug-fixes (editing scheduled posts, quick filter, mentions in Yahoo! Answers and others) were implemented in BuzzBundle.


  • OS X 10.5.8 or later
  • Java Runtime Environment 1.4



More information

SEO SpyGlass 5.10 - Retrieve information about top-performing Internet rivals.

Posted: 23 May 2013 09:00 PM PDT



Top-ranking begins with SEO SpyGlass. The tool lets you spy on your Google competitors to know exactly how they make their sites top-ranking. It reveals their backlinks, the best keywords, anchor texts and titles.The application shows you what worked and didn't work for your Internet rivals. Using the best of your competition techniques and applying minimal efforts you work out your own winning SEO strategy and outperform your Google competitors.

Version 5.10:
  • 3 new search engines were added to SEO SpyGlass: Google Cote d'Ivoire (google.ci), Google Cameroon (google.cm) and Google Gabon (google.ga).


  • OS X 10.5 or later
  • Java 1.5 or later



More information

FormEntry 2.3 - Create native form-based apps for iOS devices.

Posted: 24 May 2013 02:29 AM PDT



FormEntry is the only development toolkit you need to build productive, great-looking applications for the iPad, iPhone, or iPod touch.

Not everyone has the patience to learn software development, however anyone can be an app developer with FormEntry. Designed from the ground up to be easy-to-use Mac software, FormEntry can turn anyone into an app author.

Another reason to love it: "It Just Works." FormEntry uses the ecosystem of Macs, iPads, iPhones, and iPod touches to bring your form-based apps to life. Simple design and simple to use.



Version 2.3:

FormEntry for Mac
  • Added auto increment number with a defined start number. Number can persist after multiply updates
  • PIN mode 4 digit code to see form before loading at Current Form Screen. Add label "Hold Share Button for 5 seconds to display PIN code screen"
  • Added ability to "Display Cancel Button" in top left for 1) new form, 2) draft form 3) both 4) none
  • Added ability for all Transmittal plugins to display on 1) New form button 2) Send All Drafts button 3) Both
  • Added ability to place any non image value into recipient email address
  • Added ability to use any non image field data into email subject line
  • Added Portrait Mode only for iPad
  • Base File names on field values (XLS, PDF, CSV, TEXT, JPG and PNG)
  • Added ability to use Param ID in Rule Builder conditions.
  • Add Web URL check for form version numbers, can prevent user from access to form if lower version.
  • Add reserved parameter IDs can be used in filenames, Rule Builder conditions and actions: $form_name, $form_version, $form_total_sent_count, $form_author, $form_email, $form_website, $form_company, $form_address1, $form_address2, $form_city, $form_state, $form_zip, $form_country, $form_unix_timestamp, $form_auto_increment, $form_sent_count, $form_drafts_count, $form_trash_count
  • Added ability to create and store local RDMS database(s) for a form
  • Dynamically populate the local form database from a remote web service, which can then populate controls
  • Text Field auto complete from database
  • Added ability to populate Icons and Images from the Rule Builder
  • Enable Debug Mode on iOS device.
FormEntry Touch
  • Reduced form import time with Rules by 50% by compressing Rule Actions.
  • Show Progress Bar when sending forms from PDF, looks like its not being sent
  • Added Progress Indicator when importing new Forms and updating forms
  • Dynamically update database from web server, pulls down refresh
  • Support Retina Display of icons, images and Section and Control Icons.
  • Push FormEntry Server to FormEntry Touch automatically retrieving new forms when launched.
  • Converted CSV and TXT files to generate UTF16 instead of UTF8
  • Moved Device UDID 8 to Unique FormEntry Touch Device UUID 8
  • Add Alert confirmation when deleting forms
  • Minimum requirement is iOS 6 and higher
New Plug-Ins
  • Alias control (for PDF duplicating) Control Plugin
  • Image control with drawing capabilities - Control Plugin
  • Ratings control - Control Plugin
  • WebBrowser control - Control Plugin
  • Save Plugin - options to save directly to drafts with checkmark to immediately load a new form.
Paid Mac In-App Purchase Plug-Ins
  • Barcode control ($399.99) - Control Plugin
  • PIN Code control ($149.99) - Control Plugin
  • SFTP added to FTP Plugin ($199.99) - Transmittal Plugin
  • Open In Plugin ($199.99) - Transmittal Plugin
  • WebDav Plugin ($199.99) - Transmittal Plugin
  • XLS plugin - ($149.99) - Transmit Type Plugin
Bug Fixes:
  • Fixed bug when duplicating a Grouping that prevent the footer text and icon from being duplicated.
  • Fixed iPad issue where Forms icon was accessible after horizontal launch
  • Fixed keyboard from dropping during typing into Text Fields and Text boxes
  • Fixed issue of Secure Text Field showing in actual value in Sent Forms


  • OS X 10.7 or later



More information

Website Auditor 3.10 - Improve your website ranking.

Posted: 23 May 2013 09:00 PM PDT



WebSite Auditor is an extremely efficient SEO tool that introduces a creative and smart approach to onpage SEO. This software product is a must-have for anyone engaged in website promotion, be it a professional SEO or a beginner webmaster.

Website Auditor comes in three editions: Basic (free), Professional ($99.75), and Enterprise ($249.75), all using the same download file linked to above. For more information on the differences between the editions see this page.

WebSite Auditor takes your top 10 rivals and analyzes why they rank so high in search engine results. After presenting detailed analysis of your competitors' webpage promotion strategies in a report, WebSite Auditor produces a unique optimization plan for your website, based on your competitors' strategies. The reports are written in plain English, easy to read and consistent.

WebSite Auditor quickly suggests the optimal keyword density in all the elements of your website - title, body, headers h1-h6 etc. Helpful tips come in easy to follow step-by-step sequence.

Using WebSite Auditor you will:

  • Look into your competitors' strategies for ranking so high.
  • Learn what exactly search engines need to rank websites high.
  • Find out how to make your pages meet search engines' conditions for success.
  • Easily perform necessary changes under professional guidance.
  • Find out if there are any problem areas on your page.
  • Eliminate the problem areas by onpage optimization.
  • Effectively use unique report's features, such as step-by-step advice.
  • Leave no more open SEO questions for yourself.



Version 3.10:
  • 4 new search engines were added to Rank Tracker: Google Cote d'Ivoire (google.ci), Google Cameroon (google.cm), Google Gabon (google.ga) and Google Images Netherlands (www.google.nl/imghp).


  • OS X 10.5 or later
  • Java 1.5 or later



More information

LinkAssistant 4.10 - Build links easily with this SEO tool.

Posted: 23 May 2013 09:00 PM PDT



LinkAssistant is a powerful yet easy to use search engine optimization tool for link management. The unique features of this software let you run all link development tasks in one complete environment. Includes 6 methods of link partner search, a full-fledged email client for sending link exchange requests and receiving incoming mail, a module for generation and FTP-upload of link directories and an incoming links verification facility.

Version 4.10:
  • You can now store all Events you consider important for your SEO progress in LinkAssistant with the Events module.
  • Mechanisms for collecting and processing all ranking factors got updated.
  • The number of supported search engines has been revised and is now 342.


  • OS X 10.5 or later
  • JRE 1.4 or later



More information

Rank Tracker 6.10 - Search engine ranking monitor for webmasters and SEO.

Posted: 23 May 2013 09:00 PM PDT



Rank Tracker is the #1 SEO software for webmasters and SEOs who need to quickly and efficiently check their rankings on a regular basis. The tool lets you see at a glance where your website ranks across 370 search engines, generate profitable keywords you can target, keeps track of your ranking fluctuations, draws visual graphs, generates and publishes SEO reports.

Please note that there are two versions of Rank Tracker available: Professional ($99.75) and Enterprise ($249.75). The differences between the versions are detailed here.



Version 6.10:
  • 4 new search engines were added to Rank Tracker: Google Cote d'Ivoire (google.ci), Google Cameroon (google.cm), Google Gabon (google.ga) and Google Images Netherlands (www.google.nl/imghp).


  • OS X 10.5 or later
  • Java 1.5 or later



More information

Graph Builder 10.8.9 - Chart and graph system (was Vvidget Builder).

Posted: 24 May 2013 02:16 AM PDT



Graph Builder (was Vvidget Builder) is a powerful point-and-click graph building tool. With it, you can fine tune data presentations, add graphics and figures, layout entire pages, drag-and-drop charts and a whole lot more. In addition, chart tasks provide quick starts with a table interface. With Graph Builder you are given the freedom and power to layout presentations the way you want them. Graph Builder is both powerful and intricate, so view the movies at http://www.vvidget.org/build for a good introduction.

Version 10.8.9:
  • Improved the help manual.
  • Fixed user reported deficiencies.


OS X 10.6 or later


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Synalyze It! 1.5.1 - Analyze and edit binary files of any size.

Posted: 24 May 2013 02:03 AM PDT



Synalyze It! is a simple-to-use OS X Hex Editor which will allow you to easily edit and analyze binary files of any size.

Synalyze It! features enhanced support for many character encodings and enables you to interactively define "grammars" for various file formats to speed up analysis and reduce manual decoding of files. Incremental search for strings and numbers, printing and other features make it a quite powerful tool.

Here are some key features of Synalyze It!

  • Hex Editor
  • Printing
  • Histogram view
  • Automatic suggestion of grammars
  • Compare code pages
  • Incremental text search with encoding selection
  • Find text
  • Find numbers
  • Search for masks
  • See all strings in a file



Version 1.5.1:
  • New: Description for structures and elements
  • New: Binary/string length of 0 doesn't mean "unlimited"
  • Fixed text alignment for non-proportional fonts
  • Fixed structure length evaluation
  • Fixed setting of child structure
  • Fixed repeat count expressions
  • Fixed crashes in histogram and checksum panels
  • Several other fixes


OS X 10.6 or later


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IJMS, Vol. 14, Pages 11061-11071: Ubiquitin-Conjugating Enzyme 9 Promotes Epithelial Ovarian Cancer Cell Proliferation in Vitro

Posted: 24 May 2013 12:00 AM PDT

Epithelial ovarian cancer (EOC) is one of the leading causes of cancer deaths in women worldwide. Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays an important role in sumoylation-mediated cellular pathways. Although sumoylation plays a key role in DNA repair and tumorgenesis, whether Ubc9 is involved in EOC progression remains unknown. In the present study, we constructed Ubc-9 expressed recombined plasmid pEGFP-N1-Ubc9. The mRNA levels of Ubc9 were confirmed in human ovarian cell lines before and after transfection with pEGFP-N1-Ubc9 or small interfering RNA (siRNA) targeted Ubc9 by real-time polymerase chain reaction (PCR). The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to observe the effect of Ubc9 on cell proliferation. The protein levels of Ubc9, and proliferation-related signals Akt and physphorylated Akt were determined by Western blot. Our results showed that proliferation of EOC cells increased significantly in Ubc9 overexpressing cells, but decreased in Ubc9 knockdown cells. The physphorylation of Akt showed similar trends. In addition, the inhibitor of PI3K/Akt signaling pathway, LY294002, dramatically inhibited the growth of Ubc9 overexpressing cells. Therefore, Ubc9 gene plays an important role in cell proliferation in EOC through PI3K/Akt signaling pathway.

IJMS, Vol. 14, Pages 11034-11060: Current Status of Biomarkers for Prostate Cancer

Posted: 24 May 2013 12:00 AM PDT

Prostate cancer (PCa) is a leading cause of cancer-related death of men globally. Since its introduction, there has been intense debate as to the effectiveness of the prostate specific antigen (PSA) test as a screening tool for PCa. It is now evident that the PSA test produces unacceptably high rates of false positive results and is not prognostic. Here we review the current status of molecular biomarkers that promise to be prognostic and that might inform individual patient management. It highlights current efforts to identify biomarkers obtained by minimally invasive methods and discusses current knowledge with regard to gene fusions, mRNA and microRNAs, immunology, and cancer-associated microparticles.

IJMS, Vol. 14, Pages 11024-11033: Chemoresistance Is Associated with MUC1 and Lewis y Antigen Expression in Ovarian Epithelial Cancers

Posted: 24 May 2013 12:00 AM PDT

Objective: The aim of this study was to analyze the correlation and clinical significance between the expression of Mucin-1 (MUC1) and the Lewis y antigen with chemoresistance in ovarian epithelial cancers. Methods: Ovarian cancer patients (n = 92) treated at our hospital from May 2005 to July 2009 were divided, according to their treatment and follow-up outcomes, into a resistant group (n = 37) or sensitive group (n = 55). The expression of MUC1 and Lewis y antigen in ovarian cancer tissues was detected using immunohistochemistry and correlated with chemoresistance. Results: The positive rates of MUC1 and Lewis y antigen in the resistant group were both 91.89%, significantly higher than their positive rates in the sensitive group (65.45% and 69.09%, respectively, and both p < 0.05). MUC1 or Lewis y expression and the pathological stage of the tissue were independent risk factors for chemoresistance (all p < 0.05). Conclusion: The increased expression of MUC1 and the Lewis y antigen is a significant risk factor for chemoresistance in patients with ovarian epithelial cancer.

IJMS, Vol. 14, Pages 11011-11023: Characterization and Antimicrobial Property of Poly(Acrylic Acid) Nanogel Containing Silver Particle Prepared by Electron Beam

Posted: 24 May 2013 12:00 AM PDT

In this study, we developed a one step process to synthesize nanogel containing silver nanoparticles involving electron beam irradiation. Water-soluble silver nitrate powder is dissolved in the distilled water and then poly(acrylic acid) (PAAc) and hexane are put into this silver nitrate solution. These samples are irradiated by an electron beam to make the PAAc nanogels containing silver nanoparticles (Ag/PAAc nanogels). The nanoparticles were characterized by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). In addition, the particle size and zeta-potential were confirmed by a particle size analyzer (PSA). The antibacterial properties of the nanogels were evaluated by paper diffusion test. The Ag/PAAc nanogels had an antibacterial effect against Escherichia coli and Staphylococcus aureus. The nanogels also demonstrated a good healing effect against diabetic ulcer. The size of the Ag/PAAc nanogels decreased with increasing irradiation doses, and the absolute value of the zeta potential increased with increasing irradiation doses. Also, the Ag/PAAc nanogels exhibited good antibacterial activity against both Gram-negative and Gram-positive bacteria. In in vivo wound healing, the Ag/PAAc nanogels have a good healing effect.

IJMS, Vol. 14, Pages 10998-11010: Sod1 Loss Induces Intrinsic Superoxide Accumulation Leading to p53-Mediated Growth Arrest and Apoptosis

Posted: 24 May 2013 12:00 AM PDT

Oxidative damages induced by a redox imbalance cause age-related changes in cells and tissues. Superoxide dismutase (SOD) enzymes play a major role in the antioxidant system and they also catalyze superoxide radicals (O2·−). Since the loss of cytoplasmic SOD (SOD1) resulted in aging-like phenotypes in several types of mouse tissue, SOD1 is essential for the maintenance of tissue homeostasis. To clarify the cellular function of SOD1, we investigated the cellular phenotypes of Sod1-deficient fibroblasts. We demonstrated that Sod1 deficiency impaired proliferation and induced apoptosis associated with O2·− accumulation in the cytoplasm and mitochondria in fibroblasts. Sod1 loss also decreased the mitochondrial membrane potential and led to DNA damage-mediated p53 activation. Antioxidant treatments effectively improved the cellular phenotypes through suppression of both intracellular O2·− accumulation and p53 activation in Sod1-deficient fibroblasts. In vivo experiments revealed that transdermal treatment with a vitamin C derivative significantly reversed the skin thinning commonly associated with the upregulated p53 action in the skin. Our findings revealed that intrinsic O2·− accumulation promoted p53-mediated growth arrest and apoptosis as well as mitochondrial disfunction in the fibroblasts.

IJMS, Vol. 14, Pages 10979-10997: Immune-Pineal Axis: Nuclear Factor κB (NF-kB) Mediates the Shift in the Melatonin Source from Pinealocytes to Immune Competent Cells

Posted: 24 May 2013 12:00 AM PDT

Pineal gland melatonin is the darkness hormone, while extra-pineal melatonin produced by the gonads, gut, retina, and immune competent cells acts as a paracrine or autocrine mediator. The well-known immunomodulatory effect of melatonin is observed either as an endocrine, a paracrine or an autocrine response. In mammals, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) blocks noradrenaline-induced melatonin synthesis in pinealocytes, which induces melatonin synthesis in macrophages. In addition, melatonin reduces NF-κB activation in pinealocytes and immune competent cells. Therefore, pathogen- or danger-associated molecular patterns transiently switch the synthesis of melatonin from pinealocytes to immune competent cells, and as the response progresses melatonin inhibition of NF-κB activity leads these cells to a more quiescent state. The opposite effect of NF-κB in pinealocytes and immune competent cells is due to different NF-κB dimers recruited in each phase of the defense response. This coordinated shift of the source of melatonin driven by NF-κB is called the immune-pineal axis. Finally, we discuss how this concept might be relevant to a better understanding of pathological conditions with impaired melatonin rhythms and hope it opens new horizons for the research of side effects of melatonin-based therapies.

IJMS, Vol. 14, Pages 10958-10978: Integrated -Omics: A Powerful Approach to Understanding the Heterogeneous Lignification of Fibre Crops

Posted: 24 May 2013 12:00 AM PDT

Lignin and cellulose represent the two main components of plant secondary walls and the most abundant polymers on Earth. Quantitatively one of the principal products of the phenylpropanoid pathway, lignin confers high mechanical strength and hydrophobicity to plant walls, thus enabling erect growth and high-pressure water transport in the vessels. Lignin is characterized by a high natural heterogeneity in its composition and abundance in plant secondary cell walls, even in the different tissues of the same plant. A typical example is the stem of fibre crops, which shows a lignified core enveloped by a cellulosic, lignin-poor cortex. Despite the great value of fibre crops for humanity, however, still little is known on the mechanisms controlling their cell wall biogenesis, and particularly, what regulates their spatially-defined lignification pattern. Given the chemical complexity and the heterogeneous composition of fibre crops' secondary walls, only the use of multidisciplinary approaches can convey an integrated picture and provide exhaustive information covering different levels of biological complexity. The present review highlights the importance of combining high throughput -omics approaches to get a complete understanding of the factors regulating the lignification heterogeneity typical of fibre crops.

IJMS, Vol. 14, Pages 10944-10957: Impact of an Altered Wnt1/β-Catenin Expression on Clinicopathology and Prognosis in Clear Cell Renal Cell Carcinoma

Posted: 24 May 2013 12:00 AM PDT

In renal cell carcinoma (RCC), single members of the Wnt/β-catenin signaling cascade were recently identified to contribute to cancer progression. However, the role of Wnt1, one of the key ligands in β-catenin regulation, is currently unknown in RCC. Therefore, alterations of the Wnt1/β-catenin axis in clear cell RCC (ccRCC) were examined with regard to clinicopathology, overall survival (OS) and cancer specific survival (CSS). Corresponding ccRCCs and benign renal tissue were analyzed in 278 patients for Wnt1 and β-catenin expression by immunohistochemistry in tissue microarrays. Expression scores, including intensity and percentage of stained cells, were compared between normal kidney and ccRCCs. Data was categorized according to mean expression scores and correlated to tumor and patients' characteristics. Survival was analyzed according to the Kaplan-Meier and log-rank test. Univariable and multivariable Cox proportional hazard regression models were used to explore the independent prognostic value of Wnt1 and β-catenin. In ccRCCs, high Wnt1 was associated with increased tumor diameter, stage and vascular invasion (p ≤ 0.02). High membranous β-catenin was associated with advanced stage, vascular invasion and tumor necrosis (p ≤ 0.01). Higher diameter, stage, node involvement, grade, vascular invasion and sarcomatoid differentiation (p ≤ 0.01) were found in patients with high cytoplasmic β-catenin. Patients with a high cytoplasmic β-catenin had a significantly reduced OS (hazard ratio (HR) 1.75) and CSS (HR 2.26), which was not independently associated with OS and CSS after adjustment in the multivariable model. Increased ccRCC aggressiveness was reflected by an altered Wnt1/β-catenin signaling. Cytoplasmic β-catenin was identified as the most promising candidate associated with unfavorable clinicopathology and impaired survival. Nevertheless, the shift of membranous β-catenin to the cytoplasm with a subsequently increased nuclear expression, as shown for other malignancies, could not be demonstrated to be present in ccRCC.

Epic Mickey 2 hits Vita this June

Posted: 24 May 2013 01:24 AM PDT

Game offers Wi-Fi co-op mode for local

IJMS, Vol. 14, Pages 10926-10943: Mechanisms by Which Licochalcone E Exhibits Potent Anti-Inflammatory Properties: Studies with Phorbol Ester-Treated Mouse Skin and Lipopolysaccharide-Stimulated Murine Macrophages

Posted: 24 May 2013 12:00 AM PDT

In this study we found that licochalcone E (LicE), a recently isolated retrochalcone from Glycyrrhiza inflata, exhibits potent anti-inflammatory effects in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema and lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage models. Topical application of LicE (0.5–2 mg) effectively inhibited TPA-induced (1) ear edema formation; (2) phosphorylation of stress-activated protein kinase/c-Jun-N-terminal kinase (SAPK/JNK), c-Jun, and extracellular signal regulated kinase 1/2; and (3) expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins in mouse skin. The treatment of RAW 264.7 cells with LicE (2.5–7.5 μmol/L) induced a profound reduction in LPS-induced (1) release of NO and prostaglandin E2; (2) mRNA expression and secretion of interleukin (IL)-6, IL-1β and tumor necrosis factor-α; (3) promoter activity of iNOS and COX-2 and expression of their corresponding mRNAs and proteins; (4) activation of AKT, p38 mitogen activated protein kinase (MAPK), SAPK/JNK and c-Jun; (5) phosphorylation of inhibitor of κB (IκB) kinase-αβ and IκBα, degradation of IκBα, translocation of p65 (RelA) to the nucleus and transcriptional activity of nuclear factor (NF)-κB; and (6) transcriptional activity of activator protein (AP)-1. These results indicate that the LicE inhibition of NF-κB and AP-1 transcriptional activity through the inhibition of AKT and MAPK activation contributes to decreases in the expression of pro-inflammatory cytokines and the inducible enzymes iNOS and COX-2.

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