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Home > Learning Curved: Flying the F-35 Is Becoming Easier Than Ever
Learning Curved: Flying the F-35 Is Becoming Easier Than Ever
April 1, 2021 Topic: Security Region: Americas Blog Brand: The Reboot Tags: MilitaryTechnologyJetsStealth FighterTraining
Many F-35 pilots say that flying the fifth-generation fighter is an entirely new and different experience in many respects.
by Kris Osborn
Here's What You Need to Remember: One such example is something called Delta Flight Path, a special software program tailored to help with the take-off and landing process; advanced computer algorithms account for, integrate and balance a host of otherwise separated variables such as wind-speed, trajectory, angle of descent and other atmospheric conditions such as sea state or ship movement for maritime landing, in order to automate procedures for the pilot.
The U.S. Air Force is working to expedite the learning curve for pilots who are learning to fly the fifth-generation F-35 stealth fighter jet for the first time. The Air Force hopes to achieve this feat by offering a set of specifics and training instructions from pilots to enable countries that are acquiring the F-35 jet for the first time to adjust to its technologies quickly.
The experience of flying the aircraft, as well as the performance of the aircraft in a number of live-fire exercises and combat drills, might be one reason why international demand for the F-35 jet continues to climb quickly.
There is much discussion, speculation and debate about several possible, but yet-to-be-confirmed F-35 jet customers, such as the United Arab Emirates or even Greece, while at the same time the fourteen existing nations currently operating F-35 jets continue to request more of the planes. The existing program includes eight international program partners: The United States, UK, Italy, Netherlands, Australia, Norway, Denmark and Canada. This group has in recent years been joined by six Foreign Military Customers to include Israel, Japan, South Korea, Poland, Belgium and Singapore.
"We engage in collaboration and cooperation to help them bring on their aircraft in a way that takes advantage of the lessons learned we've had. We have decades of operating 5th gen aircraft but this is the first time when these nations have had a fifth-gen aircraft," Gen. Kenneth Wilsback, the commander of the Pacific Air Forces, told The Mitchell Institute for Aerospace Studies in a special video interview.
There are a number of added advantages associated with having a number of allied F-35 jet partners, the most significant of which is interoperability. A common data link and technical architecture allows otherwise separated groups of F-35 jets from different countries to coordinate mission specifics, share targeting information and make adjustments in connection with one another. Of course, it is helpful to the United States for its allied partners to possess F-35s for deterrence strategies and combat capacity in the event that it were needed, yet having an ability to integrate otherwise dispersed or disaggregated operations across wide swaths of territory massively expands theater attack dynamics and mission reach.
"When we sell them the aircraft we include the maintenance and interoperability," Wilsback said.
What makes flying the F-35 jet so different? Many F-35 pilots say that flying the fifth-generation fighter is an entirely new and different experience in many respects. While pilot skill is, of course, essential, what the F-35 jet's computing and sensing architecture does is allow pilots to prioritize pressing, high-priority functions, which rely upon human decisionmaking, because so many procedural and flight-path specifics are automated and computer-enabled.
"We want our partners to cycle through our lessons learned faster and fly it like an F-35 straight up from the beginning. Don't revert to flying the F-35 like an F-15. Don't fly it like a fourth-gen. Take advantage of the capability," Wilsback said.
One such example is something called Delta Flight Path, a special software program tailored to help with the take-off and landing process; advanced computer algorithms account for, integrate and balance a host of otherwise separated variables such as wind-speed, trajectory, angle of descent and other atmospheric conditions such as sea state or ship movement for maritime landing, in order to automate procedures for the pilot.
This massively reduces the procedural and cognitive workload typically required by pilots, especially when it comes to difficult landing conditions in either high-threat areas or rough seas in the case of the F-35B or F-35C variants. The F-35B's vertical take-off-and-landing hover and descent, for example, happens somewhat independently of the pilot, meaning that it is controlled by and at the direction of the pilot even though much of the stabilization, navigational specifics and aerial maneuvers are autonomously performed by the aircraft's sensors and computer systems.
Of course, there is also the well-known and often discussed sensor fusion, meaning that navigational, targeting and threat data are gathered, organized and integrated by computer algorithms and presented in a unified, readable way on a single screen for pilots. This naturally prevents a pilot from needing to look at disparate screens and monitors before comparing a number of interwoven variables such as speed, altitude, aircraft maintenance information, video feeds from sensor cameras, threat library target identification specifics and atmospheric details.
Aircraft functionality details, coupled with maintenance and performance specifics are analyzed, compiled and presented by the F-35's Autonomic Logistics Information System, a computer system engineered to monitor and transmit key details regarding the aircraft's many subsystems such as engine reliability, cooling, sensor conditions and other things.
An F-35 stealth fighter draws upon threat information from its Electro-Optical Targeting System long-range, high-fidelity sensors, and merges the intelligence with input from 360-degree cameras surrounding the aircraft called the Distributed Aperture System. Data from these computer-enabled systems is then integrated with the F-35's Mission Data Files threat library offering specs, specifics, configurations and details identifying enemy aircraft from designated areas around the globe.
Kris Osborn is the defense editor for the National Interest. Osborn previously served at the Pentagon as a Highly Qualified Expert with the Office of the Assistant Secretary of the Army—Acquisition, Logistics & Technology. Osborn has also worked as an anchor and on-air military specialist at national TV networks. He has appeared as a guest military expert on Fox News, MSNBC, The Military Channel, and The History Channel. He also has a Masters Degree in Comparative Literature from Columbia University. This article first appeared last year.
Image: Flickr.
Source URL: https://nationalinterest.org/blog/reboot/learning-curved-flying-f-35-becoming-easier-ever-181725


Awesome « Nightlights » review in Rock Tribune Magazine #129 (BE), 92/100 !
5 octobre 2013 12 janvier 2016 adminComments are off for this post.
Great « Nightlights » review on Spirit of Metal Webzine.
30 septembre 2013 12 janvier 2016 adminComments are off for this post.
In the meantime you will find the first « Nightlights » french review here… and the first interview in here as well.
14 septembre 2013 12 janvier 2016 adminComments are off for this post.
You can listen to « Haste to decline », the first track of the upcoming album here, enjoy !
23 août 2013 12 janvier 2016 adminComments are off for this post.
The new album « Nightlights » is now available for pre-order here.
A new t-shirt is also available for pre-order. Don't miss it, it's limited edition !
7 août 2013 12 janvier 2016 adminComments are off for this post.
SOLEKAHN inked a deal with danish label MIGHTY MUSIC to release its new album « Nightlights » on the 14th of October 2013 !
19 juillet 2013 12 janvier 2016 adminComments are off for this post.


The Intelligent Design Zana Comforter Set provides a mature update to your space with its decorative paisley design. The charcoal grey and soft teal provide the perfect base for the pops of yellow and green in the motif. Two decorative pillows use embroidery and fabric manipulation techniques to coordinate back to this collection.


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Home News International News Chinese Christian Woman Arrested, Criminally Detained for Attempting to Share Gospel With...
Chinese Christian Woman Arrested, Criminally Detained for Attempting to Share Gospel With President Xi Jinping
By pkay Darko -
A Chinese Christian woman was arrested by public security bureau officers and criminally detained after she attempted to share the gospel with President Xi Jinping.
Persecution watchdog China Aid reports that on March 15, Zhou Jinxia, a Christian who traveled to Beijing from Dalian, arrived at the front gate of the former imperial garden Zhongnanhai, holding a sign that read, "God loves the people of the world and is calling out to Xi Jinping."
Her objective, the outlet says, was to reach Xi while the National People's Congress (NPC) and the Chinese People's Political Consultative Conference (CPPCC) convened.
However, a short time later, the director of the Huanghe Street Police Station, based in Dalian, brought her away, and she was escorted back to her hometown overnight. The next day, the Xigang Branch of the Dalian Municipal Public Security Bureau criminally detained her.
Days before, her friend called to inform her that the police have accused her of being a suspect at large and are looking for her.
The incident was not the first time Zhou had come under fire for her religious zeal; China Aid reports that she had traveled to Zhongnanhai several dozen times in the past few years to spread the Gospel and has either been detained or abducted each time.
In 2016, the Christian woman spent 10 days in administrative detention after another visit to Zhongnanhai, where she held a sign that said "God loves the people of the world and is calling out to Xi Jinping and [Xi's wife] Peng Liyuan. Atheism nurtures sin and brings down the people. The kingdom of heaven is at hand; you should repent." The police called this act "disturbing social order" and confiscated her materials.
Last year, Zhou and another Christian from Anhui, Shi Xinhong, went to the Great Hall of the People in Beijing and attempted to preach to the attendees of that year's meeting of the NPC and CPPCC. Both of them received the charge of "picking quarrels and provoking troubles" and were criminally detained.
However, China Aid warns that due to China's revised Religions Affairs Regulations, which came into effect in February, the latest incident may result in Zhou being prosecuted by authorities.
The regulations, which define the administrative framework around religious activities, have the stated aim of "protecting citizens' freedom of religious belief".
"Religious affairs maintenance should persist in a principle of maintaining legality, curbing illegality, blocking extremism, resisting infiltration and attacking crime," the regulations say.
"Any group or individual must not create conflict or contention between different religions, with a single religion or between religious individuals and non-religious individuals," they say.
According to Reuters, fines for breaking the rules have also been increased in the new version and the organizers of unapproved events can now be subject to fines from 100,000 to 300,000 yuan, rather than the previous 1 to 3 times the amount spent on the event.
Persecution watchdog Open Doors USA has ranked China 43rd on its World Watch List of 50 countries where Christians face the most persecution.
A primary source of persecution, Open Doors says, is the Communist government.
"Christians, in particular, are hedged in by authorities, as they are the largest social force in China not controlled by the state," notes the outlet.
source: gospelherald
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With Black Friday & Cyber Monday out the way, we're well and truly entering the festive period.
Your Facebook feed will soon be filled with decorated Christmas trees, while your Snapchat will definitely see stories related to Christmas jumpers.
I'm not afraid to admit it - I'm definitely one of those people that is difficult to buy for.
I don't think I need anything.
I'm not sure I know what I want.
I accidentally bought that myself earlier on this month.
I am, however, better at advising other people of potential gifts! If there's a runner in your family, Scimitar Shop is the perfect destination for your Christmas presents.
With rapid delivery, a few secret freebies in every December order and a product range that is sure to bring a smile to anyone's face, we've got you covered.
You don't need us to dive into heavy detail about the product quality. Our custom products are the UK's choice for running clubs, top charities and corporate companies; a quality that is replicated across our range of premium retail products.
Here's a breakdown of our top 5 2016 Christmas presents for runners. Let us know your thoughts!
Designed for those that run with a huge smile on their face, the Mr Happy Running Vest is finished in a vibrant yellow, with a host of premium features.
You'll find mesh side panels and flatlock stitching on this lightweight vest, offering an unrivalled level of comfort and ventilation. What's more, reflective panels sewn into the rear seams help enhance the safety of our running vest.
The most surprising element of this running vest? The price.
£24.95 gets you all of these premium features, along with an attractive and vibrant design. It certainly puts a smile on my face.
Now, we had to include this product as the polar-opposite of the above.
Do you know a runner who likes a good old moan? This product is sure to trigger the tiniest, smallest little grin!
As part of our new 2016 collection, the Mr Grumpy Running Vest benefits from our mesh side panels and reflective seams, providing comfort and safety when it matters the most.
Go on. Trigger a smile this Christmas, and join the many other Mr Grumpy's who will be wearing this vest in the new year!
Funky leggings are definitely in.
Our range of technical leggings are designed to offer enhanced technical performance while fitting in with fitness trends across the UK.
The newest products to join our range, the Little Miss Running Leggings benefit from an all over print, and make the perfect present for any fitness fanatic.
These leggings are perfect for yoga, cross-fit, running, pole-dancing and training in the gym - whatever the purpose, these technical leggings are sure to go down as a top-notch Christmas present.
A very popular product since we launched it in October 2016, gifting the Little Miss Chatterbox Running Vest offers a superb premium product for the runner, and a stark warning for other runners in the vicinity!
Featuring all of the premium features mentioned above, our close-fit womens cut offers a tighter fit under the arms, with a comfy fit across the bust and waist.
Finally, there's no escaping the fact that it's winter. As I write this blog, temperatures are plummeting to -3 degrees, and runners face additional challenges out on the road.
Designed to bounce light, our fluorescent running jacket is a brilliant product for ensuring safety during the winter months.
Made from a lightweight, windproof and waterproof fabric, the Scimitar Fluorescent Jacket is designed to offer a weather-resistant coat for runners without the prohibition of movement and freedom.
A Christmas gift or a necessary accessory in the winter months? You decide.
There you have it. Five of the best Christmas gifts for runners, from Scimitar Shop. We've created a whole section dedicated to Christmas presents this year - click here to take a look at our recommendations.


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Brief Definitive Report| February 16 2009
A novel myelin P0–specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy
Cédric Louvet,
Cédric Louvet
Diabetes Center and the Department of Medicine, University of California, San Francisco, San Francisco, CA 94143
Beniwende G. Kabre,
Beniwende G. Kabre
Dan W. Davini,
Dan W. Davini
Nicolas Martinier,
Nicolas Martinier
Maureen A. Su,
Maureen A. Su
Jason J. DeVoss,
Jason J. DeVoss
Wendy L. Rosenthal,
Wendy L. Rosenthal
Mark S. Anderson,
Mark S. Anderson
Hélène Bour-Jordan,
Hélène Bour-Jordan
Jeffrey A. Bluestone
CORRESPONDENCE Jeffrey A. Bluestone: jbluest@diabetes.ucsf.edu
H. Bour-Jordan and J.A. Bluestone contributed equally to this paper.
Received: September 23 2008
Accepted: January 23 2009
© 2009 Louvet et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
Cédric Louvet, Beniwende G. Kabre, Dan W. Davini, Nicolas Martinier, Maureen A. Su, Jason J. DeVoss, Wendy L. Rosenthal, Mark S. Anderson, Hélène Bour-Jordan, Jeffrey A. Bluestone; A novel myelin P0–specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy. J Exp Med 16 March 2009; 206 (3): 507–514. doi: https://doi.org/10.1084/jem.20082113
Autoimmune-prone nonobese diabetic mice deficient for B7-2 spontaneously develop an autoimmune peripheral neuropathy mediated by inflammatory CD4+ T cells that is reminiscent of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. To determine the etiology of this disease, CD4+ T cell hybridomas were generated from inflamed tissue–derived CD4+ T cells. A majority of T cell hybridomas were specific for myelin protein 0 (P0), which was the principal target of autoantibody responses targeting nerve proteins. To determine whether P0-specific T cell responses were sufficient to mediate disease, we generated a novel myelin P0–specific T cell receptor transgenic (POT) mouse. POT T cells were not tolerized or deleted during thymic development and proliferated in response to P0 in vitro. Importantly, when bred onto a recombination activating gene knockout background, POT mice developed a fulminant form of peripheral neuropathy that affected all mice by weaning age and led to their premature death by 3–5 wk of age. This abrupt disease was associated with the production of interferon γ by P0-specific T cells and a lack of CD4+ Foxp3+ regulatory T cells. Collectively, our data suggest that myelin P0 is a major autoantigen in autoimmune peripheral neuropathy.
Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are autoimmune diseases characterized by inflammatory demyelinating lesions of the peripheral nervous system (PNS) that cause devastating neurological deficits and paralysis. Multifocal demyelination associated with perivascular mononuclear cell infiltrates in the PNS is the pathological hallmark of GBS and CIDP, and autoreactive T and B cell responses are believed to be essential in both diseases (1). Defining self-antigens targeted by the autoimmune response can lead to a better understanding of the immunopathology of the disease and can potentially lead to antigen-specific tolerogenic therapies (2); however, progress has been limited by the paucity of animal models. We previously described the first spontaneous model of autoimmune disease of the PNS, called spontaneous autoimmune peripheral polyneuropathy, in autoimmune-prone nonobese diabetic (NOD) mice deficient for the co-stimulatory molecule B7-2 (NOD-B7-2KO mice) or mimicked many pathophysiological characteristics of GBS and CIDP (3). NOD-B7-2KO mice exhibit a progressive and generalized limb paralysis associated with severe demyelination and axonal damage caused by an autoimmune attack of the PNS (3). Inflammatory CD4+ T cells are essential for the development of autoimmune peripheral neuropathy, and NOD-B7-2KO mice deficient for IFN-γ were protected from disease (3, 4). In this report, we examined the antigen specificity of autoreactive T cells infiltrating the nerves of neuropathic mice and found that myelin protein 0 (P0) is a dominant self-antigen recognized by T cells and autoantibodies. We generated a TCR transgenic (TCR-Tg) mouse specific for a P0 epitope and demonstrated that these T cells were sufficient to induce a fulminant form of peripheral neuropathy.
Generation of peripheral nerve–specific T cell hybridomas
We previously demonstrated that CD4+ T cells from neuropathic NOD-B7-2KO mice could transfer disease, suggesting that the site of infiltration and tissue destruction would be enriched in pathogenic autoreactive T cells specific for nerve antigens. CD4+ T cells were isolated from the infiltrated nerves of neuropathic NOD-B7-2KO mice (Fig. 1) and were expanded with anti-CD3 and anti-CD28 mAbs, and IL-2 by 20–100-fold after 2 wk in culture, as previously described (Fig. 1 B) (5).
Transfer of 2–5 × 106 expanded CD4+ T cells into immunodeficient recipients led to neuropathy within 5 wk (Fig. 1 C and not depicted). Expanded CD4+ T cells from nerves were fused with TCR− BW1100 cells (6) to generate antigen-specific T cell hybridomas. Stable CD4+ TCR+ T cell hybridomas, responsive to anti-CD3 stimulation, were tested further for their ability to be activated by protein lysates prepared from sciatic nerves. A small subset of CD4+ T cell hybridomas (11 out of 56) derived from the infiltrated nerves of neuropathic mice responded to sciatic nerve antigens as measured by up-regulation of CD69 (Fig. 1 D). 1 out of these 11 hybridoma responded to an antigen shared between the PNS and central nervous system (CNS; Table S1, available at http://www.jem.org/cgi/content/full/jem.20082113/DC1), supporting the previous finding that neuropathy in NOD-B7-2KO mice preferentially targeted the PNS without affecting CNS tissues (3). As expected, up-regulation of CD69 on T cell hybridomas in response to nerve lysate was inhibited in the presence of anti–MHC class II blocking mAbs (Fig. S1), confirming that the response of T cell hybridomas to nerve antigens was dependent on recognition of a peptide–MHC class II complex.
Antigen specificity of nerve-derived CD4+ T cell hybridomas
Neural proteins targeted by autoantibodies in NOD-B7-2KO mice were determined to identify potential targets of autoreactive T cells (7, 8). Protein extracts prepared from the sciatic nerve were immunoblotted with sera from neuropathic mice (4). The majority of sera (27 out of 50; 54%) from individual neuropathic T reg cell–depleted NOD-B7-2KO mice reacted strongly against an antigen migrating at ∼25–30 kD (Fig. 2 A). Immunoprecipitation was performed on columns containing protein G agarose coupled to sera from neuropathic animals, followed by peptide mass fingerprinting, and unequivocally identified the 28-kD protein P0, a major component of the myelin sheath expressed exclusively in the PNS but not in the CNS. 6 out of 11 hybridomas that were activated by peripheral nerve lysate up-regulated CD69 in the presence of P0 peptides, suggesting that P0 is a major autoantigen targeted by T cells in neuropathic mice (Fig. 2 B). Of these six P0-specific hybridomas, four recognized P0 peptides in the putatively extracellular portion of the protein (peptide pool #1), whereas the other two hybridomas were specific for P0 peptides located in the cytoplasmic portion of the protein (peptide pool #4; Fig. 2 B). Three out of the four extracellular P0-specific hybridomas were responsive to the same P0 peptide (amino acids 1–25), suggesting the presence of an immunodominant epitope in this portion of the P0 protein (Fig. 2 C and not depicted). We should emphasize that the four hybridomas specific for P0 1–25 were generated from distinct T cell clones, because the TCR Vα and Vβ combination was unique to each hybridoma (Table S1).
Generation of a myelin P0–specific TCR-Tg (POT) mouse
Next, we generated a POT mouse by cloning the rearranged TCR α (Vα9) and β (Vβ11) chains from hybridoma 2E7, which was strongly activated in response to peripheral nerve lysate and P0 immunodominant peptide 1–25 in vitro (Fig. 2 C). The POT mice showed no difference in the total cell numbers of the spleen cells or thymocytes as compared with non-Tg littermates (unpublished data). The percentages of CD4 and CD8 single-positive cells were decreased in the thymus in POT mice as compared with control littermates, and the CD4/CD8 ratio was slightly increased (4.9 ± 0.8% compared with 3.6 ± 0.2%, respectively; P < 0.05; Fig. 3 A, left). Similar data were observed in the spleen (Fig. 3 A, right). Analysis of TCR expression confirmed the expression of the Tg TCR and showed very efficient allelic exclusion in POT mice (Fig. 3 A, right). Indeed, >90% of CD4+ T cells were Vβ11+ in the spleen of POT mice versus <10% in non-Tg littermates (90.6 ± 5.4% in POT mice versus 6.5 ± 0.5% in controls). Conversely, POT splenic CD4+ T cells contained <2% Vβ8+ T cells, whereas Vβ8+ T cells represented >20% of CD4+ T cells in control littermates (1.2 ± 1.3% in POT mice versus 22.8 ± 1.2% in controls). These results suggested that T cells expressing the POT TCR were positively selected to generate a normal population of mature T cells in the periphery, similar to other TCR-Tg mice specific for autoantigens such as islet-specific BDC2.5 (9). Analysis of POT mice, crossed onto a RAGKO background to eliminate the potential influence of endogenous TCR α chains on the thymic selection, confirmed that TCR-Tg T cells were positively selected in the thymus, although the cell numbers were greatly reduced compared with RAG+/− or POT-RAG+/− mice (Fig. S2, available at http://www.jem.org/cgi/content/full/jem.20082113/DC1), suggesting a more effective negative selection induced by P0-expressing thymic stromal cells in this setting (10). Although the total spleen cell number was reduced in POT-RAGKO compared with POT mice, the majority of mature T cells from POT-RAGKO mice were CD4+Vβ11+ T cells, with few CD8+Vβ11+ T cells (a mean ratio of 10.6 ± 1.2% versus 3.7 ± 0.3% in POT-RAG+/− mice; Fig. 3 B and Fig. S2). Thus, P0-specific POT TCR-Tg T cells successfully survived thymic selection to generate a population of mature autoreactive T cells in the periphery even on a RAGKO background. Finally, we examined the presence of T reg cells and the activation status of TCR-Tg T cells in POT mice. There was no difference in the expression of CD69, CD62L, and CD44 on CD4+ T cells isolated from POT mice compared with non-Tg littermates (unpublished data), showing that POT T cells were not activated in the periphery. Furthermore, a similar percentage of CD4+ T cells expressed the T reg cell marker Foxp3 in POT mice compared with controls (Fig. 3 C). However, CD4+ Foxp3+ T reg cells could not be detected in the spleen and thymus of POT-RAGKO mice (Fig. 3 D; and Figs. S3 and S4), thus confirming that the thymic selection of T reg cells in POT mice involved TCRs using endogenous α chains.
Proliferation and cytokine production of P0-specific TCR-Tg T cells
POT CD4+ T cells proliferated strongly in response to protein extracts prepared from sciatic nerves but not spinal cord or brain, confirming their strict PNS specificity (Fig. 4 A). Furthermore, POT T cells displayed a similarly strong proliferation when cultured with P0 protein (including the P0 peptide 1–25) but not with another myelin protein (P2), confirming the P0 specificity and demonstrating that the T cells are fully functional and not anergic in the periphery. We examined the capacity of activation of PNS-specific autoreactive T cells to proliferate in NOD (resistant) versus NOD-B7-2KO (susceptible) mice. POT T cells proliferated extensively in several lymph nodes in NOD-B7-2KO but not NOD recipients, including brachial, axillary, and inguinal lymph nodes (Fig. 4 B; and Fig. S5, available at http://www.jem.org/cgi/content/full/jem.20082113/DC1), illustrating a clear dichotomy between NOD and NOD-B7-2KO mice, as the development of diabetes versus neuropathy directly correlates with the ability of islet versus nerve antigen-specific autoreactive T cells to proliferate in relevant lymph nodes (Fig. 4 B) (11). Finally, we detected high levels of IFN-γ and IL-17 in the culture supernatant of POT T cells upon in vitro stimulation in the absence of any skewing culture conditions (Fig. 4 C). Surprisingly, intracellular cytokine staining revealed that 40–50% of T cells isolated from POT-RAGKO mice produced IFN-γ but no IL-17 ex vivo, whereas only 2.5% of POT T cells on a RAG-sufficient background produced IFN-γ and <1% produced IL-17, similar to what was observed in NOD littermates (Fig. 4 D). This result suggested that cytokine production observed in a RAG-sufficient background was influenced by endogenous TCR α chains and/or regulatory cell populations that could limit the activation and differentiation of autoreactive POT T cells.
Pathogenicity of P0-specific TCR-Tg T cells in vivo
Although mononuclear infiltration could be detected in the nerves of some POT mice as early as 3 wk of age (Fig. 5 A), many POT mice did not show any sign of inflammation in sciatic nerves or clinically detectable peripheral neuropathy by 15–17 wk of age (Fig. 5 A and not depicted). However, adoptive transfer of in vitro–activated or CD25-depleted POT T cells led to peripheral nerve infiltration and induced neuropathy in immunodeficient recipients (unpublished data). These results suggested that the lack of spontaneous neuropathy in POT mice may have been a consequence of increased numbers of antigen-specific Tg+Foxp3+ T reg cells as compared with Tg-negative NOD mice. Thus, we examined T reg cell–deficient POT-RAGKO mice for tissue infiltration and clinical disease (Fig. 3 D; and Figs. S3 and S4). POT-RAGKO mice displayed a dramatic phenotype characterized by early weight loss and premature death by 3–5 wk of age (Fig. 5, B and C; and not depicted), and spontaneously developed a fulminant form of neuropathy that started as early as 18 d and affected all mice by 3–4 wk of age (Fig. 5, C and D). The spontaneous peripheral neuropathy induced by POT T cells led to motor dysfunction indicated by clasping of the limbs and difficulty walking (Fig. 5 C; and Videos 1–3, available at http://www.jem.org/cgi/content/full/jem.20082113/DC1), similar to what we originally observed in NOD-B7-2KO mice (3). Development of neuropathy was accompanied by a heavy infiltrate in the sciatic nerves of NOD-RAGKO-POT mice (Fig. 5, A and E), as well as myelin destruction (Fig. S6). The infiltration in the sciatic nerves of NOD-RAGKO-POT mice was strikingly higher than in their RAG-sufficient counterparts at 3–4 wk of age (P = 0.01 using a Mann-Whitney U test; Fig. 5 A), correlating with clinical disease. Indeed, adoptive transfer of 1.3 × 106 splenocytes from a 25-d-old neuropathic NOD-RAGKO-POT mouse induced severe neuropathy in all NOD-SCID recipients in <2 wk (Fig. 5 F). Finally, the peripheral neuropathy induced by P0-specific POT TCR-Tg T cells was extremely severe and led to death of the animals, usually within 24 h after clinical disease onset, either spontaneously in NOD-RAGKO-POT mice or after adoptive transfer of T cells from NOD-RAGKO-POT or NOD-POT mice (unpublished data).
Collectively, our data demonstrate that myelin P0 is a major autoantigen targeted by autoantibodies and autoreactive T cells in a spontaneous mouse model of peripheral neuropathy. Importantly, the development of an abrupt form of disease in NOD-RAGKO-POT mice reveals that P0-specific CD4+ T cells were sufficient to induce catastrophic damage in the PNS and suggests that P0-specific T cells could play a central role in inducing tissue destruction in autoimmune neuropathy. P0 is a major component of the PNS that represents >50% of the peripheral myelin protein content. Experimental autoimmune neuritis can be induced in rats and mice by immunization with P0 protein or peptides in adjuvant or by adoptive transfer of P0-specific T cell lines (1). However, these models involve active immunization and powerful adjuvants, which does not mirror the spontaneous disease in individuals genetically prone to autoimmunity. Reports of immune responses to P0 in GBS and CIDP patients have generated conflicting results that could be explained by different techniques and patient populations. Nevertheless, of all neural proteins tested, P0 has been the most consistent reactivity detected in the serum of patients with active GBS or CIDP (12–14). Khalili-Shirazi et al. initially reported proliferative responses to P0 protein or peptides in 9 out of 19 GBS patients (15). More recently, P0-specific T cell responses measured by proliferation or ELISPOT were not statistically different in GBS and CIDP patients as compared with nonautoimmune neuropathies (16), whereas another report described P0-specific IL-10 production in GBS patients (17), raising the possibility that immune responses to P0 may be regulatory rather than pathogenic. These findings were reminiscent of the glutamic acid decarboxylase 65-kD isoform (GAD65) autoantigen in type 1 diabetes. Similar to P0, autoantibodies to GAD were readily detected in type 1 diabetes patients and in the NOD mouse (18, 19), and GAD-specific T cells could adoptively transfer diabetes in the NOD mouse model (20). However, GAD-specific TCR-Tg or retrogenic mice revealed that GAD-specific T cells did not induce diabetes but rather exerted a protective effect (21). In contrast, our report of an aggressive form of peripheral neuropathy spontaneously occurring in P0-specific POT TCR-Tg mice strengthens the potential role of P0 as a central autoantigen involved in disease development and tissue damage in autoimmune neuropathy. While this paper was being reviewed, Kim et al. published a report (22) showing that autoimmune neuropathy in NOD-B7-2KO mice could be prevented by tolerance induction using a specific P0 peptide. Although the peptide specificity (P0 180–199) was different from the POT TCR epitope (P0 1–25), the epitope overlapped with two of our peripheral nerve–specific hybridoma clones (Fig. 2 B; and Table S2, available at http://www.jem.org/cgi/content/full/jem.20082113/DC1). In their report, the adoptive transfer of a P0-specific line only led to very mild disease (grade 1). The difference with our results may be because of the specificity differences or their use of a T cell line.
Our results suggest that neuropathy induced by P0-specific POT T cells involves mainly IFN-γ–producing Th1 cells in agreement with a central role of IFN-γ in the development of peripheral neuropathy in NOD-B7-2KO mice (4). Furthermore, elevated serum levels of IFN-γ have been reported in GBS patients, and the percentage of IFN-γ+ CD4+ T cells was markedly increased in the cerebrospinal fluid of CIDP patients (23, 24). Th17 cells have been suggested to play a major role in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (25). Although increased levels of IL-17 have been described in the spinal fluid of CIDP patients (24), it is still unclear whether Th17 cells are important for autoimmune peripheral neuropathies. We found that low levels of IL-17 were produced by POT T cells on a RAG-sufficient background in vitro. It was recently reported that Th1 and Th17 cells may have different abilities to infiltrate the CNS and cause experimental autoimmune encephalomyelitis depending on the level of local tissue inflammation (26). Thus, our report does not preclude a role for IL-17 in spontaneous autoimmune peripheral polyneuropathy and other PNS autoimmune diseases but suggests that IFN-γ is the dominant cytokine associated with peripheral neuropathy induced by P0-specific POT T cells.
Another important insight revealed by our report is the control of P0-specific T cells and, hence, the development of neuropathy by CD4+ Foxp3+ T reg cells. Indeed, the development of the fulminant form of neuropathy in POT-RAGKO mice was associated with a complete absence of CD4+ Foxp3+ T reg cells, suggesting that antigen-specific T reg cells are key to controlling the disease. Because the percentage of T reg cells has been shown to be lower in the peripheral blood of GBS and CIDP patients (27–29), our findings suggest that immunotherapy using P0-specific T reg cells may be an important future therapeutic option for these patients, as similar treatments are now being developed for several autoimmune diseases (2).
Mice.
NOD and NOD-SCID mice were purchased from Taconic. NOD-B7-2KO (3), NOD-TCRαKO, and NOD-RAG2KO mice were bred in our facility. Neuropathy was assessed weekly (3). All mice were housed in a specific pathogen-free University of California, San Francisco (UCSF) facility. All animal experiments were approved by the Institutional Animal Care and Use Committee of UCSF.
Peripheral nerve–specific hybridomas.
Cells from sciatic nerves of neuropathic NOD-B7-2KO mice were prepared as previously described (3), stained with CD4-FITC and CD8-allophycocyanin. CD4+ CD8− cells were sorted on a cytometer (MoFlo; Dako) and expanded with anti-CD3– and anti-CD28–coated beads supplemented with 2,000 IU/ml rhIL-2, as previously described (5). The expanded CD4+ T cells were fused to the TCR-negative thymoma partner BW1100 (provided by E. Palmer, University Hospital Basel, Basel, Switzerland) using standard protocols. TCR-expressing hybridoma clones were tested for antigen specificity by incubating 50,000 cells with 0.2 × 106 APCs (NOD-TCRαKO spleen cells, irradiated NOD spleen cells, or NOD BM-derived DCs) with the stimulus indicated in the figures for 16–24 h, followed by staining with CD69-PE. Overlapping peptides spanning the sequence of human P0 (which is 94% homologous to mouse P0 at the amino-acid level) were provided by N. Gregson (King's College London, London, England, UK; Table S2).
Generation of POT TCR-Tg mice.
The full-length coding sequences for the TCR α and β chains were cloned by PCR from 2E7 hybridoma cDNA using the indicated primers (Table S3, available at http://www.jem.org/cgi/content/full/jem.20082113/DC1), and were subcloned into a CD2 and CD4 expression vector, respectively (30), allowing expression of the transgenes in both CD4 and CD8 T cells. Tg mice were generated by microinjection of CD2-TCRα and CD4-TCRβ constructs into NOD embryos. Vectors were provided by N. Killeen (UCSF, San Francisco, CA).
Statistical analysis.
All statistical analyses were performed using an unpaired two-tailed Mann-Whitney U test with Prism software (GraphPad Software, Inc.). P ≤ 0.05 was considered significant.
Table S1 shows the characteristics of nerve-specific hybridomas. Tables S2 and S3 show the sequences of peptides and primers used in this report. Fig. S1 shows the inhibition of hybridoma activation by anti–MHC class II mAbs. Figs. S2–S4 show CD4, CD8, Vβ, CD25, and Foxp3 FACS analysis of thymus and spleen cells from NOD-RAGKO-POT mice. Fig. S5 shows the enhanced proliferation of NOD-POT cells in NOD-B7-2KO mice compared with NOD recipients. Fig. S6 shows sciatic nerve demyelination in NOD-RAGKO-POT mice. Videos 1 and 2 show a grid test to assess neuropathy in a NOD-RAGKO-POT mouse and a NOD-RAGKO littermate, respectively. Video 3 shows the clasping phenotype and weight deficit in a NOD-RAGKO-POT mouse compared with the normal plantar reaction in a NOD-RAGKO littermate.
The authors wish to thank H. Lu and N. Killeen for the vectors and microinjections, C. Austin for histology, S. Jiang for cell sorting, D. Vignali and A. Burton for discussions, N. Gregson for providing P0 peptides, and A. Weishaupt and R. Gold for providing P0 and P2 recombinant proteins.
This work was supported by National Institutes of Health grant R01 AI50834, a UCSF Research Evaluation and Allocation Committee grant, and a Neuropathy Association scientific research grant.
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Distinct effector mechanisms in the development of autoimmune neuropathy versus diabetes in nonobese diabetic mice
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Physiologic expression of two superantigens in the BDF1 mouse
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Antibody responses to P0 and P2 myelin proteins in Guillain-Barre syndrome and chronic idiopathic demyelinating polyradiculoneuropathy
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On the pathogenicity of autoantigen-specific T-cell receptors
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Abnormality of circulating CD4(+)CD25(+) regulatory T cell in patients with Guillain-Barre syndrome
Increased levels of activated T-cells and reduced levels of CD4/CD25+ cells in peripheral blood of Guillain-Barre syndrome patients compared to controls
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Impairment of circulating CD4+CD25+ regulatory T cells in patients with chronic inflammatory demyelinating polyradiculoneuropathy
Zingler
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CD4 promotes breadth in the TCR repertoire
Figures S1–S6, Tables S1–S3- pdf file
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Generation of peripheral nerve–specific T cell hybridoma. (A and B) CD4+ T cells were sorted from the nerves of neuropathic NOD-B7-2KO mice (A) and expanded in vitro (B). Data are representative of 15 sorts and expansions. (C) 2–5 × 106 expanded cells were transferred into NOD-SCID or NOD-RAGKO immunodeficient mice, and recipients were followed for the development of neuropathy (n = 5 mice from two independent experiments). (D) CD4+ T cell hybridomas were stimulated with APCs alone (open histogram) or in the presence of the indicated stimulus (shaded histograms), and CD69 up-regulation was assessed. Clone 2E7 is shown. Data are representative of four experiments.
Myelin P0 is targeted by the autoimmune response in NOD-B7-2KO mice. (A) Immunoblotting of sciatic nerve extracts with serum from individual anti–B7-1–treated NOD-B7-2KO neuropathic mice (lanes 1–9), nonneuropathic NOD mice (lanes 10 and 11), or BALB/c controls (lanes 12 and 13). Data are representative of five to nine independent experiments for each serum. The predominant 25–30-kD reactivity is indicated with an arrow. (B) Nerve-specific CD4+ T cell hybridomas were examined for reactivity to P0 as in Fig. 1 D, using pools of overlapping peptides spanning the P0 protein. Data are representative of two experiments. Arrows indicate reactive clones to a specific pool of peptide. (C) Activation of the 2E7 hybridoma by individual P0 peptides from pools #1 and #4. Data are representative of two experiments.
Phenotypic analysis of POT TCR-Tg mice. (A) Phenotyping of CD4+ and CD8+ T cells in the thymus (left) and spleen (right) of NOD-POT TCR-Tg mice (top) and transgene-negative littermates (bottom). (B) Phenotyping of CD4+ T cells in the spleens of NOD-RAGKO-POT TCR-Tg mice. (C) Foxp3 expression in the spleens of the indicated 12-wk-old mice (histograms are gated on CD4+ T cells). Numbers indicate percentages of Foxp3+ cells in the CD4 population. (A–C). (D) CD25 and Foxp3 expression among CD4+ cells in the spleens of the indicated 19-d-old mice. Percentages ± SD are indicated. Data are representative of two or more experiments.
Proliferation and cytokine production of P0-specific NOD-POT T cells. (A) Proliferation of CFSE-labeled NOD-POT T cells in the presence of APCs alone (gray histogram) or APCs and the indicated stimulus (black histograms). Histograms are gated on the CD4+ population. (B) Proliferation of CFSE-labeled NOD-POT spleen cells in NOD or NOD-B7-2KO recipients (22 wk of age) after 4 d (inguinal lymph nodes are shown). Histograms are gated on the Thy1.1+CD4+ population. (C) Production of IFN-γ (left) and IL-17 (right) in the culture supernatant of NOD-POT cells activated by the indicated stimulus. (D) Production of IFN-γ and IL-17 after stimulation of spleen cells from the indicated mice with PMA and ionomycin. Dot plots are gated on CD4+ T cells. Numbers indicate percentages of cells in the quadrants. Data are representative of two or more experiments.
Spontaneous development of a fulminant form of neuropathy in NOD-RAGKO-POT mice. (A) Quantification of infiltration in the nerves of indicated mice at 3–4 wk of age. Horizontal bars indicate means. *, P < 0.05. (B) Weight in the indicated mice as a function of age. Results represent cumulated data from two different experiments. Data are means ± SEM. (C) Clasping phenotype in a representative NOD-RAGKO-POT mouse compared with the normal plantar reaction in a NOD-RAGKO littermate, and weight deficit in NOD-RAGKO-POT mice at 3–4 wk of age. (D) Neuropathy in the indicated mice as a function of age. (E) Intense infiltrate in the sciatic nerve of NOD-RAGKO-POT mice. Bars, 250 µm. (F) Adoptive transfer of neuropathy by spleen cells from NOD-RAGKO-POT mice into NOD-SCID recipients (n = 4). Data are representative of two independent transfers. Videos 1–3 are available at http://www.jem.org/cgi/content/full/jem.20082113/DC1.
A bacterium lipopolysaccharide that elicits Guillain-Barré syndrome has a GM1 ganglioside-like structure.
Vincristine-induced peripheral neuropathy is driven by canonical NLRP3 activation and IL-1β release


The Bernard O. Dow Leasing Institute – Texas' preeminent leasing conference – brings together experts in real estate law and finance for a focused day of programming on the latest leasing issues.
All this, plus 1.00 hours of ethics on-demand (provided after the Institute) and multiple networking opportunities make this a must-attend event!
Tenants in today's business environment demand leases that will not restrict their ability to respond to changing circumstances. Structuring leases that afford flexibility for tenants requires knowledge of the current market and possible solutions for given business objectives. This presentation will address lease provisions that appear to be rigid, but in fact, permit creativity for tenants in structuring "yoga" leases.
Review some of the negotiating objectives the parties to a typical ground lease may have, and hear suggestions for achieving those objectives effectively.
Examine common issues encountered in retail lease negotiations and get practical drafting tips and sample provisions for your practice.
Amidst industry consolidation and the pursuit of increased efficiency and competitiveness, the current real estate cycle has everyone looking for their next move. Hear the latest market analysis, and learn what its implications are for practitioners.
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The two volumes contain a broad selection from 200 years of music. Eight Baroque sonatas are included, apart from the famous D minor one by Corelli, some appear in a modern edition for the first time. In addition to cyclical works (Haydn: Sonatina, Mozart: Divertimento, Vivaldi: Concerto) and sets of variations (Beethoven, Tartini), there are many shorter pieces as well, not only the famous minuets by Boccherini, Mozart and Beethoven but also works published for the first time here. Virtuoso pieces are represented by Goltermann's Etude-caprice and Jenkinson's Dance of the sylphids, the lighter kind include Joplin's Ragtime.


Most Christians are puzzled by the Trinity, and therefore, can't explain it very well. Let's change that!
In all transparency, I feel like I did a pretty mediocre job of explaining the Trinity to them in a way they could grasp. (Heavy sigh.) I've been thinking about it a lot, doing some research to see how people smarter than I have explained the Trinity, and come to a better understanding of the Trinity – and how to explain the Trinity in simpler terms.
Today begins Week 2 of the 3-Week Thankfulness Challenge. Have you joined? How has it been? Have you invited anyone to join you? Have you grabbed your FREE Printable Scripture Cards?
NOTE: Last week, I invited you to join me in spending 5 minutes a day, for 3 weeks, being thankful in 5 different categories. If you haven't read that post – or joined the challenge – here's the link to find out all about it. And remember, if you're going to share or tweet about it, make sure to use #ThankfulnessChallenge so I can follow along!
Here are seven more verses that remind of us some of the why, what for, and how of being thankful. Maybe you should take one of these each day and weave it into your 5-Minute Thankfulness Challenge.
I love the Thankfulness Challenge each year. After all, we'd all be better off if we spent more time soaking in and giving thanks for what has always been true, rather than complaining about the temporary circumstances we see around us.
Get your very own printable templates with all 21 Thankfulness Scriptures!
A PDF file with all 21 images as printable POSTCARDS.
A PDF file with all 21 images as printable BUSINESS CARDS.
A PDF file with all 21 images as printable 4″x6″ photos.
Download the FREE Thankfulness Scripture Cards!
QUESTION: What is your favorite 'thankfulness' verse?
Today begins Week 2 of the 3-Week Thankfulness Challenge. Have you joined? How has it been? Have you invited anyone to join you? Have you grabbed your printable Scripture Cards?
I'm Back…with 3 New Adventures!
Adventure #1 – The Complete Communication System™ online training.
I can't overstate how excited I am about this! You might know this already, but I have spent the last dozen years or so working with companies like (Microsoft, Amazon, medical sales, financial planners, etc.) to train them how to communicate more effectively – spoken and written, internally and externally. I love it.
Other than attending a workshop or hiring me for one-on-one coaching, there hasn't been a "middle ground." No way for people to get the training AND have interaction with me for a couple months to make sure the training sticks.
That's all changing. I have a beta group of 14 people from vastly different companies big and small, huge corporations, non-profits, and one lead pastor.
I'll be telling you more about this in about a month. If you want to find out more and make sure you get early access, you'll want to let me know on this page. [Read more…] about I'm Back…with 3 New Adventures!
Will You Do a Bible Study with Me?
You may – or may not – know this, but I spend the first four months of every year doing a Rapid Bible Read Thru. Well, it's May. Which means I just finished. And I want you to join me for what's next.
I first made the invitation using Facebook Live over at my Facebook Page. You can certainly watch it there, or I've trying out my first "Facebook Live embed video" right below this sentence… [Read more…] about Will You Do a Bible Study with Me?


So you "think" you have bed bugs or you "do have" bed bugs. Either way, it is important to know what to do if you have them and especially important to know the serious mistakes that many people make.
Because there is a general lack of public education of bed bugs and some pretty bad suggestions all over the internet, people risk their health, homes, environments, relationships and finances daily. Although this list is not in any particular chronological order, please read through the whole list to make sure your approach with any bed bug situation is with common sense and knowledge!
Lack of awareness: Where Were You 40-50 Years Ago? Decades have passed since we last had bed bugs infiltrating our lives as they are today. The general over-all lack of awareness turns people to the standard pest control that is used for the common everyday pests that we are used to. Be careful NOT to reach for RAID!
People Hide The Fact They Have Bed Bugs From Landlord, Friends, Relatives (Keeping It A Secret).
Don't keep bed bugs a secret – get help! People just don't understand that bed bugs are something every single living human that has blood can fall victim to. I believe that covers about 7 billion people worldwide. There is no reason a person should be ashamed if they get them.
Self-Treatment : Using Bed Bug Bombs (Foggers), Certain Liquids, Contact Killers, Etc. People have driven bed bugs deeper into hiding places because of "bed bug bombs" and in some cases have needlessly started fires in their homes. Also, grabbing for a bottle of bleach or anything under the kitchen sink can cause total failure of treatment of bed bugs. Be extremely careful here!
Improper Removal of Infested Items: Moving infested items without proper wrapping and labeling of them can spread bed bugs to other parts of people's home as well as stairways, hallways and trails to disposal areas. This has caused a multitude of problems for many people. People "drop" bed bugs in otherwise clear of bed bug locations and unsuspecting people pick infested items at the curb.
"Move" To Get Away From Bed Bugs without Complete Elimination. When treatment methods fail or an unreasonable landlord doesn't treat the building properly, people "think" that if they move they will leave the problem of bed bugs behind. Unfortunately, they travel right along with you infesting yet another premise.
Sleeping In another Room In Order To "Get Away From the Bed Bugs": Bed bugs are drawn to warmth and the carbon dioxide we expel as we breathe as we sleep. Bed bugs will "follow" you were ever you go to sleep. This causes the spread of bed bugs into other parts of the home. Stay where you are!
Staying at a Friend's House without Taking Proper Precautions: Again, don't keep bed bugs a secret. Bringing bed bugs with you in your personal items or on your clothing can cause an innocent person to deal with bed bugs in a short period of time.
Coming Home From a Trip – (Bringing Infested Items into Car Or Home): The importance of checking all items you carry with you during a trip takes precedence over all when returning so that you don't introduce a hitchhiker to your home. Properly protect your belongings whenever traveling.
Not Checking Hotel Rooms before Occupancy: One of the biggest mistakes one can do is not check the room before you enter with your belongings. Ask questions and thoroughly check your surroundings!
Moving Into Homes and Apartments without a "Bed Bug Background Check": Bed bugs can cost you plenty. Not just the frustration of bites but treatment of your personal belongings. Ask before you move into a residence about their policies, previous bed bug infestations and treatments. Always be cautious!
Allowing Friends and Family to Visit without an Established Protocol: We all love our friends and families and want them to visit us. When people travel they can easily pick up a hitchhiker here or there. Carefully inspect all visitors' belongings before you place them into your guest room.
Proper Identification of the "Bug"(S) By A Trained Professional: Don't treat for any bug that you are not sure of what it is. People use the wrong products all the time and in most cases make matters worse!
Using Unlabeled Chemical Products a Friend Gave You: NEVER, EVER USE ANY PRODUCT THAT DOES NOT COME WITH A MATERIAL SAFETY DATA SHEET! People and have literally poisoned themselves and their environments using unlabeled products.
Not Doing Follow up Treatments: The affordability of bed bugs treatments can cause undue stress but cannot be overlooked. Depending upon the extent of some infestations and the type of treatment used, it may take several treatments before all bed bugs are gone. Always follow your bed bug professional's advice!
Leaving Post Treatment and Used Vacuum Bags inside the Vacuum and In the House: Often people get caught up in the process and forget to clean out the vacuum and tools used for treatments. Any live bed bug sucked up can crawl out. Always empty the vacuum of the bag, place in another sealed bag and remove to the trash. Move the vacuum to the garage or bag it!
Placing Freshly Laundered Items Back Into Infested Premises: Until all bed bugs are cleared from the premises do not return your clean items back into dressers or closets. And remember do not re-use the bags you originally used to transport the laundry. Don't risk being re-infected!
Allowing "Clutter" To Build Up: Many people just "can't" get rid of their "stuff". Clutter can cause a complete failure of any bed bug program. I use the rule if you haven't used it in a year – get rid of it. Clean it up!
Over Use and Placement of Dusts products: Dusts were designed to be used "sparingly". If you can see the dusts pilled in snow type drifts you are probably using too much.
People Don't Prevent Re-Infestations: Don't adopt the expression of "out of sight – out of mind" after the fact. Now is the time to become pro-active with the possibilities of getting them again. Learn all you can to avoid picking up another hitchhiker.
Purchasing Furniture and Items From Second Hand Stores: Thoroughly check EVERYTHING purchased from any store before bringing them into your home or car! Especially second hand stores.
Picking Up Furniture on The Street Or Out Of The Dumpster: Your neighbor got the "ick factor" because she discovered she had bed bugs and just threw her designer couch to the curb. Be extra cautious when picking anything up from the streets. The likelihood is that beautiful couch has a "secret problem".
Putting Things Outside In the Heat/Cold: The temperatures needed to get rid of bed bugs are extreme in both heat and cold and must be carefully monitored by a professional who knows what they are doing. Don't think your methods have reached the ambit temperature needed.
Treating Mattresses with Pesticides: Again, this is a place where your body can come in contact with pesticides which can be absorbed in your body. Don't take the chance!
I can "do it myself" people: Some people make the decision to self-treat. And it many cases when the bed bugs have just been introduced, it can be done with great success. But, when bed bugs are allowed to establish and reproduce after several months – can be a nightmare! Think it out before you make the decision to self-treat.


Sofina Foods installed a Maxitech gas stunning system at its new turkey plant in late-2017.
Chanelle Taylor had always wanted to be a veterinarian from the time she could talk. She worked for a small animal clinic in Oakville, Ont., when she was 14 to see what that would be like. As a university student, she'd pass many farms on her way to Guelph and dabbled with a few job opportunities to get some farm experience. Somewhere along the way she discovered that she really loved working with birds of all kinds.
One of the greatest pioneering poultry breeders, Donald McQeen Shaver, passed away in late July, a few days before his 98th birthday.
The laying hen industry in Canada is at the beginning of a 20-year transition. Following the lead of worldwide efforts to improve laying hen welfare, in February 2016 the Egg Farmers of Canada (EFC) announced that a move away from conventional egg production to alternative production methods would begin.
Since last September, Cindy Huitema, egg producer from Haldimand County, Ont., has been documenting her family's journey transitioning to a new layer housing system with her blog, Cindy Egg Farmerette. In the final installment of her blog, Cindy discusses the process of placing her initial flock and how everyone on the farm is adapting to the new enriched barn and its added technology.
We know the ink has barely dried on this year's Who's Who edition – our previous issue where we profiled rising poultry stars from across the country. However, we're already planning ahead for next year. And we once again want your input.
Are you or do you know a Canadian poultry operation or industry member that prospers through diversification? Nominate them today to potentially have them recognized in our 2019 Who's Who issue!
Canadian Poultry magazine's Who's Who issue is released every July with the goal of shining a light on stand-out members of the Canadian poultry industry.
The theme for the 2019 Who's Who issue is diversity. We're searching across the country and in different parts of the poultry industry for people who have an interesting and broad mix of focuses.
Dr. Elijah Kiarie's interest in farm animals originated from growing up on a small family farm in Kenya. He described obtaining a bachelor's degree in agriculture, majoring in animal science, as the catalyst for fueling his interest in animal nutrition.
Poultry veterinarian Ben Schlegel's resume reads more like that of someone who is on the brink of retirement, not someone who's barely in his 30s.
Tim Lambert, CEO of the Egg Farmers of Canada (EFC) was recently honoured at the University of Guelph Alumni Awards of Excellence Gala.
Lambert has an honours degree in animal and poultry science and is the longest-serving CEO of EFC. Lambert is a leader, advocate and change-agent in both the Canadian and global agricultural sectors. Well known for his pursuit of excellence in management, evidence-based decision-making, and organizational culture, Tim has spurred tremendous growth in production and sales for egg farmers in Canada.
He was a driving force in establishing the International Egg Foundation (IEF), which helps develop local knowledge in remote locations around the world. The IEF builds expertise and entrepreneurial skills to increase the production and consumption of the high-quality protein found in eggs. Tim oversaw construction of a sustainable operation in Swaziland that now delivers thousands of eggs to orphaned children.
Many successful programs and initiatives have taken shape under Lambert's leadership at EFC— particularly, a unique multidisciplinary network of university research chairs, including one at the University of Guelph, that pairs the latest scientific evidence with innovation, sustainability and growth within the egg industry.
Lambert is an esteemed alumnus whose outstanding accomplishments in the agricultural industry, along with his humanitarian efforts, bring great pride to the University of Guelph.
Have you ever seen the Scottish Highland Games and wondered what these people do for their day job? If you guessed that the burly, bearded guy in a kilt tossing a caber was a turkey geneticist, you would have been cheering on Owen Willems.


Though Sean Payton and his staff didn't need the help, perhaps New Orleans' locker room had Fox's and Loozyanna's Terry Bradshaw piped into it on a video screen. About 10 minutes before kickoff, Bradshaw went on a lecture, sermon, or whatever you want to call it, about how the Saints needed to throw the ball down the field and play aggressive, opportunistic defense. 'Dis was true, and a quick hitting, underneath running game, completed the equation, as did the kind of fun Heath Evans had, after rumbling into the end zone with a swing pass and spiking the ball like an offensive lineman. Dr. Bradshaw!
A miserly loss to the Cards, followed by a blowout of the weak Bucs in Week 6, hardly makes anyone's NFL season. However, the Saints display in Tampa was reassuring in that fans of the team were treated to the same type that went on a double digit winning streak a year ago. There was evidence that this team, for the first complete time in a still early '10, can still do what they do – best. This page has freedom of the press rights, too, so we'll go out on the left wing and just say the Saints had a 9 game pre-season, and the regular one didn't start until Sunday. Or we could really cavort in the air, and say they are providing the plot for a new book, A Tale Of Two Seasons, A Siesta And Another Super Bowl.
Everyone here has been bemoaning the injury losses of Pierre Thomas and Reggie Bush. All the while, Chris Ivory kept his nose to the grindstone, tried not to fumble, and kept running. He had some upside in improving with more real time. The result the other day was a spectacular, ten plus yards a carry average. Ivory has an urgent, physical, nasty mentality to his vertical running style that is just what the doctor ordered for this team right now. The Stones Of The Saints may have been motivated by him, too, as the holes to run through were as wide as a Harley Davidson, plus an attached sidecar. Coach Payton's new, welcome dilemma may be how to keep him involved enough as the others return. Good for him – Ivory is a Saint!
As per other seeds of youth, cornerback Patrick Robinson does resemble a young Mike McKenzie for reasons other than his number 34 and the locks streaming out of the back of his helmet. This kid is not out of position much, has ball skills, and most encouragingly, may be more aggressive than his elder in not being hesitant to put his hat down – on somebody else. Tight end Jimmy Graham made some errors as youngsters are prone to do, but has obvious, wing span receiving range for the position, which Coach Payton likes to have in his scheme of things.
It was surprising that the young underdog Bucs were as flat as they were at home on Sunday. But no matter, the better team won, never allowing the hosts to really even be in the game. The only close contest was which team would miss the most field goals. Only a fourth down converted pass prevented a shutout, and 'dat is no small accomplishment in this league. The Saints got out there and, hopefully not with the same fate as the Titanic, stretched their legs a little.
When then owner Art Modell finally took the Browns and turned them into the Baltimore Ravens in 1996, in a deal laden with gold, Commissioner Paul Tagliabue made league precedent, insisting that the simple but attractive logo stay in town, in the assumption that a new franchise would return (in part to appease the mass deserted). It did, in 1999, and Cleveland's infamous Dog Pound has since been waiting for the Browns to be any good. Tagliabue's efforts were important to that city, like his here in New Orleans, when it loomed that the Saints may have to leave post-Katrina. The more time that has gone by, history may show that "Tags" may have been the last fan friendly commissioner (as much as possible) in the league, as the job has evolved into a corporate homogenization of contract negotiating, lawyering, and public relations. The Browns, the improving Detroit Lions, and the Saints are a troika of Soul Brothers, in that they represent hopes of urban renewal from decay. Pittsburgh, next week's opponent, used to be in that number, until Dr. Bradshaw, et al, started winning all those Super Bowls.
With only one win, this is not the Browns' year, though they have played most teams close (common when good teams fail to get excited about playing bad ones). They may start a rookie at quarterback instead of ex-Saint Jake Delhomme, the accomplished and aptly named former Texas Longhorn, Colt McCoy. Joshua Cribbs has returned kicks all the way to China, but suffered what appeared to be a bad concussion on Sunday, in a loss to the Steelers. The departed Scott Fujita, still well liked and having some of his heart in New Orleans, returns to the Superdome in an attempt to anchor whatever it is they have on defense (can't say he is unfamiliar with what the Saints like to do). Sentimentally, Sean Payton's first team in '06 opened the season with a win over the Browns. Repeat!
Head coach Eric Mangini has not won over the fans in Cleveland, as his record has been poor since his arrival, nor did he win over many players when he first got there with lots of new conduct rules that were criticized as small time. His image is one of these His Way Or The Highway types. Fortunately, his bad nickname from when he was with the Jets, Mangenius, has mostly worn off, except in critical irony. He needs to show his team is on the upswing in the near future, or he will likely know the directions to and be given a map to the interstate. General Manager Mike Holmgren came over this year after a brief retirement from coaching, and his ego has been quoted to effectively take up most of the square footage in a given room, thus his own nickname, The Big Show. Together, one wonders if they have knocked some heads other than their players', and if the NFL Network is considering Mangenius and The Big Show for a reprise of The Odd Couple.
But Bucs, Browns, whomever, it really is mostly about how the Saints handle themselves more than their opponents at this point. Yet the Black & Gold does look familiar again. Game On (er, Season).


text:
Q: How to keep track of a score -- C++ Console I am making a poker game in C++ for a my intro to C++ class (should tell you that I am only a beginner so please excuse any bad programmer practice here). I am currently working on the betting system, in which I am quite pleased it does what I need it to do. Except that it doesn't carry on - the game just resets after the hand. Here's my code, I was thinking I need to make separate classes and then call those classes in the main, but I'm just not sure how that would be any different, if that's the case then I'll delete this question.
{// ConsoleApplication71.cpp : Defines the entry point for the console application.
//

#include "stdafx.h"
#include <iostream>
#include <string>
#include <vector>
#include "Bet.h"
using namespace std;

//Bet P = int betP(int money);

int main()
{
bool win;
bool lose;
int Omoney = 100;
int money = 0;
int Tmoney = 0;
int bet = 0;
int earn = (bet * 2) + Omoney;

int loseM = 0;
loseM = loseM + bet;

cout << "Your start money = " << Omoney << " \n\n\n" << endl;
cout << "Place your bet here!" << endl;
cin >> bet;

money = Omoney - bet;
cout << "Your total money after bet is " << money << "\n\n";

//betP(int money)
//{
//  money - bet = money;
//}
if (bet > 10)
{
    win = true;
    if (win = true)
    {
        cout << "YOU WIN! \n\n" << endl;
        /*earn = (earn) + Omoney;*/
        cout << "You earned: \n" << earn;
        Tmoney = earn + (Omoney - bet);
        cout << "\nTotal money: \n" << Tmoney;
    }
}
else if (bet <= 10)
{
    lose = true;
    if (lose = true)
    {
        cout << "You Lose!\n\n\n" << endl;
        int Mlose= loseM + bet;
        cout << "You lost: \n" << Mlose;
        Tmoney = loseM + (Omoney - bet);
        cout << "\nTotal money: \n" << Tmoney;
        cout << "\n\n\n\n";
        Omoney = Tmoney;
        main();
    }
}

cin.get();
cin.get();
return 0;
}

A: Use a for loop instead of calling main() again. When you call main(), the local variables are re-initialized.
Alternatively, make the variables global scope (declare them outside of main()).

A: Read from user "start money" before the loop, and then inside the loop read the bet and do something with the bet. I guess the loop should repeat reading the bets until the user runs out of money.

redpajama_set_name: RedPajamaStackExchange


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Graphene Finds its Tune
By National University of Singapore | August 8, 2018
National University of Singapore researchers have discovered a simple and effective method to produce a large area pseudo-magnetic field (PMF) on graphene, and demonstrated how it can be tuned with desired spatial distribution and intensity for data storage and logic applications ("Tailoring sample-wide pseudo-magnetic fields on a graphene-black phosphorus heterostructure").
The field of electronics focuses on how to control and exploit the properties of electrons. To study or modify the properties of these electrons at the quantum regime, a magnetic field has to be applied.
Another way of achieving this effect is to mechanically create a special type of strain in graphene, where the electrons behave as if they are under the influence of an externally applied magnetic field. In this case, no magnetic field is physically applied and this is explained by the presence of strain-induced PMF.
Electrons have additional degrees of freedom (independent parameter describing the electronic state) other than its charge. These are known as the spins and valley degree of freedom. Strain-induced PMFs in graphene have been explored as a promising approach to pull apart the valleys in graphene and make their energies non-equivalent, producing intriguing physics such as valley-polarized current. Many researchers have been attracted by the enormous PMFs (up to 300 teslas) observed in non-planar, strained graphene nanostructures such as graphene nanobubbles.
However, these are distributed randomly and they are not feasible for practical implementation. Although theory predicts that strains with triangular symmetry are able to create PMF in materials, there is currently no known experimental technique which can create the specific strain texture to generate a uniform PMF with the desired spatial distribution and intensity.
(Left) The lattice mismatch between the monolayer graphene (black) on multilayer black phosphorous (blue) generates PMF on the graphene layer. (Right) The spatial distribution and intensity of the PMF can be tailored by changing the rotation angle between the graphene and black phosphorous. Image: NUS
A team led by Professor Loh Kian Ping from the Department of Chemistry and Centre for Advanced 2D Materials has discovered a way to generate PMFs on graphene by overlaying graphene on black phosphorous (BP) to form a graphene-on-BP heterostructure. The research team also includes surface chemist Professor Lu Jiong and theoretician Professor Adam Shaffique from NUS. The large lattice mismatch and shear strain imposed by the lattices on each other give rise to PMFs on graphene, which can be measured directly using scanning tunneling microscopy.
In addition, they discovered a way to tailor the intensity and spatial distribution of the PMFs on graphene by changing the rotation angle between the crystallographic directions of the graphene and the BP. When an external magnetic field is applied in the presence of the PMF, they are able to create two types of non-equivalent currents, known as the valley-polarized current in electrical transport measurements.
Loh says, "Controlling PMFs at the nanoscale allows the following extreme physics to be tested: first, the PMF fields can serve as energy barriers to efficiently confine currents into a one-dimensional channel. In addition, valley filters can be developed based on valley polarization. Importantly, we discovered that a complex strain texture formed by placing a hexagonal crystal (graphene) on an orthorhombic crystal (BP) is suitable for generating a large area PMF.
"The implication is that there might be other combinations of two-dimensional crystals which have not been discovered yet. Our study thus opens up new opportunities for strain engineering with a view towards tailoring the spatial distribution and intensity of the PMFs."
Mathematically Designed Graphene Possesses Superior Electrocatalytic Activity
Plumbene, Cousin of Graphene, Created by Researchers
Researchers Develop Wearable Sensor Inspired by Octopus Suckers
New Applications of 2D Materials Enabled by Strain
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Den udiskuterbare favoritten. Lengre intervju med bra damer, ein layout som får magen til einkvar grafisk designar til å kile, og sterke foto trykka på fleire papirkvalitetar. Kjem ut to gonger i året men kan takast fram igjen og igjen heilt til neste utgåve.
Rein inspirasjon. Tjukke herlege sider fylt med foto og kortare tekstar. Kvart nummer har eit tema, som «weekend» eller «imperfect» så her kan ein plukke ut dei tema som er mest intressant for ein sjølv.
Eit Islandsk minimagasin som kjem ut to gonger i året. Handlar om kreative menneske og initiativ på Island, og her er det mykje intressant sjølv for dei som ikkje bur her.
Eg kjøper alltid septemberutgåva av Vogue. Det er like stort, om ikkje større, enn ei bok (i år på heile 800 sider) og kostar det same som ei vanleg utgåve. Bra med valuta for pengane altså, dessutan er haustkolleksjonane mine favorittar.
Interiør, design, og annan bra inspo. Trykka på tjukt grovt papir.
Italiensk interiørmagasin. Med mindre du kan italiensk kjøper ein ikkje dette magasinet for artikkel-delen, men for bilder og layout. Det meste av magasinet er kun atmosfæriske bilder, absolutt det perfekte søndagsmagasin.
Alltid kjekt med nye tips og ideer, var et par der jeg aldri har hørt om, så skal sjekke de ut!
Jeg er også glad i Kinfolk, enig i at det er skikkelig inspirerende. De finner frem til så mange spennende mennesker!
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