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Pigs as Models of Preclinical Studies and In Vivo Bioreactors for Generation of Human Organs
By Yujiro Kawai, Shugo Tohyama, Hideyuki Shimizu, Keiichi Fukuda and Eiji Kobayashi
Submitted: June 5th 2019Reviewed: October 18th 2019Published: November 22nd 2019
Home > Books > Xenotransplantation - Comprehensive Study
Pigs are valuable and essential large animal models for human medical applications, including for stem cell therapy. Moreover, substantial effort has been made to directly engraft genetically engineered pig organs in the human body and to use pigs as in vivo bioreactors for the growth and development of human cells, tissue, or organs. However, engraftment of human cells in pigs has not yet been achieved. Although severe combined immunodeficient pigs have been developed, which can accept human biological materials, these pigs do not have practical value at present owing to difficulty in their care. To overcome these current limitations, we have proposed the generation of operational immunodeficient pig models by simply removing the thymus and spleen, enabling the long-term accommodation of human tissue. In this review, we summarize research progress on xenotransplantation animal models that accept human cells, tissues, or organs.
regenerative therapy
immune tolerance
Yujiro Kawai
Department of Cardiovascular Surgery, Keio University School of Medicine, Japan
Shugo Tohyama*
Department of Organ Fabrication, Keio University School of Medicine, Japan
Department of Cardiology, Keio University School of Medicine, Japan
Hideyuki Shimizu
Keiichi Fukuda
Eiji Kobayashi*
*Address all correspondence to: shugotohyama@keio.jp and organfabri@keio.jp
XenotransplantationComprehensive StudyEdited by Shuji Miyagawa
Xenotransplantation - Comprehensive Study
Edited by Shuji Miyagawa
Organ transplantation is often the only possible treatment for a patient with organ failure. The organs are donated from either living or deceased donors, and thus the number of transplantable organs is limited and insufficient to meet the clinical demand. Consequently, some illegal or unethical transplantations along with transplant commercialism and tourism have emerged, representing a worldwide problem.
The discovery of the potential of pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), to regenerate tissues or organs offers new hope to overcome this situation. Human ESCs [1] and iPSCs [2] are now widely used to generate tissues or organs, and techniques for the in vitro production of specific cell types have been developed [3]. However, these strategies still have several limitations for clinical application, including the size, maturity, function, and risk of tumor formation after transplantation [4].
To solve these problems, large animal models for the transplantation of human PSC-derived cells, tissues, or organs are required. In this review, we summarize the animal models currently used in the development for xenotransplantation and highlight the efficacy and prospects of pig models to accept human tissues or organs.
2. Xenotransplantation in small animals (mouse and rat)
Immunosuppression is a key requirement for an animal to accept human tissues or organs, as a functional immune system will result in the host animals rejecting the human grafts. The nude mouse was the first immunosuppressed animal model developed in 1962 [5]. Nude mice lack T cells and can therefore accept human tumor cells. Subsequently, severe combined immunodeficient (SCID) mice were developed in 1983, which lack both B cells and T cells [6]. McCune et al. [7] successfully transplanted a human fetal thymus, liver cells, and lymph node into SCID mice, resulting in the differentiation of human T cells and B cells. However, the rate of engraftment of human cells in these mice was low due to maintenance of their natural killer (NK)-T cell activity. Gerling et al. [8] developed NOD/SCID mice by crossbreeding SCID mice with NOD mice, a diabetes model due to autoimmunity in the pancreas, which also show low NK-T cell activity and macrophage function [9]. Combining the low activity of NK-T cells and macrophages in NOD mice with the lack of B cells and T cells in SCID mice, the use of NOD/SCID mice improved the engraftment rate of hematopoietic stem cells [10]. Ito et al. [11] produced NOG mice as a crossbreed of NOD/SCID mice and gamma(c)(null) mice, which completely lack NK-T cells, and achieved a dramatically improved engraftment rate of human hematopoietic cells.
We previously reported the successful transplantation of rat cells into SCID mice [12]. Isolated hepatocytes obtained from the rat liver were injected into urokinase-type plasminogen activator (uPA)/SCID mice, in which urokinase-type plasminogen accumulates specifically in the native liver causing the damaged liver. The mice served as bioreactors to allow the transplanted rat hepatocytes to proliferate in the mouse host, resulting in more than 95% of cells in the mouse liver being of rat origin. Oldani et al. [13] successfully developed a mouse-rat chimeric liver, which was transplanted in rats. They injected hepatocytes isolated from Lewis rats into C57Bl/6Fah−/−Rag2−/−Il2rg−/− mice to create chimeric livers, which were transplanted into rats with or without immunosuppression. Without immunosuppression, the recipient rats died from acute rejection, whereas rats with immunosuppression survived for more than 112 days and maturation of rat bile ducts was observed 4 months after transplantation. We also demonstrated that the nude rat model could serve as an in vivo bioreactor. Liver grafts from Syrian hamsters were transplanted into nude rats that administered several immunosuppressive agents, including tacrolimus and mycophenolate mofetil (MMF). After auxiliary xenogenic partial liver transplantation, regeneration of the liver graft was observed, and its weight increased from pre-transplant to 7 days after transplantation [14].
These immunodeficient mouse models, including SCID, NOD/SCID, and NOG mice, are useful for research on regenerative medicine using human PSCs, allowing for evaluation of teratoma formation to confirm the differentiation of the cells into the three germ layers [1]. In addition, these models are widely utilized for evaluation of tumorigenicity in human PSC-derived cells after transplantation [4], since human PSC-derived cells or tissues have a risk of tumor formation from contamination of undifferentiated PSCs [15, 16]. Small animals such as mice and rats are widely applied as models in cell transplantation research owing to their ease of handling. However, small animals have limitations in terms of the number of cells that can be transplanted and evaluation of therapeutic efficacy, that is, a human clinical application might require the transplantation of several hundreds of million cells, which is impossible to accomplish in small animals. Moreover, large animal models are required for accurate evaluation of the efficacy of cell transplantation. Furthermore, large animal models are expected to play roles as bioreactors for functionally mature human tissues or organs.
3. Xenotransplantation in middle and large animals (monkey and pig)
Chong et al. [17] transplanted human ESC-derived cardiomyocytes into the hearts of pig-tailed macaques as a nonhuman primate model. The main advantage of this model is that the hearts are much larger (37–52 g) than those of mice (0.15 g), rats (1 g), and guinea pigs (3 g), which allowed for the transplantation of 1 × 109 cells into the infarcted myocardium and subsequent engraftment. The macaques were administered methylprednisolone, cyclosporine, and abatacept (a CTLA4 immunoglobulin) to prevent immune rejection. The efficacy of human ESC-derived cardiomyocytes in the infarcted hearts of pig-tailed macaques was demonstrated, and maturation of the transplanted ESC-derived cardiomyocytes was observed [18]. However, compared to an adult human, pig-tailed macaques are still relatively small (5.2–12.6 kg), and the heart is much smaller than that of a human (300 g).
Pigs are a suitable animal for preclinical studies and in vivo reactors in terms of their size and anatomy that correspond well to those of humans. To establish an immunosuppressed state that allows for transplantation of human PSC-derived cells or tissues into host pigs without rejection, SCID pigs were also developed [19]. Suzuki et al. [19] generated cloned pigs by serial nuclear transfer using fibroblasts with disruption of the X-linked interleukin 2 receptor subunit gamma (IL2RG) gene, as this mutation is known to cause X-linked SCID in humans. The SCID pigs accepted human cells, indicating their potential in preclinical studies and as in vivo reactors with human PSCs. However, raising these pigs is a technical challenge; among the 31 cloned piglets produced, only four survived for over 1 year. In addition, SCID pigs must be raised under meticulous hygiene conditions, which impose a further cost for their establishment and maintenance. Therefore, it is not practical to use SCID pigs as models in preclinical studies and in vivo reactors.
Total thymectomy is an alternative strategy to create immunosuppressed pigs that can accept human cells. Binns et al. [20] first proposed the concept of achieving immunosuppression by performing thymectomy in neonatal pigs in 1972. Microminiature pigs (MMPs) are smaller than domestic or ordinary miniature pigs and are thus suitable model animals for preclinical studies [21]. To develop immunodeficient MMPs, we performed thymectomy in neonatal pigs, which were transplanted with human hepatocytes that could engraft in the pig liver without any immunosuppressive agents [22]. To further improve the immunodeficient pig model, we performed splenectomy along with the thymectomy in 6–7-month-old miniature pigs and administered several immunosuppressive agents, including tacrolimus, MMF, and prednisolone, via a stomach tube [23]. This so-called operational immunodeficient miniature pig (OIDP) model allowed for the successful implantation of artificial human vascular tubes created by a three-dimensional bioprinting. Moreover, the human tube was inserted between the carotid artery and jugular vein to act as a shunt, and blood flow was observed for 3 months without immune rejection.
As mentioned above, establishment of a chimera is a potential strategy for growing human tissues or organs in large animals. Matsunari et al. [24] demonstrated that blastocyst complementation can be applied to large animals by creating chimeric pigs. Specifically, they generated embryos from clones of porcine somatic cells, which showed an apancreatic phenotype, and their complementation with allogenic blastomeres resulted in the development of a functional pancreas. Wu et al. [25] reported a successful pig-human chimera that was created by introducing human PSCs into fertilized pig eggs. Therefore, when combined with blastocyst complementation, human organs can be created in a human-pig chimera; however, these methods are associated with serious ethical and legal problems. Alternatively, the introduction of human-derived cells to pig fetuses can lead to immune tolerance, allowing for the acceptance of human PSC-derived tissues or organs.
4. Immune tolerance induction for xenotransplantation
Immune tolerance is defined as a lack of an immune response against particular antigens. In general, the immune system has tolerance to self-antigens and only responds to non-self-antigens, which is a challenge for transplantation, as the grafted cells or tissues are rejected and not able to survive in the host body. The phenomenon of immune tolerance was first described in 1945 in which anastomosis in the placenta was observed in twin calves, and they accepted each other's skin grafts [26]. Hasek et al. [27] subsequently confirmed this phenomenon in chicken and duck by producing parabiosis in fertilized eggs. In 1953, Medawar et al. [28] established actively acquired tolerance by implanting a live antigen in the fetuses of mice or embryonic chicks. Using this method, Binns et al. [29] also tried to create immune tolerance in pigs by implanting bone marrow cells or lymphocytes from another pig into fetal pigs, resulting in prolonged survival of skin graft in the treated pigs.
In addition to these examples, induction of immune tolerance to human cells or tissues has been attempted in other animals. Kenneth et al. [30] transplanted human mesenchymal stem cells into fetal sheep early in gestation. Despite the xenogeneic condition, the human mesenchymal stem cells engrafted and survived in multiple tissues for up to 13 months after transplantation. These strategies of injecting human cells into a fetus were proven to result in immune tolerance to human cells after birth.
As MMPs have emerged as suitable candidates for immune tolerance induction to accept human cells, tissues, and organs owing to their useful applications in preclinical studies and in vivo reactors, it may be possible to create MMPs with immune tolerance to human cells by injecting a human antigen into pig fetuses without requiring the need to create human-pig chimeras [31].
Our newly developed OIDPs can accept human cells, tissues, and organs derived from human PSCs. These models will allow for long-term observation after the transplantation of human PSC-derived cells or tissues to better evaluate the safety and efficacy of the procedure. Moreover, if human cells, tissues, and organs are transplanted into piglets, they will grow in vivo along with the growth of the host pig. These grafts will then mature and be of suitable size with appropriate function for human application. Therefore, pigs can be suitable models for preclinical studies and serve as in vivo bioreactors for developing human tissues or organs (Figure 1). Transplantable MMPs without immunosuppressive agents are expected to be developed in the near future as promising and valuable animal models for researchers, which can dramatically promote regenerative medicine and organ transplant therapies with human PSCs.
Schema of pigs as models of preclinical studies and in vivo bioreactors. (A) Adult operational immunodeficient miniature pigs (OIDPs) are useful for preclinical studies in regenerative medicine with human PSCs, enabling evaluation of the safety and efficacy of cell transplantation. In particular, after transplantation of human PSC-derived spheroids or organoids into the OIDPs, the risk of tumorigenicity can be evaluated. (B) Fetal or neonatal OIDPs are also useful as in vivo bioreactors, facilitating the efficient in vivo growth of immature human tissues. After immature human PSC-derived tissues or organs are transplanted into OIDPs, they will mature along with the growth of the host.
2.Xenotransplantation in small animals (mouse and rat)
3.Xenotransplantation in middle and large animals (monkey and pig)
4.Immune tolerance induction for xenotransplantation
Yujiro Kawai, Shugo Tohyama, Hideyuki Shimizu, Keiichi Fukuda and Eiji Kobayashi (November 22nd 2019). Pigs as Models of Preclinical Studies and In Vivo Bioreactors for Generation of Human Organs, Xenotransplantation - Comprehensive Study, Shuji Miyagawa, IntechOpen, DOI: 10.5772/intechopen.90202. Available from:
Biosafety Barrier to Xenotransplantation
By Wei Wang, Qi Liang, Wei Nie, Juan Zhang and Cheng Chen
XenotransplantationNew InsightsEdited by Shuji Miyagawa
Introductory Chapter: The State of Xenotransplantation
By Shuji Miyagawa, Akira Maeda, Hiroshi Eguchi, Rieko Sakai, Pei‐Chi Lo, Hantang Wang, Chihiro Takakura, Tasuku Kodama, Rei Matsuura and Hiroomi Okuyama

redpajama_set_name: RedPajamaCommonCrawl


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Britain's Got Talent is coming to Westwood Cross to host auditions for next year's series
Do you have what it takes to wow the judges?
Katie BoydenSenior Reporter
Britain's Got Talent is hitting the road to find talent to take part in the next series - and they're looking for people in Kent.
Auditions for the show's 13th series will arrive at Westwood Cross in Thanet this month, and attendees will be asked to show the judges why they deserve to win the programme.
The auditions are open to performers of all ages, with any type of talent. Comedians, magicians, drag acts, musicians and acrobatics are all welcome.
Anyone who thinks they could become the next Lost Voice Guy, Diversity, or Paul Potts, is invited to turn up and wow the judges.
Do you have what it takes to win Britain's Got Talent, like Lost Voice Guy did this year? (Image: Dymond/Thames/Syco/REX/Shutterstock)
Charlie Irwin, executive producer of the show said: "Britain's Got Talent 2018 was a fantastic year for talent full of variety with, for the first time ever, a comedian winning the show.
"We were left in stitches by runner-up Robert White, we were wiggle wining in the final with Reggae star Donchez Dacres, the incredible acrobats The Giang Brothers left us speechless and the laughs were endless with the hilarious winner the Lost Voice Guy.
Folkestone on The Hotel Inspector
Sky TV crews in Broadstairs
Chatham girl on Love Island
Channel 4 looking for badly behaved pets
"Now, we can't wait to see what talent you're ready to bring to the BGT stage in 2019.
"If you feel you have something special to show us, no matter what it is, then make sure you apply, you never know where it might take you."
Do you have what it takes to wow the BGT judges?
Auditions will be held at Westwood Cross on Monday, August 27, between 12pm and 6pm.
Successful acts will then be in with a chance of securing a place at one of the judges' auditions in 2019.


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Karpowership: we believe that everyone in the world should have electricity
Pamela Largue talks to Karpowership managing director Zeynep Harezi to unpack the concept of a floating power plant.
We started Karpowership because we believe in universal access to energy – we believe that everyone in the world should have electricity.
"A family should never have to wonder if they will have enough money for diesel.
The cost of electricity should not be a consideration in a family's budget – it's a basic human right."
So says Zeynep Harezi, managing director of Turkish firm Karpowership, which offers ship-based power generation on a rental basis.
Powerships are ship or barge-mounted, fully-integrated floating power plants. With wide ranges of installed capacities for utility size operations and no completion or construction risk, the powerships are ready for generation within a short period of time.
Power is fed directly into the transmission network from an onboard high-voltage substation, and therefore requires no land acquisition.
Powerships were initially developed by General Electric during World War II as a transportable large-scale power generation resource.
Floating power has come a long way since – and so too has the ever-increasing need for energy access.
Governments around the world are committing to electrification programmes that enable economic development and improve the lives of their citizens.
One company answering the call for energy supply is Karpowership.
The company provides up to 4300MW of electricity internationally by burning liquid natural gas in on-board power generators.
Its ships have been deployed to Lebanon, Iraq, Cuba, Sierra Leone, Senegal, Sudan, Gambia, Ghana, Guinea-Bissau, Indonesia, Zambia and Mozambique.
The ships dock in the harbour, crank up their turbines and start generating electricity for customers on land.
"And of course, the more electricity, the more jobs, education and foreign direct investment opportunities will come, and increase social and economic welfare and gender rights," says Harezi. "Electricity impacts everything about well-being and happiness. We are passionate about this."
In order for the powership to function, a floating storage regasification unit (FSRU) is moored and connected to the ship via a floating gas pipeline.
The mooring solution allows for ship to ship transfer through cryogenic hoses at -163 degrees Celcius.
The FSRU gas cargo tanker, with a capacity of up to 150,000m3, receives gas from an LNG carrier.
The FSRU contains a Regas vapouriser with a capacity of 21-168MMSCFD, an LNG feed pump 50-200m3/h and a 6000kg/h bog compressor.
The gas send-out pressure from the FSRU ship is up to 40barg.
The gas is moved through the regasification system and passed to the powership where it generates electricity. The transformers send the power the ships generate over wires to local transmission grids, and from there it goes out to end users. A variety of powerships meet differing power requirements.
The classes range from the smallest, Mermaid, which has a maximum capacity of 80MW and is 90m long and 25m wide, to the Khan class which has a capacity of 470MW and is 300m long and 50m wide. Karpowership's vessels only require a depth of five meters (16 feet) to operate at ports, which makes them suitable for multi-island countries that have long coastlines.
The ships can be installed at a coastal site where there is an available substation for electrical connection and suitable marine conditions for berthing or mooring.
Host locations require minimal onshore infrastructure and are ready to commence once Karpowership receives the go-ahead to deliver the powerships.
The ship is literally turnkey, with construction works including a transmission interconnection point, a small site office and stores adjacent to the powership.
One example of a project location is Indonesia. In 2015 and 2016, Karpowership signed five contracts with the state utility PT PLN (Persero) to deploy five powerships of 1000MW in total for a period of five years. The ships have been in operation since 2016, with one operating on indigenous gas since 2018.
Unfortunately, powerships are not always seen as the holy grail of power solutions. Many argue that use local independent power producers would likely reduce the cost of power generation and would develop the local power market.
Localisation is an important factor when considering any infrastructure development plan. However, the countries that opt for this solution simply do not have the capacity to build and operate this type and scale of technology.
In many instances, Karpowership has worked with the local utilities to help stabilise the grid, for example through helping finance transmission lines. But who carries the additional cost of the power?
This would surely be carried over to the utility customers, ultimately impacting economic development negatively, which runs contrary to Karpowerships goals.
This would only be the case if the ship's power was more e xpensive, which is seldom the case when comparing the cost of gas and diesel.
Harezi says: "On a 25-year PPA, we are cheaper than any other land-based power plant. It's cheaper for us to build and operate the ships.
We standardise design, purchase parts in bulk and build several ships at a time.
We build in a controlled environment without unforeseen costs. It's actually extremely economical." Another question is whether a long-term PPA is really necessary, when a short-term contract to provide emergency power is all that's needed.
There is no doubt powerships can play a vital role for countries that are war-torn or going through economic struggles.
The question is, do you rely on outside sources of power, or develop your own to become self-sufficient?
You can't have both, as at some point supply will outweigh demand and asset will be stranded and will stand idle.
The problem seems to be systemic in nature, occurring within the country itself. The countries being supplied seem to be unable to develop the infrastructure required to supply demand. Therefore, powerships answer the need for delivering power where it's needed and quickly.
Assessments of cumulative air pollution impacts have raised concerns, and climate and environmental justice groups are concerned that the use of gas locks a country into continued use of fossil fuels and rising greenhouse gas emissions.
Harezi explains:
"In 2010, the first round of ships that went to Iraq operated on liquid fuel. Then we realised the world was moving in an environmentally friendly direction and we wanted to be a part of this.
All ships after this were therefore built with dual fuel engines to allow for cleaner fuel options.
"The modularity of the powership really helps us to reduce emissions. For example, in the case of a Ghana project, we were able to take the ship to the gas source – as opposed to the Ghanaians pumping the gas 300km to the ship – thus reducing the carbon footprint of the project. Flexibility also supports the immediate switch to gas and our aim to convert the whole fleet to LNG in the next 3-5 years." She adds that the company wants to "improve our renewable portfolio.
Currently we have solar projects in Turkey and Ukraine but we want to build more global coverage of solar and battery storage applications as well."
One of the main challenges to Karpowership is that of third party risk, especially as countries which need the power most are often those struggling the most financially. Also, according to Harezi, "there is a psychological barrier that needs to be broken.
People tend to think the powerships are temporary and must be more expensive because they're on ships.
On the contrary, the physical and economic lifetime of ship is more than 25 years and we can provide really low cost power."
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Tags: Pamela Largue , Karpowership , Zeynep Harezi , FSRU


Without wishing to sound like Ray Mears I do find toadstools quite interesting, and, if you get your identification correct, extremely tasty! However, if you are going to be dining off of your lawn do buy a book on edible mushrooms as the consequences of getting it wrong can be serious.
Toadstools will populate your lawn, usually when the rains start in autumn and if it contains organic material. This is usually a sign of a healthy soil though not always a welcome sight on a fine lawn. Those that are edible (and a few that aren't) will be munched by insects and slugs and some are collected and eaten by squirrels. Otherwise they appear to be left alone by everything including pets and therefore pose no danger.
On occasions a crop of toadstools will grow due to an excessive thatch layer, so when you do see clusters of small mushrooms it is worth inspecting the lawn for thatch. Yet other times you will see them forming a ring known as a 'fairy ring' which indicates quite a serious soil condition.
Finally, what do you do with them if you've got them?
The first and best thing to do is to remove them to reduce the spores getting into the soil. This will reduce future crops slightly. For the larger ones or if there aren't too many just go and pick them. If this is going to be too much work either brush them or mow them. Finally, if you like the look of them just leave them and enjoy.


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SonicWALL Adds Multi-Platform Monitoring to Global Management System
GMS 2.8 and ViewPoint 2.8 products enhanced with powerful new features to enable optimal network security
London, UK – August 2, 2004 – SonicWALL, Inc. (NASDAQ: SNWL), a leading provider of integrated security, productivity and mobility solutions, today announced several significant enhancements−highlighted by new monitoring functionality−to the company's award-winning Global Management System (GMS) and ViewPoint® reporting solutions.
GMS 2.8 is a powerful network control platform, offering customers using any of SonicWALL's comprehensive layered secure networking appliances the ability to optimize globally distributed network resources and manage user security policies from a single, easy-to-use graphical interface. GMS 2.8 enables IT administrators to
•	closely monitor network usage across an entire corporate network (including remote offices and telecommuters),
•	set granular policies for and coordinate advanced security services such as intrusion prevention, anti-virus and content filtering, and
•	automatically push updates and upgrades to groups of SonicWALL appliances.
"SonicWALL's GMS 2.8 is a must-have for every service provider running client's distributed network environments," said Deepak Thadani, president and chief executive officer of SysIntegrators, LLC, a SonicWALL gold medallion partner. "Timely intelligence on attack and intrusion attempts is critical for businesses. GMS can pull together intrusion data from multiple firewall sources, and provides a complete picture of the network irrespective of vendor type. SonicWALL GMS 2.8 is a powerful tool to help users maximize the ROI and minimize the TCO of today's networks."
"Having a multi-faceted network solution is the first step protecting your network and keeping your business up and running," said Douglas Brockett, vice president of worldwide marketing at SonicWALL. "By utilizing an intuitive software platform like GMS 2.8 to manage, monitor and provision local and remote security appliances and services, our customers can significantly improve the return on investment on their network infrastructure. Significant improvements can be realized by eliminating the need for IT support at distributed offices and by increasing network performance and security."
GMS 2.8 functionality upgrades include real-time monitoring of multi-vendor networks and systems. Among the key customer benefits of proactive monitoring are reduced time and costs for resource maintenance, streamlined performance of managed security appliances, and reduced system downtime. In addition to alert features, SonicWALL's GMS 2.8 also includes new threat logging capabilities providing network administrators the latest intelligence to protect the network.
For customers with a simplified network structure or fewer offices, SonicWALL offers ViewPoint 2.8. ViewPoint provides network administrators instantaneous insight into the status of their network's security through extensive reporting and tailored monitoring. Administrators can use ViewPoint to determine suspicious activity on the network and enhance employee productivity by monitoring Internet usage and logging abuse. ViewPoint 2.8 also offers increased flexibility for automated reports and increased intelligence into potential attacks.
SonicWALL GMS 2.8 and ViewPoint 2.8 are available now, and will provide support for SonicWALL's complete line of secure networking appliances. Pricing starts at £1320 for a 10-node license.
About SonicWALL, Inc.
SonicWALL, Inc. is a leading provider of integrated network security, mobility, and productivity solutions for the SMB, enterprise, e-commerce, education, healthcare, retail/point-of-sale, and government markets. Core technologies include firewall, VPN, wireless, intrusion detection and prevention, SSL, anti-virus, and content filtering, along with award-winning security management solutions. Together, these products and technologies provide the most comprehensive distributed enforcement architecture available. SonicWALL, Inc. is headquartered in Sunnyvale, CA. SonicWALL trades on the NASDAQ exchange under the symbol SNWL. For more information, contact SonicWALL at +44 (0)1344 668090 or visit the company Web site at http://www.sonicwall.com.
SonicWALL UK, Middle East & Africa
Email: ksutcliffe@sonicwall.com
Write Angle Communications
Email: paul.shlackman@writeanglecomm.com
NOTE: SonicWALL is a registered trademark of SonicWALL, Inc. Other product and company names mentioned herein may be trademarks and/or registered trademarks of their respective companies.
This press release was distributed by ResponseSource Press Release Wire on behalf of Write Angle Communications in the following categories: Computing & Telecoms, for more information visit https://pressreleasewire.responsesource.com/about.
Release from Write Angle Communications


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Apart from the Wattage, does it matter what PSU I buy?
Efficiency rating, how much load it can actually take.
Or you can just post budget and what kind of rig you plan to put it in... and we will gladly recommend. Spend some time reading up on tests on jonnyguru or similar established sites.
I don't have a budget as such, but the cheaper (whilst still being safe and doing its job) the better.
If "upgrade everything" means a total new pc are you usually fine with a good quality psu,depending on what parts are used would a 450<->650watt psu do mostly fine. Still as with Dell make sure you get one for the right form factor of the case,there are cases for instance that use a SFX psu which are smaller than a normal atx form factor psu.
If you want to upgrade what you have is form factor with Dell something to keep in mind and even the motherboard might have proprietary connections so look at that in this last case.


Newcomers to Sotogrande can rest assured that they will have access to excellent local services. You'll find everything from nurseries, schools and colleges, pharmacies, health clinics, vets, banks and property and garden management facilities in the area.
Health is a concern for us all; fortunately there are three pharmacies plus a number of private health clinics in the area. Residents and visitors may also use the Spanish health service "ambulatorio", although it is important to remember that you need either a resident's health card or a European Health Insurance Card. There are two general hospitals nearby: one on the city of Algeciras and the other in the town of La Línea.
Sotogrande International School (SIS) is both a day and boarding school for ages 3 to 18+. The school's curriculum is based on the International Baccalaureate providing the Primary Years Programme ( 3-11), the Middle Years Programme (12-16) and the Diploma (16-18).
The school is truly international, with students from over 40 nationalities and a 100-member staff of full and part-time teachers, administrators and support staff from the UK, Ireland, USA, Spain and several other countries. The school campus is surrounded by woods and golf courses and the school's growth from a small British-style school in 1978 to its current status as one of southern Spain's top international schools with 650 pupils, is a testament to SIS's result-based reputation.
A strong focus on the individual plus progressive in values and a network of support mechanisms for learning or language difficulties ensures that students achieve the best they can, and many SIS diploma students have gone on to study at the world's top universities.
SIS can also boast that its staff tend to stay long-term. Retaining staff is often a challenge for international schools in any country. SIS prides itself on employing fully-qualified specialists who enjoy good salaries and benefits, including opportunities for professional development. As a result, students benefit from committed staff who provide a stable learning environment.
Technology plays an important role at SIS and the school is an Apple-certified high tech school that integrates technology into learning. Four iMac labs are available for all ages and SIS has worked closely with Apple to create a cutting-edge teaching environment. In addition, every child has access to laptop and desktop computers and it is also a "Google Apps for Education" school, which promotes a truly 21st century method of education.
Students with a talent for the performing arts and music are well-catered for at SIS, where these subjects are strongly supported and the facilities include a theatre.
Sporty students will find an astroturf pitch, a swimming pool and fully-equipped gymnasium. SIS has always encouraged use of the many recreational activities available in Sotogrande and students can tennis, sailing, horse-riding and, of course, golf are also offered. Indeed, SIS offers scholarships for budding golf professionals who can complete a full IB diploma and develop golf skills with professionals.
Sotogrande International School is fully accredited by the Council of International Schools, the IBO and the Association of British Schools in Spain. In addition, the school is also authorized by the Spanish Ministry of Education and Science and offers a convalidated programme for students wishing to go to Spanish universities.


text: Array.prototype.skip = Array.prototype.slice;

redpajama_set_name: RedPajamaGithub


SCVHistory.com LW3334 | William S. Hart | 'Riddle Gawne' (1918): Publicity Still No. A47-39.
Original publicity still No. A47-39, 8x10 inches.
LW3334: 9600 dpi jpeg from original photograph purchased 2018 by Leon Worden.


text:
Q: What is the best way to recreate a xcode project file? Somehow in my project, after many svn commits, merges and conflicts, my xcode project file was messed up for real.
So, I would like to recreate it, including all my source files in it.
The only naive solution that comes to my mind is to create a new project and add all my files again into it. But I'll need to recreate all my groups and organize it again.
Is that the only solution for me? Is there a easier/better solution?
Edit:
PS.: Xcode 4.2.1

A: Recreate the project and import all of your classes.
That is the easiest and safest way, unless you want to risk more problems down the road.

redpajama_set_name: RedPajamaStackExchange


Take on your most challenging digital prototyping, visual effects, and geophysical or architectural visualization workloads with the graphics horsepower, realism, and interactivity that only NVIDIA® Quadro® can deliver.
As registered member of the PNY Partner Portal you can download below the datasheet, a WebKit (e.g. pictures, Reviewers Guide, Copy blocks, web banners and a detailed board description), high quality pictures and a Logistic datasheet.


text:
El Hospital Universitario 12 de Octubre es un complejo hospitalario gestionado por el Servicio Madrileño de Salud, ubicado en la avenida de Córdoba, en el distrito de Usera, de la ciudad de Madrid.

En la actualidad cuenta con 1196 camas, convirtiéndose así en uno de los hospitales de mayor capacidad de España.

Historia
El hospital se inauguró el 2 de octubre de 1973, por Francisco Franco y Licinio de la Fuente, en la zona sur de la ciudad de Madrid en una parcela de 178 000 metros cuadrados, con el nombre Ciudad Sanitaria Primero de Octubre, cuyo nombre hacía referencia a la fecha de la proclamación de Francisco Franco como jefe de Estado el 1 de octubre de 1936. El edificio de hospitalización, con una extensión de 75 000 metros cuadrados, tenía 15 plantas en altura y 3 en subsuelo, con 250 camas en aquel momento que llegarían a 1250 en el año 1974. En 1975 se prevé la construcción de un Materno-Infantil, que fue inaugurado el 25 de mayo de 1980, con 455 camas, 11 salas de dilatación, 5 paritorios y urgencias pediátricas y ginecológicas, llegando a atender más de 8000 partos anuales. El 12 de octubre de 1988 cambió su denominación por la actual, en referencia esta vez al Descubrimiento de América.

Desde su inauguración, el hospital integró una amplia cartera de servicios, dando cabida a un gran número de especialidades que se fueron incrementando con el tiempo hasta alcanzar la práctica totalidad de las médicas y quirúrgicas e incorporando el más moderno equipamiento tecnológico de diagnóstico y tratamiento.

Hoy trabajan en el centro alrededor de 7000 profesionales, que hacen posible la realización de casi 40 000 intervenciones quirúrgicas, más de 40 000 ingresos y aproximadamente un cuarto de millón de urgencias. El 12 de Octubre es el hospital de referencia para la zona sur de Madrid, aunque también lo es para otras áreas sanitarias de la región y otras comunidades autónomas. Es uno de los hospitales más grandes y prestigiosos de España y puede resolver la mayoría de los problemas de salud que sufre un paciente.

El hospital pertenece al área 11 (actualmente Dirección Asistencial Centro), que atiende a los distritos de Usera, Villaverde y Carabanchel y a los centros de especialidades de Orcasitas, Villaverde y Carabanchel. Anteriormente a la apertura de los hospitales Infanta Elena y del Tajo en 2007, el hospital también atendía a las poblaciones de Valdemoro y Aranjuez. También tenía un centro de especialidades y consultas en el Centro de Salud de Valdemoro, con las especialidades más demandadas, pero estos dos fueron cerrados.

También atendía a la población de Arganzuela en el centro de especialidades de Pontones, pero para este distrito el hospital de referencia es la Fundación Jiménez Díaz (propiedad de Capio (actual Quirónsalud)) para urgencias y hospitalización. Desde abril de 2008, Pontones fue privatizado y pasó a depender de la Fundación Jiménez Díaz, quién hizo obras la cuarta planta que, antes de la apertura del Centro de Salud Paseo Imperial, era un centro de atención primaria y el hospital tenía las plantas primera y segunda hasta, más o menos 2010.

Hospital universitario
El hospital está vinculado a la docencia universitaria desde sus comienzos. El convenio con el Ministerio de Educación se firmó en septiembre de 1974, menos de un año después de su inauguración. Poco después se construyó un edificio anexo, inaugurado en 1976, que dotó al hospital de un equipamiento adecuado para la docencia, con capacidad para 500 alumnos. En el 12 de Octubre se forman actualmente más de 400 alumnos de Medicina de la Facultad de Medicina de la Universidad Complutense de Madrid y un número similar de Enfermería, junto a 500 profesionales en periodo de formación tras la obtención de su título universitario.

Investigación
Cuenta con un centro de investigación biomédica en un edificio anexo de 1500 metros cuadrados. Este centro dispone de ocho laboratorios de investigación, áreas de apoyo científico tecnológicas, dos quirófanos experimentales y dependencias diferenciadas para los animales. Aquí desempeña su actividad un importante número de profesionales -médicos, biólogos, bioquímicos y químicos- y se realiza investigación en enfermedades raras -mitocondriales-, oncológicas, inflamatorias, neurológicas y de salud mental. El 12 de Octubre desarrolla actualmente en todos sus edificios más de 200 proyectos de investigación, centrados principalmente en cáncer, enfermedades raras y modelos de enfermedad, enfermedades infecciosas y sida, otras enfermedades crónicas e inflamación, y enfermedades neurológicas y mentales. En esta actividad investigadora participan alrededor de 300 profesionales.

Trasplantes, cáncer, politraumatizados, mujer y niño
El prestigio de este hospital es especialmente significativo en algunas áreas de actividad, como trasplantes, diagnóstico y tratamiento del cáncer, asistencia al paciente politraumatizado y atención de la mujer y el niño. El 21 de septiembre de 1987, por primera vez en España, se practicó un trasplante simultáneo de hígado y riñón.

Futuro
Su futuro pasa por la construcción y desarrollo de lo que se ha dado en llamar Nuevo 12 de Octubre, un ambicioso proyecto, con un coste aproximado de unos 230.000.000€, que supondrá la renovación completa de sus instalaciones mediante nuevos edificios. Por ahora, las estrellas de este conjunto arquitectónico lo constituyen la Central Térmica -ya en funcionamiento- y el nuevo Centro de Actividades Ambulatorias que comenzó su actividad a mediados de 2011. Actualmente está en construcción el nuevo edificio de hospitalización y materno-infantil, con 9 plantas en altura, un sótano y una planta baja e incluye una reforma de una parte de la Residencia General. Comenzó a construirse en agosto de 2021.

Cómo llegar

El hospital cuenta con numerosas líneas de autobús tanto urbano como interurbano con paradas cerca del recinto. También prestan servicio una línea de metro y otra de cercanías

Autobuses de la EMT

Diurnos: 18, 22, 59, 76, 79, 81, 85, 86 y 121.

Nocturnos: N13 y N14.

Autobuses interurbanos

Diurnos: 411, 421, 422, 423, 424, 426, 429, 447 y 448.

Nocturnos: N401 y N402

Autobús de largo recorrido diurno

Línea VAC158 y VAC231-R6

Renfe Cercanías
Doce de Octubre, línea C-5.

Metro de Madrid

Hospital 12 de Octubre, línea 3.

Véase también
 Hospital universitario
 Seguro Obligatorio de Enfermedad
 Javier Esparza, fundador del Servicio de Neurocirugía en 1982.

Referencias

Enlaces externos

12 de octubre
12 de octubre
Usera
Entidades vinculadas a la Universidad Complutense de Madrid
Servicio Madrileño de Salud

redpajama_set_name: RedPajamaWikipedia


In-person pre-session consultation to explain the details, plan the location, and answer any questions.
A private Reveal-Ordering Session, to go over all your previews and choose your favourites.
This is not the average pet portrait session! If you love art as much as you love your pet, then this is the dream portrait session for you. It was specially designed to please creative and artsy pet owners. The resulting conceptual piece of art is intended to bring out the personality of your pet in a very unique way. Let your imagination fly and travel beyond different worlds to customize it as you want. Your furry friend can be anything you've dreamt of, there are no limits… You just dream it, and I will make it happen!
All my dedication, love and talent to make your dream session come true. Not only during the session, but through the whole process.
In-person pre-session meeting to create the concept and clarify any doubts.
Session is as long as it needs to be. I will take photographs until I'm certain I have all the essential images to create the final master piece.
Reveal session to view the final version and get assistance from me to place your order.


From around 1909 until 1937, Sagarra was one of the most prominent Catalan photographers from the first half of the twentieth century.
The playbill collection of The University and National Library of Debrecen is a valuable source of the intellectual life and theatre history of an Eastern Hungarian town in the second half of the 19th and the beginning of the 20th century.
A collection of more than 3,000 photographs of public houses from the early 20th century up to the late 1960's.
A fine collection of around 3,000 18th- to 20th-century maps and drawings from the archives of the Spanish Ministry of Defence.


text:
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