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It is well known that the expansion of the universe is accelerating due to a mysterious dark energy. Within galaxies, stars also experience an acceleration, though this is due to some combination of dark matter and the stellar density. In a new study to be published in Astrophysical Journal Letters researchers have now obtained the first direct measurement of the average acceleration taking place within our home galaxy, the Milky Way. Led by Sukanya Chakrabarti at the Institute for Advanced Study with collaborators from Rochester Institute of Technology, University of Rochester, and University of Wisconsin-Milwaukee, the team used pulsar data to clock the radial and vertical accelerations of stars within and outside of the galactic plane. Based on these new high-precision measurements and the known amount of visible matter in the galaxy, researchers were then able to calculate the Milky Way's dark matter density without making the usual assumption that the galaxy is in a steady-state.

"Our analysis not only gives us the first measurement of the tiny accelerations experienced by stars in the galaxy, but also opens up the possibility of extending this work to understand the nature of dark matter, and ultimately dark energy on larger scales," stated Chakrabarti, the paper's lead author and a current Member and IBM Einstein Fellow at the Institute for Advanced Study.

Stars hurtle through the galaxy at hundreds of kilometers per second, yet this study indicates that the change in their velocities is occurring at a literal snail's pace--a few centimeters per second, which is about the same speed as a crawling baby. To detect this subtle motion the research team relied on the ultraprecise time-keeping ability of pulsars that are widely distributed throughout the galactic plane and halo--a diffuse spherical region that surrounds the galaxy.

"By exploiting the unique properties of pulsars, we were able to measure very small accelerations in the Galaxy. Our work opens a new window in galactic dynamics," said co-author Philip Chang of the University of Wisconsin-Milwaukee.

Extending outwards approximately 300,000 light years from the galactic center, the halo may provide important hints to understanding dark matter, which accounts for about 90 percent of the galaxy's mass and is highly concentrated above and below the star-dense galactic plane. Stellar motion in this particular region--a primary focus of this study--can be influenced by dark matter. Utilizing the local density measurements obtained through this study, researchers will now have a better idea of how and where to look for dark matter.

While previous studies assumed a state of galactic equilibrium to calculate average mass density, this research is based on the natural, non-equilibrium state of the galaxy. One might analogize this to the difference between the surface of a pond before and after a stone is tossed in. By accounting for the "ripples" the team was able to obtain a more accurate picture of reality. Though in this case, rather than stones, the Milky Way is influenced by a turbulent history of galactic mergers and continues to be perturbed by external dwarf galaxies like the Small and Large Magellanic Clouds. As a result, stars do not have flat orbits and tend to follow a path similar to that of a warped vinyl record, crossing above and below the galactic plane. One of the key factors that enabled this direct observational approach was the use of pulsar data compiled from international collaborations, including NANOGrav (North American Nanohertz Observatory for Gravitational Waves) that has obtained data from the Green Bank and Arecibo telescopes.

This landmark paper expands upon the work of Jan H. Oort (1932); John Bahcall (1984); Kuijken & Gilmore (1989); Holmberg & Flynn (2000); Jo Bovy & Scott Tremaine (2012) to calculate the average mass density in the galactic plane (Oort limit) and local dark matter density. IAS scholars including Oort, Bahcall, Bovy, Tremaine, and Chakrabarti have played an important role in advancing this area of research.

"For centuries astronomers have measured the positions and speeds of stars, but these provide only a snapshot of the complex dynamical behavior of the Milky Way galaxy," stated Scott Tremaine, Professor Emeritus at the Institute for Advanced Study. "The accelerations measured by Chakrabarti and her collaborators are directly caused by the gravitational forces from the matter in the galaxy, both visible and dark, and thereby provide a new and promising window on the distribution and the composition of the matter in the galaxy and the universe."

This particular paper will enable a wide variety of future studies. Accurate measurements of accelerations will also soon be possible using the complementary radial velocity method that Chakrabarti developed earlier this year, which measures the change in the velocity of stars with high precision. This work will also enable more detailed simulations of the Milky Way, improve constraints on general relativity, and provide clues in the search for dark matter. Extensions of this method may ultimately allow us to directly measure the cosmic acceleration as well.

While a direct picture of our home galaxy--similar to the ones of Earth taken by the Apollo astronauts--is not yet possible, this study has provided essential new details to help envision the dynamic organization of the galaxy from within.

In diseases characterized by bone loss -such as periodontitis, rheumatoid arthritis, and osteoporosis- there is a lot that scientists still don't understand. What is the role of the immune response in the process? What happens to the regulatory mechanisms that protect bone?

In a paper published recently in Scientific Reports, researchers from the Forsyth Institute and the Universidad de Chile describe a mechanism that unlocks a piece of the puzzle. Looking at periodontal disease in a mouse model, scientists found that a specific type of T cell, known as regulatory T cells, start behaving in unexpected ways. These cells lose their ability to regulate bone loss and instead begin promoting inflammation.

"That is important because, in many therapies analyzed in in-vivo models, researchers usually check if the number of regulatory T cells has increased. But they should check if these cells are indeed functioning," says Dr. Carla Alvarez, a postdoctoral researcher at Forsyth and lead author of the paper.

Regulatory T cells control the body's immune response. In periodontal disease, bone loss occurs because the body's immune system responds disproportionately to the microbial threat, causing inflammation and destroying healthy tissue. Normally, regulatory T cells help suppress that destruction, but they appear to lose their suppressive abilities during periodontal disease.

In scientific terms, this process is analyzed in the field of osteoimmunology, which explores the complex interactions between the immune system and bone metabolism.

"This is an interesting mechanism highlighting how the bone loss is taking place in periodontal disease," says Dr. Alpdogan Kantarci, Senior Member of Staff at Forsyth and co-author of the paper together with Dr. Rolando Vernal, Professor from the School of Dentistry at Universidad de Chile.

In the case of periodontal disease, a potential therapy targeting regulatory T cells could restore the T cells' normal functioning, not just increase their numbers.

"Unfortunately, this is not a linear process--that's the complicated part," Kantarci says.

Periodontal disease is initiated by microbes in the mouth, making it all the more complex.

"The relationship between immune response and bone is not so straightforward," says Alvarez. "There are multiple components. You have to imagine a complex network of signaling and cells that participate."

This cellular and microbial complexity is what makes the disease so difficult to study in humans. However, examining this mechanism in humans is the next step of the research, Alvarez says. The research team is planning a collaborative study to look at healthy and diseased patients, intending to observe similar mechanisms to what was seen in the animal model.

BUFFALO, N.Y. -- Scientists have known for years that mutations in the MLL4 gene can cause Kabuki syndrome, a rare developmental disorder.

But a study published on Jan. 11 in Nature Communications illuminates new details regarding how this occurs. (Images are available by contacting Charlotte Hsu in UB Media Relations at chsu22@buffalo.edu.)

The research suggests that MLL4 controls the production of neurons that secrete growth hormone-releasing hormone (GHRH) in a part of the brain called the hypothalamus. Mice without working copies of the MLL4 gene in this area had stunted growth and markedly fewer GHRH neurons. Mice with only one functioning copy of the gene had similar problems.

These are important insights, as GHRH stimulates production of the growth hormone in the pituitary gland in both mice and people. While the effects of Kabuki syndrome vary, delayed growth and short stature are common among patients.

"Given our findings, inactivation of MLL4 is presumed to lead to a loss of GHRH-neurons, resulting in lack of typical growth in Kabuki patients," says Jae Lee, PhD, professor of biological sciences in the University at Buffalo College of Arts and Sciences. "We also researched the epigenetic activity of MLL4, and our studies suggest that MLL4 could be a great epigenetic target molecule to treat various symptoms of Kabuki syndrome."

"This is the first study that demonstrates roles of MLL4 in fate determination of neuronal cell types during development, a significant advance in our efforts to understand how cell fates are determined epigenetically, an important question remaining to be answered in modern neurobiology," says Seunghee Lee, associate professor of pharmacy at Seoul National University.

Jae Lee and Seunghee Lee are the study's senior authors. The first author is Christian Huisman, PhD, a postdoctoral scholar at Oregon Health & Science University.

A detailed look at the work of MLL4

For patients, parents and caregivers, new knowledge about the biology of rare diseases provides hope, laying a foundation for the development of treatments, says Jae Lee, who is the parent of a child with a different rare genetic disorder (FOXG1 syndrome).

Though mutations in different genes can lead to Kabuki syndrome, mutations in MLL4 are one of the most common causes of the disorder.

As part of the new study, the team used cutting-edge techniques to investigate the molecular mechanisms by which MLL4 controls the creation of GHRH-neurons in embryonic development in mice. The research shows that MLL4 helps to activate various genes involved in producing GHRH neurons, and finds that a transcription factor called NRF1 is a key partner in this process.

Moreover, the scientists showed that small chemicals that mimic the epigenetic actions of MLL4 can help to restore production of GHRH neurons.

While growth hormone therapies already exist, Jae Lee says the new research creates opportunities for exploring treatment pathways for other Kabuki syndrome symptoms.

"Kabuki syndrome has many other symptoms that are not treatable, and targeting the epigenetic activities of MLL4 could be a feasible strategy for treating other symptoms," Jae Lee says. "The principle we found -- dealing with the roles of the epigenetic activity of MLL4 in cell-type specification -- may apply to various symptoms."

CLEVELAND - As reported in Nature Communications, researchers from Cleveland Clinic's Lerner Research Institute have developed a novel, patient-derived model of ulcerative colitis, which will help advance studies into new treatments for the chronic inflammatory bowel disease.

The team used the model to identify a promising target that could be inhibited to slow disease progression.
Ulcerative colitis is characterized by abnormal reactions of the immune system that lead to inflammation and ulcers on the inner lining of the large intestines. It is a highly heterogeneous condition, both in terms of patients' symptoms and disease pathology.

Suppressing the overactive immune response with anti-inflammatory drugs is the current mainstay treatment for inflammatory bowel diseases, although these therapies have limited long-term efficacy in ulcerative colitis patients.

Research suggests that elements of both the immune system and the ulcerative colitis microenvironment (the surrounding, less diseased cellular components) interact to drive disease development and progression.

Considering that immune-suppressing drugs have demonstrated limited success in treating ulcerative colitis, researchers are interested to learn whether targeting elements of the microenvironment--including components of the intestinal lining (called the epithelium) and stem cell-like cells called stromal cells--may be a better or complementary treatment approach.

"Gaining a more comprehensive understanding of the complex interplay between immune and other cell types will be critical to developing new and more effective ulcerative colitis therapies and tailored, patient-specific treatment approaches," said Emina Huang, MD, staff in the Departments of Cancer Biology and Colorectal Surgery, and the study's lead author.

Dr. Huang, who is also a practicing colorectal surgeon, and her team developed their model using tissue samples from patients with ulcerative colitis who underwent surgery at Cleveland Clinic. They isolated a specific type of cell (called fibroblasts) that can be "reprogrammed" to develop into all-purpose, undifferentiated cells called induced pluripotent stem cells, which have emerged as a growing research priority.

The researchers then grew the stem cells in the lab into tiny, three-dimensional tissues that mimic actual organs (called organoids). They found that compared to healthy colon organoids, the diseased organoids reflected histological and functional features commonly observed in ulcerative colitis patients, including reduced mucus secretions, faulty barrier integrity of the intestinal lining and overexpression of select proteins (including one called CXCL8).

"Our in vitro model accurately mirrors what we observe in patients in the clinic and is much more dynamic than current models. For example, other organoid models only focus on the contributions of the epithelium, where ours reflects the contributions of other microenvironment components, too, like the stroma," said Dr. Huang.

After developing the model, the team was able to rapidly identify novel drug targets and candidates. They showed that inhibiting CXCL8 expression with a small molecule called repertaxin helped to slow disease progression.

"We look forward to further exploring repertaxin's potential benefit in other preclinical and eventual clinical studies," said Dr. Huang. "We are hopeful that others will also find this model useful in identifying other potential anti-ulcerative colitis drugs." She also noted that the approach used to develop this new ulcerative colitis model may also be used to model other complex diseases.

Oncotarget recently published "PD-1/PD-L1 expression in anal squamous intraepithelial lesions" which reported that the presence and distribution of CD8 lymphocytes and the presence of PD-1 lymphocytes and PD-L1 epithelial cells were assessed.

CD8 lymphocytes were observed more frequently in HSIL versus LSIL in the lamina propria or intra epithelial.

PD-1 lymphocytes were observed more frequently in HSIL versus LSIL.

There was no difference between HSIL and LSIL for PD-L1 epithelial cells.

Anal dysplastic lesions are accompanied by an inflammatory lymphocytic infiltrate expressing CD8 and PD-1, more frequent in high-grade lesions.

Dr. Margot Bucau from The Hôpital Bichat-Claude Bernard said, "Anal intraepithelial neoplasia (AIN) is the precursor lesion for anal squamous cell carcinomas (ASCC)."

Dr. Margot Bucau from The Hôpital Bichat-Claude Bernard said, "Anal intraepithelial neoplasia (AIN) is the precursor lesion for anal squamous cell carcinomas (ASCC).

Since 2012, the Lower Anogenital Squamous Terminology recommended denomination for HPV-associated squamous lesions of the lower anogenital tract as low-grade and high-grade squamous intraepithelial lesion.

Oncogenic HPV infection plays a crucial role in developing both cervical and anal lesions, by the integration of the viral DNA into the epithelial cells and activation of oncogenic early proteins E6 and E7. This causes downregulation of suppressing tumor genes, especially TP53 and Rb, and upregulation of p16.

In the cervix, HPV related cancer often have increased infiltration by immune cell populations, including cytotoxic CD8 T cells, that correlates with better response to chemoradiotherapy and increased survival compared to immune-deprived tumors.

Moreover, p16 positive tumors were shown to present higher tumor-infiltrating lymphocytes density and better recurrence-free survival.

The Bucau Research Team concluded in their Oncotarget Research Paper, "our exploratory study highlights the interest of the PD-1/PD-L1 pathway in anal dysplasia and the importance to further explore the different mechanisms of immune micro environment in the progression of anal intra epithelial lesion. It suggests the potential role of therapeutic molecules targeting the immune response to slow down the tumor progression in selected patients with HSIL."

A team led by University of Minnesota Twin Cities researchers has discovered a groundbreaking one-step process for creating materials with unique properties, called metamaterials. Their results show the realistic possibility of designing similar self-assembled structures with the potential of creating "built-to-order" nanostructures for wide application in electronics and optical devices.

The research was published and featured on the cover of Nano Letters, a peer-reviewed scientific journal published by the American Chemical Society.

In general, metamaterials are materials made in the lab so as to provide specific physical, chemical, electrical, and optical properties otherwise impossible to find in naturally occurring materials. These materials can have unique properties which make them ideal for a variety of applications from optical filters and medical devices to aircraft soundproofing and infrastructure monitoring. Usually these nano-scale materials are painstakingly produced in a specialized clean room environment over days and weeks in a multi-step fabrication process.

In this new research, a University of Minnesota team was studying a thin-film material called strontium stannate or SrSnO3. During their research, they noticed the surprising formation of checker-board patterns at the nano scale similar to the metamaterial structures fabricated in the costly, multistep process.

"At first we thought this must be a mistake, but soon realized that the periodic pattern is a mixture of two phases of the same material with different crystal structures" said Bharat Jalan, the senior author of the study and an expert in material synthesis who is the Shell Chair in the University of Minnesota's Department of Chemical Engineering and Materials Science. "After consulting with colleagues at the University of Minnesota, University of Georgia, and City University of New York, we realized that we may have discovered something quite special that can potentially have some unique applications."

The material had spontaneously organized into an ordered structure as it changed from one phase to another. During what is called a "first-order structural phase transition" process, the material moved into a mixed-phase in which some parts of the system completed the transition and others did not.

"These nanoscale periodic patterns are the direct consequence of the first-order structural phase transition in this material," said University of Minnesota aerospace engineering and mechanics Professor Richard James, a co-author of the study and a Distinguished McKnight University Professor. "For the first time, our work enables a host of possibilities for utilizing reversible structural phase transformations with nanoelectronic and photonic systems."

In fact, the team demonstrated a process for the first-ever, self-assembled, tunable nanostructure to create metamaterials in just one step. The researchers were able to tune the ability to store electrical charge property within a single film using temperature and laser wavelength. They effectively created a variable photonic crystal material with 99 percent efficiency.

Using high-resolution electron microscopes, the researchers confirmed the unique structure of the material.

"We observed that the boundaries between these crystallographic phases were sharply defined at the atomic scale, which is remarkable for a self-assembled process," said Professor Andre Mkhoyan, a co-author of the study, an expert in advanced electron microscopy, and the Ray D. and Mary T. Johnson/Mayon Plastics Chair in the Department of Chemical Engineering and Materials Science at the University of Minnesota.

The researchers are now looking to future applications for their discovery in optical and electronic devices.

"When we started this research, we never thought about these applications. We were driven by the fundamental study of the physics of the material," Jalan said. "Now, all of a sudden, we seem to have opened up a completely new area of research, which is driven by the possibility of many new and exciting applications."

(Boston)--Little previous research has examined the effects of Dense Breast Notifications (DBNs), but a new study suggests the legislatively required notifications have achieved partial success: women living in states in which in DBNs are mandated had higher rates of being informed about personal breast density and of having had breast density discussions with providers, though rates were low overall.

DBNs are a written notification to a woman after a mammogram with information about breast density. The goal is to motivate her to speak with her doctor about her personal risk and determine if supplemental screening for breast cancer is appropriate. DBNs are mandated in more than 38 states and the Food Drug Administration (FDA) is developing standardized language for a federal/nationwide notification.

Prior findings from these same researchers at Boston University School of Medicine (BUSM) showed many states' DBNs are written at a higher literacy level than women residing in that state, which suggests that some women may find it hard to understand the notifications. They have now conducted one of the first national surveys to ask women about their reactions to these notifications and to understand their knowledge, awareness and plans about breast density while examining whether these findings vary among women of varying race/ethnicity, income, and health literacy levels.

In this new study, the researchers investigated whether there were differential breast density awareness, knowledge or discussions among women residing in states with and without DBN legislation or based on sociodemographic characteristics.

Although the study did show that DBN laws are associated with more women receiving information about personal breast density and increased likelihood of having a discussion with a healthcare provider about breast density, women of color, those with lower incomes and those with lower health literacy were generally less likely to have received personal breast density information or to speak with their providers. However, while DBN laws were not generally associated with differences in women's knowledge about risks associated with breast density, Hispanic, lower income, and low health literacy women had less knowledge regarding density's tendency to mask cancers on mammograms, and were less likely to recognize the increased breast cancer risk.

"These findings suggest that 'one size does not fit all' when breast density information is conveyed and suggests that the message or the mode of dissemination may need to be tailored for different populations to achieve knowledge equity," explained corresponding author Nancy Kressin, PhD, professor of medicine at BUSM.

Given that women in DBN states were twice as likely to speak with their doctors, the researchers believe physicians seem a natural conduit for tailored discussions that meet each woman's needs. However, Kressin points out that prior studies have shown that for this approach to be most effective, further physician education will be needed.

Scientists from the University of Bath have made a sustainable polymer using the second most abundant sugar in nature, xylose.

Not only does the new nature-inspired material reduce reliance on crude oil products, but its properties can also be easily controlled to make the material flexible or crystalline.

The researchers, from the University's Centre for Sustainable and Circular Technologies, report the polymer, from the polyether family, has a variety of applications, including as a building block for polyurethane, used in mattresses and shoe soles; as a bio-derived alternative to polyethylene glycol, a chemical widely used in bio-medicine; or to polyethylene oxide, sometimes used as electrolyte in batteries.

The team says additional functionality could be added to this versatile polymer by binding other chemical groups such as fluorescent probes or dyes to the sugar molecule, for biological or chemical sensing applications.

The team can easily produce hundreds of grams of the material and anticipate that production would be rapidly scalable.

Dr Antoine Buchard, Royal Society University Research Fellow and Reader at the Centre for Sustainable and Circular Technologies, led the study.

He said: "We're very excited that we've been able to produce this sustainable material from a plentiful natural resource - wood.

"The reliance of plastics and polymers on dwindling fossil fuels is a major problem, and bio-derived polymers - those derived from renewable feedstocks such as plants - are part of the solution to make plastics sustainable.

"This polymer is particularly versatile because its physical and chemicals properties can be tweaked easily, to make a crystalline material or more of a flexible rubber, as well as to introduce very specific chemical functionalities.

"Until now this was very difficult to achieve with bio-derived polymers.

"This means that with this polymer, we can target a variety of applications, from packaging to healthcare or energy materials, in a more sustainable way."

Like all sugars, xylose occurs in two forms that are mirror images of each other - named D and L.

The polymer uses the naturally occurring D-enantiomer of xylose, however the researchers have shown that combining it with the L-form makes the polymer even stronger.

The research team has filed a patent for their technology and is now interested in working with industrial collaborators to further scale up production and explore the applications of the new materials.

An international team of researchers, including Professor Roberto Morandotti of the Institut national de la recherche scientifique (INRS), just introduced a new photonic processor that could revolutionize artificial intelligence, as reported by the prestigious journal Nature.

Artificial neural networks, layers of interconnected artificial neurons, are of great interest for machine learning tasks such as speech recognition and medical diagnosis. Actually, electronic computing hardware are nearing the limit of their capabilities, yet the demand for greater computing power is constantly growing.

Researchers turned themselves to photons instead of electrons to carry information at the speed of light. In fact, not only photons can process information much faster than electrons, but they are the basis of the current Internet, where it is important to avoid the so-called electronic bottleneck (conversion of an optical signal into an electronic signal, and vice versa).

Increased Computing Speed

The proposed optical neural network is capable of recognizing and processing large-scale data and images at ultra-high computing speeds, beyond ten trillion operations per second. Professor Morandotti, an expert in integrated photonics, explains how an optical frequency comb, a light source comprised of many equally spaced frequency modes, was integrated into a computer chip and used as a power-efficient source for optical computing.

This device performs a type of matrix-vector multiplication known as a convolution for
image-processing applications. It shows promising results for real-time massive-data machine learning tasks, such as identifying faces in cameras or pathology identification in clinical scanning applications. Their approach is scalable and trainable to much more complex networks for demanding applications such as unmanned vehicles and real-time video recognition, allowing, in a not-so-far future, a full integration with the up-and-coming Internet of Things.

Oncotarget recently published "Targeted lymphodepletion with a CD45-directed antibody radioconjugate as a novel conditioning regimen prior to adoptive cell therapy" which reported that Chimeric antigen receptor T cell therapies, and adoptive cell therapy in general, represent one of the most promising anti-cancer strategies.

In contrast to relatively non-specific chemotherapy-derived lymphodepletion, targeted lymphodepletion with radioimmunotherapy directed to CD45 may be a safer and more effective alternative to target and deplete immune cells. Here the authors describe the results of preclinical studies with an anti-mouse CD45 antibody 30F11, labeled with two different beta-emitters 131Iodine and 177Lutetium, to investigate the effect of anti-CD45 RIT lymphodepletion on immune cell types and on tumor control in a model of adoptive cell therapy.

Treatment of mice with 3.7 MBq 131I-30F11 or 1.48 MBq 177Lu-30F11 safely depleted immune cells such as spleen CD4 and CD8 T Cells, B and NK cells as well as Tregs in OT I tumor model while sparing RBC and platelets and enabled E. G7 tumor control. These results support the application of CD45-targeted RIT lymphodepletion with a non-myeloablative dose of 131I-30F11 or 177Lu-30F11 antibody prior to adoptive cell therapy.

Dr. Dale L. Ludwig from Actinium Pharmaceuticals said, "Chimeric antigen receptor (CAR) T cell therapies, and adoptive cell therapy (ACT) in general, represent one of the most promising anti-cancer strategies."

It is unclear why some patients respond to treatment with adoptive cell therapies such as CAR-T, and others do not, though the tumor immune microenvironment is a likely contributor to variable effect of cell therapy in both hematologic and solid cancers.

Other cell types that contribute to an immunosuppressive tumor microenvironment that may negatively impact CAR-T efficacy include myeloid derived suppressor cells and tumor-associated macrophages.

The CD45 antigen is found on all nucleated immune cells, with increased expression on mature lymphoid and myeloid lineages, leading to preferential depletion of mature immune cells compared to progenitor hematopoietic cells.

Importantly, immunomodulatory cells such as Tregs and MDSC express CD45 and are targets of lymphodepletion with a CD45-targeting antibody-radionuclide conjugate, potentially resulting in better engraftment, activation and persistence of the exogenously added CAR-T cells in patients.

Here the Oncotarget authors describe the results of preclinical studies with an anti-mouse CD45 antibody 30F11, labeled with two different beta-emitters - 131I and 177Lutetium, to investigate the effect of anti-CD45 RIT lymphodepletion on immune cell types and on tumor control in a model of adoptive cell therapy.

The Ludwig Research Team concluded in their Oncotarget Research Paper, "our data supports CD45 targeted RIT lymphodepletion with a non-myeloablative dose of 131I-30F11 or 177Lu-30F11 prior to adoptive cell therapy."

For the brain to learn, retain memories, process sensory information, and coordinate body movements, its groups of nerve cells must generate coordinated electrical signals. Disorder in synchronous firing can impair these processes and, in extreme cases, lead to seizures and epilepsy.

Synchrony between neighboring neurons depends on the protein connexin 36, an essential element of certain types of synaptic connections that, unlike classical chemical synapses, pass signals between neurons through direct electrical connections. For more than 15 years, scientists have debated the tie between connexin 36 and epilepsy.

Now, a team of Virginia Tech scientists led by Yuchin Albert Pan, an associate professor at the Fralin Biomedical Research Institute at VTC, have identified a new link between seizures and connexin 36 deficiency. The discovery, published today (Jan. 11, 2021) in Frontiers in Molecular Neuroscience,, found that this interaction may make the brain more prone to having seizures.

Alyssa Brunal, a recent graduate of Virginia Tech's translational biology, medicine, and health doctoral program, working with her mentor Pan, developed new models for studying the relationship between connexin 36 and seizures and confirmed the relationship.

Zebrafish serve as a powerful animal model, allowing researchers to evaluate the effects of connexin 36 on the whole brain in an intact living system during neural hyperactivity.

As an essential component of electrically coupled synapses between neurons, connexin 36 plays an important role in rapid and synchronous activation of interconnected neworks of neurons within the brain, which is necessary for normal brain processes.

"In previous studies, people weren't using the same model organisms. They weren't looking at the same brain regions. They weren't using the same methods for inducing seizures," Brunal said. "I thought, because the zebrafish is such a versatile model organism, we could use it to try to discern what actually is going on."

Pan, who frequently uses larval zebrafish in studies, said the fish are ideal because they develop outside the womb, are translucent, and their entire brains are small enough to fit entirely under a microscope.

"Using modern microscopy techniques, we can see in an intact animal what is happening inside the brain," said Pan, who is also the research institute's Commonwealth Center for Innovative Technology Eminent Research Scholar in Developmental Neuroscience, and an associate professor in the department of biomedical sciences and pathobiology of the Virginia-Maryland College of Veterinary Medicine.

Brunal created dozens of whole-brain maps of zebrafish for the study.

The researchers used varying doses of a seizure-inducing drug, which causes neuronal hyperactivation, one of the main contributors to seizures. By comparing normal, wild-type zebrafish and mutant zebrafish with connexin 36 deficiencies, they found that connexin 36 deficiency altered the susceptibility to neuronal hyperactivity in a brain-region and drug-dose dependent manner.

Having established that a lack of connexin protein changed seizure susceptibility, they wondered if the hyperactivity associated with seizures, in turn, affected the expression of the protein. To test this, they applied the seizure-inducing drug to only the wild-type zebrafish, but this time, instead of looking for hyperactivity in the brain, they looked for expression of connexin 36. The results were striking.

The drug-induced hyperactivity caused an acute drop in connexin 36 levels across the brain, which recovered over time.

"I was like, holy cow, there's something actually happening to the protein. So not only is the protein affecting hyperactivity, we're also having some effect on the protein itself," Brunal said. "I think that's what really broke the project wide open."

The results were impressive, Pan said.

"A lot of times in science, you don't know what's going on until you painstakingly quantify the microscope images and see something that emerges from statistical analysis to a level of significance, but in one instance in this study, the connexin 36 was visibly gone," Pan said. "We thought, there's got to be something important there."

They applied a connexin 36-blocking drug on wild-type zebrafish, before administering the seizure-inducing drug. They compared the results to a control group of wild-type zebrafish that received only the seizure-inducing drug. The first group had significantly more neuronal hyperactivity, suggesting that an acute loss of connexin 36 may lead to more seizures.

While it's well known that having one seizure increases the likelihood of subsequent events, the mechanisms underlying this clinical phenomena are not well understood. This study describes a novel mechanism: seizures reduce connexin 36 levels in zebrafish models, and may contribute to the onset of subsequent seizures.

Many policymakers and educational institutions hope to boost their economies by stimulating students' entrepreneurial intentions. To date, most research concluded that entrepreneurship education could increase these intentions by improving the image that students have of entrepreneurship as a career option, making them see how their environment can help them become entrepreneurs or increasing their self-confidence regarding their entrepreneurial skills. However, recent studies show that even if these goals are achieved, students' entrepreneurial intentions often do not grow.

Anne van Ewijk, an associate professor of Management at Abu Dhabi University, and Wiebke Weber, deputy director of the Research and Expertise Centre for Survey Methodology (RECSM) at the UPF Department of Political and Social Sciences, launched an international project that involved several universities in nine countries on six continents: Argentina, Australia, Belgium, Finland, Kenya, Malaysia, Netherlands, UAE and the United States. The article has been published recently in the online edition of Journal of Business Venturing Insights, which specializes in research related to entrepreneurial phenomena.

As part of the results of this project, the researchers confirmed an alternative dynamics to entrepreneurial intentions in education: "Students make more pronounced decisions for or against entrepreneurship when they are highly aware of what they want in life", they say. And they add: "Unfortunately, entrepreneurship courses included in the study, on average, did not help students better understand their life goals", which is a skill that did not increase greatly either with older age or with a higher level of studies.

According to the authors, when trainers facilitate an understanding of these life goals, they will improve the "sorting effect" (whereby students become more convinced about whether entrepreneurship is right for them or not): "Thus, enterprise training will contribute to the selection of aspiring entrepreneurs who are more motivated", they assure.

This study is a first step towards a new idea of what to measure in studies on the formation of entrepreneurial intentions in entrepreneurship education, in addition to the variables from dominant intention models. Future studies with larger samples could complete these findings with more information of what is happening inside and outside the classroom, or investigating solving possible goal conflicts of future entrepreneurs.

HOUSTON - (Jan. 11, 2021) - Rice University scientists have extended their technique to produce graphene in a flash to tailor the properties of other 2D materials.

The labs of chemist James Tour and materials theorist Boris Yakobson reported in the American Chemical Society's ACS Nano they have successfully "flashed" bulk amounts of 2D dichalcogenides, changing them from semiconductors to metallics.

Such materials are valuable for electronics, catalysis and as lubricants, among other applications.

The process employs flash Joule heating -- using an electrical charge to dramatically raise the material's temperature -- to convert semiconducting molybdenum disulfide and tungsten disulfide. The duration of the pulse and select additives can also control the now-metallic products' properties.

"This rapid process permits us to make an entirely new class of highly valued materials in large scale and without the use of solvents or water," Tour said.

Two-dimensional dichalcogenides look like hexagonal graphene from above, but viewing them from an angle reveals a sandwichlike structure. In molybdenum disulfide, for instance, a single plane of molybdenum atoms sits between similar, but offset, planes of sulfur.

Making each material in its metallic phase (known as 1T) previously required far more complex processes, according to the researchers. Even then, the products were known to be unstable in ambient conditions. Flash Joule heating appears to solve that problem, producing metastable dichalcogenides in a thousandth of a second.

Powdered, commercially available dichalcogenides mixed with carbon black or tungsten powder to increase their conductivity were placed in a ceramic tube capped with electrodes and flashed with more than 1,350 amps of power for a fraction of a second, then rapidly cooled. With the tube under vacuum, extraneous gases were vented, leaving mostly pure metallics to be harvested.

According to the Yakobson team's calculations, the large energy input forces structural defects to appear in the materials' crystal lattices, adding negative charges that make 1T the thermodynamically preferred phase.

"It is an interesting fast-forward incarnation of Le Chatelier's principle: Under voltage, the material changes to a more conducting 1T phase, to counteract/reduce the applied electric fields," said co-author Ksenia Bets, a researcher in the Yakobson group. "Our detailed computations reveal that the kinetic path is indirect: The sublimating sulfur creates a vacancy-rich lattice that energetically prefers a 1T structure."

The fact that conditions and additives can influence the final product should lead to a systematic study about possible variations, Tour said.

Rice graduate student Weiyin Chen is lead author of the paper. Additional co-authors are Rice graduate students Zhe Wang, Emily McHugh, Wala Algozeeb and Jinhang Chen; postdoctoral researchers Duy Xuan Luong and Bing Deng; alumni Muqing Ren and Michael Stanford; assistant research professor Hua Guo; research scientist Guanhui Gao; and undergraduates John Tianci Li and William Carsten.

Tour is the T.T. and W.F. Chao Chair in Chemistry as well as a professor of computer science and of materials science and nanoengineering. Yakobson is the Karl F. Hasselmann Professor of Materials Science and NanoEngineering and a professor of chemistry.

The Air Force Office of Scientific Research, the Department of Energy (DOE) National Energy Technology Laboratory and DOE Basic Energy Sciences supported the research.

DURHAM, N.C. - A Duke-led team of scientists has developed a bio-compatible surgical patch that releases non-opioid painkillers directly to the site of a wound for days and then dissolves away.

The polymer patch provides a controlled release of a drug that blocks the enzyme COX-2 (cyclooxygenase-2,) which drives pain and inflammation. The study appears Jan. 10, 2021 in the Journal of Controlled Release.

When they started "We were making hernia meshes and different antimicrobial films," said Matthew Becker, the Hugo L. Blomquist professor chemistry at Duke, and last author on the paper. "We thought you could potentially put pain drugs or anesthetics in the film if you just sew it in as you're stitching the person up, then you wouldn't necessarily have to prescribe any opioids," Becker said.

The work grew out of a $2 million grant Becker received from the state of Ohio at his previous institution to investigate non-opioid pain management , one measure toward fighting a nationwide epidemic of opioid drug abuse. Since arriving at Duke in 2019, Becker's team has partnered with Duke pain control expert Dr. Ru-Rong Ji and his team to refine the idea.

The polymer itself, comprised of poly(ester urea) homopolymers and co-polymers, is also special, Becker said.

"Most polymers that are used in medicine swell, and everything comes out at once," Becker said. But this polymer erodes slowly, and its painkiller dose and longevity can be controlled simply by varying the surface area and thicknesses. "The film is about like a piece of paper."

"If you can get four or five days of pain control out of the patch and not have to take those other pain drugs, not only do you avoid some of the side effects and risks of addiction, you're concentrating therapy where you need it," Becker said.

Rat studies also showed that the painkiller stayed in tissues close to the patch site, rather than dissolving into circulating plasma.

Becker said the patch should be able to provide three or four days of wound-pain management, which is the critical period for post-surgical pain. The implantable film would be particularly useful in endoscopic procedures and instances where the physicians and patients would like to avoid opioid exposure such as Cesarean births and pediatric surgeries. In studies with mice that mimic the neuropathic pain of diabetes, the pain patch was placed against a nerve and provided a four-day nerve block.

University of Wyoming researchers headed a study that shows nonnative birds in Oahu, Hawaii, have taken over the role of seed dispersal networks on the island, with most of the seeds coming from nonnative plants.

"Hawaii is one of the most altered ecosystems in the world, and we are lucky enough to examine how these nonnative-dominated communities alter important processes, such as seed dispersal," says Corey Tarwater, an assistant professor in the UW Department of Zoology and Physiology. "What we have found is that not only do nonnative species dominate species interactions, but that these nonnative species play a greater role in shaping the structure and stability of seed dispersal networks than native species. This means that loss of a nonnative species from the community will alter species interactions to a greater extent than loss of a native species."

Tarwater was the anchor author of a paper, titled "Ecological Correlates of Species' Roles in Highly Invaded Seed Dispersal Networks," which was published Jan. 11 (today) in the Proceedings of the National Academy of Sciences (PNAS). PNAS is the official journal of the National Academy of Sciences and an authoritative source of high-impact, original research that broadly spans the biological, physical and social sciences.

Jeferson Vizentin-Bugoni, a postdoctoral researcher at UW and the U.S. Army Research Laboratory at the time of the research, is the paper's lead author. He performed most analyses and conceptualized and outlined the first version of the manuscript.

Becky Wilcox, of Napa, Calif., a recent UW Ph.D. graduate and now a postdoctoral researcher, and Sam Case, of Eden Prairie, Minn., a UW Ph.D. student in the Program in Ecology as well as in zoology and physiology, worked with Tarwater. The two aided in field data collection, processing all of the footage from the game cameras, and assisted in writing the paper. Patrick Kelley, a UW assistant research scientist in zoology and physiology, and in the Honors College, helped with developing project ideas, data processing and management, and writing the paper.

Other researchers who contributed to the paper are from the University of Hawaii, University of Illinois, Northern Arizona University and the U.S. Army Corps of Engineers in Champaign, Ill.

"This is one of the first studies showing that nonnative species can take over the most important roles in seed dispersal networks. This means that Oahu's ecosystems have been so affected by species extinctions and invasions that most of the seeds dispersed on the island belong to nonnative plants, and most of them are dispersed by nonnative birds," Vizentin-Bugoni says. "This forms what has been called 'ecological meltdown,' which is a process occurring when nonnative mutualistic partners benefit each other and put the system into a vortex of continuous modification."

Seed dispersal by animals and birds is one of the most crucial ecosystem functions. It is linked to plant population dynamics, community structure, biodiversity maintenance and regeneration of degraded ecosystems, according to the paper.

Before Hawaii became the extinction and species invasion capital of the world, its ecological communities were much more diverse. Experts estimate that, in the last 700 years, 77 species and subspecies of birds in the Hawaiian Archipelago have gone extinct, accounting for 15 percent of bird extinctions worldwide.

"The Hawaiian Islands have experienced major changes in flora and fauna and, while the structure of seed dispersal networks before human arrival to the islands is unknown, we know from some of our previous work, recently published in Functional Ecology, that the traits of historic seed dispersers differ from the traits of introduced ones," Case says. "For instance, some of the extinct dispersers were larger and could likely consume a greater range in seed sizes compared to the current assemblage of seed dispersers."

Because of the large number of invasive plants and the absence of large dispersers, the invasive dispersers are incompletely filling the role of extinct native dispersers, and many native plants are not being dispersed, Tarwater says. On the island of Oahu, 11.1 percent of bird species and 46.4 percent of plant species in the networks are native to the island. Ninety-three percent of all seed dispersal events are between introduced species, and no native species interact with each other, the paper says.

"Nonnative birds are a 'double-edged sword' for the ecosystem because, while they are the only dispersers of native plants at the present, most of the seeds dispersed on Oahu belong to nonnative plants," Vizentin-Bugoni says. "Many native plant species have large seeds resulting from coevolution with large birds. Such birds are now extinct, and the seeds cannot be swallowed and, thus, be dispersed by the small-billed passerines now common on Oahu."

Researchers compiled a dataset of 3,438 fecal samples from 24 bird species, and gathered 4,897 days of camera trappings on 58 fruiting species of plants. It was determined that 18 bird species were recorded dispersing plant species.

In contrast to predictions, the traits that influence the role of species in these novel networks are similar to those in native-dominated communities, Tarwater says.

"In particular, niche-based traits, such as degree of frugivory (animals that feed on fruit, nuts and seeds) and lipid content, rather than neutral-based traits, such as abundance, were more important in these nonnative-dominated networks," Tarwater says. "We can then use the niche-based traits of dispersers and plants to predict the roles species may play in networks, which is critical for deciding what species to target for management."

Tarwater adds that the roles of different species in Oahu's seed dispersal networks can be predicted by the species' ecological traits. For example, the research group found that bird species that consume a greater amount of fruit in their diets are more likely to disperse seeds from a greater number of plant species. Likewise, the team found that plants that fruit for extended periods of time have smaller seeds and have fruits rich in lipids, will get dispersed more frequently.

"Land managers can use these ecological traits to identify species that can be removed or added to a system to improve seed dispersal," Tarwater explains. "For example, removal of highly important nonnative plants or the addition of native plants with traits that increase their probability of dispersal, could aid in restoration efforts."

Kelley and Tarwater obtained funding for the project. The research was funded by a U.S. Department of Defense award, UW, University of Hawaii, University of New Hampshire and Northern Arizona University.

"This upcoming year, we will be experimentally removing one nonnative plant species that is incredibly important for network structure and examining how the seed dispersal network changes in response," Tarwater says. "The results of this experiment can inform land managers as to whether removal of a highly invasive plant will improve seed dispersal for the remaining native plants, or whether it does not."