вторник, 11 декабря 2012 г.

Games

Games

Cancers, Vol. 4, Pages 1333-1348: Immunotherapy: Shifting the Balance of Cell-Mediated Immunity and Suppression in Human Prostate Cancer

Posted: 11 Dec 2012 12:00 AM PST

Active immunotherapy is dependent on the ability of the immune system to recognize and respond to tumors. Despite overwhelming evidence to support a cell-mediated immune response to prostate cancer, it is insufficient to eradicate the disease. This is likely due to a high level of suppression at the tumor site from a variety of sources, including immunosuppressive cells. Immune cells entering the tumor microenvironment may be inhibited directly by the tumor, stromal cells or other immune cells that have been induced to adopt a suppressive phenotype. The resurgence of interest in immunotherapy following the approval of sipuleucel-T and ipilimumab by the Food and Drug Administration has brought about new strategies for overcoming tumor-mediated suppression and bolstering anti-tumor responses. Improved understanding of the immune response to prostate cancer can lead to new combination therapies, such as the use of vaccine with small molecule and checkpoint inhibitors or other immunotherapies.

Agriculture, Vol. 2, Pages 414-435: Biofuels and the Future of Food: Competition and Complementarities

Posted: 11 Dec 2012 12:00 AM PST

In this paper, we draw the key linkages between future biofuels growth on agricultural commodity prices, and highlight some of the key uncertainties over OECD fuel and energy policies, and their implications for global agricultural markets and the world food situation. Our results show some of the implications that biofuels expansion has on crop area expansion in regions where environmental concerns exist over land use change and the possible impacts on the environment. We also point to some promising areas for future research and specify some implications for policy interventions.

Viruses, Vol. 4, Pages 3647-3664: Endocytic Pathways Involved in Filovirus Entry: Advances, Implications and Future Directions

Posted: 11 Dec 2012 12:00 AM PST

Detailed knowledge of the host-virus interactions that accompany filovirus entry into cells is expected to identify determinants of viral virulence and host range, and to yield targets for the development of antiviral therapeutics. While it is generally agreed that filovirus entry into the host cytoplasm requires viral internalization into acidic endosomal compartments and proteolytic cleavage of the envelope glycoprotein by endo/lysosomal cysteine proteases, our understanding of the specific endocytic pathways co-opted by filoviruses remains limited. This review addresses the current knowledge on cellular endocytic pathways implicated in filovirus entry, highlights the consensus as well as controversies, and discusses important remaining questions.

Viruses, Vol. 4, Pages 3625-3646: A Systems Biology Starter Kit for Arenaviruses

Posted: 11 Dec 2012 12:00 AM PST

Systems biology approaches in virology aim to integrate viral and host biological networks, and thus model the infection process. The growing availability of high-throughput “-omics” techniques and datasets, as well as the ever-increasing sophistication of in silico modeling tools, has resulted in a corresponding rise in the complexity of the analyses that can be performed. The present study seeks to review and organize published evidence regarding virus-host interactions for the arenaviruses, from alterations in the host proteome during infection, to reported protein-protein interactions. In this way, we hope to provide an overview of the interplay between arenaviruses and the host cell, and lay the foundations for complementing current arenavirus research with a systems-level approach.

Materials, Vol. 5, Pages 2757-2772: An Ultrasensitive Electrochemical Immunosensor for Alpha-Fetoprotein Using an Envision Complex-Antibody Copolymer as a Sensitive Label

Posted: 11 Dec 2012 12:00 AM PST

A novel strategy is presented for sensitive detection of alfa-fetoprotein (AFP), using a horseradish peroxidase (HRP)-functionalized Envision antibody complex (EVC) as the label. The Envision-AFP signal antibody copolymer (EVC-AFP Ab2) was composed of a dextran amine skeleton anchoring more than 100 molecules of HRP and 15 molecules of secondary antibody, and acted as a signal tag in the immunosensor. The sensor was constructed using the following steps: First, gold electrode (GE) was modified with nano-gold (AuNPs) by electro-deposition in HAuCl4 solution. The high affinity of the AuNPs surface facilitates direct formation of a self-assembled thiolated protein G layer. Next, the coated GE was incubated in a solution of AFP capture antibody (AFP Ab1); these antibodies attach to the thiolated protein G layer through their non-antigenic regions, leaving the antigen binding sites for binding of target analyte. Following a sandwich immunoreaction, an EVC-AFP Ab2-AFP-AFP Ab1 immunocomplex was formed on the electrode surface, allowing large amounts of HRP on the complex to produce an amplified electrocatalytic current of hydroquinone (HQ) in the presence of hydrogen peroxide (H2O2). Highly amplified detection was achieved, with a detection limit of 2 pg/mL and a linear range of 0.005–0.2 ng/mL for AFP in 10 μL undiluted serum; this is near or below the normal levels of most cancer biomarker proteins in human serum. Measurements of AFP in the serum of cancer patients correlated strongly with standard enzyme-linked immunosorbent assays. These easily fabricated EVC-modified immunosensors show excellent promise for future fabrication of bioelectronic arrays. By varying the target biomolecules, this technique may be easily extended for use with other immunoassays, and thus represents a versatile design route.

Materials, Vol. 5, Pages 2731-2756: Scanning Electron Microscopy with Samples in an Electric Field

Posted: 11 Dec 2012 12:00 AM PST

The high negative bias of a sample in a scanning electron microscope constitutes the “cathode lens” with a strong electric field just above the sample surface. This mode offers a convenient tool for controlling the landing energy of electrons down to units or even fractions of electronvolts with only slight readjustments of the column. Moreover, the field accelerates and collimates the signal electrons to earthed detectors above and below the sample, thereby assuring high collection efficiency and high amplification of the image signal. One important feature is the ability to acquire the complete emission of the backscattered electrons, including those emitted at high angles with respect to the surface normal. The cathode lens aberrations are proportional to the landing energy of electrons so the spot size becomes nearly constant throughout the full energy scale. At low energies and with their complete angular distribution acquired, the backscattered electron images offer enhanced information about crystalline and electronic structures thanks to contrast mechanisms that are otherwise unavailable. Examples from various areas of materials science are presented.

Alpha Zero - Screenshots

Posted: 11 Dec 2012 03:14 AM PST

Features:
- Fast and furious action
- Amazing special effects and beautiful 3D graphics
- Unique backgrounds for every level
- Natural multi-touch gameplay
- 8 challenging missions and boss-fights (more to come)
- 35 different enemies
- Numerous upgrades and special weapons.
- Over 15 ship skins
- Full epic soundtrack
- Three challenging difficulty levels (cadet, ace and elite)
- Campaign story-line, fully voiced and subtitled
- Optimized for retina display iPhones and iPads

Eve of the Genesis - Screenshots

Posted: 11 Dec 2012 02:47 AM PST

A simple and classic RPG
Easy and fun to play, for anyone from beginners to seasoned gamers.

Beautiful, old-style graphics
The dungeons contain many traps, and are satisfyingly challenging. You will need to explore every inch of the dungeons, to open the doors to paths that will enable you to proceed.
The characters are rendered in a classic, 'eight-bit' style, and appear completely old-style when they move, one next to the other, but they are beautifully detailed and a delight to watch.
Don't miss the butterflies that flutter through the towns, the reflections of the characters in pools and rivers, and the many other wonderful details!

Flexible character development and easy battles
Battles are simple and straightforward to control. Direct control makes for a stress-free game.
By using stronger skills, you can deal with a number of enemies in one fell swoop.
Using gems, you can strengthen the skills you have acquired, changed their elements, and so on. Customize skills to suit your preferences, and develop your characters in just the ways you want to!

Complete with a variety of record books
The skills and items you have gained, the monsters you have encountered, and so on, are all recorded in the record books.
This convenient feature allows you to check a whole range of information, for example the items you gain when you defeat a certain monster. It could even be said that you have only really cleared the game when you have completed all the record books!

Wizard Defenders - Screenshots

Posted: 11 Dec 2012 02:53 AM PST

Features include:
- Special enchanting spells to create powerful attacks - Magical Explosion & Call to Arms
- Various monsters and obstacles to keep you constantly immersed in puzzling action
- Adjustable pace and difficulty level to suit all players
- Never-ending magical entertainment in Endless mode

Aurora Mac Blu-ray Copy 1.0.0.0456 - Burn blu-ray discs. .. (Free)

Posted: 11 Dec 2012 02:39 AM PST

Aurora Mac Blu-ray Copy is especially designed for clone/burn/backup any Blu-ray on Mac. With this Blu-ray Copy for Mac, you can easily make Blu-ray disc copied in 1:1 without quality loss, directly backup into hard disc as ISO image file, and burn the ISO image file into disc as you want. This Mac Blu-ray Copy tool can copy your Blu-ray without any quality loss and is easy to handle.

Version 1.0.0.0456: Release notes were unavailable when this listing was updated.

Mac OS X 10.5 or later

Download Now

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

Anomaly Korea - Screenshots

Posted: 11 Dec 2012 02:42 AM PST

Features:
• A sequel to the award-winning "Anomaly Warzone Earth"
• Think tactically across 12 new missions
• Deploy new player powers and units to take on new enemies
• Put your skills to the test in 'Art of War' mode
• Cutting-edge visuals and a stunning soundtrack with full voice acting
• Graphics optimized for today's most powerful Android devices

Assassin's Creed III DLC trailer: The Tyranny of King Washington

Posted: 11 Dec 2012 02:43 AM PST

Assassin's Creed III is getting new DLC in the shape of The Tyranny of King Washington, having had its pre-order bonus content already made available

IJERPH, Vol. 9, Pages 4626-4638: Pertussis: A Review of Disease Epidemiology Worldwide and in Italy

Posted: 11 Dec 2012 12:00 AM PST

Pertussis continues to be a relevant public-health issue. The high coverage rates achieved have decreased the spread of the pathogen, but the waning of immunity implies a relevant role of adolescents and adults in the infective dynamics as they may represent a significant source of infection for unvaccinated or incompletely immunized newborns. The passive surveillance system is affected by many limitations. The underestimation of pertussis in adolescents, young adults and adults is mainly related to the atypical clinical characteristics of cases and the lack of lab confirmation. The real epidemiological impact of pertussis is not always perceived, anyway, the unavailability of comprehensive data should not hamper the adoption of active prophylactic interventions aimed at preventing the impact of waning immunity on pertussis. To avoid an increase of the mean age of acquisition of the infection, a booster dose of low-antigen content combined vaccine should be adopted in adolescents and adults. A decreased risk of infection in newborns can be achieved with the cocoon strategy, although the debate on this aspect is still open and enhanced surveillance and further studies are needed to fine-tune the pertussis prevention strategy.

IJMS, Vol. 13, Pages 16971-16985: Increased Insulin Sensitivity and Distorted Mitochondrial Adaptations during Muscle Unloading

Posted: 11 Dec 2012 12:00 AM PST

We aimed to further investigate mitochondrial adaptations to muscle disuse and the consequent metabolic disorders. Male rats were submitted to hindlimb unloading (HU) for three weeks. Interestingly, HU increased insulin sensitivity index (ISI) and decreased blood level of triglyceride and insulin. In skeletal muscle, HU decreased expression of pyruvate dehydrogenase kinase 4 (PDK4) and its protein level in mitochondria. HU decreased mtDNA content and mitochondrial biogenesis biomarkers. Dynamin-related protein (Drp1) in mitochondria and Mfn2 mRNA level were decreased significantly by HU. Our findings provide more extensive insight into mitochondrial adaptations to muscle disuse, involving the shift of fuel utilization towards glucose, the decreased mitochondrial biogenesis and the distorted mitochondrial dynamics.

IJMS, Vol. 13, Pages 16961-16970: Effects of Sesamin on Streptozotocin (STZ)-Induced NIT-1 Pancreatic β-Cell Damage

Posted: 11 Dec 2012 12:00 AM PST

The protective effect of sesamin (SES) from sesame meal on NIT-1 pancreatic β-cells damaged by streptozotocin (STZ) in vitro was investigated. The cell viability, insulin secretion, the activity of superoxide dismutase(SOD), glutathione peroxidase (GSHpx) and the content of reduced glutathione (GSH) increased significantly when incubated with SES (400, 200 µg mL−1). The content of malondialdehyde (MDA), nitric oxide (NO) production, and the activity of NO synthase (NOS), inducible NOS (iNOS), decreased significantly when incubated with SES. The destructive changes of NIT-1 cells were ameliorated when treated with SES under microscopic observation. These data suggested that SES had obvious protective effect on NIT-1 pancreatic β-cells damaged by STZ, which might be related to its effects of decreasing levels of β-cell-destroying factors such as oxidative stress and NO synthesis.

IJMS, Vol. 13, Pages 16945-16960: Oxidative Stress Mediated-Alterations of the MicroRNA Expression Profile in Mouse Hippocampal Neurons

Posted: 11 Dec 2012 12:00 AM PST

Oxidative stress plays a critical role in the etiology and pathogenesis of neurodegenerative disorders, and the molecular mechanisms that control the neuron response to ROS have been extensively studied. However, the oxidative stress-effect on miRNA expression in hippocampal neurons has not been investigated, and little is known on the effect of ROS-modulated miRNAs on cell function. In this study, H2O2 was used to stimulate the mouse primary hippocampal neurons to develop an oxidative stress cell model. The alterations of miRNAs expression were detected by microarray analysis and five miRNAs were validated by real-time RT-PCR. The bioinformatic analysis of deregulated miRNAs was performed to determine their potential roles in the pathogenesis of neurological disorders. We found that H2O2 mediated a total of 101 deregulated miRNAs, which mainly took part in the regulation of the MAPK pathway. Among them, miR-135b and miR-708 were up-regulated significantly and their targets were predicted to be involved in DNA recombination, protein ubiquitination, protein autophosphorylation and development of neurons. These results demonstrated that oxidative stress alters the miRNA expression profile of hippocampal neurons, and the deregulated miRNAs might play a potential role in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease (AD).

IJMS, Vol. 13, Pages 16929-16944: DNA Damage and Repair in Atherosclerosis: Current Insights and Future Perspectives

Posted: 11 Dec 2012 12:00 AM PST

Atherosclerosis is the leading cause of morbidity and mortality among Western populations. Over the past two decades, considerable evidence has supported a crucial role for DNA damage in the development and progression of atherosclerosis. These findings support the concept that the prolonged exposure to risk factors (e.g., dyslipidemia, smoking and diabetes mellitus) leading to reactive oxygen species are major stimuli for DNA damage within the plaque. Genomic instability at the cellular level can directly affect vascular function, leading to cell cycle arrest, apoptosis and premature vascular senescence. The purpose of this paper is to review current knowledge on the role of DNA damage and DNA repair systems in atherosclerosis, as well as to discuss the cellular response to DNA damage in order to shed light on possible strategies for prevention and treatment.

IJMS, Vol. 13, Pages 16916-16928: Evaporation Rate of Water as a Function of a Magnetic Field and Field Gradient

Posted: 11 Dec 2012 12:00 AM PST

The effect of magnetic fields on water is still a highly controversial topic despite the vast amount of research devoted to this topic in past decades. Enhanced water evaporation in a magnetic field, however, is less disputed. The underlying mechanism for this phenomenon has been investigated in previous studies. In this paper, we present an investigation of the evaporation of water in a large gradient magnetic field. The evaporation of pure water at simulated gravity positions (0 gravity level (ab. g), 1 g, 1.56 g and 1.96 g) in a superconducting magnet was compared with that in the absence of the magnetic field. The results showed that the evaporation of water was indeed faster in the magnetic field than in the absence of the magnetic field. Furthermore, the amount of water evaporation differed depending on the position of the sample within the magnetic field. In particular, the evaporation at 0 g was clearly faster than that at other positions. The results are discussed from the point of view of the evaporation surface area of the water/air interface and the convection induced by the magnetization force due to the difference in the magnetic susceptibility of water vapor and the surrounding air.

IJMS, Vol. 13, Pages 16899-16915: Electrochemical Characterization of Escherichia coli Adaptive Response Protein AidB

Posted: 11 Dec 2012 12:00 AM PST

When exposed to known DNA-damaging alkylating agents, Escherichia coli cells increase production of four DNA repair enzymes: Ada, AlkA, AlkB, and AidB. The role of three enzymes (Ada, AlkA, and AlkB) in repairing DNA lesions has been well characterized, while the function of AidB is poorly understood. AidB has a distinct cofactor that is potentially related to the elusive role of AidB in adaptive response: a redox active flavin adenine dinucleotide (FAD). In this study, we report the thermodynamic redox properties of the AidB flavin for the first time, both for free protein and in the presence of potential substrates. We find that the midpoint reduction potential of the AidB flavin is within a biologically relevant window for redox chemistry at −181 mV, that AidB significantly stabilizes the flavin semiquinone, and that small molecule binding perturbs the observed reduction potential. Our electrochemical results combined with structural analysis allow for fresh comparisons between AidB and the homologous acyl-coenzyme A dehydrogenase (ACAD) family of enzymes. AidB exhibits several discrepancies from ACADs that suggest a novel catalytic mechanism distinct from that of the ACAD family enzymes.

IJMS, Vol. 13, Pages 16880-16898: Bacterial Over-Expression and Purification of the 3'phosphoadenosine 5'phosphosulfate (PAPS) Reductase Domain of Human FAD Synthase: Functional Characterization and Homology Modeling

Posted: 11 Dec 2012 12:00 AM PST

FAD synthase (FADS, EC 2.7.7.2) is a key enzyme in the metabolic pathway that converts riboflavin into the redox cofactor, FAD. Human FADS is organized in two domains: -the 3'phosphoadenosine 5'phosphosulfate (PAPS) reductase domain, similar to yeast Fad1p, at the C-terminus, and -the resembling molybdopterin-binding domain at the N-terminus. To understand whether the PAPS reductase domain of hFADS is sufficient to catalyze FAD synthesis, per se, and to investigate the role of the molybdopterin-binding domain, a soluble “truncated” form of hFADS lacking the N-terminal domain (Δ1-328-hFADS) has been over-produced and purified to homogeneity as a recombinant His-tagged protein. The recombinant Δ1-328-hFADS binds one mole of FAD product very tightly as the wild-type enzyme. Under turnover conditions, it catalyzes FAD assembly from ATP and FMN and, at a much lower rate, FAD pyrophosphorolytic hydrolysis. The Δ1-328-hFADS enzyme shows a slight, but not significant, change of Km values (0.24 and 6.23 µM for FMN and ATP, respectively) and of kcat (4.2 × 10−2 s−1) compared to wild-type protein in the forward direction. These results demonstrate that the molybdopterin-binding domain is not strictly required for catalysis. Its regulatory role is discussed in light of changes in divalent cations sensitivity of the Δ1-328-hFADS versus wild-type protein.
Автор: на

Комментариев нет:

Отправить комментарий

Подписаться на: Комментарии к сообщению (Atom)