An infection with the human immunodeficiency virus (HIV) was previously considered incurable. The reason for this is that the virus “sleeps” in the genome of infected cells for long periods of time, making it invisible and inaccessible to both the immune system and antiviral drugs. The “Düsseldorf patient,” a 53-year-old man, is now the third person in the world to be completely cured of the HI virus by a stem cell transplant.

The patient, treated at the University Hospital Düsseldorf for his HIV infection, had received a stem cell transplant due to a blood cancer. As in the cases of the first two patients named “Berlin” and “London,” the Düsseldorf patient received stem cells from a healthy donor whose genome contains a mutation in the gene for the HIV-1 co-receptor CCR5. This mutation makes it impossible for most HI viruses to enter human CD4+ T-lymphocytes, their major target cells.

Following transplantation, the patient was carefully monitored virologically and immunologically for almost ten years. Using a variety of sensitive techniques, the researchers analysed the patient’s blood and tissue samples to closely monitor immune responses to HIV and the continued presence or even replication of the virus. Already shortly after transplantation and over the entire course of the study years, neither replicating virus nor antibodies or reactive immune cells against HIV were detected. More than four years ago, the antiviral therapy against HIV was discontinued. Ten years after transplantation and four years after the end of anti-HIV therapy, the Düsseldorf patient could be declared cured by the international research consortium.

“This case of curing a chronic HIV infection by stem cell transplantation shows that HIV can in principle be cured,” says Prof. Julian Schulze zur Wiesch, DZIF scientist at the University Medical Center Hamburg-Eppendorf and one of the study leads. “In particular, the results of this study are also enormously important for further research into a cure for HIV for the vast majority of people living with HIV for whom stem cell transplantation is not an option.”

“This method we developed allows us to easily create very large bulk samples within several minutes, rather than days or weeks using traditional methods,” said Luyao Zheng, a postdoctoral researcher in the Department of Materials Science at Penn State and lead author on the study. “And our materials are high quality — their properties can compete with single-crystal perovskites.”

The researchers used a sintering method called the electrical and mechanical field-assisted sintering technique (EM-FAST) to create the devices. Sintering is a commonly used process to compress fine powders into a solid mass of material using heat and pressure.

A typical process for making perovskites involves wet chemistry — the materials are liquefied in a solvent solution and then solidified into thin films. These materials have excellent properties, but the approach is expensive and inefficient for creating large perovskites and the solvents used may be toxic, the scientists said.

“Our technique is the best of both worlds,” said Bed Poudel, a researcher professor at Penn State and a co-author. “We get single-crystal-like properties, and we don’t have to worry about size limitations or any contamination or yield of toxic materials.”

Because it uses dry materials, the EM-FAST technique opens the door to include new dopants, ingredients added to tailor device properties, that are not compatible with the wet chemistry used to make thin films, potentially accelerating the discovery of new materials, the scientists said.

“This opens up possibilities to design and develop new classes of materials, including better thermoelectric and solar materials, as well as X- and γ-ray detectors,” said Amin Nozariasbmarz, assistant research professor at Penn State and a co-author. “Some of the applications are things we already know, but because this is a new technique to make new halide perovskite materials with controlled properties, structures, and compositions, maybe there is room in the future for new breakthroughs to come from that.”

In addition, the new process allows for layered materials — one powder underneath another — to create designer compositions. In the future, manufactures could design specific devices and then directly print them from dry powders, the scientists said.

“We anticipate this FAST perovskite would open another dimension for high throughput material synthesis, future manufacturing directly printing devices from powder and accelerating the material discovery of new perovskite compositions,” said Kai Wang, an assistant research professor at Penn State and a co-author.

EM-FAST, also known as spark plasma sintering, involves applying electric current and pressure to powders to create new materials. The process has a 100% yield — all the raw ingredients go into the final device, as opposed to 20 to 30% in solution-based processing.

The technique produced perovskite materials at .2 inch per minute, allowing scientists to create quickly create large devices that maintained high performance in laboratory tests. The team reported their findings in the journal Nature Communications.

Penn State scientists have long used EM-FAST to create thermoelectric devices. This work represents the first attempt to create perovskite materials with the technique, the scientists said.

“Because of the background we have, we were talking and thought we could change some parameters and try this with perovskites,” Nozariasbmarz said. “And it just opened a door to a new world. This paper is a link to that door — to new materials and new properties.”

Other Penn State researchers on the project were Wenjie Li and Dong Yang, assistant research professors; Ke Wang, staff scientist in the Materials Research Institute; Jungjin Yoon, Tao Ye and Yu Zhang, postdoctoral researchers; Yuchen Hou, doctoral candidate; and Shashank Priya, former associate vice president for research and director of strategic initiatives and professor of materials science and engineering.

Also contributing was Mohan Sanghadasa, U.S. Army Combat Capabilities Development Command Aviation and Missile Center.

Researchers received support from the National Science Foundation Industry-University Research Partnerships’ Center for Energy Harvesting Materials and Systems, U.S. Department of Energy’s Office of Energy Efficiency and Renewable Energy, Air Force Office of Scientific Research, and Office of Naval Research and Army Research.

The findings, published Feb. 9 in the journal Population Studies, counter prevailing wisdom that excess weight boosts mortality risk only in extreme cases.

The statistical analysis of nearly 18,000 people also shines a light on the pitfalls of using body mass index (BMI) to study health outcomes, providing evidence that the go-to metric can potentially bias findings. After accounting for those biases, it estimates that about 1 in 6 U.S. deaths are related to excess weight or obesity.

“Existing studies have likely underestimated the mortality consequences of living in a country where cheap, unhealthy food has grown increasingly accessible, and sedentary lifestyles have become the norm,” said author Ryan Masters, associate professor of sociology at CU Boulder.

“This study and others are beginning to expose the true toll of this public health crisis.”

Challenging the obesity paradox

While numerous studies show that heart disease, high blood pressure and diabetes (which are often associated with being overweight) elevate mortality risk, very few have shown that groups with higher BMIs have higher mortality rates.

Instead, in what some call the “obesity paradox,” most studies show a U-shaped curve: Those in the “overweight” category (BMI 25-30) surprisingly have the lowest mortality risk. Those in the “obese” category (30-35) have little or no increased risk over the so-called “healthy” category (18.5-25). And both the “underweight” (less than 18.5) and extremely obese (35 and higher) are at increased risk of death.

“The conventional wisdom is that elevated BMI generally does not raise mortality risk until you get to very high levels, and that there are actually some survival benefits to being overweight,” said Masters, a social demographer who has spent his career studying mortality trends. “I have been suspicious of these claims.”

He noted that BMI, which doctors and scientists often use as a health measure, is based on weight and height only and doesn’t account for differences in body composition or how long a person has been overweight.

“It’s a reflection of stature at a point in time. That’s it,” said Masters, noting that Tom Cruise (at 5 feet 7 inches and an extremely muscular 201 pounds at one point), had a BMI of 31.5, famously putting him in the category of “obese.” “It isn’t fully capturing all of the nuances and different sizes and shapes the body comes in.”

To see what happened when those nuances were considered, Masters mined the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2015, looking at data from 17,784 people, including 4,468 deaths.

He discovered that a full 20% of the sample characterized as “healthy” weight had been in the overweight or obese category in the decade prior. When set apart, this group had a substantially worse health profile than those in the category whose weight had been stable.

Masters pointed out that a lifetime carrying excess weight can lead to illnesses that, paradoxically, lead to rapid weight loss. If BMI data is captured during this time, it can skew study results.

“I would argue that we have been artificially inflating the mortality risk in the low-BMI category by including those who had been high BMI and had just lost weight recently,” he said.

Meanwhile, 37% of those characterized as overweight and 60% of those with obese BMI had been at lower BMIs in the decade prior. Notably, those who had only recently gained weight had better health profiles.

“The health and mortality consequences of high BMI are not like a light switch,” said Masters. “There’s an expanding body of work suggesting that the consequences are duration-dependent.”

By including people who had spent most of their life at low-BMI weight in the high-BMI categories, previous studies have inadvertently made high BMI look less risky than it is, he said.

When he looked at differences in fat distribution within BMI categories, he also found that variations made a huge difference in reported health outcomes.

Exposing a public health problem

Collectively, the findings confirm that studies have been “significantly affected” by BMI-related bias.

When re-crunching the numbers without these biases, he found not a U-shape but a straight upward line, with those with low BMI (18.5-22.5) having the lowest mortality risk.

Contrary to previous research, the study found no significant mortality risk increases for the “underweight” category.

While previous research estimated 2 to 3% of U.S. adult deaths were due to high BMI, his study pegs the toll at eight times that.

Masters said he hopes the research will alert scientists to be “extremely cautious” when making conclusions based on BMI. But he also hopes the work will draw attention to what he sees not as a problem for individuals alone to solve but rather a public health crisis fueled by an unhealthy or “obesogenic” environment in the U.S.

“For groups born in the 1970s or 1980s who have lived their whole lives in this obesogenic environment, the prospects of healthy aging into older adulthood does not look good right now,” he said. “I hope this work can influence higher-level discussions about what we as a society can do about it.”

This problem was tackled in a multidisciplinary project led by Prashant Mehta and Mattia Gazzola, professors of mechanical science & engineering at the University of Illinois Urbana-Champaign. As reported in Proceedings of the Royal Society A, the two researchers and their groups have developed a physiologically accurate model of octopus arm muscles. “Our model, the first of its kind, not only provides insight into the biological problem, but a framework for design and control of soft robots going forward,” Mehta said.

The impressive capabilities of octopus arms have long served as an inspiration for the design and control of soft robots. Such soft robots have the potential to perform complex tasks in unstructured environments while operating safely around humans, with applications ranging from agriculture to surgery.

Graduate student Heng-Sheng Chang, the study’s lead author, explained that soft-bodied systems like octopuses’ arms present a major modeling and control challenge. “They are driven by three major internal muscle groups — longitudinal, transverse, and oblique — that cause the arm to deform in several modes — shearing, extending, bending, and twisting,” he said. “This endows the soft muscular arms with significant freedom, unlike their rigid counterparts.”

The team’s key insight was to express the arm musculature using a stored energy function, a concept borrowed from the theory of continuum mechanics. Postdoctoral scholar and corresponding author Udit Halder explained that “The arm rests at the minimum of an energy landscape. Muscle actuations modify the stored energy function, thus shifting the equilibrium position of the arm and guiding the motion.”

Interpreting the muscles using stored energy dramatically simplifies the arm’s control design. In particular, the study outlines an energy-shaping control methodology to compute the necessary muscle activations for solving manipulation tasks such as reaching and grasping. When this approach was numerically demonstrated in the software environment Elastica, This model led to remarkably life-like motion when an octopus arm was simulated in three dimensions. Moreover, according to Halder, “Our work offers mathematical guarantees of performance that are often lacking in alternative approaches, including machine learning.”

“Our work is part of a larger ecosystem of ongoing collaborations at the University of Illinois,” Mehta said. “Upstream, there are biologists who perform experiments on octopuses. Downstream, there are roboticists who are taking these mathematical ideas and applying them to real soft robots.”

Mehta’s and Gazzola’s groups collaborated with Rhanor Gillette, Illinois Professor Emeritus of molecular and integrative physiology, to incorporate observed octopus physiology into their mathematical model for this study. Future work will discuss the biological implications of energy-based control. In addition, the researchers are collaborating with Girish Krishnan, an Illinois professor of industrial & enterprise systems engineering, to incorporate their mathematical ideas into real soft robot design and control. This will not only create a systematic way of controlling soft robots, but will also provide a deeper understanding of their working mechanisms.

This work was part of the CyberOctopus project, a multidisciplinary university research initiative in the University of Illinois’ Coordinated Science Laboratory supported by the Office of Naval Research.

Now, having examined the evolution of X7 using 20 years of data gathered by the Galactic Center Orbit Inintiative, astronomers from the UCLA Galactic Center Group and the Keck Observatory propose that it could be a cloud of dust and gas that was ejected during the collision of two stars.

Over time, they report, X7 has stretched, and it is being pulled apart as the black hole drags it closer, exerting its tidal force upon the cloud. They expect that within the next few decades, X7 will disintegrate and the gas and dust of which it is composed will eventually be drawn toward the black hole, which is called Sagittarius A*, or Sgr A*.

The study is published in The Astrophysical Journal.

“No other object in this region has shown such an extreme evolution,” said Anna Ciurlo, a UCLA assistant researcher and the paper’s lead author. “It started off comet-shaped and people thought maybe it got that shape from stellar winds or jets of particles from the black hole. But as we followed it for 20 years we saw it becoming more elongated. Something must have put this cloud on its particular path with its particular orientation.”

X7 has a mass of about 50 Earths and is on an orbital path around Sgr A* that would take 170 years to complete.

But that might never happen. Based on its trajectory, the team estimates that X7 will make its closest approach to Sgr A* around the year 2036, and then likely spiral toward Sgr A* and disappear.

“We anticipate the strong tidal forces exerted by the galactic black hole will ultimately tear X7 apart before it completes even one orbit,” said co-author Mark Morris, UCLA professor of physics and astronomy.

Tidal forces are the gravitational pull that cause an object approaching a black hole to stretch; the side of the object closest to the black hole is pulled much more strongly than the opposite end.

X7 shows some of the same properties as the other strange dusty objects orbiting Sgr A*. Those so-called G objects look like gas but behave like stars. But X7’s shape and velocity have changed more dramatically than G objects’ have. As it accelerates toward the black hole, X7 is moving rapidly, clocking in at speeds of up to around 700 miles per second.

“It’s exciting to see significant changes of X7’s shape and dynamics in such great detail over a relatively short time scale as the gravitational forces of the supermassive black hole at the center of the Milky Way influences this object,” Randy Campbell, a co-author of the paper and the science operations lead at the Keck Observatory, said in a statement.

Although X7’s origin is still the subject of debate, the finding suggests that it arose after two stars collided.

“One possibility is that X7’s gas and dust were ejected at the moment when two stars merged,” Ciurlo said. “In this process, the merged star is hidden inside a shell of dust and gas, which might fit the description of the G objects. And the ejected gas perhaps produced X7-like objects.”

The merger of two stars is very common, especially when they are near black holes, Ciurlo said.

“This is a very messy process: The stars circle each other, get closer, merge, and the new star is hidden within a cloud of dust and gas,” she said. “X7 could be the dust and gas ejected from a merged star that’s still out there somewhere.”

The findings are the first estimate of X7’s mildly elliptical orbit and the most robust analysis to date of the remarkable changes to its appearance, shape and behavior. The research team will continue to use the Keck Observatory to monitor X7’s dramatic changes as the power of the black hole’s gravity yanks it apart.

“It’s a privilege to be able to study the extreme environment at the center of our galaxy,” Campbell said in the statement. “This study can only be done using Keck’s superb capabilities, and performed at the very special and revered Maunakea, with honor and respect to the mauna.”