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Ginkgo Bioworks Strengthens End-to-End R&D Capabilities in Gene … – PR Newswire

Platform includes large library of existing capsids, which have been optimized for performance and targeting across a range of application areas through validation in large animal models

The addition of StrideBio's structure-guided AAV engineering capabilities combined with Ginkgo's already extensive assets make Ginkgo a unique one-stop shop capable of providing R&D services for gene therapy manufacturing across capsid, payload, and cell line optimization

As part of the transaction, Ginkgo also receives IP and data for StrideBio's lead preclinical asset for Arrhythmogenic Right Ventricular Cardiomyopathy, a rare genetic heart disease, which Ginkgo plans to sell or outlicense to a commercial partner

BOSTON, April 5, 2023 /PRNewswire/ --Ginkgo Bioworks (NYSE: DNA), which is building the leading platform for cell programming and biosecurity, today announced the acquisition of StrideBio's adeno-associated virus (AAV) capsid discovery and engineering platform assets with a secondary close scheduled upon the transfer of certain additional in-license agreements to Ginkgo. Ginkgo will incorporate these capabilities and IP into its end-to-end AAV gene therapy development platform, allowing Ginkgo's customers to leverage new tools to effectively target many different tissue types, and potentially to improve the safety profile of their future gene therapies. Ginkgo is also receiving StrideBio's existing library of capsids, which includes advanced candidates extensively tested in large animal models, and which are now available for licensing and broader partnership. Additionally, Ginkgo receives the IP and data for StrideBio's lead preclinical asset for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), a rare genetic heart disease, which Ginkgo plans to sell or outlicense to a commercial partner. The acquisition is focused on the enabling platform IP of StrideBio and does not include any real estate. One employee of StrideBio will transfer to Ginkgo as part of the transaction, joining Ginkgo's mammalian engineering team.

AAV remains the preferred viral vector for gene therapy, used in hundreds of active clinical trials. However, pharmaceutical developers focusing on AAV still face challenges pertaining to limitations in targeted biodistribution, pre-existing immunogenicity and manufacturability. StrideBio's STRIVE platform which uses a structural-engineering approach for generating novel AAV capsids to address these limitations has produced a library of candidates that includes mature assets with strong evidence demonstrated for both performance and targeting across multiple animal models.

StrideBio's platform generates capsids that are designed to overcome current limitations of first-generation gene therapies, including reduced seroprevalence, improved tropism for cell types beyond the liver such as those in the central nervous system and muscle tissue, and increased gene transfer efficiency, with the potential for improved safety and reduced doses in the clinic.

"The StrideBio team has built a deep pipeline of AAV capsids and libraries to address critical challenges facing clinical gene therapy with a focus on reducing vector dose and improving safety by limiting off-target biodistribution," said Aravind Asokan, Ph.D, who co-founded StrideBio with Pat Ritschel and the late Mavis Agbandje-McKenna. "With Ginkgo's expertise and scale, we hope to amplify this effort and deploy this platform to the gene therapy industry and ultimately, patients."

"Combining Ginkgo's engineering and discovery capabilities in enzymes, regulatory elements, and capsids enables a holistic approach to designing an AAV gene therapy, so that we can support our partners across the entire process of designing the viral vector," said Narendra Maheshri, Head of Mammalian Engineering at Ginkgo. "We are thrilled to integrate the STRIVE platform and know-how into our foundry to augment our capabilities in capsid engineering, and we look forward to continuing to expand our existing end-to-end capabilities in AAV discovery and manufacturing."

Ginkgo has significantly expanded its work and capabilities in gene therapy in recent years by acquiring Circularis' proprietary circular RNA and promoter screening platform, partnering with Biogen to improve AAV manufacturing, and partnering with Selecta Biosciences to develop AAV capsids with altered tropism and immunogenicity. Ginkgo has developed several capabilities which enhance its ability to leverage assets like those in this acquisition, including its ability to efficiently and quickly generate a massive set of candidates for testing, its scaled approach to protein engineering, and its ability to apply sequencing and computational pipelines to accelerate the analysis of capsid effectiveness in tissues of interest. To discuss how you can benefit from Ginkgo's biopharma and life science R&D capabilities, sign up for Ginkgo Office Hours to speak with our team today.

Foley Hoag LLP is providing legal counsel to Ginkgo, while Ropes & Gray LLP is serving as legal advisor to StrideBio.

About Ginkgo Bioworks

Ginkgo Bioworks is the leading horizontal platform for cell programming, providing flexible, end-to-end services that solve challenges for organizations across diverse markets, from food and agriculture to pharmaceuticals to industrial and specialty chemicals. Ginkgo's biosecurity and public health unit, Concentric by Ginkgo, is building global infrastructure for biosecurity to empower governments, communities, and public health leaders to prevent, detect and respond to a wide variety of biological threats. For more information, visit ginkgobioworks.com and concentricbyginkgo.com, read our blog, or follow us on social media channels such as Twitter (@Ginkgo and @ConcentricByGBW), Instagram (@GinkgoBioworks and @ConcentricByGinkgo), or LinkedIn.

Forward-Looking Statements of Ginkgo Bioworks

This press release contains certain forward-looking statements within the meaning of the federal securities laws, including statements regarding the capabilities and potential success of the acquisition and Ginkgo's cell programming platform. These forward-looking statements generally are identified by the words "believe," "can," "project," "potential," "expect," "anticipate," "estimate," "intend," "strategy," "future," "opportunity," "plan," "may," "should," "will," "would," "will be," "will continue," "will likely result," and similar expressions. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. Many factors could cause actual future events to differ materially from the forward-looking statements in this press release, including but not limited to: (i) volatility in the price of Ginkgo's securities due to a variety of factors, including changes in the competitive and highly regulated industries in which Ginkgo operates and plans to operate, variations in performance across competitors, and changes in laws and regulations affecting Ginkgo's business, (ii) the ability to implement business plans, forecasts, and other expectations, and to identify and realize additional business opportunities, (iii) the risk of downturns in demand for products using synthetic biology, (iv) the unpredictability of the duration of the COVID-19 pandemic and the demand for COVID-19 testing and the commercial viability of our COVID-19 testing business, (v) changes to the biosecurity industry, including due to advancements in technology, emerging competition and evolution in industry demands, standards and regulations, (vi) our ability to realize the expected benefits of merger and acquisition transactions, (vii) the outcome of any legal proceedings against Ginkgo, including as a result of recent acquisitions, (viii) our ability to realize the expected benefits from and the success of our Foundry platform programs, (ix) our ability to successfully develop engineered cells, bioprocesses, data packages or other deliverables, and (x) the product development or commercialization success of our customers. The foregoing list of factors is not exhaustive. You should carefully consider the foregoing factors and the other risks and uncertainties described in the "Risk Factors" section of Ginkgo's annual report on Form 10-K filed with the U.S. Securities and Exchange Commission (the "SEC") on March 13, 2023 and other documents filed by Ginkgo from time to time with the SEC. These filings identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements. Forward-looking statements speak only as of the date they are made. Readers are cautioned not to put undue reliance on forward-looking statements, and Ginkgo assumes no obligation and does not intend to update or revise these forward-looking statements, whether as a result of new information, future events, or otherwise. Ginkgo does not give any assurance that it will achieve its expectations.

GINKGO BIOWORKS INVESTOR CONTACT:[emailprotected]

GINKGO BIOWORKS MEDIA CONTACT:[emailprotected]

SOURCE Ginkgo Bioworks

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W&L Engineering Professor Publishes Articles in Two Renowned … – The Columns

By Emily InnesApril 4, 2023

Jon Erickson, professor of engineering at Washington and Lee University, recently published two papers regarding advances in non-invasive gastrointestinal electrical mapping techniques.

The first paper, Validation of noninvasive body-surface gastric mapping for detecting gastric slow-wave spatiotemporal features by simultaneous serosal mapping in porcine, was featured on the cover of the October 2022 issue of The American Journal of Physiology. The second paper, co-authored with Emily Hassid 22 and Elen Stepanyan 22, is titled Comparison of dry and wet electrodes for detecting gastrointestinal activity patterns from body surface electrical recordings and was published in the Annals of Biomedical Engineering in January 2023.

Erickson is an expert in the field of signal processing with applications to gastrointestinal motility. Validation of noninvasive body-surface gastric mapping was written in collaboration with the Auckland Bioengineering Institute at the University of Auckland, New Zealand. Comparison of dry and wet electrodes stems from research conducted at W&L.

I feel very fortunate to have worked with such an exceptional group of surgeons, doctors, and biomedical engineers as well as outstanding undergraduate research students during this process, Erickson said. With a multidisciplinary team, everyone brings their own angles and backgrounds that are crucial to make projects like this work.

The purpose of Ericksons research is to develop non-invasive biomedical tools to monitor motility of the stomach and colon, which may facilitate the diagnosis and phenotyping of gastrointestinal abnormalities. When Erickson began collaborating with the Auckland Bioengineering Institute in 2009, very little was known about the electrical conduction system of the stomach. Over the course of a decade, the research team developed the instruments, technology, and algorithms to successfully detect the electrical waves that move through the stomach, first using surgically implanted electrodes and then with non-invasive electrode arrays placed on the skin surface like a big band-aid. Ericksons primary role in the project was developing the signal processing techniques to pluck out the microvolt-level signals generated internally by the stomachs electrical waves.

The next phase of research, explored in Comparison of dry and wet electrodes, addressed the time limits on studies because of peoples potential sensitivity to the wet electrodes. The study found that dry electrodes are just as effective at recording gastrointestinal electrical signals, which opens the possibility of being able to study gastrointestinal activity over multiple days, instead of just in three- to four-hour increments. W&L students made valuable contributions to designing and conducting the study with human subjects, as well as providing unique insights during the analysis phase.

Its exciting to work on something thats brand new, and the student insights are so important, Erickson said. It has been a delight to work with students who are deeply engaged with the research and helping pioneer this field. Their roles have been crucial to our recent contributions and collective success, and it is very rewarding to see their skill and confidence rapidly grow in the lab.

I was delighted to have so many students interested and deeply engaged with the research. Their roles have been crucial to making this work, and I hope theyve had a good experience with it, too.

Ericksons collaboration with students is representative of the hands-on and personalized education W&L provides. In addition to conducting real-world research, they also participated in the academic journal review and publication process. Both Hassid and Stepanyan have carried their research experience to postgraduate opportunities, with Hassid pursuing a masters degree in chemical engineering at Columbia University and Stepanyan pursuing a masters degree in engineering and management at Dartmouth University.

For Erickson, the next step in this ongoing research project is to begin conducting overnight studies of the gastrointestinal system using dry electrodes and continue advancing the diagnostic capabilities of the technology.

In the near future, we plan to apply this technology to compare and contrast motility patterns in healthy people versus those with a known gastrointestinal abnormality. This is a magical moment in the research field because we finally have the research tools in hand to attempt this study for the first time, Erickson said.

Erickson joined the W&L faculty in 2009 and currently serves as the faculty advisor for the Engineering Community Development club on campus. He received his bachelors degree in physics from Harvey Mudd College and his doctorate in bioengineering from the California Institute of Technology.

If you know a W&L faculty member who has done great, accolade-worthy things, tell us about them! Nominate them for an accolade.

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The tale of the ‘ubiquitous’ Stanford Bunny | Stanford University … – Stanford University

In the early 1990s, Stanford professor Marc Levoy and his postdoc, Greg Turk, created the worlds first seamless 3D computer model of a complex object using a range-finding laser scanner. Their object of choice, a terra cotta garden decoration, is now known worldwide as The Stanford Bunny. Computer graphics researchers still use it today. Approaching Easter, we talked to Levoy about what has kept his bunny going even three decades later.

I was a new professor at Stanford. Three-dimensional scanning seemed like an interesting problem, trying to get the shape of an object accurately recorded in a computer. There were scanners at the time that could do some modest range scanning like the front of your face or one that could go completely around you and build a crude model of the surface of an object, but not a complete one, with a top and a bottom and interstices and all that. My postdoc at the time, Greg Turk, and some grad students started to work on this. Its hard to scan an object all at once, so you do it in parts, little meshes, like pieces of fabric, from all around the object. Greg created an algorithm called Zipper that could take a bunch of these meshes and stitch them together to create a seamless, three-dimensional model. We needed a test object. It was around Eastertime, and Greg was out shopping and saw this bunny on a store shelf a terra cotta garden sculpture. It was about the right size. So we scanned it. It was the first model of its kind. It became a popular computer graphics model for people to render on to add fur, or melt, or break, or whatever you can imagine doing to a 3D object.

It was the first detailed polygon mesh model of a very complicated object with lots of little nooks, crannies, and crevices. There had been models of complicated stuff before, but it was all built by hand airplanes and things like that. The idea of just taking an object, sticking it on a platter, and being able to scan it more-or-less automatically and produce a model was new. We put the data online and we made it freely available. It just became ubiquitous; one of the standard models for computer graphics researchers to practice on. If you page through the proceedings of any computer graphics conference today, maybe a third of the papers use the Stanford Bunny. Just Google Stanford Bunny. Youll see.

The bunny replaced what was the iconic computer graphics model, the Utah Teapot. The Computer History Museum approached me a while ago wanting to put the bunny in their museum. So theres a spot for it next to the Utah Teapot, but not yet. The original is still in my office at Stanford. One of the reasons the bunny is popular is because theres no IP associated with it. It was just a simple garden decoration, and anybody could just do anything with it. Its also kind of innocuous, not a religious icon that people could desecrate. And its just the right size to do a lot of experiments on. It just became really popular. Its fun to see the stuff people have done with it. Adding fur. The breakages. The textures.

A lot of people think its LIDAR, the technology used in autonomous vehicles, that measures distance using time of flight how quickly a laser light bounces back to a sensor after striking an object. The technology we used was different. The laser and the sensor are separate, allowing you to triangulate distance like a range finder. The problem was, at the time you could only do one side of an object or a specific area, not an entire object. What we brought to the table were the algorithms for combining multiple scans to make a seamless object. We scanned the bunny all over the place and created mathematical triangles between the measurements. Gregs algorithm was able to match up the edges of these meshes and stitch them together or zip them, as he called it, hence the name Zipper. Those triangles represent the surface of the object and animators can use the data to render pictures. There are exactly 69,451 triangles making up the Stanford Bunny.

Yes, there were several projects after that and some very sophisticated models of very complicated objects. The best known is probably the Digital Michelangelo project where we traveled to Florence to scan Michelangelos David in situ. Our model of the David has a billion polygons which is a lot. That required many, many sweeps, but used a more complicated laser scanner. Our approach not the bunny per se was used quite a bit in the entertainment industry. We made models for Industrial Light & Magic in the making of Star Wars: Episode I The Phantom Menace. We scanned their models in our lab. That was kind of a dramatic day at Stanford where they came in this van with these sealed boxes. They didnt want anyone getting a sneak peek. We had to disconnect our computers in the graphics lab from the internet. We had curtains across all the doorways. They put burly guards at the entrances. And, for a whole day, we scanned their models of various objects and creatures for The Phantom Menace. Then, we gave them a copy of the disk and they watched while we wrote zeros over our data, and that was that.

Related:Marc Levoy, VMware Founders Professor of Computer Science, Emeritus

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Patients’ perspectives on, experience with and concerns about … – BMC Gastroenterology

Health and disease belong to the category of biomedicine but also involve social, political and economic dimensions [22]. Our research summarized posts in the Crohns disease bar over the previous 12years and conducted a comprehensive analysis through two methods: grounded theory and the LAD topic model. In contrast to previous interview studies with small sample sizes, this study analyzed Chinese patients with Crohn's disease from the perspective of social media. An enormous and comprehensive dataset identified the prominent concerns of patients with Crohn's disease. This study provides novel insight into patients experiences with Crohn's disease and identifies actionable needs that may improve their quality of life.

The need for shared decision making in IBD has become a consensus among IBD physicians worldwide [23]. However, there is a large gap between doctors and patients in their knowledge and information about diseases. Apart from online consultation, Crohn's disease patients seem to have few ways to acquire such knowledge. Our study confirmed that 56.9% of Crohn's disease patients urgently want more information about the disease, including diagnosis, symptoms, pathology, complications, surgery, new therapies and professional treatment support. This need is more urgent for patients who have symptoms but have not been diagnosed or have difficulty in diagnosis. Consulting patients who have been diagnosed is the most common method. For instance, some people described their symptoms and indicated that they have undergone some physical examination (but had not received feedback). They were very afraid, especially after they searched for information about Crohn's disease on the internet. Some low-quality answers often have this effect. Patients' consultation of social media negatively influenced the diagnostic and therapeutic decisions. For example, some posts mentioned that the anesthetics used in painless enteroscopies would damage the memories. This misunderstanding has always existed in China and has negatively affected many people, causing them to suffer needlessly by refusing to undergo anesthesia during an enteroscopy. In addition, some posts mentioned consulting experts and hospitals with experience in treating Crohn's disease. Some patients find their disease progressing because of misdiagnosis, untimely treatment and nonstandard treatment.

Encouragingly, many Crohn's disease patients in China had shared their experiences through video platforms, such as the Chinese Tik Tok and Bilibili video platforms; some self-media medical accounts also disseminated Crohn's disease knowledge through popular science articles and videos. In recent years, the Chinese Crohn's and Colitis Foundation (CCCF) [24], a large nongovernmental public welfare organization that is committed to improvingthe quality of life of IBD patients in China by providing social resources, has made great contributions through patient education, public awareness, helping to train IBD specialists, etc. In addition, an increasing number of hospitals are actively training IBD specialists and establishing multidisciplinary teams (MDTs) [25].

Pharmacotherapy is the first step in treating IBD [26]. The main medicine for the management of Crohn's disease works by suppressing an overly active intestinal immune system [26]. Several monoclonal antibodies have been approved for the treatment of Crohn's disease, such as anti-TNF agents [27] and anti-integrin agents. In addition, the use of these biologics in combination with a conventional immunosuppressant may yield superior outcomes and improve the durability of therapy [28, 29]. In our analyses, we also found that more than 1/4 of the posts discussed the drug treatment of Crohn's disease, and seven subthemes were mentioned repeatedly. Biological agents, traditional therapeutic drugs, hormones and TCM were the drugs of most concern to patients. Other patients' medication experience (efficacy and recommendations) and side effects also affected their medication decisions. Medical insurance policies and their own financial situation restricted them from choosing better drugs.

Interestingly, Chinese patients with Crohn's disease were willing to use TCM for treatment, especially when biological agents failed. Cai et al. used semistructured interviews with 14 IBD patients using TCM and explored their reasons and experience of decision-making [30]. The results showed that patients initiated TCM treatment due to the unsatisfactory effects of other therapies. TCM has been widely used to treat IBD in China; however, systematically determining its efficacy in IBD treatment is still challenging [31].

The benefits and risks of treatment are the primary consideration of doctors, which also places huge decision-making pressure on patients. A previous network survey on Crohn's disease patients found that the acceptable risk of drug treatment for Crohn's disease patients depends on the severity of the disease and the expected benefits. Especially for patients with mild to moderate cases, the acceptance of risk is low [23]. Another study showed that when Crohn's disease patients decide to use biological agents, they will comprehensively consider the safety and efficacy of those agents. Among them, safety accounted for 54% of the attention and the efficacy only 28% [32]. Our results are consistent with these findings. Many patients posted questions about the side effects of drugs and expressed their concerns. The experience of other patients often affected their decisions about medicine.

In our study, financial burden was another important influencing factor of drug use decisions, which was closely related to medical insurance policies. A retrospective study of the medical expenses of Crohn's disease patients based on a medical insurance database in the United States showed that the average lifetime medical cost of Crohn's disease patients was $416,352 higher than that of non-IBD patients, and the younger the diagnosis age was, the higher the lifelong medical expenses [33]. One two-center study on the treatment costs of Chinese Crohn's disease patients found that by 2011, the average hospitalization expenses of Crohn's disease patients had risen to CNY25504.21, an increase of 237% over 10years ago [34]. The medical insurance policies of different provinces in China differ, and different reimbursement policies are formulated according to the severity of Crohn's disease, which also leads to different drug choices for patients.

Depression and anxiety are common in patients with IBD and are increasingly being recognized by gastroenterologists [35]. The psychological burden in IBD patients is threefold higher than that in the general population [36]. It is well documented that depression and anxiety may affect more than 25 to 30 percent of individuals with IBD [37, 38]. As expected, the results of the mixed methods in our study indicated that psychological burden is an unavoidable theme for patients with Crohn's disease. These psychological burdens come mainly from personal, family and social pressures. Some posts stated that the disease had caused many impacts on their families and made them vulnerable. These patients lived with low self-esteem, depression and anxiety. Patients with stoma mentioned suicide and death in some posts. A cohort study showed that intestinal surgery and stoma formation are positively associated with subsequent antidepressant medication use [39]. Some people could not support their parents and felt that they were a burden on their family, which caused them to bear a heavy mental burden. In addition, some patients had given up their original work, lifestyle and social contacts, and some had experienced great changes in their lives, such as breakups and divorce. IBD affects women differently than men. Trutas review summarized the impact of IBD, Crohn's disease and ulcerative colitis on women's health, and found that women with Crohn's disease report worse psychological wellbeing less resilience than men but develop more escape and avoidance strategies to cope with the disease [40]. Our results also support the conclusion. We also found that most women with Crohn's disease were concerned about pregnancy. This is usually an important factor affecting marital happiness and family harmony, as traditional Chinese families need children to carry on the family lineage. IBD frequently affects women of childbearing age and may have implications for pregnancy [41]. Therefore, preconception counseling is pertinent to provide patient education, medication review for risk of teratogenicity and objective disease assessment.

Fortunately, we also found that peer support can play a role in encouragement. Psychological support is not incorporated into the routine care of persons with IBD. Some patients shared their successful treatment experiences, which relieved stress and gave confidence to other patients. Peer support provides a unique perspective of shared experience that can instill hope and assist coping efforts of patients and family [42]. A systematic review found that psychotherapeutic interventions can improve quality of life in patients with IBD and that early intervention after diagnosis leads to better coping strategies and quality of life throughout life [43]. Cumulatively, based on these results, we confirm that psychotherapy is necessary for IBD patients with mental stress.

Diet and nutrition are increasingly becoming matters of interest for Crohn's disease treatment, although they formerly played a marginal role [44]. Decreased dietary intake, nutrient malabsorption and weight loss are some of the nutritional challenges that Crohn's disease patients face [45]. Paradoxically, dietary intake may also trigger the symptoms of Crohn's disease patients [46]. Indeed, a Western-style diet rich in saturated fat and low in fiber has been implicated in the onset of the disease. This leads patients to seek dietary solutions for disease management [47]. However, current dietary recommendations are based largely on low-quality studies. At present, no clear indications of a specific diet are available. However, personalized nutrition is considered a potential way to treat patients with Crohn's disease [44]. One study explored the experience of dietary practices of Chinese patients with IBD and believed that health care professionals should encourage patients to report diet modification and be aware of both personal and environmental barriers to diet modification. [48]. Our study showed that patients with Crohn's disease are confused about their diet. Some posts shared menus and diet experiences with other patients. Vegetables, meat, fruits and beverages were mentioned repeatedly in posts. Malnutrition is detected in approximately 6575% of patients with Crohn's disease [49]. Enteral nutrition (EN) and parenteral nutrition (PN) are recommended by the guidelines of the European Society of Clinical Nutrition and Metabolism (ESPEN) for malnourished patients [50]. Due to the high cost and side effects of PN, EN is often the first choice for Crohn's disease patients [51], and nasogastric feeding is the main EN method. One study explored the initial factors and experiences of nasogastric feeding by Crohn's disease patients from China, and the results suggested that many patients rejected nasogastric feeding due to fear, image and activity restrictions [52]. Nasogastric feeding is also an important term in our results. As mentioned above, the appearance problem caused by nasal feeding is one of the social pressures of Crohn's disease patients. Given womens more fragile profile, they tend to be more affected by the effects of the disease than men, so it is necessary to carry out personalized nursing for female patients and improve their quality of life [40].

Weight is one of the nutritional concerns of Crohn's disease patients, who can simply judge their nutritional status by weight changes. However, 15 to 40% of patients with IBD are obese, which may lead to the development of IBD and make colorectal surgery technically challenging [53]. Recently, an integrative review suggested that physical activity can improve quality of life, mental health, sleep quality, fatigue and body weight [54]. In our study, exercise was one of the topics of concern for people with Crohn's disease. Many Crohn's disease patients do not know what and how much exercise will be beneficial. This suggests that the treatment of Crohn's disease requires the participation of nutritionists and exercise scientists to provide a more reasonable plan.

Our results reveal the poor quality of life of patients with Crohn's disease who suffer from intestinal symptoms, systemic symptoms, emotional function, etc. The Inflammatory Bowel Disease Questionnaire (IBDQ) is a valuable disease-specific quality of life questionnaire, that aids in identifying clinical disorientation in patients [55]. The IBDQ has been translated into many languages since its inception [56, 57], and has been used in many ways given its good reliability and validity. It has greatly contributed to evaluating the quality of life of patients and promoting the improvement of IBD diagnosis and treatment strategies. The mainland Chinese IBDQ has proven to be a valid, discriminative, and reliable instrument for assessing health-related quality of life in patients with ulcerative colitis and Crohn's disease in mainland China [57].

COVID-19 has caused a global health crisis, precisely in the country that is the cradle of the COVID-19 infection. In this study, four topics emerged on social media as the ones most discussed by Crohn's disease patients. In the face of this pandemic, patients with Crohn's disease are eager to receive advice on prevention and protection measures. Some researchers have recently provided patients with suggestions on IBD management [58], but at the beginning of the pandemic, there were no suggestion to provide. In addition, patients with Crohn's disease expressed concern about the shortage of medical resources. A study from the Netherlands showed that patients with IBD showed an overall low health-related quality of life during the COVID-19 pandemic, especially the older patients, women and patients who underwent surgical procedures [59]. Many hospitals temporarily closed the biological reagent injection room for the sake of epidemic safety, which led to many patients not being treated on time. Some radical and unprecedented health policies, such as shielding, disrupted patientstreatment and lives. Mass vaccination programs provide the best opportunity for controlling transmission and protecting populations [60], but this is a difficult decision for IBD patients as no confirmed data are presently available regarding COVID-19 vaccines in this population due to their exclusion from the conducted clinical trials [61]. The good news is that some recent studies have provided some clinical evidence [62,63,64]. Drug use after COVID-19 infection has also become a psychological burden for Crohn's disease patients. A clinical study of 1439 IBD patients from 47 countries showed that combination therapy (TNF antagonist and thiopurine) and thiopurine drugs may increase the risk of severe COVID-19. No significant differences were observed when comparing classes of biological agents [65], although post-acute COVID-19 is characterized by gut viral antigen persistence in IBD [66]. More clinical and basic studies are needed to confirm the problem of drug use after COVID-19 infection.

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National structural engineering firm breaks into U.S. – Construction Canada

Stephan Kordt, founder of Kordt Engineering Group, is now serving as the president of U.S. operations with RJC Engineers. Photo courtesy RJC Engineers.

Operating from 14 locations in Canada and specializing in structural engineering, the design consultant, RJC Engineers (RJC), has acquired the U.S. firm, Kordt Engineering Group (KEG) from the latters Las Vegas and Reno, Nevada, offices.

The move will help RJC gain a foothold all over North America and endow its experience, capabilities, and depth of services to help KEG better cater to their clients. Both firms will continue offering services in structural, facade, structural glass engineering, and more.

KEG has clients in structural engineering all over North America and Europe, in various domains, from commercial buildings sector to landmark structures. The firm is well-known for its exceptional client service and both firms cultures match in relation to prioritising their employees and customers.

Stephan Kordt, KEGs founder, has been appointed as the president of U.S. operations at RJC. As a reputable engineer and reliable leader, Kordt has earned recognition for completing high-quality projects under strict time constraints. His extensive technical expertise, industry connections, and skill in devising sophisticated and fitting structural solutions have made him a highly sought-after professional in the U.S. Kordts notable undertakings comprise The Watermark, Project 63, Crystals at CityCenter, Golden Gate Hotel & Casino expansion, Venetian Casino Resort, Venezia Hotel Tower, and the World Market Center.

RJC is excited to further establish ourselves in the U.S. through acquiring KEG. Our firms and people have worked together for over a decade and share a history of successfully delivering projects throughout the U.S., says Mike Moffatt, executive principal of RJC. Our strategic expansion into the U.S. allows RJC to bring its expertise in many building sectors and service offerings to a broader client base.

We are thrilled to join forces with RJC and look forward to working with an even wider group of clients across the U.S., says Kordt. We will continue to deliver the high-quality client service and innovative structural engineering solutions we are known for, while bringing the expanded depth of expertise, resources, and services offerings now available to us as part of RJC.

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Congressional Democrats on TikTok defend app’s reach to voters – Hot Springs Sentinel

WASHINGTON -- Rep. Jeff Jackson of North Carolina has used it to explain the complex fight over raising the debt limit. Rep. Robert Garcia of California has used it to engage with members of the LGBTQ+ community. And Sen. Bob Casey of Pennsylvania has used it to give an overview of Election Day results.

As pressure against TikTok mounts in Washington, the more than two dozen members of Congress -- all Democrats -- who are active on the social media platform are being pushed by their colleagues to stop using it. Many defend their presence on the platform, saying they have a responsibility as public officials to meet Americans where they are -- and more than 150 million are on TikTok.

"I'm sensitive to the ban and recognize some of the security implications. But there is no more robust and expeditious way to reach young people in the United States of America than TikTok," Democratic Rep. Dean Phillips of Minnesota told The Associated Press.

Yet the lawmakers active on TikTok remain a distinct minority. Most in Congress are in favor of limiting the app, forcing a sale to remove connections to China or even banning it outright. The U.S. armed forces and more than half of U.S. states have already banned the app from official devices, as has the federal government. Similar bans have been imposed in Denmark, Canada, Great Britain and New Zealand, as well as the European Union.

Criticism of TikTok reached a new level last week as CEO Shou Zi Chew testified for more than six hours at a contentious hearing in the House. Lawmakers grilled Chew about the implications of the app for America's national security and the effect on the mental health of its users. And the tough questions came from both sides of the aisle, as Republicans and Democrats alike pressed Chew about TikTok's content moderation practices, its ability to shield American data from Beijing and its spying on journalists.

"I've got to hand it to you," said Rep. August Pfluger, R-Texas, as members questioned Chew over data security and harmful content. "You've actually done something that in the last three to four years has not happened except for the exception of maybe (Russian President) Vladimir Putin. You have unified Republicans and Democrats."

While the hearing made plain that lawmakers view TikTok as a threat, their lack of first-hand experience with the app was apparent at times. Some made inaccurate and head-scratching comments, seemingly not understanding how TikTok connects to a home Wi-Fi router or how it moderates illicit content.

Rep. Mark Pocan, D-Wis., who is active on the app and opposes a nationwide ban, called the hearing "cringeworthy."

"It was just so painful to watch," he told the AP on Friday. "And it just shows the real problem is Congress doesn't have a lot of expertise, whether it be social media or, for that matter, more importantly, technology."

Garcia, who said he uses TikTok more as a consumer, said most of his colleagues who are proposing a nationwide ban told him they had never used the app. "It gets hard to understand if you're not actually on it," the freshman Democrat said. "And at the end of the day, a lot of TikTok is harmless people dancing and funny videos."

"It's also incredibly rich educational content, and learning how to bake and learning about the political process," he said.

Rep. Jamaal Bowman, D-N.Y., who has more than 180,000 followers on the app, held a news conference with TikTok influencers before the hearing. He accused Republicans of pushing a ban on TikTok for political reasons.

"There are 150 million people on TikTok and we are more connected to them than Republicans are," Bowman said. "So for them, it's all about fear-mongering and power. It's not TikTok, because, again, we've looked the other way and allowed Facebook and other platforms to do similar things."

Critics of TikTok in Congress say their opposition is rooted in national security, not politics. TikTok is a wholly owned subsidiary of Chinese technology firm ByteDance Ltd., which appoints its executives. They worry Chinese authorities could force ByteDance to hand over TikTok data on American users, effectively turning the app into a data-mining operation for a foreign power. The company insists it is taking steps to make sure that can never happen.

"The basic approach that we're following is to make it physically impossible for any government, including the Chinese government, to get access to U.S. user data," general counsel Erich Andersen said during an interview with the AP on Friday at a cybersecurity conference in California.

TikTok has been emphasizing a $1.5 billion proposal to store all U.S. user data on servers owned and maintained by the software giant Oracle. Access to U.S. data would be managed by U.S. employees through a separate entity run independently of ByteDance and monitored by outside observers.

Republican Sen. Thom Tillis of North Carolina took the unusual step of releasing a public statement urging all members of Congress to stop using TikTok, including from his home state -- seemingly a jab at Jackson, who is one of the more active members with more than 1.8 million followers.

"I was just saying if we're having a discussion about TikTok then I think we ought to at least reduce the pull factor by elected officials who can simply come off of it," Tillis said this week, when asked about his statement. "I don't have a TikTok account. So that was an easy separation for me."

Loud warnings about TikTok have also been coming from President Joe Biden's administration. Secretary of State Antony Blinken and FBI Director Christopher Wray have told Congress in recent weeks that TikTok is a national security threat. Blinken told lawmakers the threat "should be ended one way or another."

But some members are unconvinced.

"It's like turning your cell phone off on an airplane. You're supposed to do. And if it was super dangerous, I don't think we will be allowed to have the phone on the plane," Rep. Greg Landsman, D-Ohio, said Wednesday, "So if it was super dangerous for members of Congress to have this app on their phone, you have to imagine the administration or our government would say absolutely not, you can't have it on a government phone."

Concerns about what kind of content Americans encounter online, or how their data is collected by technology companies, also aren't new. Congress has been wanting to curtail the amount of data tech companies collect on consumers through a national privacy law, but those efforts have stalled repeatedly over the years.

Supporters of TikTok on Capitol Hill are urging their colleagues to educate themselves about social media as a whole so Congress can pass legislation that deals with broader issues of data privacy, instead of hyper-focusing on a ban of TikTok, which could risk political backlash and a court fight over the reach of the First Amendment.

"We are uninformed and misinformed. We don't even understand how social media works. We don't know anything about data brokers and how data brokers sell our data to foreign countries and foreign companies right now," Bowman said. "So ban TikTok tomorrow, this stuff is still going to be happening."

Associated Press writer Haleluya Hadero in Sausalito, California, contributed to this report.

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James Webb peers even further back in time to reveal most distant … – Interesting Engineering

James Webb observes the oldest galaxies ever seen

The two new papers present analyses of redshift light observed by James Webb. Redshift light refers to light that has been traveling for such a long time that the expansion of the universe has stretched its wavelength into the red part of the electromagnetic spectrum.

From early on in its scientific operations, James Webb has used this method to break records by observing the most ancient galaxies ever observed.

For the new observations, the scientists measured the redshift of the light observed by Webb and found that it was at the extreme end of the spectrum, stretched all the way into the infrared end of the spectrum.

Webb's spectra analyses.

The analyses show that the galaxies present in the new observations existed when the universe was less than 350 million years old.

Webb used its near-infrared camera (NIRCam) and Near-Infrared Spectrograph (NIRSpec) instrument to detect a total of four new ancient galaxies. These have been dubbed JADES-GS-z100, JADES-GS-z110, JADES-GS-z120, and JADES-GS-z130. JADES stands for "JWST Advanced Deep Extragalactic Survey."

After measuring the redshift of the ancient galaxies, the astronomers confirmed their findings using spectroscopy.

"It was crucial to prove that these galaxies do, indeed, inhabit the early universe. It's very possible for closer galaxies to masquerade as very distant galaxies," Emma Curtis-Lake, a co-author of one of the new studies and an astronomer at the University of Hertfordshire in England explained in ESAs press statement.

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James Webb peers even further back in time to reveal most distant ... - Interesting Engineering

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UI College of Engineering lab in Coralville destroyed by tornado – UI The Daily Iowan

The research laboratory, used by the UI College of Engineering and located on James Street in Coralville, became unusable as a result of storms that came through the area on March 31.

A University of Iowa research lab in Coralville used by the College of Engineering was destroyed by the March 31 storm that caused damage across the city, the university announced Tuesday.

In an IowaNow article, the UI stated that the research lab, located at 2421 James St. in Coralville, will not be repaired and has to be completely rebuilt.

The building that housed the lab was built in 2003 and is one of several in Johnson County that were destroyed in the storm. The lab was unoccupied at the time and no one was injured, it states.

Harriet Nembhard, the dean of the UI College of Engineering, said in the article that she is devastated about the destruction caused to the facility, but was relieved that no one was hurt in the storm.

Engineers are resilient. We will rebuild, and we will continue our critically important research, Nembhard said in the article.

Both residential and commercial properties were damaged or destroyed by the tornado March 31.

Coralville was one of multiple areas hit that night, along with the nearby communities of Hills, Solon, North Liberty, West Branch, and Tiffin. The National Weather Service estimates more than 20 tornadoes tore across Iowa Friday.

Johnson County is currently under a tornado watch until 10 p.m. Tuesday.

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UI College of Engineering lab in Coralville destroyed by tornado - UI The Daily Iowan

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Research of deformation law about guide rails under the action of … – Nature.com

MSD not only causes GRD, but also easily leads to the disconnection between the shaft, bunton and GR. The GRD characteristics are analyzed under the normal connection between them, the disconnection of the shaft from the bunton, and the disconnection of the bunton from the GR. The instability of the hoisting conveyance is mainly caused by the horizontal deformation of the GR. It can be seen from Fig.6 that the horizontal deformation of the guide rail in the same direction as the shaft deformation has a good follow-up to the shaft deformation, is highly correlated with the shaft deformation trend, and other horizontal directions are relatively low, so the main focus is on the deformation characteristic and law of the GR corresponding to the shaft deformation in the horizontal direction. Owing to the action mechanism of vertical compression deformation of shaft is different from other deformation types, it mainly focuses on inclination, bending, dislocation and horizontal section deformation of the shaft.

Starting from the position of 250m, the shaft is inclined in the positive direction of the x-axis, and the inclination rates are 0.2, 0.4, 0.6, 0.8 and 1mm/m, respectively. The GRD corresponding to the x-direction is shown in Fig.9. It can be found that the GRD is roughly linear and basically consistent with the shaft deformation. Its maximum deformation values are 49.1, 97.9, 146.5, 195.5 and 244.2mm, and it is reduced to a certain extent compared with the shaft inclination deformation. The GR within a certain depth from the upper surface of the shaft has both linear and fluctuating deformation. The period of the fluctuation deformation is 4m, which is the interval between adjacent buntons, and its amplitude and deformation range increase with the aggravation of the inclination deformation. The GR below the starting position of the inclination deformation only produces fluctuation deformation with a period of 4m, and the amplitude increases with the aggravation of the inclination deformation.

GRD in x-direction under inclination.

The lower GR has a stretching action on the upper part, but the support action of the bunton on the GR hinders the stretching, which leads to the reverse deformation of the GR with the bunton as the center, forming the fluctuation deformation in the upper part. The GR above the starting position of the inclined deformation makes the lower part tend to incline, and the constraint of the bunton on the GR restricts this deformation, resulting in the fluctuation deformation of the lower part. With the aggravation of the inclination deformation, the GRD basically increases linearly, and the amplitude and range of the fluctuation deformation increase, which has a good characterization relationship for the type and degree of the inclination deformation of the shaft.

To make the disconnection representative between bunton, GR and shaft under inclined deformation, the disconnection positions are selected at the upper, middle and lower parts of the shaft, which are 239, 119, 71 and 11m respectively. Figure10 shows the x-direction deformation of the GR under inclined deformation when the bunton is disconnected from the GR. In Fig.10a, the deformation is basically the same as the normal connection except near the disconnection position. At the disconnected position 239m, it is stepped with heights of 0.4, 1.8, 2.3, 4.3 and 4.9mm, respectively. It increases with the aggravation of the inclination deformation, and the change rate first increases and then decreases. The disconnected position is affected by the inclined deformation of the shaft, and the accumulated length of the GR below it is relatively small, resulting in a relatively small cumulative deformation energy of the GR near the lower part of the disconnection position, but the deformation energy near the upper part of the disconnection position is much larger than that of the lower part. When the bunton is disconnected from the GR, the deformation energy is released, so that the deformation of the GR in the upper part of the disconnection position is larger than that in the lower part, forming a stepped shape.

GRD in x-direction under inclination when bunton is disconnected from GR.

The deformation law near the disconnected position at 119 and 71m is basically the same, as shown in Fig.10b,c, with a sawtooth shape, the height increases with the aggravation of inclined deformation, and its minimum value is 3.1mm and the maximum value is 9.4mm. Since the disconnection position is located in the middle of the inclination deformation of the shaft, the difference in the accumulated deformation energy near the upper and lower part of the disconnection position is relatively small, and the deformation caused by the release of the deformation energy is basically the same, so it has a sawtooth shape. When the bunton and GR are disconnected at 11m as shown in Fig.10d, the GR on both sides of the disconnected position is deformed in reverse, showing a two-way sawtooth. The peak-to-peak value of the two-way sawtooth increases with the aggravation of the inclined deformation, and the minimum value is 9.8mm and the maximum value is 36.5mm, which far exceeds the allowable value of the GRD stipulated by the coal mine safety regulations. The stretching of the upper GR to the lower causes the upper bunton to be greatly stretched downward, induces the bunton to bend downward. When the upper bunton is disconnected from the GR, the bending deformation of the bunton at the disconnected position is greatly released, and the deformation at other positions is reduced to a certain extent, but the curvature is still large. Under the action of bending deformation, GR deforms to the side with smaller curvature, that is, the negative x-axis direction, forming a two-way sawtooth. Through the above analysis, it is found that the deformation laws of GR corresponding to different disconnected position are distinct. The bottom is stepped, the middle is sawtooth, and the upper part is two-way sawtooth. As the inclination deformation increases, its deformation amplitude augments. The disconnection position near ground has the greater impact on the GRD and is easy to cause hoisting accidents.

When the bunton is disconnected from the shaft at different positions, the x-direction deformation of the GR under inclination deformation is shown in Fig.11. The GRD law is basically unchanged at the disconnected position of 239, 119 and 71m, and the overall GRD law is fundamentally the same as that in the normal connection state. The period becomes 8m at 11m, as shown in Fig.11d, and it is twice the distance between adjacent buntons, but the amplitude basically unchanged. The disconnection between the shaft and the bunton loses its supporting effect on the bunton, the constraining effect of the disconnected bunton on the GR is invalid, and the GR deforms under the action of the interval bunton, which finally causes the period of the GRD to change at this position. Since the supporting effect of the upper bunton on the GR is much stronger than that of the middle and lower parts, the upper disconnection position easily affects the guide deformation. The disconnection of the bunton and shaft has less influence on the GRD than the separation of the bunton and GR, hence the attention should be paid to the connection state of the bunton and GR under the inclined deformation of the shaft.

GRD in x-direction under inclination when bunton is disconnected from Shaft.

The 140 to 120m segment of the shaft acts on the given of x-direction bending deformation, which is cosine type, the amplitudes are 1, 2, 3, 4 and 5mm in turn. The GRD in the x-direction is shown in Fig.12, there is approximately symmetrical bending from 146 to 119m, and the deformation ranges are (143.1, 119.1), (147.1, 119.1), (147.9, 119.1), (148.7, 119.1) and (149.8, 119.1) m, which are larger than the bending deformation range of the shaft. The maximum value of GRD is 0.99, 1.96, 2.93, 3.90, and 4.87mm, the corresponding position is 130.2m, and it is maximum deflection position of the shaft. There are differences in the GRD law on both sides of the maximum deflection, the right side is a smooth curve, and the left side is an inclined stepped curve. The inclined stepped curve is mainly due to the asymmetry of the bunton with respect to the maximum deflection position of the shaft. The bunton closest to the maximum deflection position of the shaft is located on its lower side, the maximum deflection of GR appears near the bunton under its action, and the distance relationship causes the above action on the lower side of the maximum deflection of the shaft to be much greater than the upper side, so the attenuation rate of the guide deformation is relatively slowly above the maximum deflection position of the shaft. Nevertheless, the effect of the farther upper adjacent bunton on it further increases its attenuation rate and it becomes the stepped shape. There is a corresponding relationship between the GRD and the bending deformation of the shaft. As the amplitude of the bending deformation of the shaft increases, the amplitude and range of the bending deformation of the GR enlarge, and the deformation law is the same. It indicates the sensitivity and reliability of the GRD to characterize the bending deformation of shaft.

GRD in x-direction under bending.

GRD appears periodic weak fluctuation outside a certain distance from the shaft bending region, its period is 4m, and its amplitude basically does not change with shaft bending deformation, which indicates that its influence on the GR is limited. From 119 to 106m, the deformation generally exhibits an inverted arch, and its amplitude is larger than other positions of the fluctuation deformation and it increases with the aggravation of the shaft bending deformation. The buntons constraint on the bending deformation of the GR makes it subject to a force in the negative x-direction, and drives the GR to move along the negative x-direction within a certain range, and finally the inverted arch occurs. The fluctuation is mainly caused by the constraint effect of bunton on the GR. The action of gravity leads the GR to deform in the vertical direction, and the constraints limit this deformation, which makes the upper half of the GR between adjacent buntons deforms along the negative x-direction, the lower half deforms along the positive x-direction, and the joint has the smallest deformation and is the starting point of periodic fluctuation. The maximum amplitude of the above fluctuations is only 0.02mm, the verticality and straightness meet the requirements of the GR installation specification, and it is generally straight, which further indicates the rationality of the initial connection parameters of the bunton, GR and shaft.

The disconnection positions are 11, 47, 83, 107, 119, 131, 143, 155, 179, 215 and 251m in sequence, and are all over the bending position and both sides of the shaft. Owing to the same of GRD law under different degrees of shaft bending deformation, it is studied that the shaft bending deformation amplitude of 1mm on disconnection. Figure13 shows the GRD law when the bunton is disconnected from the GR under bending action. The GR at the disconnected position deforms in opposite direction, and its amplitude is 0.38mm outside the range of shaft bending deformation, which is about 7 times the amplitude of the fluctuation deformation. The maximum amplitude occurs at 119m, and it is about 14 times the amplitude. This disconnection position is located at the junction of the shaft bending deformation, and the bunton below it is situated in the action area of the shaft bending deformation, so the GR below it is subjected to the above action, resulting in its abnormally prominent amplitude. The disconnected position at 131m is located in the middle of the bending deformation area of the shaft, the GR above it produces the reverse deformation and its amplitude is 5 times that of the fluctuation deformation, and the deformation below it is basically the same as that of the normal connection. Due to the bending deformation of the shaft, the end of the adjacent bunton at the disconnected position is bend towards the inside of the shaft, it causes the bunton near the disconnection position is bent downward, the lower GR is bent in the positive x-direction, and the upper GR is deformed in the opposite direction, which eventually leads to the GR occurs opposite deformation at the disconnected position between the bunton and GR.

GRD in x-direction under bending when bunton is disconnected from GR.

When the bunton is disconnected from the shaft under the action of the shaft bending deformation, the GRD is shown in Fig.14. When the disconnection is outside the shaft bending deformation, the period of the fluctuation deformation changes at the disconnection position and becomes 8m, and the amplitude basically does not change. When the disconnected position is located at 119m at the upper junction of the shaft bending deformation, the GRD law on the lower side of the disconnected position is basically the same as the normal connection. The deformation on the upper side of the disconnected position extends in the negative x-direction, which is mainly due to the bending effect of the lower GR in the positive x-direction and the reverse restraint effect of the upper GR in the disconnected position. When the disconnected position is located at 143m at the lower junction, the deformation decreases on the upper side near the disconnected position, and it increases on the lower side. The GR above this disconnected position is located in the bending deformation area of the shaft, it acts on the GR with an active force in the positive x-direction, thereby producing a pulling effect on the lower GR in the positive x-direction. The bunton at this disconnection position is located outside the bending deformation area of the shaft. When it is normal connection, it produces a negative x-direction constraint on the GR to slow down its attenuation rate of the bending deformation, the above restraint is eliminated under the disconnection state cause an increase in the attenuation rate of the GR bending deformation, which induces a diminution in the upper GRD near the disconnected position. and the bending deformation range of the GR and the deformation value below it increases.

GRD in x-direction under bending when bunton is disconnected from shaft.

When the disconnected position is 131m in the bending deformation area of the shaft, the deformation law near the disconnected position is basically the same as the normal connection, and the period and amplitude do not change significantly. When the disconnected bunton is located in the bending deformation area of the shaft, and the adjacent bunton has a strong bending deformation force on the GR at the same time, so even if a single bunton is disconnected from the GR, its force condition is basically unchanged, resulting in basically no change in its deformation law and amplitude. When the disconnected bunton is outside the bending deformation range of the shaft, the GR deformation period at the disconnected position changes, but the amplitude does not change. When the disconnected bunton is located at the junction of the shaft bending deformation, the deformation and period at the disconnected position change at the same time. The disconnection between the bunton and shaft under the bending deformation action has little influence on the deformation law of the GR, and the connection between the bunton and the GR should be focused on.

For a given shaft dislocation deformation in the x-direction from 130 to 90m, the amplitude is 1, 2, 3, 4 and 5mm at dislocation position of 130m and becomes 0mm at the 90m, and the attenuation rate is 0.025, 0.05, 0.075, 0.010 and 0.0125mm/m. The GRD under dislocation action is shown in Fig.15. The maximum deformation of the GR is 0.94, 1.88, 2.82, 3.78 and 4.72mm, and its position is 126.2m, which is higher than the dislocation position of the shaft, but its amplitude is basically unchanged compared with the dislocation amplitude of the shaft. The distance between the adjacent bunton makes it difficult to coincide with the position of the dislocation deformation of the shaft, and the dislocation deformation effect is transmitted to the GR through the bunton, so this effect causes the maximum deformation of the GR to occur near the bunton, and its position is moved up than the dislocation position of the shaft. The influence range of the dislocation deformation on the GRD is (143.5, 88.3), (143.9, 88.3), (146.7, 88.3), (146.9, 88.3) and (146.9, 88.3) m, which is much larger than the action scope of the shaft dislocation deformation. The shaft above the dislocation interface produces a stretching effect on the lower part, its lower part moves to the positive x-direction and expands the shaft deformation range, but the resistance from the SRSM to shaft restricts the transmission range of the above effect, which induces the deformation range of the GR is much larger than the action range of the shaft dislocation deformation. There are differences in the deformation law of the GR on both sides of the maximum amplitude, the upper side shows the attenuation trend of inclination deformation, and its attenuation rate is basically the same as the shaft dislocation deformation, accompanied by fluctuation deformation. The lower side has a bending deformation trend, and the attenuation rate first increases and then decreases as it moves away the maximum amplitude, which is mainly caused by the follow-up deformation of the shaft below the dislocation interface. The GRD corresponding to the shaft dislocation is a combination of inclination and bending. With the increase of the dislocation deformation, the slope of the inclined deformation of GR, the curvature of the bending deformation and the maximum amplitude increase, which are obviously different from the deformation feature of GR under shaft bending or inclination, and there is a good mapping relationship for the shaft dislocation.

GRD in x-direction under dislocation.

Figure16a shows the x-direction deformation of the GR when it is disconnected from the bunton under the action of the shaft dislocation, its position is 11, 47, 83, 107, 119, 131, 143, 155, 179, 215 and 251m, and the GR in the disconnected position generates the opposite deformation. The peak-to-peak value of the opposite deformation outside the shaft dislocation range is about 0.4mm, and it is about 20 times fluctuation deformation, which is mainly caused by the release of the interaction between the GR and bunton under the action of gravity. When the disconnection between the bunton and GR is 107 and 119m in the shaft dislocation area, the peak-to-peak value of the opposing deformation is 0.53 and 0.57mm, respectively, and its value increases less compared to outside of the shaft dislocation deformation region. Moreover, the peak-to-peak value at the junction of the shaft bending deformation is basically the same as that outside the shaft dislocation area. When the bunton is disconnected from the shaft at different positions, the GRD is shown in Fig.16b. The deformation decreases near the upper side of the disconnected position of 143m, the lower side augments, and its deformation mechanism is the same as at this position under the action of the bending deformation of the shaft, hence the explanation is not repeated here. Other disconnected position is basically unchanged in amplitude, and only the period becomes twice the fluctuation deformation. The deformation law is basically the same as the normal connection except the above disconnection position, hence the influence of shaft dislocation deformation on the GR has no obvious attenuation due to the disconnection between the bunton and GR.

GRD in x-direction under dislocation when connection is abnormal.

The shaft of the 130 to 110m segment imposes a given displacement in the x-direction so that its cross-section is approximately elliptical, the short axis is the x-axis and the long axis is the y-axis, and the amplitude occurs at the intersection of the outer wall of the shaft and x-axis. It attenuates uniformly on both sides along the y-axis and becomes 0mm at the intersection of the shaft and y-axis, and the attenuation curve is cosine. Figure17 shows the GRD when the amplitudes of the horizontal section change of the shaft are 1, 2, 3, 4 and 5mm in turn. The GRD from 134.9 to 107.4m is mainly affected by the horizontal section change, and the interval is basically unchanged with the aggravation of the horizontal section change. The deformation is generally trapezoidal, the middle section is a horizontal straight line accompanied by fluctuation deformation, and the transition area decays rapidly, generally an inclined straight line. With the increase of the deformation amplitude of the horizontal section change, the GRD from 134.9 to 130.5m shows the local arching phenomenon, which becomes more severe with the aggravation of the above deformation. The above phenomenon occurs near the junction of the action and influence zone of the horizontal section change. The bunton in action area follows the shaft to deform in the positive x-direction, and the GRD in the affected aera is less affected by the horizontal section change of shaft and bunton in affected area has a strong constraining effect on the guide deformation in the positive x-direction, and the GR in action area exists a strong stretching effect on GR in this position, which induces the local arching phenomenon.

GRD in x-direction under horizontal section change.

The amplitudes of the GRD are 0.33, 0.70, 1.04, 1.38, and 1.73mm corresponding to each horizontal section change, and it is a large attenuation relative to the shaft deformation. The fluctuation deformation amplitude from 107.4 to 73.1m augments with the aggravation of the horizontal section change, its amplitude is no obvious change rule from 73.1 to 46.9m, and the amplitude of 46.9 to 0m decreases. The above phenomenon is mainly caused by the strong constraint effect of bunton of the transition zone on the GR, and the strong stretching effect of the lower GR on the upper part. The deformation law of the GR is basically the same under the different amplitude of horizontal section change of the shaft, but there are obvious differences in the amplitude, which exists a good corresponding relationship between the horizontal section change of the shaft and the deformation law of the GR.

When the bunton is disconnected from GR, its position is 11, 47, 83, 107, 119, 131, 143, 179, 215 and 251m, respectively, and the GRD is shown in Fig.18a under horizontal section change. It generates the opposite deformation at the disconnected position, and its maximum peak to peak occurs in the transition zone of the horizontal section change at 107m and its value is 0.94mm. The disconnected bunton in the transition area locates in the outside of the shaft deformation and has little deformation effect on the GR, and the bunton below the transition area locates in the shaft deformation area and follows the shaft deformation to drive the GRD, which causes a large difference in force between adjacent buntons, and the maximum peak-to-peak value appears. In the horizontal section change area of the shaft at 119m, the peak-to-peak value is 0.43mm, and its value is basically the same as the disconnection position outside action area of the horizontal section change of the shaft. The disconnection between the bunton and GR in the transition area has the greatest influence on the GRD, which can easily lead to the abnormal deformation.

GRD in x-direction under horizontal section change when connection is abnormal.

Figure18b is the GRD corresponding the disconnection between the bunton and shaft under the horizontal section change of the shaft. The disconnection outside the action and transition area of the shaft deformation only changes the fluctuation deformation period near the disconnection position and its value is 8m, and the amplitude is basically unchanged. In the shaft deformation action area, the maximum peak-to-peak value is 1.12mm at disconnection position of 119m, and the peak-to-peak value at 107 and 131m in the upper and lower transition areas are 0.57 and 0.62mm respectively. The buntons on both sides of the disconnected position are located in the shaft deformation action area, are subjected to the pulling effect of the shaft in the positive x-direction, but the bunton at the disconnection position lacks the above effect, which eventually leads to local inverted arch near the position. The deformation principle of the GR at the disconnection position of the transition zone is the same as the above, except that one side of the bunton is located in the action zone, and the other side is located in the transition zone. However, the effect in transition zone is relatively weak, resulting in a relative lower peak-to-peak value. When the bunton is disconnected from the GR or shaft, the horizontal section change has a great influence on the GRD, so attention should be paid to the connection state.

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Hell, prayer rug and Turkish opposition’s reverse engineering efforts | Daily Sabah – Daily Sabah

Political parties in Trkiye are working hard to finalize their candidate lists by the April 9 deadline. The relevant committees probably find it more difficult to select candidates today than ever. The already-complex selection process is further complicated by electoral alliances producing joint lists in certain districts and trying to predict how those decisions may influence the allocation of parliamentary seats.

Although the campaign period is already underway, presidential candidates largely refrain from picking rhetorical fights in the holy month of Ramadan.

President Recep Tayyip Erdoans schedule features iftar dinners, groundbreaking ceremonies in the earthquake-hit zone, and the inauguration of significant projects. In this sense, the incumbent keeps reminding voters that he distinguishes himself from the rest through his history of public service, projects, and actions.

Meanwhile, the main opposition Republican Peoples Party (CHP) Chairperson Kemal Kldarolu, having received the opposition blocs endorsement, attempts to replace his combative attitude with a more inclusive approach. Yet some pro-CHP media personalities continue to threaten to hold the ruling Justice and Development Party (AK Party) circles accountable and put them on trial. In this sense, what we see is reminiscent of the 2019 municipal elections. The CHP leadership claims to welcome everyone, but it continues to fuel polarization in an attempt to consolidate its base. As a result, it wont be surprising to encounter more heated debates after April 9, especially after Ramadan.

What caught my attention in the current election cycle is the Hell, prayer rug, and reverse engineering, which support certain politicians, to make radical and essentialist distinctions and accusations. Let me elaborate: The essentialist, extreme, and alienating tone that pro-opposition commentators, academics, and media personalities have adopted to "unite the opposition and mobilize voters have become a cause of concern. For example, the Good Party (IP) Chairperson Meral Akeners metaphorical stoning upon leaving the opposition bloc and Muharrem nces ongoing treatment over his decision to contest the presidential election reflect the massive anger that the ultra-secularist opposition has accumulated. By contrast, the Felicity Party (SP), the Democracy and Progress Party (DEVA), and the Future Party (GP) did not encounter a similar reaction from conservatives for joining the CHP-dominated opposition bloc, also known as the "table for six. In other words, Trkiyes conservatives some like to criticize for supposedly being obedient and believing in pre-determinism have been reflecting on the countrys issues more rationally and with greater common sense than the ultra-secularists.

Domestic and international audiences agree that the May 14 elections are critically important. One must ask, however, what to make of the ultra-secularist rage that causes them to "lynch fellow members of the opposition as "separatists? How does referring to the next elections as "the last" makes sense? What kind of a metaphor has a former diplomat used by claiming they will "close the gates of hell by changing the government?

I doubt that labeling the AK Party government in such ways could influence voters. Equating the current situation with "hell is no less tragicomical than Kemal Kldarolu clumsily reciting a Quranic verse at an iftar dinner hosted by the Felicity Party.

Has the main opposition party already exhausted the discourse of one-man rule? Is that why they exploit religious symbols and concepts at the expense of the AK Party and conservatives? That ultra-secularist reverse engineering attempt shall fail as soon as the CHP chairperson steps on a prayer rug with his shoes.

The Peoples and Nation Alliance represent two different visions for Trkiyes future. It is the job of opinion-makers to compare and interpret their respective policy papers, statements, and campaign pledges.

Why would anyone subject the country to an essentialist choice between power and morality? In an attempt to support Kldarolu, some left-wing academics have been portraying the government as "evil and the opposition as "good which suffers from essentialist radicalism. Their actions have long exceeded the limits of the all-too-familiar divide between "us and "them in politics. Are we to believe that allying with the Free Cause Party (HDA-PAR) and the New Welfare Party (Yeniden Refah Partisi) amounts to "misogyny, but joining forces with the Peoples' Democratic Party (HDP) and receiving PKKs endorsement is about "working for people with problems in Trkiye?

That academics assess the AK Party experience from an essentialist and radical standpoint, which goes beyond politicization, is a source of concern for the entire country.

Continued here:

Hell, prayer rug and Turkish opposition's reverse engineering efforts | Daily Sabah - Daily Sabah

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