пятница, 20 января 2012 г.

Games

Games

Demolicious - Screenshots

Posted: 20 Jan 2012 03:03 AM PST

Test your skills in over 60 unique destruction arenas and mini-games. Destroy all crates in the arena in any way imaginable in order to win. Use the full 3D environment to solve puzzles and destroy explosive crates to do heavy damage. Switch between cannons and viewpoints at any time in order to destroy with tactical precision from multiple firing angles. Create havoc with ricochets, explosions, and domino effects! Enjoy the spectacular fireworks as a barrage of instant replays celebrates your success or failure in all its' destructive glory!

UK library lending down, generation of readers to go missing?

Posted: 20 Jan 2012 03:02 AM PST

Charlie Stross looks at some leading indicators of library decline in the UK, which he attributes to cuts and closures, and notes: "if the drop in my PLR loans reflects library closures, then we have just slammed the door in the face of a new generation of readers. I got my start reading fiction from my local library; the voracious reading habits of a bookish child aren't easily supported from a family budget under strain from elsewhere during a time of cuts. I hate to think what the long term outcome of this short-term policy is going to be, but I don't believe any good will come of it."

Cancers, Vol. 4, Pages 55-76: Tumor-Promoting Circuits That Regulate a Cancer-Related Chemokine Cluster: Dominance of Inflammatory Mediators Over Oncogenic Alterations

Posted: 20 Jan 2012 12:00 AM PST

Here, we investigated the relative contribution of genetic/signaling components versus microenvironmental factors to the malignancy phenotype. In this system, we took advantage of non-transformed fibroblasts that carried defined oncogenic modifications in Ras and/or p53. These cells were exposed to microenvironmental pressures, and the expression of a cancer-related chemokine cluster was used as readout for the malignancy potential (CCL2, CCL5, CXCL8, CXCL10). In cells kept in-culture, synergism between Ras hyper-activation and p53 dysfunction was required to up-regulate the expression of the chemokine cluster. The in vivo passage of RasHigh/p53Low-modified cells has led to tumor formation, accompanied by potentiation of chemokine release, implicating a powerful role for the tumor microenvironment in up-regulating the chemokine cluster. Indeed, we found that inflammatory mediators which are prevalent in tumor sites, such as TNFa and IL-1β, had a predominant impact on the release of the chemokines, which was substantially higher than that obtained by the oncogenic modifications alone, possibly acting through the transcription factors AP-1 and NF-kB. Together, our results propose that in the unbiased model system that we were using, inflammatory mediators of the tumor milieu have dominating roles over oncogenic modifications in dictating the expression of a pro-malignancy chemokine readout.

Michael Jackson: The Experience - Screenshots

Posted: 20 Jan 2012 02:32 AM PST

Michael Jackson, one of the most widely beloved entertainers and the most popular global icons of all time, leaves an indelible imprint on popular music and culture. During his extraordinary career Jackson sold an estimated 750 million records worldwide, released 13 No.1 singles and became one of a handful of artists to be inducted twice into the Rock and Roll Hall of Fame. He won 13 Grammy Awards and received the American Music Award's Artist of the Century Award. His album Thriller is the worlds best-selling album of all time with more than 110 million copies sold.

Cancers, Vol. 4, Pages 39-54: Diagnosis and Treatment of Gastrinomas in Multiple Endocrine Neoplasia Type 1 (MEN-1)

Posted: 20 Jan 2012 12:00 AM PST

Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal-dominant disease. It is associated with a broad range of endocrine tumours, most frequently arising in the parathyroid glands, the pituitary and the pancreas. Most neuroendocrine tumours will be diagnosed in the pancreas as non-functioning neuroendocrine tumours or insulinomas. Forty-two percent of the patients will develop a gastrin-secreting neuroendocrine tumour, a gastrinoma. Gastrinomas in MEN-1 tend to be small, multiple and preferentially located in the duodenum. This paper will focus on the specific characteristics of gastrinomas in the setting of MEN-1 compared to sporadic gastrinomas. The developments in understanding the tumorigenesis of these tumours and the consequences for diagnosis and therapy will be discussed.

Molecules, Vol. 17, Pages 1103-1112: The Newly Isolated Endophytic Fungus Paraconiothyrium sp. LK1 Produces Ascotoxin

Posted: 20 Jan 2012 12:00 AM PST

We have isolated five endophytic fungi from the roots of Capsicum annuum, Cucumis sativus and Glycine max. The culture filtrates (CF) of these endophytes were screened on dwarf mutant rice (Waito-C) and normal rice (Dongjin-byeo). Endophyte CAC-1A significantly inhibited the growth of Waito-C and Dongjin-byeo. Endophyte CAC-1A was identified as Paraconiothyrium sp. by sequencing the ITS rDNA region and phylogenetic analysis. The ethyl acetate fraction of Paraconiothyrium sp. suppressed the germination of Lactuca sativa and Echinochloa crus-galli seeds. The ethyl acetate fraction of the endophyte was subjected to bioassay-guided isolation and we obtained the phytotoxic compound ascotoxin (1) which was characterized through NMR and GC/MS techniques. Ascotoxin revealed 100% inhibitory effects on seed germination of Echinochloa crus-galli. Compound (1) was isolated for the first time from Paraconiothyrium sp.

Molecules, Vol. 17, Pages 1074-1102: Diversity Oriented Syntheses of Conventional Heterocycles by Smart Multi Component Reactions (MCRs) of the Last Decade

Posted: 20 Jan 2012 12:00 AM PST

A collection of smart multicomponent reactions (MCRs) with continuative post condensation cyclizations (PCCs) is presented to construct conventional three- to seven-membered heterocyclic compounds in diversity oriented syntheses (DOS). These will provide a high degree of applying economical and ecological advantages as well as of practicability. Water, ionic liquids, and solvent-less syntheses as well as use of various forms of energy as microwave and ultrasonic irradiation are examined and discussed.

Molecules, Vol. 17, Pages 1055-1073: Fluorescent Lipids: Functional Parts of Fusogenic Liposomes and Tools for Cell Membrane Labeling and Visualization

Posted: 20 Jan 2012 12:00 AM PST

In this paper a rapid and highly efficient method for controlled incorporation of fluorescent lipids into living mammalian cells is introduced. Here, the fluorescent molecules have two consecutive functions: First, they trigger rapid membrane fusion between cellular plasma membranes and the lipid bilayers of their carrier particles, so called fusogenic liposomes, and second, after insertion into cellular membranes these molecules enable fluorescence imaging of cell membranes and membrane traffic processes. We tested the fluorescent derivatives of the following essential membrane lipids for membrane fusion: Ceramide, sphingomyelin, phosphocholine, phosphatidylinositol-bisphosphate, ganglioside, cholesterol, and cholesteryl ester. Our results show that all probed lipids could more efficiently be incorporated into the plasma membrane of living cells than by using other methods. Moreover, labeling occurred in a gentle manner under classical cell culture conditions reducing cellular stress responses. Staining procedures were monitored by fluorescence microscopy and it was observed that sphingolipids and cholesterol containing free hydroxyl groups exhibit a decreased distribution velocity as well as a longer persistence in the plasma membrane compared to lipids without hydroxyl groups like phospholipids or other artificial lipid analogs. After membrane staining, the fluorescent molecules were sorted into membranes of cell organelles according to their chemical properties and biological functions without any influence of the delivery system.

Bankster might lose his knighthood

Posted: 20 Jan 2012 02:00 AM PST

Fred "the Shred" Goodwin, an infamous figure in Britain's aristocracy and a symbol of finance industry greed and incompetence, stands to lose his knighthood. Goodwin was knighted for "services to banking," and a few years later presided over the collapse of the Royal Bank of Scotland, which the British public had to bail out. Goodwin walked away with a titanic, multimillion-pound pension. The Prime Minister David Cameron has asked the relevant committees to have a go at taking away Goodwin's knighthood.

Allods Online - Screenshots

Posted: 20 Jan 2012 01:54 AM PST

MOSCOW & DUBLIN - April 23, 2009 - Nival Online, the Russian game developer behind the Allods series of role-playing strategy games (known as Rage of Mages in Europe and America), and Gala Networks Europe, the free-to-play MMORPG publisher that operates the gPotato.eu gaming portal are proud to announce Allods Online, a massively multiplayer online role-playing game based on Russia's most successful gaming series.

The free-to-play title brings MMO fans across Europe into a universe of epic fantasy and fierce conflict with a deep and captivating storyline. Allods Online takes place after the destruction of the planet of Sarnout and the subsequent formation of the namesake Allods. These mystical islands float in the Astral, an expansive living substance that makes up the compelling game world. Adventurers will explore the numerous Allods as they battle against a wide range of enemies – and each other.

Allods Online will feature classic fantasy MMORPG gameplay that fans of the genre's most successful titles can enjoy. It features extensive questing, intense player-versus-player combat, grand exploration, in-depth character development and plenty of social interaction. In the Astral, players will have the chance to put their wits and brawn to the test in larger-than-life Astral battles, the game's giant fights between competing 'Astral ships' manned by multiple players. Adventurers from all over the world will have to choose between six races and eight character classes before choosing their allegiance between the two warring factions: the League and the Empire.

With over 12 million USD in funding, Allods Online is the best-funded Russian game development project in history. In addition, the team behind the title at Nival Online recently ...

IJMS, Vol. 13, Pages 1209-1224: Targeting Protective Autophagy Exacerbates UV-Triggered Apoptotic Cell Death

Posted: 20 Jan 2012 12:00 AM PST

Autophagy is activated by various stresses, including DNA damage, and previous studies of DNA damage-induced autophagy have focused on the response to chemotherapeutic drugs, ionizing radiation, and reactive oxygen species. In this study, we investigated the biological significance of autophagic response to ultraviolet (UV) irradiation in A549 and H1299 cells. Our results indicated that UV induces on-rate autophagic flux in these cells. Autophagy inhibition resulting from the knockdown of beclin-1 and Atg5 reduced cell viability and enhanced apoptosis. Moreover, we found that ATR phosphorylation was accompanied by microtubule-associated protein 1 light chain 3B II (LC3B-II) expression during the early phases following UV irradiation, which is a well-established inducer of ATR. Knocking down ATR further attenuated the reduction in LC3B-II at early stages in response to UV treatment. Despite the potential role of ATR in autophagic response, reduced ATR expression does not affect autophagy induction during late phases (24 and 48 h after UV treatment). The result is consistent with the reduced ATR phosphorylation at the same time points and suggests that autophagic response at this stage is activated via a distinct pathway. In conclusion, this study demonstrated that autophagy acts as a cytoprotective mechanism against UV-induced apoptosis and that autophagy induction accompanied with apoptosis at late stages is independent of ATR activation.

IJMS, Vol. 13, Pages 1186-1208: Inhibition of AKT2 Enhances Sensitivity to Gemcitabine via Regulating PUMA and NF-κB Signaling Pathway in Human Pancreatic Ductal Adenocarcinoma

Posted: 20 Jan 2012 12:00 AM PST

Invasion, metastasis and resistance to conventional chemotherapeutic agents are obstacles to successful treatment of pancreatic cancer, and a better understanding of the molecular basis of this malignancy may lead to improved therapeutics. In the present study, we investigated whether AKT2 silencing sensitized pancreatic cancer L3.6pl, BxPC-3, PANC-1 and MIAPaCa-2 cells to gemcitabine via regulating PUMA (p53-upregulated modulator of apoptosis) and nuclear factor (NF)-κB signaling pathway. MTT, TUNEL, EMSA and NF-κB reporter assays were used to detect tumor cell proliferation, apoptosis and NF-κB activity. Western blotting was used to detect different protein levels. Xenograft of established tumors was used to evaluate primary tumor growth and apoptosis after treatment with gemcitabine alone or in combination with AKT2 siRNA. Gemcitabine activated AKT2 and NF-κB in MIAPaCa-2 and L3.6pl cells in vitro or in vivo, and in PANC-1 cells only in vivo. Gemcitabine only activated NF-κB in BxPC-3 cells in vitro. The presence of PUMA was necessary for gemcitabine-induced apoptosis only in BxPC-3 cells in vitro. AKT2 inhibition sensitized gemcitabine-induced apoptosis via PUMA upregulation in MIAPaCa-2 cells in vitro, and via NF-κB activity inhibition in L3.6pl cells in vitro. In PANC-1 and MIAPaCa-2 cells in vivo, AKT2 inhibition sensitized gemcitabine-induced apoptosis and growth inhibition via both PUMA upregulation and NF-κB inhibition. We suggest that AKT2 inhibition abrogates gemcitabine-induced activation of AKT2 and NF-κB, and promotes gemcitabine-induced PUMA upregulation, resulting in chemosensitization of pancreatic tumors to gemcitabine, which is probably an important strategy for the treatment of pancreatic cancer.

IJMS, Vol. 13, Pages 1173-1185: microRNA Response to Listeria monocytogenes Infection in Epithelial Cells

Posted: 20 Jan 2012 12:00 AM PST

microRNAs represent a family of very small non-coding RNAs that control several physiologic and pathologic processes, including host immune response and cancer by antagonizing a number of target mRNAs. There is limited knowledge about cell expression and the regulatory role of microRNAs following bacterial infections. We  investigated whether infection with a Gram-positive bacterium leads to altered expression of microRNAs involved in the host cell response in epithelial cells. Caco-2 cells were infected with Listeria monocytogenes EGD-e, a mutant strain (∆inlAB or ∆hly) or incubated with purified listeriolysin (LLO). Total RNA was isolated and microRNA and target gene expression was compared to the expression in non-infected cells using microRNA microarrays and qRT-PCR. We identified and validated five microRNAs (miR-146b, miR-16, let-7a1, miR-145 and miR-155) that were significantly deregulated following listerial infection. We show that expression patterns of particular microRNAs strongly depend on pathogen localization and the presence of bacterial effector proteins. Strikingly, miR-155 which was shown to have an important role in inflammatory responses during infection was induced by wild-type bacteria, by LLO-deficient bacteria and following incubation with purified LLO. It was downregulated following ∆inlAB infection indicating a new potent role for internalins in listerial pathogenicity and miRNA regulation. Concurrently, we observed differences in target transcript expression of the investigated miRNAs. We provide first evidence that L. monocytogenes infection leads to deregulation of a set of microRNAs with important roles in host response. Distinct microRNA expression depends on both LLO and pathogen localization.

Molecules, Vol. 17, Pages 1039-1054: The Metal Cation Chelating Capacity of Astaxanthin. Does This Have Any Influence on Antiradical Activity?

Posted: 20 Jan 2012 12:00 AM PST

In this Density Functional Theory study, it became apparent that astaxanthin (ASTA) may form metal ion complexes with metal cations such as Ca+2, Cu+2, Pb+2, Zn+2, Cd+2 and Hg+2. The presence of metal cations induces changes in the maximum absorption bands which are red shifted in all cases. Therefore, in the case of compounds where metal ions are interacting with ASTA, they are redder in color. Moreover, the antiradical capacity of some ASTA-metal cationic complexes was studied by assessing their vertical ionization energy and vertical electron affinity, reaching the conclusion that metal complexes are slightly better electron donors and better electron acceptors than ASTA.

MapleStory Adventures receives social update

Posted: 19 Jan 2012 09:41 PM PST

Facebook version of game to get two new dungeons and new bosses for fighting.

 

The last time MapleStory Adventures for social network sites made headlines, it was when the game reached 1,261,046 monthly users within two weeks of its open beta phase. Now, publisher Nexon has announced that this version of the MMORPG will receive some major updates.

New dungeons in the update for the new year include the Wasteland of Souls, where fans will encounter ghost boss Papa Pixie, and the level 50-only Forgotten Temple filled with wild plants capped off with a boss fight against the multi-armed Ravana. Killing the aforementioned bosses will give players a chance to earn rare and legendary gear drops.

Also new is a Cash Shop item called The Horn of Friendship, which calls upon four other players to help the user overcome bosses in dungeons. All items in the game now have three new attributes: Luck, Critical and Dodge. Luck determines a player's drops, Critical determines a user's critical attack rating, and Dodge determines a character's chance to evade attacks.

MapleStory isn't the only RPG franchise that has a social game spin-off: Bioware's Dragon Age Legends and Square Enix's Knights of the Crystals are two well-known examples. For more information on the franchise, check out GameSpot's feature on the MMORPG.

Read and Post Comments | Get the full article at GameSpot

"MapleStory Adventures receives social update" was posted by Jonathan Leo Toyad on Thu, 19 Jan 2012 21:41:53 -0800

Diablo III to experience system changes

Posted: 19 Jan 2012 08:35 PM PST

Tweaks will be seen in latest beta patch of action RPG.

 

There has been a lot of rumbling about Diablo III as of late, with the most recent being its supposed leaked release date. Game director Jay Wilson recently posted on the official Diablo III blog on Blizzard Entertainment's site that the team will also be changing some of the systems they have received the most feedback about from the game's extended beta.

According to the post, scrolls of identification will no longer be in the game. Instead, a player just has to right-click on an unidentified object and wait a few seconds before its stats are revealed. Wilson also said that the team will remove the Cauldron of Jordan and Nephalem Cube options currently present in the beta. He elaborates that because the Stone of Recall allows players to return to town, keeping the cauldron and cube may not give players enough of an incentive to occasionally return to town. The blacksmith will now also salvage items for players.

Other changes include rearranging core character attributes to the four stats (strength, dexterity, intellect, and vitality), displaying character stats on the inventory user interface, and not making common items salvageable. All the changes will be seen in the latest beta patch. For a detailed explanation of the changes, head to the post on the game's official blog.

Diablo III is the next entry in the action RPG franchise. New features include five new classes, new multiplayer modes, and an auction house. For more information, check out GameSpot's coverage of the third game.

Read and Post Comments | Get the full article at GameSpot

"Diablo III to experience system changes" was posted by Jonathan Leo Toyad on Thu, 19 Jan 2012 20:35:12 -0800

This posting includes an audio/video/photo media file: Download Now

IJMS, Vol. 13, Pages 1161-1172: High-Dimensional Descriptor Selection and Computational QSAR Modeling for Antitumor Activity of ARC-111 Analogues Based on Support Vector Regression (SVR)

Posted: 20 Jan 2012 12:00 AM PST

To design ARC-111 analogues with improved efficiency, we constructed the QSAR of 22 ARC-111 analogues with RPMI8402 tumor cells. First, the optimized support vector regression (SVR) model based on the literature descriptors and the worst descriptor elimination multi-roundly (WDEM) method had similar generalization as the artificial neural network (ANN) model for the test set. Secondly, seven and 11 more effective descriptors out of 2,923 features were selected by the high-dimensional descriptor selection nonlinearly (HDSN) and WDEM method, and the SVR models (SVR3 and SVR4) with these selected descriptors resulted in better evaluation measures and a more precise predictive power for the test set. The interpretability system of better SVR models was further established. Our analysis offers some useful parameters for designing ARC-111 analogues with enhanced antitumor activity.

IJMS, Vol. 13, Pages 1154-1160: Isolation and Characterization of New 24 Microsatellite DNA Markers for Golden Cuttlefish (Sepia esculenta)

Posted: 20 Jan 2012 12:00 AM PST

Twenty-four microsatellite DNA markers were isolated and characterized for golden cuttlefish (Sepia esculenta) from a (GT)13—enriched genomic library. Loci were tested in 48 individuals from Jiaozhou bay of China. The numbers of alleles per locus ranged from two to 25 with an average of 10.3. The observed and expected heterozygosities ranged from 0.063 to 0.896 and from 0.137 to 0.953, with averages of 0.519 and 0.633, respectively. Six loci significantly deviated from Hardy-Weinberg equilibrium after Bonferroni's correction and no significant linkage disequilibrium between loci pairs was detected. These microsatellite markers would be useful for analyzing the population genetic structure to make conservation and management decisions for S. esculenta.

IJMS, Vol. 13, Pages 1126-1153: Clinical Significance of Serum Biomarkers in Pediatric Solid Mediastinal and Abdominal Tumors

Posted: 20 Jan 2012 12:00 AM PST

Childhood cancer is the leading cause of death by disease among U.S. children between infancy and age 15. Despite successes in treating solid tumors such as Wilms tumor, disappointments in the outcomes of high-risk solid tumors like neuroblastoma have precipitated efforts towards the early and accurate detection of these malignancies. This review summarizes available solid tumor serum biomarkers with a special focus on mediastinal and abdominal cancers in children.

MegaUpload raided, founder arrested; Anonymous launches mass DDoS against entertainment companies and US law enforcement

Posted: 20 Jan 2012 12:24 AM PST

New Zealand police, responding from a request from the US government, raided MegaUpload today, arresting founder and CEO Kim "Dotcom" Schmitz and three "associates." The service, which allowed users to upload files that were too big to email, claimed 150 million users. The entertainment industry alleged that the service was primarily intended to facilitate copyright infringement, since people could use it to illegally share music and movies, but the company claimed that while some users might infringe copyright with MegaUpload, others simply used it to share files that belonged to them. For example, I use a comparable service, YouSendIt, to exchange large MP3 files of my podcast with John Taylor Williams, the sound engineer who masters them. At other times, companies that wanted me to review their movies and music have uploaded them to a file locker and supplied me with the link and password to get them.

In response, a large denial-of-service attack ("OpMegaupload") has been launched against the US Department of Justice, the FBI, Universal Music and other entertainment and law-enforcement sites, by activists operating under the Anonymous banner.

MegaUpload has been waging an online campaign against Universal Music and US law enforcement and trade representatives, first releasing a video featuring famous artists singing an anthem in praise of MegaUpload, then suing Universal Music over false copyright claims that had the video removed from YouTube.

The Swedish Pirate Party strongly condemns raid against MegaUpload

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