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COVID-19: Can we tackle the root cause of inflammation? – Medical News Today

Researchers in Spain and the United States have proposed that an existing drug may help prevent an excessive, life threatening immune reaction to SARS-CoV-2 in susceptible individuals.

In people with severe COVID-19, which is the disease that SARS-CoV-2 causes, hyperinflammation exacerbates breathing difficulties and can lead to potentially fatal acute respiratory distress syndrome.

However, there is good evidence to suggest that drugs that reduce inflammation, such as the steroid dexamethasone, can save the lives of patients already on ventilators and those receiving supplemental oxygen.

Now, though, scientists at the University of Mlaga in Spain and the University of California, Los Angeles, have proposed a novel way to identify patients at high risk of developing hyperinflammation and prevent it from occurring.

They hypothesize that healthcare providers could give an existing drug to such patients early in the infection to address the root cause of the excessive immune response.

Their proposal appears in the journal Cytokine & Growth Factor Reviews.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

The researchers suggest that initial infection with the virus causes stress at the cellular level. In particular, this is stress involving an organelle within cells called the endoplasmic reticulum (ER).

The ER is where the cell manufactures its proteins. When a virus invades a cell, it hijacks this cellular machinery to make its own proteins.

In 2019, scientists discovered that SARS-CoV, which is the coronavirus that caused the 20022003 SARS outbreak, triggers an inflammatory response by making a particular protein.

Molecules of the protein stress the ER by clumping together. These insoluble aggregates either kill the cells directly or activate the innate immune system.

This branch of the immune system is the first line of defense against pathogens. It deploys signaling molecules called cytokines that recruit immune cells to the site of infection as part of an inflammatory response.

In the new paper, the researchers suggest that ER stress is also a feature of early SARS-CoV-2 infections. They also propose that a drug called 4-phenylbutyric acid (4-PBA), which healthcare providers use to treat urea cycle disorders, could prevent ER stress in COVID-19.

4-PBA acts as a chemical chaperone, stabilizing proteins and preventing them from clumping together.

By preventing ER stress in this way, the researchers say that it reduces the inflammatory response in a range of other conditions, including lung and cardiovascular disease, liver failure, pancreatitis, and diabetic encephalopathy.

They report that they recently developed a 4-PBA treatment for lung disease and tested it successfully in mice. However, they have not yet published their results.

The scientists speculate that people at high risk of developing severe COVID-19 such as older adults and those with cardiovascular conditions, diabetes, or obesity already have underlying ER stress in their cells.

They believe that this makes them especially vulnerable to further ER stress, and the resulting inflammation, if they contract SARS-CoV-2.

When cells are stressed by infection, they call the cytokines, and the more stressed they are, the more persistent they become, provoking this uncontrolled inflammation, explains senior study author Ivn Durn, of the Department of Cell Biology, Genetics, and Physiology at the University of Mlaga.

Hence, one possible treatment for COVID-19 is to reduce cellular stress.

Because 4-PBA is already an approved drug, the authors say that healthcare providers could start using it immediately in patients at high risk of cellular stress and hyperinflammation.

There are people already [living with conditions] that cause cellular stress, and when they [contract] coronavirus, they are more likely to fall ill or die, says Durn.

Therefore, if we know that the patient [has] cellular stress, we can kill two birds with one stone: We can detect susceptibility before infection occurs and know how to treat it in due time.

A protein in the ER called binding immunoglobulin protein (BiP) increases in concentration in response to cellular stress and finds its way into the bloodstream.

The study authors believe that healthcare providers could use the concentration of BiP in the blood to indicate a patients risk of developing hyperinflammation. They could also use it to measure the patients response to treatment with 4-PBA.

However, the authors caution that much more work is necessary to test their proposals.

They write:

It is necessary to do further research to prove the inflammatory component of this model, but our results suggest that 4-PBA treatment could be used to prevent respiratory failure in COVID-19 patients if the ER stress is confirmed to be part of the mechanism.

The team has secured funding to conduct in vivo and in vitro research into the inflammatory response in SARS-CoV-2 infection and the possibility of using 4-PBA as a treatment.

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COVID-19: Can we tackle the root cause of inflammation? - Medical News Today

City of Hope Enters Licensing Agreement With Chimeric to Develop Its Pioneering Chlorotoxin CAR T Cell Therapy – Business Wire

DUARTE, Calif.--(BUSINESS WIRE)--City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases, today announced that it has licensed intellectual property relating to its pioneering chlorotoxin chimeric antigen receptor (CLTX-CAR) T cell therapy to Chimeric Therapeutics Limited, an Australian biotechnology company.

The therapy is currently being used in a phase 1 clinical trial at City of Hope to treat glioblastoma (GBM), a type of brain tumor. The first patient in the trial was recently dosed; Behnam Badie, M.D., chief of City of Hopes Division of Neurosurgery and The Heritage Provider Network Professor in Gene Therapy, is leading this innovative, first-of-its-kind trial.

Chimeric has acquired the exclusive worldwide rights to develop and commercialize certain patents relating to City of Hopes CLTX-CAR T cells, as well as to further develop the therapy for other cancers.

City of Hope is excited to enter into this agreement with Chimeric as it supports our innovative research in CAR T cell therapy and our commitment to extend these therapies to more patients, particularly those with GBM and other solid tumors that are difficult to treat, said Christine Brown, Ph.D., The Heritage Provider Network Professor in Immunotherapy and deputy director of City of Hopes T Cell Therapeutics Research Laboratory. Chimeric shares our goal of providing effective CAR T cell therapies to more patients with current unmet medical needs.

Led by Brown and Michael Barish, Ph.D., chair of City of Hopes Department of Developmental and Stem Cell Biology, and Dongrui Wang, Ph.D., a recent graduate of City of Hopes Irell & Manella Graduate School of Biological Sciences, the team developed and tested the first CAR T cell therapy using CLTX, a component of scorpion venom, to direct T cells to target brain tumor cells. The research was published this past March in Science Translational Medicine.

Chimeric is excited to join City of Hope in its quest to find more effective cancer therapies. This is an exceedingly rare opportunity to acquire a promising technology in one of the most exciting areas of immuno-oncology today, said Paul Hopper, executive chairman of Chimeric. Furthermore, the CLTX-CAR T cell therapy has completed years of preclinical research and development, and recently enrolled its first patient in a phase 1 clinical trial for brain cancer.

CARs commonly incorporate a monoclonal antibody sequence in their targeting domain, enabling CAR T cells to recognize antigens and kill tumor cells. In contrast, the CLTX-CAR uses a synthetic 36-amino acid peptide sequence first isolated from death stalker scorpion venom and now engineered to serve as the CAR recognition domain.

In this recent study, City of Hope researchers used tumor cells in resection samples from a cohort of patients with GBM to compare CLTX binding with expression of antigens currently under investigation as CAR T cell targets. They found that CLTX bound to a greater proportion of patient tumors, and cells within these tumors.

CLTX binding included the GBM stem-like cells thought to seed tumor recurrence. Consistent with these observations, CLTX-CAR T cells recognized and killed broad populations of GBM cells while ignoring nontumor cells in the brain and other organs. The study team demonstrated that CLTX-directed CAR T cells are highly effective at selectively killing human GBM cells without off-tumor targeting and toxicity in cell-based assays and in animal models.

City of Hope, a recognized leader in CAR T cell therapies for GBM and other cancers, has treated more than 500 patients since its CAR T program started in the late 1990s. The institution continues to have one of the most comprehensive CAR T cell clinical research programs in the world it currently has 30 ongoing CAR T cell clinical trials, including CAR T cell trials for HER-2 positive breast cancer that has spread to the brain, and PSCA-positive bone metastatic prostate cancer. It was the first and only cancer center to treat GBM patients with CAR T cells targeting IL13R2, and the first to administer CAR T cell therapy locally in the brain, either by direct injection at the tumor site, through intraventricular infusion into the cerebrospinal fluid, or both. In late 2019, City of Hope opened a first-in-human clinical trial for patients with recurrent GBM, combining IL13R2-CAR T cells with checkpoint inhibitors nivolumab, an anti-PD1 antibody, and ipilimumab, blocking the CTLA-4 protein.

Both an academic medical center and a drug development powerhouse, City of Hope is known for creating the technology used in the development of human synthetic insulin and numerous breakthrough cancer drugs. Its unique research and development hybrid of the academic and commercial creates an infrastructure that enables City of Hope researchers to submit an average of 50 investigational new drug applications to the U.S. Food and Drug Administration each year. The institution currently holds more than 450 patent families.

"City of Hope is delighted to license this technology to Chimeric, said Sangeeta Bardhan Cook, Ph.D., City of Hope director of the Office of Technology Licensing. We are impressed with the ability of their executive team to push and bring therapies to market expeditiously. At City of Hope, our mission is to transform the future of health care. We believe Chimeric has the vision to offer innovative therapies to cancer patients.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hopes translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope has been ranked among the nations Best Hospitals in cancer by U.S. News & World Report for 14 consecutive years. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

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City of Hope Enters Licensing Agreement With Chimeric to Develop Its Pioneering Chlorotoxin CAR T Cell Therapy - Business Wire

Shared protein fingerprint could simplify treatment of common inherited heart disease – Newswise

Newswise MADISON, Wis. Hypertrophic cardiomyopathy is the most common inherited heart disease, marked by an abnormally thickened heart muscle that can obstruct blood flow and lead to sudden death in young adults.

A dizzying array of over 1,400 genetic mutations can lead to the disease, puzzling doctors on how to treat so many unique varieties. But in new research, University of WisconsinMadison scientists discovered that many different genetic mutations result in surprisingly similar changes to heart muscle proteins in patients with the most severe manifestations of hypertrophic cardiomyopathy. This shared protein fingerprint suggests that shared treatments could treat the disease.

This could be good news for doctors treating obstructive hypertrophic cardiomyopathy patients, because our data suggest theres a convergent pathway in these patients, allowing development of treatments that generally target patients with severe obstruction from their cardiomyopathy instead of targeting a patient's individual genetic mutations, says Ying Ge, a professor of cell and regenerative biology and chemistry at UWMadison who headed the new study.

Ge and an international collaboration of researchers published their findings the week of Sept. 21 in the Proceedings of the National Academy of Sciences. UWMadison graduate students Trisha Tucholski and Wenxuan Cai led the work, which analyzed in detail the protein signatures of diseased and normal hearts using advanced protein-measurement technology.

The team collected samples of diseased heart tissue from 16 patients who underwent corrective surgery to fix impaired blood flow in their hearts. Hypertrophic cardiomyopathy in eight of these patients was due to eight distinct mutations across two genes; for the other eight patients, the disease-causing mutations were unknown. Proteins from the diseased heart samples were compared to those from healthy donor hearts.

Despite the variation in underlying genetic mutations, Ges team discovered a general pattern in hearts from patients with the disease. For example, many key muscle proteins from diseased hearts had fewer molecular tags known as phosphates. While the exact consequence of having fewer phosphates is unknown, its likely that these altered proteins contribute to a general state of dysregulation in the heart, leading to the thickened muscle characteristic of the disease.

The findings reinforce that genetic mutations arent always enough to explain diseases, says Ge. The proteins those genes encode have the ultimate impact on health, and the bodys proteins can be altered in subtle but consequential ways during disease.

When we first performed these experiments, this similarity at the protein level was quite surprising to us because it is generally expected that different mutations could lead to different changes in the proteins, says Ge. But in reality, these results make sense, because when the patients with this disease present to the hospital for surgery, their hearts exhibit similar dysfunction.

The results are still preliminary. Ges group wants to expand to study hundreds of additional patients with a wide array of underlying hypertrophic cardiomyopathy mutations to see if the similar protein fingerprint trend holds. They also plan to study heart stem cells with disease-causing mutations in an effort to study early stages of the disease, which isnt possible with human patients.

But with additional research, this kind of in-depth analysis of protein fingerprints could guide future treatments.

This data opens the door with evidence showing that protein-level changes might be a better reflection of the patients disease than their genes, and if we can examine patients' samples at the protein level, that could help us provide precision-medicine treatments, says Ge.

This work was supported in part by the National Institutes of Health (grants R01 HL096971, R01 GM117058, GM125085, HL109810, S10 OD018475, T32 GM008505, T32 GM008688, R01 HL129798, U01 HL134764, and R01 HL139883) and the National Science Foundation (grant EEC-1648035).

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Shared protein fingerprint could simplify treatment of common inherited heart disease - Newswise

‘Fall Guys’ Developers Have Revealed the Character’s Anatomy – HYPEBEAST

Despite having just released for a little less than two months,Fall Guys has taken the Internet by storm, becoming a massively-popular title almost overnight. While fans have been indulging in its simple yet addictive gameplay, theres one thing that has left its players less than satisfied: the lore and origin of the cute and plump avatars, simply named Fall Guys.

To give fans what they want,Fall Guys have now taken to Twitter to answer a few of their questions, including a pretty haunting diagram of the anatomy of a Fall Guy, which the Internet has apparently asked for. While they look cute on the outside, it turns out that the characters all stand a towering six feet tall, and carry rather obscure skeletal structures underneath their well-rounded bodies. While the skeleton fills out by the hands and feet, its skull, nipples and abs are all hidden, as well as its bent legs, resembling those of birds. The most eery part, however, are the eyes: instead of sitting inside the eye sockets of the skull, theyre out by the face but connected via extremely long optic nerves.

Whether this adds or detracts from the game for fans, its developers have made clear that this lore is now official, and said we cant take it back.

Elsewhere in gaming, demand for the Xbox Series X and S have crashed major pre-ordering websites.

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'Fall Guys' Developers Have Revealed the Character's Anatomy - HYPEBEAST

As med ed goes remote, gross anatomy offers in-person learning – American Medical Association

The first semester of medical school aims to lay a foundation of knowledge on which medical students can grow into physicians. Among the key foundational pieces laid in those opening months of training is a familiarity and understanding of the human body, often introduced through anatomy.

The COVID-19 pandemic has shifted much of the opening months of medical school from in-person learning to online learning for many preclinical medical students. Still, at some schools, when it comes to anatomy, there is no digital replacement for the real thing.

At the Heritage College, cadaveric anatomy is a priority, said Isaac J. Kirstein, DO, a dean at the Cleveland campus of Ohio University Heritage College of Osteopathic Medicine (OUHCOM), which is a member school of theAMAsAccelerating Change in Medical Education Consortium. There are two key reasons for this. First, the cadaver is the medical students first patient; the students engage with the humanism of the experience, and it forms their professional identity. Second, to truly learn osteopathic principles requires an understanding of anatomy that simulation alone cannot provide.

Learn five tips to survive first-year anatomy.

Opting to offer in-person anatomy meant putting in place several safety protocols. Students spend less time in labsroughly a half day per weekand learn in smaller groups. Instead of performing dissections, cadavers are dissected prior to students arriving in the lab.

Theres a lot to be said for learning the art of dissection to help students pick up some basic techniques, Dr. Kirstein said. We are confident that can be learned during their second year.

OUHCOM first-year medical students began anatomy in late August. Even without dissection, working with a cadaver, rather than attempting to learn the body via some sort of simulation medium, has proven valuable.

Its really important that we learn the 3D aspect to a body versus simply learning from a textbook, said Ashley Aslo, a first-year student at OU. Trying to conceptualize in our brains, its really important to understand that theres layering. And on the other hand, not just science but also being introduced to our first patient and understanding that these people donated their bodies for us to learn fromlearning how to respect them was really important. By doing anatomy in person, we have learned all of those aspects.

As far as any potential safety concerns students might have, Aslo said the systems put in place have largely negated them for her.

Its a scary time, Aslo said, but she believes the university has done an amazing job of adhering by social distancing rules while providing the opportunity to get a good education.

Medical schools will continue to adjust to disruptions related to COVID-19, balancing safety concerns with ensuring that students are appropriately trained to care for patients, families and communities.

The AMA has curateda selection of resourcesto help residents, medical students and faculty during the COVID-19 pandemic manage the shifting timelines, cancellations and adjustments to testing, rotations and other events at this time.

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As med ed goes remote, gross anatomy offers in-person learning - American Medical Association

Six degrees of separation: From starry-eyed start to messy finish, the anatomy of Tata-Mistry divorce – Economic Times

For two of India's premier business groups, September 22 marked the beginning of a bitter end to an association that had begun 70 years ago.

After four years of rough litigations, Shapoorji Pallonji Group on September 22nd said it would be exiting Tata Sons as minority shareholder. This is likely to bring the curtains down on the decades-long partnership between the two Parsi business families that had soured since the ousting of Cyrus Mistry in 2016.

The time between Mistry's entry and exit was marred with rifts, charges and legal battles, turning Ratan Tata's legacy-building decision of handing the reins to an outsider (a non-Tata) into an eventual courtroom nightmare for both the parties involved. Heres a summarised timeline of how the Tata-Mistry relationship came to this pass, from a starry-eyed start to a disgruntled finish.Chairman-in-lawIn 2011, many were left witless when a 43-year old Cyrus Mistry who at the time was primarily known for heading SP Group was announced as Ratan Tatas successor and the sixth chairman of one of the nations largest businesses.

It was well known that SP Group and Tata Groups relationship existed outside of business too. During the long-drawn search for Tata's successor, there were expectations of Tatas half-brother Noel Tata who is married to Aloo Mistry, daughter of Pallonji Mistry taking the reins, doing the rounds till before the day of the announcement.

Mistry had joined the Tata board in 2006 after taking his fathers vacated seat, and during his time there had impressed Ratan Tata with his "quality of work, astute observations and humility". Many business insiders recounted the resemblance that Mistry had with Tata, pointing at similar temperaments and hobbies.

Paradise lostThe Tata Group had pushed hard for the youth to pave the way forward in leading positions during hiring and promotions in those years. "Be your own man" is what Tata advised the fledgling chairman while passing the baton. And that Mistry did.

The ultimate blow which immediately preceded the unceremonious ouster and which many see as a direct factor behind Tata's ire was Mistrys June 2016 clearance for Tata Powers $1.4 billion acquisition of Welspuns solar farms without seeking the approval of Tata or other key shareholders.

"Tata Power is a cash guzzler but generates very little profit. Yet, when its embarking on its biggest buyout, a principal shareholder is kept in the dark. Thats unprecedented in Bombay House (Tata Group headquarters)," said an old-time group insider.

But for some, Mistry was somewhat inept for the role from the very start. They perceived him as precocious and wayward to the group's core values. There was a clear disconnect between how Mistry and Tata operated with regard to the old cadres ethos and vision. Some even complained that letters questioning future plans sent to Mistry only got lukewarm responses, adding to a growing schism between the Tata Sons chairman and Tata Trusts.

Mistrys decision to dispose of some Indian Hotels overseas properties, bundled with the move to shut UK steel operations, did not sit well with the latter. Tata Trusts believed that Mistry did not take shareholders and the groups global ecosystem into account. "Tata was unhappy with the decision to shut down or sell the groups steel business in Europe," said a person close to Tata. "He wanted the group to turn around the loss-making business rather than sell it."

Other areas of discontent included legal battles with NTT Docomo, the collapse in negotiations with Vodafone, and the sacking of Indian Hotels MD Raymond Bickson. In a few cases, things got so out of hand that Tata himself would have to get involved to mediate. Furthermore, some began questioning the Chairmans eye for talent. "The people he hired are not inspirational leaders, just individuals," said a former Tata Motors executive.

Coup d'tatAlthough Mistry's ouster came as a bombshell announcement, for insiders the decision was a long time coming.

According to sources, Mistry was not consulted regarding the appointments and was even offered an opportunity to resign beforehand, which he refused. The growing frustrations within the Tata Group were sure to end in confrontation, said Tata group insiders.

A day before the infamous Tata Sons board meet, a message was conveyed to Mistry from Tata Trusts Chairman Ratan Tata regarding what might be discussed in the meeting. On October 24th 2016, Tata Sons board announced the ousting of Mistry as Chairman, and Ratan Tata was named interim Chairman of the group. By February next year, Mistry was removed from the boards of all Tata Group firms.

Hell hath no fury, like a Chairman scornedAfter the ousting, Mistry accused the boards trustees of 'shadow control', alleging legacy issues in the group. Tata, on the other hand, justified the decision citing performance issues.

The days that followed saw accusations and counter-accusations intensify. Mistry denied the allegation outright that the board had not been consulted regarding Welspun Power acquisition.

Regardless, in early 2017, N Chandrashekaran at the time TCS chairman was named Tata Sons Chairman.

In December 2016, two Mistry family-backed investment firms Cyrus Investments and Sterling Investments moved the NCLT Mumbai alleging mismanagement and oppression of minority stakeholders by Tata Sons, further challenging Mistrys removal by the company's board. At this point, Tata Sons served Mistry a legal notice alleging breach of confidentiality.

The Mistry family filed a contempt plea alleging that Cyrus removal was in violation of the courts order under which the involved parties were not to initiate any actions against one another while the matter was under consideration. This ignited a back-and-forth court brawl spanning three years or so.

In March 2017, NCLT set the plea aside over maintainability issues, as the two investment firms didnt meet the criterion of 10 per cent ownership in Tata Sons under the Companies Act. The Mistry family owns 18.4 per cent in the company, but the holding is below 3 per cent when excluding preferential shares. NLCT also rejected the firms plea seeking waiver.

Objection!After a joust with NCLT that didn't go in their favour, the Mistry-backed firms moved the NCLAT, challenging NCLTs order and the rejection of their waiver plea. During this period, a proposal to turn Tata Sons into a private company was passed by its shareholders in August 2017. NCLAT allowed pleas by the two firms seeking waiver, but dismissed Mistry's other petition on maintainability.

In July 2018, NCLT Mumbai also dismissed the pleas challenging Mistrys removal and allegations of misconduct on Ratan Tata, saying it found no merit in these allegations on Tata group firms. Unfazed, the two firms approached the NCLAT against this order too.

A month later, Cyrus Mistry approached the NCLAT in his personal capacity. NCLAT finally admitted the petition, and decided to hear it along with the main petitions filed by the two Mistry-backed firms. In May of 2019, the NCLAT reserved its order after completing the hearing and in December 2019, Mistry was restored as executive chairman of Tata Sons.

However, the NCLAT suspended implementation for four months to give time for the Tatas to file an appeal. And so they did, challenging NCLATs order in the Supreme Court, which stayed the order. Mistry claimed he did not seek to return as Tata Sons Chairman, but rather was protecting the Mistry familys rights as a minority shareholder.

In July this year, Tata Sons said in a filing that financial performance and the companys brand diminished under Mistrys leadership. Mistry-backed firms pointed at Tata Sons turning into a private company amid the NCLAT hearing in their affidavit to the SC, which Cyrus had earlier claimed was gone under nefarious circumstances.

New normal"The current situation has forced the Mistry family to sit back and reflect on the past, present and possible future for all stakeholders. The past oppressive actions, and the latest vindictive move by Tata Sons that impact the livelihoods of the wider SP Group community leads to the inexplicable conclusion that the mutual co-existence of both groups at Tata Sons would be infeasible," the SP Group said in a statement on September 22.

The SP Group has now made public its plan to sell its Tata stakes in order to raise capital. Tata Sons will now need to buy out the 18.37 per cent stake, which is valued at around $20 billion, bringing a possible end to the court battles and the 70-year long corporate partnership.

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Six degrees of separation: From starry-eyed start to messy finish, the anatomy of Tata-Mistry divorce - Economic Times

anatomy of bananas – Brooklyn Reader

the soft yellow phased with brown speckles skin rusty at its ends, smooth along the surface peel away the velvet yellow layerif you are skillful, no strings are left behind

a perfect slate

but if youre clumsy like methe stringy yellow strands clings onto life

corea pale cream of whiteglimmers behind the afternoon sunnext to the tossed away banana peels

phloem bundles pray for survival

inside that metal binsurfing among a treasure island forgotten

bananas i chew it away, the ghost in my stomach

yellow skin, tossed away

(published on dreamwalking mag)

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anatomy of bananas - Brooklyn Reader

Still Anatomy 101: Exploring The Anatomical Depths Of Batch Distillation – The Whiskey Wash

Pot stills are special vessels they possess this ability (superpower, really) to transform this slightly acidic, alcoholic, carbonated liquid into a more refined, grown-up version of itself. To some, theyre just a shiny pot with a funny looking arm, used to produce higher-proof alcohol; while not untrue, pot stills can be quite diverse. Coming in a range of heights, widths, shapes, and materials from round to square, squat to tall, and copper to clay each still can have its own character. Some might even have unique damage or dents that the distiller believes is the secret sauce.

Many of these characteristics can impact the process or the flavor profile of the spirit. Either way, the still is the heart and soul of the distillery and their uniqueness should be celebrated. However, there are some components that are essential to operation, which can be categorized as: safety, practical features and heating, reflux and flavor development, and condensing and collection. Certainly, there can be variations within each category, and this is what makes distillation such an exciting venture.

Although, there is one area where minimal variation should exist safety.

Distillation is an inherently dangerous process. Heating a solution to remove and concentrate alcohol by vaporization creates a risk for fires and explosions. Therefore, equipment must be designed and operated by trained professionals to prevent such events from occurring. Additionally, the distillery must have standard operating procedures (SOPs) to ensure correct and safe operation of the equipment.

Outside of fire suppression systems, SOPs, and facility layout, still design should incorporate a few key elements to minimize the risk of explosion or collapse. Pressure relief valves (PRVs) are spring-loaded safety valves that are designed to vent excess pressure to atmosphere when its setpoint is exceeded. However, one must also consider the flammable vapors inside the still and what might happen when they are released. Anti-collapse valves (ACVs) are installed to prevent still collapse due to the formation of a vacuum.

While the activation of the ACV possesses less risk to the operation or distillers safety, it does signal the occurrence of an event that could cause damage to the still. These valves are critical in minimizing the risks of explosion, damage to equipment and property, and injury of personnel. Although, safety doesnt stop here and should be woven into every aspect of still design and operation.

Aside from charging and discharging lines, manways are another essential element; this is a medium-sized opening with a sealed door that allows for cleaning, inspection, and maintenance activities. While it sounds like an entrance, stills are not designed to have people inside and only trained professionals under strict supervision should enter them. When done inappropriately, entering the still can pose serious safety risks and violate safety regulations.

Sight glasses provide a window into the soul of the wash still, which gives the distiller valuable information about what is happening inside. For example, during this initial distillation, foaming can occur inside the still due to the still charge containing a lot of particulate (yeast and/or grain) and dissolved carbon dioxide; the sight glass gives the distiller visibility to prevent flare-ups.

Excessive foaming can lead to entrainment (aka puking) of solids or liquid in the passing vapor and into the spirit, negatively impacting quality. When observed, the distiller can mitigate entrainment by reducing the heat input.

Still heating methods have evolved as the industry has matured and two major types are in use: direct and indirect. Direct-fire is a more traditional practice, where more archaic fuels include the use of wood or coal. While direct-fire stills are still in use, most have been upgraded to more efficient gas burners or electrical elements.

Indirect-fire utilizes steam as the heating medium, typically delivered by coils and/or pans within the pot. Steam is generally preferred due to enhanced safety, improved consistency, and increased operational efficiency.

Although direct-fire has advantages, such as the creation of unique flavor profiles; this is due to the localization of heat and its intimate interaction with components within the wash or beer. In fact, some distilleries have attempted to switch to steam but quickly reverted back due to a shift in flavor profile.

While important, the heating method employed only plays a smaller role in flavor development, especially when compared with elements impacting reflux and rectification level.

During distillation, reflux is essentially a purification step (aka rectification) where liquid is vaporized and condenses back into itself. Rectification is closely tied to the volatility of the components of the matrix. Compounds with lower volatility (water) will readily participate in reflux, therefore enriching compounds with higher volatility (ethanol) in the spirit-stream. In general, this creates a lighter flavor profile with higher alcohol content.

In batch distillation, there are several design elements that can impact the level of reflux, such as: the shoulders, neck, lyne arm, and the pot itself.

Inherently pot design is critical for practical reasons; but, standing out in importance from a rectification standpoint are the pots fill level and construction materials. Fill level impacts the amount of surface area that can participate in heat exchange with the environment; higher fill levels decrease the heat transfer surface area. Heat transfer is also impacted by construction materials; copper is commonplace due to its excellent heat transfer properties. This exchange helps facilitate reflux on the walls of the pot, neck, and shoulders of the still.

Thus, the shape, curvature, width, and height can all have an impact. Above the pot and shoulders is a frustoconical section called the neck. Common designs include plain, ball, lantern, and tray-inserts (in order of rectification). Pot stills with trays within their necks are referred to as hybrid stills, or batch rectifiers, as trays are key design elements of continuous distillation.

Connecting the neck to the condenser is the lyne arm. While the lyne arms primary function is directing vapors to the condenser, it also provides an opportunity for condensation or reflux. Depending on the angle of the lyne arm connection (aka swan neck), there can be an impact on the flavor profile with obtuse angles providing more reflux and acute angles providing the least.

Other rectification design elements exist, such as dephlegmators and purifiers. While not always essential, they provide another opportunity to create a unique spirit. Commonly, these devices use cooling water to condense the passing vapors. Dephlegmators are located in the neck of a hybrid still and the condensed liquid naturally refluxes down. Installed in a downward-sloped lyne arm, purifiers require additional piping to route the condensed liquid back to the pot.

While these partial condensers can be optional, complete condensation of the vapor is requisite in making the final spirit.

Condensation of vapor into liquid (distillate) is usually performed by one of two condenser types: shell and tube or worm and tub. Before the advent of the modern shell and tube condenser, worm and tubs were state-of-the-art. All vapor is routed through a coiled pipe (normally copper) in a tub of cooling water and the condensed vapor is collected.

While not as efficient as their modern-day equivalent, they do have some advantages by providing potentially richer and stronger flavor profiles (i.e. meatiness). Shell and tube condensers are made of tubes within a metal cylinder (shell) filled with water; vapor enters the tubes and condenses on the water-cooled surface. Once condensed, the distiller embarks on the most critical steps of the batch distillation: cuts and collection.

Collection generally occurs through an intermediary glass box en route to collection vessel(s), called the spirit safe. This is the first opportunity the distiller has to assess and analyze the newly condensed distillate, typically by measuring alcohol with a hydrometer in the spirit safe. With this information, the distiller can determine when to divert to heads, hearts, or tails collection or to terminate distillation altogether.

Samples may also be taken for external assessments, such as appraisal of aromatic properties. Sensory and alcohol level are often used to determine cut points, although it could also be time-based. As with most elements of still design, variation exists; regardless, some version of a spirit safe is integral as the cutting process plays a vital role in final distillate quality.

Pot still to pot still, a Sherry Butt-load of variations can exist. While not entirely responsible for the amount of diversity within the whisk(e)y space or other distilled spirits categories, these differences can play a significant part. Personally, its exciting as a distiller and consumer to reflect on and appreciate this.

Even though some anatomical elements are essential, such as safety features, heat, and the pot itself, still design can be quite dynamic. From frustoconical configurations to dephlegmator, the distiller has many options to contemplate as the still will inevitably become the distillerys heart and soul (dents optional).

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Still Anatomy 101: Exploring The Anatomical Depths Of Batch Distillation - The Whiskey Wash

Anatomy of a powerhouse: Expectations at Ohio State now go beyond the Big Ten and Rose Bowl – Buckeye Extra

Rob Oller| roller@dispatch.com

Editors note: How did Ohio State football become a Buckeye Nation of true believers? In a 14-part series, we explore aspects that shaped OSUs evolution from Saturday afternoon diversion to near-religious experience. Today: Chase

Not even two Heisman Trophies can bookend the regret that slides off the shelf of Archie Griffins most painful Pasadena memory, when undefeated Ohio State lost to underdog UCLA in the 1976 Rose Bowl, costing the Buckeyes a national championship.

Thats the one that haunts me, Griffin said, grimacing more from the recollection of that 23-10 loss than from the sore back that now hampers his golf game.

The Buckeyes were ranked No. 1 in both the Associated Press and United Press International polls, had defeated the Bruins 41-20 in the Los Angeles Coliseum earlier in the season and entered the New Years Day game as two-touchdown favorites.

Yet despite coming up short again Griffin finished 1-3 in Rose Bowls, with two lost chances at national titles the former tailback would not describe 1975 as a failed season just because the Buckeyes were not voted No. 1.

It cant be national championship or bust, he said.

It cant? Try telling that to Ohio State fans too young to recall when a successful season could be defined by a win over Michigan and playing in the Rose Bowl. These days, anything short of a College Football Playoff appearance, culminating in a national championship, leaves many fans, players and coaches feeling frustrated.

Before the Big Ten reinstituted football on Wednesday, Ohio State coach Ryan Day tweeted … we still have an opportunity to give our young men what they have worked so hard for: a chance to safely compete for a national championship this fall.

Woody Hayes did not think that way. The former OSU coach considered a national championship the outcome of a special season not the goal. Win the Big Ten and Rose Bowl and the chances of being voted poll champions were pretty good.

But there were no guarantees, which explains why Hayes and the next two Buckeyes coaches, Earle Bruce and John Cooper, focused their attention more on winning the conference than winning a national championship that was decided by media and coaches poll voters. During Hayes time, and before, voting to determine the national champion took place before the bowl games were played.

As Griffin explained it, You could win your bowl game and might win the national championship, but it in the end it was still up to the voters.

Cooper learned that the hard way in 1996 the penultimate season before the Bowl Championship Series began when the Buckeyes lone blemish was a 13-9 loss to Michigan in The Slip game. Ohio State dropped from No. 2 to No. 4 in the polls, then defeated No. 2-ranked Arizona State 20-17 in the Rose Bowl.

Cooper hoped voters would bump the Buckeyes to No. 1, but OSU finished No. 2 to Florida after the Gators defeated No. 1 Florida State 52-20 in the Sugar Bowl.

Im envious of the (playoff) system, the 83-year-old Cooper said. I had a couple teams that, Im not saying they would have won it but they would have played for the national championship.

Cooper admitted, however, that such wishful thinking fails to consider context and a changing win-at-all-cost culture.

Times have changed, he said. The goal back then seemed like it was win your games, beat Michigan and go to the Rose Bowl. It used to be you win the Big Ten, youre going to play in the Rose Bowl.

I coached at Oregon State and UCLA, and even out there the goal was to go to the Rose Bowl. Bowls were a reward for a good season. Later on, it became you had to win the Rose Bowl.

The BCS changed everything when it arrived in 1998, pitting No. 1 vs. No. 2 in a championship game that removed some subjectivity from the equation. Schools still had to be voted into the top two spots, but the title was decided on the field.

By the time Ben Hartsock arrived at Ohio State, in 1999, the tight end already had put most of the Rose Bowl mystique in his rearview mirror. He grew up listening to his father rave about The Granddaddy of them All, but as a player, Hartsock knew there were bigger fish to fry.

The importance of the Rose Bowl felt to me like something my dad focused on, Hartsock said. I knew how big it was because I was raised in a house that taught that curriculum, but I transitioned away from it.

When Jim Tressel arrived at Ohio State in 2001, he immediately replaced Rose Bowl with national title.

When Tressel came in, the main focus was Michigan. It starts with beating Michigan, then winning the Big Ten and the national title, Hartsock said. And winning the Big Ten was the only way to get to the national title. You could argue thats not the case today.

A team now can fail to win its regular-season conference championship and still win a national title, as Alabama did in 2011 (BCS) and 2017 (College Football Playoff). The playoff selection committee emphasizes that its only mission is to choose the four best teams.

Left unsaid is the reality that any team outside the top four and any bowl outside the two semifinals and championship game becomes an afterthought.

Its now all about making the playoff. Ohio State coach Urban Meyer in 2014 even gave a name to the quest: The Chase.

That doesnt mean coaches minimize conference championships. Meyer stressed in 2014 that we wake up every day to compete for championships in November. But those conference titles are more a means to an end than the ultimate goal. In Ohio States case, the first job is to win the Big Ten East Division, which gets you into the conference championship game, then win in Indianapolis to hopefully earn a playoff berth.

As for the players, todays Buckeyes are more aware of the drive for a national championship than their predecessors. With 24/7 sports media, tuning out the playoff noise is impossible.

Of course, some things never change, no matter the ultimate goal.

In early August, when the Big Ten was adjusting its schedules to eliminate nonconference games during the coronavirus pandemic, OSU quarterback Justin Fields tweeted, I dont care when we play Michigan, I just want to play them and beat the brakes off them.

roller@dispatch.com

@rollerCD

Former Ohio State coach John Cooper said the goal used to be simply getting a spot in the Rose Bowl. He made it twice: once with Arizona State in the 1986 season, and once with OSU 10 years later.

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Greys Anatomy season 17: Are Owen and Teddy over for good? Tearful first-look released – Express

Greys Anatomyseason 17 will air this November with new episodes of the medical drama dropping weekly on ABC. Ahead of its return, a first-look trailer hinting at what is to come in the new season has been released - and it spells danger for Teddy Altman (played by Kim Raver) and Owen Hunt (Kevin McKidd).

Fans of the long-running medical drama have been anxiously awaiting the shows return since its last season was cut short.

Now ABC has revealed how the new series of Greys Anatomy will begin on November 12 on the channel.

As the show gears up to its premiere, a first-look trailer has been released which teases what is to come next.

The biggest reveal from the brief clip is what the future holds for Teddy and Owen as a couple.

READ MORE:Greys Anatomy: Is Grey's Anatomy on Netflix?

Fans will remember how season 16 ended with Owen finding out the truth about Teddys cheating.

She had been having an affair with Tom Koracick (Gregory Germann) and accidentally revealed this to her fianc on their wedding day.

The storyline was a hard one to come back from for the pair and the new trailer teases it wont be an easy journey.

During the short clip, Teddy says to Owen in tears: I love you.

Owen is seen looking back at her, also in tears, teasing more heartbreak is on its way.

The future of their storyline on the show was also previewed by actor Kim Raver in an interview with TV Line.

She explained how the drama was going to get messier as more of Teddys past with a woman named Allison is explored.

Speaking about how she will deal with this, as well as her romance issues, she said: Its amazing to watch her - and frustrating.

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You want to throw something at your TV but its not like she has this aha moment, and everything resolves itself.

Its more like she has that moment but what is she going to do with it? Its like a grenade that she's holding.

Shes like Oh my God, it might explode! What do I do? But it definitely has some effects going forward.

Theres some crazy stuff that comes up in the subsequent episodes.

Other reveals in the first-look trailer include some stills of Meredith Grey (Ellen Pompeo) and Miranda Bailey (Chandra Wilson) back in the hospital.

As well as this, viewers can see Richard Webber (James Pickens Jr) still recovering in his hospital bed.

Whatever happens next, there is sure to be some big drama coming to the Grey Sloan Memorial Hospital.

Greys Anatomy returns to ABC on November 12.

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Greys Anatomy season 17: Are Owen and Teddy over for good? Tearful first-look released - Express