Daily Archives: 17 Jan 2021

Planetary Science

Astronomers Discovered the Smallest Microlensing Planet (Planetary Science)

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Summary:

—> Astronomers Discovered the Smallest Microlensing planet OGLE-2019-BLG-0960 Lb.

—> OGLE-2019-BLG-0960Lb is the 19th microlensing planet with a mass-ratio below the fiducial power-law break in the mass-ratio distribution.

—> Astronomers claimed that such planets primarily found in moderate magnification and “Hollywood” events.

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A team of international astronomers reported on the analysis of OGLE-2019-BLG-0960, which contains the smallest mass-ratio microlensing planet, “OGLE-2019-BLG-0960 Lb”, found to date. It has a mass ratio of q ∼ 1.27 ± 0.07 or ∼ 1.45 ± 0.15 × 10^-5.

Figure 1. OGLE-2019-BLG-0960 cannot be explained by a point-lens, binary-source (1L2S) model, which is shown in two different bands (R, red line, corresponding to the Kumeu Observatory data; I, black line, corresponding to CT13 and KMT data). The dotted gray line shows the best-fit point-source/point-lens model. © Jennifer Yee et al.

The measurement of the annual parallax effect combined with the finite source effect allowed them to determine the mass of the host (M-dwarf) star (ML = 0.3–0.6 M), the mass of its planet (mp =1.4–3.1 M), the projected separation between the host and planet (a⊥ = 1.2–2.3 au), and the distance to the lens system (DL = 0.6–1.2 kpc).

OGLE-2019-BLG-0960Lb is the 19th microlensing planet with a mass-ratio below the fiducial power-law break in the mass-ratio distribution, qbr = 1.7 × 10-⁴, posited by Suzuki et al. (2016). It is the fourth planet below the revised break of qbr = 0.55 × 10-⁴ from Jung et al. (2019).

The three smallest planets (including this one) have all been discovered since the advent of continuous survey observations from KMTNet. This indicates that the current generation of microlensing experiments is now capable of measuring both the precise location of qbr and the power-law slope, p, of the mass-ratio distribution below qbr.

By comparing OGLE-2019-BLG-0960 with other published planets below qbr, they found that they (such planets) are primarily found in moderate magnification and “Hollywood” events. Moderate magnification events are the primary source of small planets because the cross-section for a planetary perturbation is largest when the planetary caustics are near resonance. In fact, the planet sensitivity is maximized for planets just outside resonance (| log s| > | log s_resonant|) because significant perturbations to the magnification field extend well beyond the caustic structures. However, the planet sensitivity decreases rapidly for |log s| & few| log s_resonant|.

They found three of the nineteen planets with mass ratios smaller than q = 1.7 × 10-⁴ in “Hollywood” events, for which the cross-section for light-curve anomalies is set by the source size rather than the caustic size. For these planets s >> s_resonant. The expected yield for such events is likely to be much lower than for moderate magnification events. Typical source sizes are ρ ∼ 0.01, and thus, the cross-section is a factor of ∼ 10 smaller than for moderate magnification events. At the same time, events with giant sources represent only a fraction of all microlensing events, making intensive work on such events tractable.

Figure 2. Left: microlensing planets with two degenerate solutions (NASA Exoplanet Archive, accessed 10/27/20). Dotted line at log s = 0, solid and dashed lines. Points are colored by Impact parameters, u0, and the symbol types indicate whether the caustics are near-resonant/resonant (triangles) or non-resonant (circles), i.e., inside or outside the dashed lines. OGLE-2019-BLG-0960 is marked by black stars. Right: difference from a “true” “close”/“wide” degeneracy. Events with a perfect s ↔ s-¹ degeneracy should have mean(log s) → 0. By contrast, most of the events shown, including OGLE-2019-BLG-0960, have resonant or semi-resonant caustics (triangles), i.e., are not in the | log s| >> 0 regime, and many do not have mean(log s) → 0. For these events, the different degenerate solutions can have significant fractional deviations in q, in contrast to the expectation that q is invariant to the “close”/“wide” degeneracy for the limit as | log s| >> 0. © Jennifer Yee et al.

Hence, the focus for discovering planets with log q ≲ – 4 should be on moderate magnification events and events with giant sources. This search could be conducted within existing survey data or be supplemented by a followup campaign. Even though OGLE-2019-BLG-0960Lb could be recovered from survey data alone (Fig 3), this recovery was aided by the special geometry of the light curve (Jung et al. 2020) and suggests that similar, but shorter and potentially more numerous, perturbations would be missed in the low-cadence survey fields. For followup observations, Abe et al. (2013) previously suggested that the focus for small planets should be events with 50 < Amax < 200. This current investigation showed that events should be monitored for the full time that they have A > 5, which suggests this focus should be extended to events with peak magnification Amax > 10 or even smaller. If additional resources are available, followup observations could be further extended to include events with giant sources. This strategy will maximize the number of small planets found and enable a robust measurement of the mass-ratio distribution of microlensing planets with q < qbr.

Figure 3. Known microlensing planets with q < 10-³ (NASA Exoplanet Archive, accessed 10/27/20). Solid points show planets with a single solution. Planets with multiple degenerate solutions are shown as open circles (one for each solution) connected by dotted lines (excludes planets with mass ratios that are ambiguous by more than a factor of 2). The two degenerate solutions for OGLE-2019-BLG-0960Lb are shown as the red stars. The gray lines show the fiducial qbr = 1.7 × 10-⁴ as proposed by Suzuki et al. (2016) (dotted) and the value proposed by Jung et al. (2019 (solid). Black solid lines show the boundary between resonant and non-resonant caustics, and the dashed lines show (3, 1.8) log sresonant for (s < 1) and (s > 1) caustic structures. The vast majority of planets are found between the dashed lines, and two are found at log s ∼ 0.2 in Hollywood events. © Jennifer Yee et al.

Finally, they demonstrated with an empirical investigation that most planets showing a degeneracy between (s > 1) and (s < 1) solutions are not in the regime (|log s|>> 0) for which the “close”/“wide” degeneracy was derived. This investigation suggested a link between the “close”/“wide” and “inner/outer” degeneracies and also that the symmetry in the lens equation goes much deeper than symmetries uncovered for the limiting cases.

Reference: Jennifer C. Yee, Weicheng Zang, Andrzej Udalski, Yoon-Hyun Ryu, Jonathan Green, Steve Hennerley, Andrew Marmont, Takahiro Sumi, Shude Mao, Mariusz Gromadzki, Przemek Mróz, Jan Skowron, Radoslaw Poleski, Michał K. Szymański, Igor Soszyński, Paweł Pietrukowicz, Szymon Kozłowski, Krzysztof Ulaczyk, Krzysztof A. Rybicki, Patryk Iwanek, Marcin Wrona, Michael D. Albrow, Sun-Ju Chung, Andrew Gould, Cheongho Han, Kyu-Ha Hwang, Youn Kil Jung, Hyoun-Woo Kim, In-Gu Shin, Yossi Shvartzvald, Sang-Mok Cha, Dong-Jin Kim, Seung-Lee Kim, Chung-Uk Lee, Dong-Joo Lee, Yongseok Lee, Byeong-Gon Park, Richard W. Pogge, Etienne Bachelet, Grant Christie, Markus P.G. Hundertmark, Dan Maoz, Jennie McCormick, Tim Natusch, Matthew T. Penny, Rachel A. Street, Yiannis Tsapras, Charles A. Beichman, Geoffery Bryden, Sebastiano Calchi Novati, Sean Carey, B. Scott Gaudi, Calen B. Henderson, Samson Johnson, Wei Zhu, Ian A. Bond, Fumio Abe, Richard Barry, David P. Bennett, Aparna Bhattacharya, Martin Donachie, Hirosane Fujii, Akihiko Fukui, Yuki Hirao, Stela Ishitani Silva, Yoshitaka Itow, Rintaro Kirikawa, Iona Kondo, Naoki Koshimoto, Man Cheung Alex Li, Yutaka Matsubara, Yasushi Muraki, Shota Miyazaki, Greg Olmschenk, Clément Ranc, Nicholas J. Rattenbury, Yuki Satoh, Hikaru Shoji, Daisuke Suzuki, Yuzuru Tanaka, Paul J. Tristram, Tsubasa Yamawaki, Atsunori Yonehara, “OGLE-2019-BLG-0960Lb: The Smallest Microlensing Planet”, ArXiv, pp. 1-32, 12 Jan 2021. https://arxiv.org/abs/2101.04696v1

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Computer Science, Engineering

Light-based Processors Boost Machine-learning Processing (Computer / Engineering)

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An international team of scientists have developed a photonic processor that uses rays of light inside silicon chips to process information much faster than conventional electronic chips. Published in Nature, the breakthrough study was carried out by scientists from EPFL, the Universities of Oxford, Münster, Exeter, Pittsburgh, and IBM Research – Zurich.

Schematic representation of a processor for matrix multiplications that runs on light. Credit: University of Oxford

The exponential growth of data traffic in our digital age poses some real challenges on processing power. And with the advent of machine learning and AI in, for example, self-driving vehicles and speech recognition, the upward trend is set to continue. All this places a heavy burden on the ability of current computer processors to keep up with demand.

Now, an international team of scientists has turned to light to tackle the problem. The researchers developed a new approach and architecture that combines processing and data storage onto a single chip by using light-based, or “photonic” processors, which are shown to surpass conventional electronic chips by processing information much more rapidly and in parallel.

The scientists developed a hardware accelerator for so-called matrix-vector multiplications, which are the backbone of neural networks (algorithms that simulate the human brain), which themselves are used for machine-learning algorithms. Since different light wavelengths (colors) don’t interfere with each other, the researchers could use multiple wavelengths of light for parallel calculations. But to do this, they used another innovative technology, developed at EPFL, a chip-based “frequency comb”, as a light source.

“Our study is the first to apply frequency combs in the field of artificially neural networks,” says Professor Tobias Kippenberg at EPFL, one the study’s leads. Professor Kippenberg’s research has pioneered the development of frequency combs. “The frequency comb provides a variety of optical wavelengths that are processed independently of one another in the same photonic chip.”

“Light-based processors for speeding up tasks in the field of machine learning enable complex mathematical tasks to be processed at high speeds and throughputs,” says senior co-author Wolfram Pernice at Münster University, one of the professors who led the research. “This is much faster than conventional chips which rely on electronic data transfer, such as graphic cards or specialized hardware like TPU’s (Tensor Processing Unit).”

After designing and fabricating the photonic chips, the researchers tested them on a neural network that recognizes of hand-written numbers. Inspired by biology, these networks are a concept in the field of machine learning and are used primarily in the processing of image or audio data. “The convolution operation between input data and one or more filters – which can identify edges in an image, for example, are well suited to our matrix architecture,” says Johannes Feldmann, now based at the University of Oxford Department of Materials. Nathan Youngblood (Oxford University) adds: “Exploiting wavelength multiplexing permits higher data rates and computing densities, i.e. operations per area of processer, not previously attained.”

“This work is a real showcase of European collaborative research,” says David Wright at the University of Exeter, who leads the EU project FunComp, which funded the work. “Whilst every research group involved is world-leading in their own way, it was bringing all these parts together that made this work truly possible.”

The study is published in Nature this week, and has far-reaching applications: higher simultaneous (and energy-saving) processing of data in artificial intelligence, larger neural networks for more accurate forecasts and more precise data analysis, large amounts of clinical data for diagnoses, enhancing rapid evaluation of sensor data in self-driving vehicles, and expanding cloud computing infrastructures with more storage space, computing power, and applications software. 

Funding

EPSRC, Deutsche Forschungsgemeinschaft (DFG), European Research Council, European Union’s Horizon 2020 Research and Innovation Programme (Fun-COMP), Studienstiftung des deutschen Volkes

References: J. Feldmann, N. Youngblood, M. Karpov, H. Gehring, X. Li, M. Stappers, M. Le Gallo, X. Fu, A. Lukashchuk, A.S. Raja, J. Liu, C.D. Wright, A. Sebastian, T.J. Kippenberg, W.H.P. Pernice, H. Bhaskaran. Parallel convolution processing using an integrated photonic tensor core. Nature 06 January 2021. https://www.nature.com/articles/s41586-020-03070-1 DOI: 10.1038/s41586-020-03070-1

Provided by EPFL

Computer Science, Engineering

EPFL Student Creates a New Language-analysis Program (Computer / Engineering)

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Jonathan Besomi, a Master’s student at EPFL, has developed a program called Texthero that lets users generate representations of textual data with just a few lines of code, thereby simplifying the analysis of natural languages.

Yale’s Beinecke Rare Book and Manuscript Library © iStock

We now live in a data-filled age that has ushered in its own distinct challenges. One of the biggest is how to analyze vast reams of information. In response, Besomi, a Master’s student in data science, has developed Texthero, a program that simplifies the task of analyzing textual data. It was created in the spring of 2020 under the supervision of Kenneth Younge, Chair of Technology and Innovation Strategy at EPFL’s Management of Technology & Entrepreneurship Institute. Designed as open-source software and written in the Python programming language, Texthero swiftly won over developers around the world.

“Texthero has been downloaded over 23,000 times so far, and has been awarded 2,000 stars on the Github platform,” says Besomi. “It got a lot of attention as soon as we released it – people even began sharing it on social media, primarily Twitter and LinkedIn. This indicates that there was strong demand for such a program in the Python/NLP [Natural Language Processing] community.”

Rapid visual representations

Using Texthero, developers can quickly visualize and understand text-based datasets. “Our program takes a text made up of unstructured data, cleans it up, generates a representation of it by converting it into digital format, and finally visualizes it. In other words, Texthero gives users an overall idea of the structure of a completely unfamiliar text,” explains Besomi.

The rudiments of Texthero first came to Besomi when he was working with Professor Younge on Fastlaw, a program for analyzing legal texts. “Fastlaw is a ‘word-embedding’ tool that was trained on a large corpus of legal data provided by Harvard University’s Caselaw Access Project (CAP) – a project to make every ruling published by US courts freely available,” says Besomi. He and Younge presented their program to the Harvard Law School Library.

“As I was developing Fastlaw, I realized there was a need for software that could quickly pre-process, represent and visualize textual data,” says Besomi. Before Texthero, developers who wanted to process natural language were forced to use a series of applications, such as spaCy, scikit-learn, Gensim and NLTK. The process was both time-consuming and complex. “Now, with Texthero, just a few lines of code are enough to plot a text to be processed.”

A new version

To date, 16 developers have contributed to Texthero through pull requests on Github. They’ve fixed bugs, introduced new features and improved the documentation. “We’re about to release a new version (1.1) that will boost text processing speeds even further,” says Besomi.

Besomi now wants to consolidate and expand the Texthero community through blog posts and tutorials, in order to increase uptake of his program. “When I think about the billions of pieces of data around us that we can’t assimilate, it would seem that text analysis – in all its forms – is the wave of the future,” says Besomi, who is currently completing an in-company internship at IBM Research Zurich and writing a thesis on text analysis. “I’m fascinated by these issues and pleased to have created a simple, straightforward program that makes natural language processing easier.”

Provided by EPFL

Neuroscience

As the Brain Plans Movements, the Middle Frontal Gyrus is Listening (Neuroscience)

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A brain-computer interface study reveals one brain region’s surprising role in planning movements exclusively in response to sounds.

In the swimming pool game Marco Polo, “Marco” navigates toward other players with eyes closed, responding only to hearing the other players say “Polo.” Success depends on the ability to move one’s body in response to sound cues alone, and a new study finds that a specific part of the brain may help make that possible.

The study, published in the journal Scientific Reports, provides evidence that neurons in the middle frontal gyrus — a part of the brain’s frontal lobe — may play a role in planning body movements, but only when those movements are in response to auditory stimuli. The findings represent what could be a previously unknown function for this part of the brain and could provide a new target for researchers developing assistive devices for both movement and hearing disorders.

The work was part of the BrainGate clinical trial, which studies a tiny investigational implant capable of recording information directly from the brain and using that information to drive the movement of computer cursors or even robotic prosthetic devices.

“One of the opportunities afforded by the BrainGate clinical trial is that at the same time as we’re working toward helping people with paralysis, we’re also learning new things about the human brain,”  said Dr. Leigh Hochberg, a neurologist, professor of engineering at Brown University and director of the trial and BrainGate consortium. “This finding turned out to be a complete surprise, which is exciting.”

Up to now, brain-computer interface (BCI) implants like BrainGate have mostly been placed in the motor cortex, a part of the brain associated with voluntary movement. But researchers are interested in harnessing additional signals for BCIs by exploring other parts of the brain, including areas that may be involved in the upstream planning of movements and actions. It was in the process of looking at a new brain region for BCI recording that the researchers made this new discovery.

“There’s a large body of literature to suggest that parts of the premotor cortex toward the front of the brain — the region we were looking at in this study — become active earlier than the more posterior regions of motor cortex during movement tasks,” said Carlos Vargas-Irwin, an assistant professor of neuroscience (research) at Brown and study co-senior author. “If we’re able to record signals from these areas, it’s possible that we could even further speed the responses of our neural interface system. That’s what we were investigating.”

For the study, a clinical trial participant with paralysis in his arms and legs from a spinal cord injury was asked to perform a simple movement-related task: after observing a shape in the corner of a computer screen, he would attempt to grab it and move it to the middle when cued. This was first done while the participant was being monitored by fMRI, a non-invasive method of studying brain signals in real time. The fMRI data suggested that a specific part of the premotor cortex — located in the middle frontal gyrus — seemed to be active during the task.

The next step was to implant a BrainGate microelectrode array near that part of brain in the same participant and repeat the attempted movement task. But to the researchers’ surprise, the array detected no informative signals during a repeat of the movement task.

“We expected, based on the fMRI data, that we’d see some related activity,” said Hochberg, who also directs the Veterans Affairs Rehabilitation Research and Development Center for Neurorestoration and Neurotechnology. “So it was puzzling, to say the least, when we didn’t.”

That’s when the study took yet another unexpected turn. When the team looked at data from a related research session — one in which they verbally told the participant which target to reach for — suddenly the array picked up a strong signal from the middle frontal gyrus.

“That’s when our puzzlement turned to pleasant surprise,” Vargas-Irwin said.

It led the team to design new research that alternated between giving auditory cues and visual-only cues. That work helped to confirm that — at least in this participant — neurons in the middle frontal gyrus produced movement-related signals only in response to auditory clues.

“It was as if these neurons simply weren’t interested in visual information,” Hochberg said. “But they reliably responded to auditory information, and that was completely unexpected.”

The researchers caution that this was research involving a single participant, so more work needs to be done to confirm and generalize the findings. But the study does suggest a new target to be explored in pursuit of improving neural interface devices.

“The decoders we use to convert neural activity into action are focused on activity that’s happening in the precentral gyrus right now,” Hochberg said. “To complement this, we’d like to train decoders to interpret and harness the activity that happens 200 milliseconds or more before the activity begins in the motor cortex. If we can do that, it could eventually lead to even more reliable and intuitive neural interfaces.”

Hochberg, who is affiliated with Brown’s Carney Institute for Brain Science, says he’s pleased that the BrainGate clinical trial has potentially revealed a new basic neuroscience finding.

“This work involved postdocs and graduate students from neuroscience as well as engineering, and I think it underscores what can be accomplished in a multi-disciplinary research environment,” he said. “We’re also thankful for all of our remarkable clinical trial participants, who really make this work possible. They join us in this research to help other people with severe speech or motor impairments, and it’s only with our participants’ incredible dedication, insights and feedback that we can create the neurotechnologies that will restore communication and mobility.”

Additional authors from Brown include: Tommy Hosman, Jacqueline Hynes, Jad Sab, Kaitlin Wilcoxen and John Simeral. Authors from Massachusetts General Hospital include Bradley Buchbinder, Nicholas Schmansky, Sydney Cash, Brian Franco and Jessica Kelemen.

The research was supported by U.S. Department of Veterans Affairs (N9228C, N2864C, B6453R, P1155R, A2295R), the National Institutes of Health (R01DC009899, U01DC017844, UH2NS095548, U01NS098968, T32MH020068, DP2 NS111817) and Massachusetts General Hospital.

Reference: Hosman, T., Hynes, J.B., Saab, J. et al. Auditory cues reveal intended movement information in middle frontal gyrus neuronal ensemble activity of a person with tetraplegia. Sci Rep 11, 98 (2021). https://www.nature.com/articles/s41598-020-77616-8 https://doi.org/10.1038/s41598-020-77616-8

Provided by Brown University

Medicine

Proteogenomics Helps Treat Certain Squamous Cell Carcinomas (Medicine)

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Proteogenomic analysis may offer new insight into matching cancer patients with an effective therapy for their particular cancer. A new study identifies three molecular subtypes in head and neck squamous cell carcinoma (HNSCC) that could be used to better determine appropriate treatment. The research led by Baylor College of Medicine, Johns Hopkins University and the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) is published in the journal Cancer Cell.

Two independent mechanisms are involved in tuberous sclerosis © Baylor College of Medicine

Researchers profiled proteins, phosphosites and signaling pathways in 108 human papillomavirus-negative HNSCC tumors in order to understand how genetic aberrations drive tumor behavior and response to therapies. Currently, there are a few FDA-approved therapies for HNSCC, including an epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) inhibitor and two PD-1 inhibitors, but response rates are moderate. In this study, researchers aimed to find out why certain patients respond to certain treatments to better match the patient to an appropriate course of treatment.

“We found three subtypes of head and neck squamous cell carcinoma, and each subtype may be good candidates for a different type of therapy – EGFR inhibitors, CDK inhibitors or immunotherapy,” said Dr. Bing Zhang, lead contact of the study and professor in the Lester and Sue Smith Breast Center and the Department of Molecular and Human Genetics at Baylor. “We also identified candidate biomarkers that could be used to match patients to effective therapies or clinical trials.”

Finding effective biomarkers

One important finding involved matching HNSCC patients to EGFR mAb inhibitors. Cetuximab, an EGFR mAb medication, was approved by the FDA in 2006 as the first targeted therapy for HNSCC, however the success rate for this treatment is low. Moreover, EGFR amplification or overexpression cannot predict response to EGFR mAbs. In this study, researchers found that EGFR ligands, instead of EGFR itself, act as the limiting factor for EGFR pathway activation. When ligand is low, the downstream pathway will not be triggered, even if EGFR protein is highly overexpressed.

“We proposed that the EGFR ligand should be used as a biomarker, rather than EGFR amplification or overexpression, to help select patients for the EGFR monoclonal antibody treatment,” said Zhang, a member of the Dan L Duncan Comprehensive Cancer Center, a Cancer Prevention & Research Institute of Texas (CPRIT) Scholar and a McNair Scholar at Baylor. “Tumors with high EGFR amplification do not necessarily have high levels of EGFR ligands, which may underlie their lack of response to EGFR mAb therapy.” The team confirmed this hypothesis by analyzing previously published data from patient-derived xenograft models and a clinical trial.

Additionally, tracking a key tumor suppressor known as Rb (retinoblastoma), the research team identified a striking finding that suggests that Rb phosphorylation status could potentially be a better indicator of a patient’s response to CDK4/6 inhibitor therapy. The study showed that the many mutations in the genes regulating CDK4/6 activity were neither necessary nor sufficient for activation of CDK4/6. The team found that the CDK4 activity was best measured through Rb phosphorylation measurements, thus identifying a potential measure for patient selection in CDK inhibitor clinical trials.

Immunotherapy insights

The research team also found important insights into the effectiveness of immunotherapy. PD-1 inhibitors target the interaction between immune checkpoints PD-1 and PD-L1, but success rates of immunotherapy are low, even when PD-L1 expression is used for patient selection. The researchers examined tumors with high expression of PD-L1 and found that when a tumor overexpresses PD-L1, it also upregulates other immune checkpoints, thus allowing the tumor growth despite the use of PD-1 inhibitors. This observation suggests that PD-1 and PD-L1 activated tumors with hot immune environments may require multiple types of immunotherapy, which target different immune checkpoint proteins, to be effective.

Conversely, tumors with cold immune environments are not good targets for immunotherapy.  Examination of how a tumor becomes immune-cold tumor showed that the problem stems from a flaw in its antigen presentation pathway where multiple key gene components of the antigen presentation pathway were deleted.  As a result, although tumor antigens are being expressed, the immune system is not able to recognize them on the surface of the cell and therefore fail to activate the body’s defense system against the tumor. These deletions have the potential to be effective targets for future therapies.

“This study extends our biological understanding of HPV-negative HNSCCs and generates therapeutic hypotheses that may serve as the basis for future studies and clinical trials toward molecularly-guided precision medicine treatment of this aggressive cancer type,” said Dr. Daniel W. Chan, co-corresponding author of the study, professor of pathology and oncology, and director of the Center for Biomarker Discovery and Translation at the Johns Hopkins University School of Medicine.

For a full list of contributing authors, see the publication. This work was supported by grants U24 CA210954, U24 CA210985, U24 CA210972, U24 CA210979, U24 CA210986, U24 CA214125, U24 CA210967, and U24 CA210993 from the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC), by a Cancer Prevention Institute of Texas (CPRIT) award RR160027, by grant T32 CA203690 from the Translational Breast Cancer Research Training Program, and by funding from the McNair Medical Institute at the Robert and Janice McNair Foundation.

Provided by Baylor College of Medicine

Medicine

Triggering Antiviral Immune Response in Certain Breast Cancers (Medicine)

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Researchers at Baylor College of Medicine have discovered how therapeutics targeting RNA splicing can activate antiviral immune pathways in triple negative breast cancers (TNBC) to trigger tumor cell death and signal the body’s immune response. A new study published in Cell shows that endogenous mis-spliced RNA in tumor cells mimics an RNA virus, leading tumor cells to self-destruct as if fighting an infection. Researchers suggest this mechanism could open new avenues for turning on the immune system in aggressive cancers like TNBC.

Generic Lab Image © Baylor College of Medicine

“We know therapeutics that partially interfere with RNA splicing can have a very strong impact on tumor growth and progression, but the mechanisms of tumor killing are largely unknown. In this study, we discovered that these therapeutics are modulators of anti-tumor immunity,” said Dr. Trey Westbrook, corresponding author of the study, executive director of the Therapeutic Innovation Center (THINC) and McNair Scholar in Cancer Research at Baylor.

RNA splicing—the removal of non-coding introns—is often deregulated in tumors, leading to tumor growth but also making the tumor hypersensitive to spliceosome-targeted therapies (STTs). Triple negative breast cancer is one of many aggressive cancers that are responsive to STTs.

Westbrook’s team wanted to understand how those drugs interfere with tumor progression. They found that in TNBC cells, STTs interfere with RNA splicing and cause a buildup of endogenous mis-spliced intron RNA in the tumor cell cytoplasm. Many of those aberrant RNAs will form double-stranded structures, just like an RNA virus. Antiviral immune pathways recognize the double-stranded RNA and then trigger apoptosis and send signals to the body’s immune system to illicit an inflammatory response.

“Our study highlights an unanticipated way to activate an inflammatory response through specifically targeting cancer cells. These findings emphasize that when we think about the activity of cancer therapeutics, we need to look both at how they impact cancer cells as well as the effect this might have on the immune system,” said Dr. Elizabeth Bowling, co-first author and member of the Westbrook lab.

“We now have a clearer understanding of how high levels of mis-splicing results in cellular stress in breast cancer. Furthermore, we suspect this RNA splicing stress may be present in many cancer types and disease states,” said Dr. Jarey Wang, co-first author, member of the Westbrook lab and graduate of the Baylor Medical Scientist Training Program.

These discoveries may also lead to new biomarkers to select patients that respond to current immune-modulating therapies. Specifically, the research suggests that a tumor cell’s endogenous mis-spliced RNA may be able to stimulate the immune system even without therapeutic (STT) treatment. The data shows a correlation between mis-spliced RNA and immune signatures, even in tumors that are typically immune-cold. The study authors hypothesize that this endogenous mis-spliced RNA could be used as a clinical biomarker to find which cancers will be sensitive to immunotherapy. The researchers say further study is needed to determine if STTs activation of anti-tumor immune pathways could make more patients eligible for immunotherapy.

“While immunotherapy is having profound effects for some cancer patients, it still only works in a minority of cancer patients. It’s imperative that we learn how to broaden the swath of patients who might benefit from immunotherapy. This discovery uncovers a new mechanism by which cancers are speaking to the immune system and gives us strategies to exploit that for the benefit of patients,” said Westbrook, Welch Chair in Chemistry, professor in the Verna and Marrs McLean Department of Biochemistry and Molecular Biology and Department of Molecular and Human Genetics and member of the Dan L Duncan Comprehensive Cancer Center at Baylor.

For a full list of authors and financial contributions, see the publication.

Provided by Baylor College of Medicine

Medicine

U of A Researchers Discover One of Our Cellular Building Blocks Acts as a Gel, Not Liquid as Previously Believed (Medicine)

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Landmark discovery of the physical state of complex DNA and protein “packages”—called chromatin—in a cell’s nucleus could lead to better understanding of diseases such as cancer.

University of Alberta researchers have found an answer to a fundamental question in genomic biology that has eluded scientists since the discovery of DNA: Within the nucleus of our cells, is the complex package of DNA and proteins called chromatin a solid or a liquid?

Michael Hendzel (right) co-led a study that revealed the gel-like nature of chromatin, the complex package of DNA and proteins contained within the nucleus of our cells. The researchers say the discovery could lead to better understanding of diseases like cancer. (Photo: Faculty of Medicine & Dentistry; taken pre-COVID-19)

In a study published in the journal Cell, the research team, led by Professor Michael Hendzel of the Faculty of Medicine & Dentistry and collaborator Jeffrey Hansen from Colorado State University, found that chromatin is neither a solid nor a liquid, but something more like a gel. 

Previously, fields such as biochemistry operated under the assumption that chromatin and other elements of the nucleus operated in a liquid state, Hendzel said. This new understanding of the physical properties of chromatin challenges that idea, and could lead to a more accurate understanding of how the genome is encoded and decoded. 

“We all know the difference between water and ice, and we all understand that if you want to tie two things together, for example, you can’t do it with a liquid. You need a rope, something that has mechanical strength,” said Hendzel, who is also a member of the Cancer Research Institute of Northern Alberta (CRINA). “That’s what we’re talking about here. Right now, all of our understanding of gene regulation is largely based on the assumption of freely moving proteins that find DNA and whose accessibility is only regulated by the blocking of that movement. So this research could potentially lead to very different kinds of ways of understanding gene expression.” 

“Another way to look at it is that bone, muscle and connective tissue all have very different physical properties, and if those physical properties break down somehow, it’s almost always associated with disease,” said Alan Underhill, associate professor in the Department of Oncology, CRINA member and contributor to the study. “In the case of chromatin, it’s about scaling this principle down to the level of the cell nucleus, because it is all connected.”

“What we’re seeing here bridges the biochemistry of cellular contents and the underlying physics, allowing us to get at the organizational principles—not just for cells, but the entire body,” he added.

All of our chromosomes are made from chromatin, which is half histone (or structural) proteins and half DNA, organized into long strings with bead-like structures (nucleosomes) on them. Inside the nucleus of a cell, the chromatin fibre interacts with itself to condense into a chromosome. The chromatin fibre also supports gene expression and replication of chromosomal DNA. Although there is some understanding of the structures that make up a nucleus, how those structures are organized and the full extent of how the structures interact with each other is not well known. 

Implications for cancer research

The team’s findings bridge research done over the past 50 years on chromatin gels produced in the laboratory to demonstrate its existence in living cells, which has major implications for interpreting their elastic and mechanical properties, Hendzel explained. 

For example, recent studies have shown that the deformability of chromatin in cancer cells is an important determinant of their ability to squeeze through small spaces to travel outside a tumour and metastasize elsewhere in the body—something that is much easier to explain if chromatin is gel-like rather than a liquid. Cancer cells do that by chemically changing the histone part of the chromatin to make it less sticky, Hendzel said. 

Based on the new research, this can now be explained as a process that reduces the strength of the gel, making it more deformable and enabling cancer cells to spread through the body. Defining how this gel state is regulated could lead to new approaches to prevent metastasis by finding drugs that maintain the chromatin gel in a more rigid state.

A better understanding of chromatin could also affect cancer diagnosis, Underhill said. 

“The texture and appearance of chromatin is something pathologists have used to do clinical assessment on tumour samples from patients,” he said. “It’s really looking at how the chromatin is organized within the nucleus that allows them to make insight into that clinical diagnosis. So now that’s a process that we can reframe in a new context of the material state of the chromatin.” 

Guiding future research

Hendzel said he is confident the discovery of the gel-like state of chromatin will provide a guiding principle for future research seeking to understand how the material properties of chromatin shape the function of the nucleus to ensure the health of cells and the organisms they make up.

“One of the most significant things to me is that this research highlights how limited our knowledge is in this area,” he said. “Currently, we are focused on testing the widely held belief that the physical size of molecules determines their ability to access the DNA. Our ongoing experiments suggest that this too may be incorrect, and we are quite excited about learning new mechanisms that control access to DNA based on the properties of the chromatin gel and the liquid microenvironments that assemble around it.”

“I think it forces us to go back and look at what’s in textbooks and reinterpret a lot of that information in the context of whether ‘this is a liquid,’ or ‘this is a gel’ in terms of how the process actually takes place,” added Underhill. “That will have a lot of impact on how we actually think about things moving forward and how we design experiments and interpret them.”

The research was supported by grants from the National Science Foundation, the Canadian Institutes of Health Research and the Cancer Research Society.

Reference: Hilmar Strickfaden, Thomas O. Tolsma, Ajit Sharma, D. Alan Underhill, Jeffrey C. Hansen, Michael J. Hendzel et al., “Condensed Chromatin Behaves like a Solid on the Mesoscale In Vitro and in Living Cells”, Cell, 183(7), pp. 1772-84, Dec 23, 2020. https://doi.org/10.1016/j.cell.2020.11.027

Provided by University of Alberta

Planetary Science

UH Astronomers Find Evidence for Planets Shrinking Over Billions of Years (Planetary Science)

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A team of astronomers led by University of Hawaiʻi Institute for Astronomy (IfA) graduate student Travis Berger has shown that an intriguing class of Neptune-sized planets shrinks over billions of years.

Credit: NASA/Ames Research Center/W. Stenzel/D. Rutter

From centuries of studying the planets within our solar system, astronomers have wondered how planets form and evolve to become the ones we observe them today. One of the most surprising findings of the past decade was the discovery of a new branch in the planetary “family tree”, separating slightly larger than Earth (super-Earths) from those somewhat smaller than Neptune (sub-Neptunes). However, it is unclear how these different-sized planets formed, as our observations are only a single snapshot out of a billions of years long lifetime for each individual planetary system.

Astronomers can’t watch planets evolve in real time, so they analyze populations of planets to infer how they form and evolve. Indeed, using observations from the NASA Kepler and the ESA Gaia missions, Berger and his team have uncovered another piece of the planet formation and evolution puzzle:  as planets are bombarded with intense light from their host stars, they gradually lose their atmospheres over billions of years.

“The loss of planet atmospheres on billion year timescales shows that these planets lose mass, even at old age,” explained Berger. “One of our main discoveries is that planet sizes shrink on longer timescales than previously thought.” 

NASA’s Kepler mission hunted for planets by staring at one patch of the sky near the constellation Cygnus for roughly four years, detecting small, regular brightness dips from hundreds of thousands of stars within our Milky Way Galaxy. The size of a dip corresponds to the relative size of the planet compared to its host star. Therefore, to determine the actual size of a planet, it is first necessary to measure the size of the star.

The ESA Gaia mission provided an essential ingredient to measuring the sizes of Kepler planet-hosting stars:  parallax. Human eyes use parallax to measure distances to objects, giving us depth perception. Similarly, astronomers use parallax for astronomical-scale depth perception to measure the distances to stars, which in turn assists in measuring the sizes of stars. Distance information is needed to distinguish between a closer small star and a distant, larger star. Combining size and stellar colors also allows astronomers to determine the relative ages of stars.

The UH team used the Gaia constraints on star sizes to revise estimates of planet sizes, and combined it with stellar color data to determine the ages of the planet-hosting stars. They then compared the effects of stellar age on over 2600 planets detected by Kepler. Some planets, especially those that receive over 150 times the light that Earth receives from the Sun, lose their atmospheres over a billion years, as they are inundated with heat and light from the host star.

“While astronomers have long predicted that planets should shrink in size as they age, we did not know whether this can occur over timescales of billions of years. We do now,” says Berger. “The fact that we see planet sizes change on billion-year timescales suggests that there is an evolutionary pathway, where highly-illuminated sub-Neptune-sized planets transition to becoming super-Earth-sized planets.”

In the future, similar work could be conducted on planets discovered by the NASA K2 and TESS Missions in order to resolve the timescale for atmosphere loss with finer precision. 

The study, titled “The Gaia-Kepler Stellar Properties Catalog. II. Planet Radius Demographics as a Function of Stellar Mass and Age,” was funded by NASA and the National Science Foundation, and is published in The Astronomical Journal.

Provided by University of Hawaiʻi at Mānoa

Planetary Science

A Rocky Planet Around One of Our Galaxy’s Oldest Stars (Planetary Science)

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University of Hawaiʻi Astronomers Using W. M. Keck Observatory Discover Ancient Magma World Orbiting a Chemically Unusual Star

“They should have sent a poet,” says Ellie Arroway in the film Contact as, suspended in outer space, she gazes upon a spiral galaxy.  Almost all of the planets discovered to date (including the solar system planets) are confined to the plane of the Milky Way, unable to glimpse such a sweeping vista of our galaxy.  However, astronomers at the University of Hawaiʻi Institute for Astronomy (IfA) using the W. M. Keck Observatory on Maunakea have discovered a rocky planet with a different kind of view.

Caption: Artist’s rendition of TOI-561, one of the oldest, most metal-poor planetary systems discovered yet in the Milky Way galaxy. This 10 billion-year-old system has a hot, rocky exoplanet (center) that’s one and a half times the size of Earth as well as two gas planets (to the left of the rocky planet) that are about twice as large as Earth. Credit: W. M. Keck Observatory/Adam Makarenko

The planet orbits the star TESS Object of Interest (TOI) 561, named for the ongoing NASA TESS planet hunting mission.  TOI-561 belongs to a rare population of stars called the galactic thick disk.  Thick disk stars are chemically distinct, with fewer trace heavy elements (and especially less iron) than typical stars of the Milky Way, suggesting they formed early, approximately 10 billion years ago.  They also have wandering motions that can lift them out of the galactic plane, providing an epic view of our own spiral galaxy.

“The rocky planet orbiting TOI-561 is one of the oldest rocky planets yet discovered.  Its existence shows that the universe has been forming rocky planets almost since its inception 14 billion years ago,” says Dr. Lauren Weiss, Beatrice Watson Parrent Postdoctoral Fellow at UH IfA and leader of the team that discovered the TOI-561 planetary system.  

The result was announced at a press conference today at the January 2021 meeting of the American Astronomical Society and is published in the Astronomical Journal.

The rocky planet orbiting TOI-561 transits its star, meaning that the planet passes in front of its star as seen from Earth, blocking a fraction of the starlight.  The planet is small, with a radius only one and a half times that of Earth. As a result, the reduction of light it causes is miniscule, just 0.025% of the star’s brightness.

Caption: Illustration showing the structural components of the Milky Way Galaxy. The star TOI-561 is located in the thick disk (marked in red-orange), which contains a rare, older population of stars. While nearly all known planets are found within the thin disk (marked in orange), the newly-discovered rock-and-lava exoplanet orbiting TOI-561 is one of the first confirmed rocky planets orbiting a galactic thick disk star. Credit: Kaley Brauer, MIT

Astronomers at UH IfA noticed this change in intensity and used Keck Observatory’s High Resolution Echelle Spectrometer (HIRES) to confirm the presence of the planet. By measuring the wobble of the star induced by the planet’s gravity, they were able to infer that the planet has three times the mass of Earth.  Combining this mass with the radius determined from the transits, the team concluded that the planet is most likely rocky, perhaps with less iron than Earth.

TOI-561 has at least two other planets transiting the star, both of which have about twice Earth’s radius and are too large and low-mass to be rocky.

The origin of stars in the galactic thick disk is unclear, with some studies suggesting that they formed in a distinct, old galaxy that our younger and more massive Milky Way galaxy later cannibalized.  Alternatively, they could be some of the first stars that formed within the Milky Way.  “I wonder what view of the night sky would have been accessible from the rocky planet during its history,” adds Weiss.

Although the past 10 billion years of the planet’s history are murky, it likely does not host life now. The planet orbits its star twice every Earth day, so close to its host star that the estimated average surface temperature is over 2000 degrees Kelvin–far too toasty for life as we know it.  However, this rocky, magma world is perhaps a harbinger of a population of rocky worlds yet to be discovered around our galaxy’s oldest stars.

The observations and analysis in this study were carried out as part of the TESS-Keck survey, a multi-institutional effort to characterize the properties of planets discovered by the NASA TESS mission.

Reference: Lauren M. Weiss, Fei Dai, Daniel Huber, John M. Brewer, Karen A. Collins, David R. Ciardi, Elisabeth C. Matthews, Carl Ziegler, Steve B. Howell, Natalie M. Batalha et al., “The TESS-Keck Survey. II. An Ultra-short-period Rocky Planet and Its Siblings Transiting the Galactic Thick-disk Star TOI-561”, Astronomical Journal, 161(2), 2021. https://iopscience.iop.org/article/10.3847/1538-3881/abd409

Provided by University of Hawai‘i at Manoa

ABOUT THE UH INSTITUTE FOR ASTRONOMY

Founded in 1967, the Institute for Astronomy at the University of Hawaiʻi at Mānoa conducts research into galaxies, cosmology, stars, planets, and the sun. Its faculty and staff are also involved in astronomy education, deep space missions, and in the development and management of the observatories on Haleakalā and Maunakea. The Institute operates facilities on the islands of Oʻahu, Maui, and Hawaiʻi.

ABOUT HIRES

W. M. Keck Observatory’s High-Resolution Echelle Spectrometer (HIRES) produces spectra of single objects at very high spectral resolution yet covers a wide wavelength range. It does this by separating the light into many “stripes” of spectra stacked across a mosaic of three large CCD detectors. HIRES is famous for finding exoplanets. Astronomers also use HIRES to study important astrophysical phenomena like distant galaxies and quasars, as well as find cosmological clues about the structure of the early universe, just after the Big Bang.

ABOUT W. M. KECK OBSERVATORY

The W. M. Keck Observatory telescopes are among the most scientifically productive on Earth. The two 10-meter optical/infrared telescopes atop Maunakea on the Island of Hawaii feature a suite of advanced instruments including imagers, multi-object spectrographs, high-resolution spectrographs, integral-field spectrometers, and world-leading laser guide star adaptive optics systems. Some of the data presented herein were obtained at Keck Observatory, which is a private 501(c) 3 non-profit organization operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation. The authors wish to recognize and acknowledge the very significant cultural role and reverence that the summit of Maunakea has always had within the Native Hawaiian community. We are most fortunate to have the opportunity to conduct observations from this mountain. For more information, visit:

www.keckobservatory.org