Tyler O'Neal, Staff Editor MIDDLEWARE

University of Minnesota CEMS professors invent a more efficient tech for making metals in components

University of Minnesota Twin Cities College of Science and Engineering researchers have invented a cheaper, safer, and simpler technology that will allow a “stubborn” group of metals and metal oxides to be made into thin films used in many electronics, computer components, and other applications.

The researchers worked with the University of Minnesota’s Technology Commercialization Office to patent the technology and have already garnered interest from the industry. By adding combinations of carbon, hydrogen, and oxygen atoms to stubborn, hard-to-evaporate metals like tungsten and platinum, University of Minnesota Twin Cities researchers were able to transform the elements into thin films in a cheaper and safer way. Photo credit: Bharat Jalan MBE Lab, University of Minnesota

Many metals and their compounds must be made into thin films before they can be used in technological products like electronics, displays, fuel cells, or catalytic applications. “Stubborn” metals, however—which include elements like platinum, iridium, ruthenium, and tungsten, among others—are very difficult to convert into thin films because they require extremely high temperatures (usually more than 2,000 degrees Celsius) to evaporate.

Typically, scientists synthesize these metal films using techniques like sputtering and electron beam evaporation. The latter consists of melting and evaporating metals at high temperatures and allowing a film to form on top of wafers. But, this conventional method is very expensive, uses a lot of energy, and may also be unsafe due to the high voltage used.

Now, University of Minnesota researchers have developed a way to evaporate these metals at significantly lower temperatures, fewer than 200 degrees Celsius instead of several thousand. By designing and adding organic ligands—combinations of carbon, hydrogen, and oxygen atoms—to the metals, the researchers were able to substantially increase the materials’ vapor pressures, making them easier to evaporate at lower temperatures. Not only is their new technique simpler, but it also makes higher quality materials that are easily scalable.

"The ability to make new materials with ease and control is essential to transition into a new era of the energy economy,” said Bharat Jalan, the senior author of the study, an expert in material synthesis, and an associate professor and Shell Chair in the University of Minnesota Department of Chemical Engineering and Materials Science (CEMS). "There is already a historical link between the innovation in synthesis science and the development of new technology. Millions of dollars go into making materials for various applications. Now, we’ve come up with a simpler and cheaper technology that enables better materials with atomic precision.”

These metals are used to make myriad products, from semiconductors for computer applications to display technology. Platinum, for example, also makes a great catalyst for energy conversion and storage and is being looked at for use in spintronic devices.

“Bringing down the cost and complexity of metal deposition while also allowing for deposition of more complex materials like oxides will play a large role in both industrial and research efforts,” said William Nunn, a University of Minnesota chemical engineering and materials science graduate student, the paper’s first author, and a recipient of the department’s Robert V. Mattern Fellowship. “Now that depositing these metals like platinum will become easier, we hope to see renewed interest in the more complex materials which contain these stubborn metals.”

In addition to Jalan and Nunn, the research team included University of Minnesota Department of Chemical Engineering and Materials Science grad students Anusha Kamath Manjeshwar, Jin Yue, Tristan K. Truttmann, and postdoctoral researcher Anil Rajapitamahuni.

Read the full paper entitled, “Novel Synthesis Approach for “Stubborn” Metals and Metal Oxides” on the PNAS website.
 

Stony Brook University scientists use new method to predict precipitation changes

Tyler O'Neal, Staff Editor MIDDLEWARE

Scientists studying global warming are able to project future spatial patterns of warming with confidence. However, changes and spatial patterns in precipitation are hard to predict. But now a study by researchers in Stony Brook University’s School of Marine and Atmospheric Sciences (SoMAS) provides a new mathematical method to understand the physical causes of future regional precipitation changes, which has an impact on the environment, climate, and many types of human activities worldwide.

The National Center for Atmospheric Research (NCAR) enabled the researchers to gain access to supercomputing with the community earth system model. This figure depicts summer and winter precipitation in East Asia based on a new mathematical method that reveals less precipitation increases in summer and larger ones in winter. Credit: Wengui Liang

Lead author Wengui Liang, a SoMAS doctoral candidate, and his Ph.D. advisor Minghua Zhang, Ph.D., Distinguished Professor, focused on the geographical area of East Asia, where the atmospheric processes related to rain can be clearly illustrated.

Using large-ensemble supercomputer simulations from the Community Earth System Model and from the Coupled Model Intercomparison Project, Liang and Zhang detailed robust precipitation scaling with temperatures in East Asia. They built their theory on the deviation of precipitation changes in the region from something called the Clausius-Clapeyron scaling of local thermodynamics. This theory connects robust climate change features of weakening westerly jet, steepening moisture gradient along the separation of dynamical and hydrological amplitudes of atmospheric eddies (or whirl of atmospheric air) with the precipitation scaling.

They found that the weakening westerlies as a result of the decreasing polar-to-Equator temperature gradient, and the increasing land-to-ocean water vapor gradient as a result of the Clausius-Clapeyron scaling, together with the wave amplitude changes of water vapor content in atmospheric eddies, cause the deviation of regional scaling of precipitation. These processes act together to diminish the thermodynamic scaling rate in summer but maintain that rate in winter – a projection that implies a less significant precipitation increase in the summer but larger increases of precipitation in the winter in East Asia.

“This finding helps us understand why predictions of regional precipitation in the future are different by different models and are more reliable in some regions than in other regions,” says Zhang. “These results can be used by scientists to reduce model uncertainties and by officials to plan for water resource usage and infrastructure management.”

The method is described in a paper to be published in Communications Earth & Environment.

The researchers believe their method can be used in other regions of the world to investigate spatial and seasonal patterns of future precipitation changes.

A more multi-omic, integrative analysis of tumors provides a complete understanding of cancer

Tyler O'Neal, Staff Editor MIDDLEWARE

New insights into lung tumor biology and potential drug targets emerge from a study integrating genomics and proteomics

Lung cancer remains the leading cause of cancer-associated death in the United States and worldwide. Patients with a subtype called lung adenocarcinoma (LUAD) have benefited from the development of new targeted medicines, but the search for effective new therapies for another subtype called lung squamous cell carcinoma (LSCC) has largely come up short. 

To learn more about the biological basis of LSCC, a team led by researchers from the Broad Institute of MIT and Harvard and the National Cancer Institute's Clinical Proteomics Tumor Analysis Consortium (CPTAC), including collaborators from the Baylor College of Medicine, have developed the largest and most comprehensive molecular map to date of LSCC. Their effort, described in Cell, brings proteomic, transcriptomic, and genomic data together into a detailed "proteogenomic" view of LSCC. Analysis of that data has revealed potential new drug targets, immune regulation pathways that might help cancer evade immunotherapies, and even a new molecular subtype of LSCC. Data from the study is available on the CPTAC portal.

"Patients with lung squamous cell cancer have very limited therapeutic options, and even modest success in understanding this disease could make a difference in people's lives," said Shankha Satpathy, a group leader in the Broad Institute's Proteomics team, and co-first and co-corresponding author on the Cell study with co-first authors Karsten Krug and Pierre Jean Beltran of Broad and Sara Savage of Baylor. "We hope the research community, from basic scientists to practicing oncologists, will make use of this new resource for testing hypotheses, stimulating further research, and opening new data-driven avenues for a clinical trial design that, in the long run, could benefit patients."

Targetable opportunities

In their study, the team analyzed DNA, RNA, proteins, and post-translational protein modifications (PTMs, i.e., phosphorylation, acetylation, and ubiquitylation) of 108 tumors before treatment, and compared them with normal tissue. Among the opportunities they saw for the development of new LSCC treatments, the researchers identified the gene NSD3 as a possible target for tumors harboring extra copies of FGFR1, another gene that is often duplicated or amplified in LSCC. Prior efforts have attempted, unsuccessfully, to target FGFR1 directly. The team's proteogenomic findings suggest that NSD3 could be a critical driver of tumor growth and survival in these tumors, making it a potential therapeutic target. 

They also noted a subset of patients whose tumors exhibited low expression of p63 but high expression of survivin, a protein that regulates cell proliferation and cell death and which is the target of clinical trials in other tumor types. 

Additionally, the team's data suggested that tumors driven by overexpression of the transcription factor SOX2 may be vulnerable to treatments directed against chromatin modifiers such as LSD1 and EZH2. SOX2 itself is generally considered an "undruggable" target; the team's observations point to an opportunity to develop a therapeutic workaround.

"Proteomic and PTM data helps us to see the functional effects of the genome," explained Michael Gillette, a senior group leader in Proteomics at Broad, an attending physician in pulmonary and critical care medicine at Massachusetts General Hospital, and a co-senior author on the study with Steven Carr and DR Mani of Broad and Bing Zhang of Baylor. "Understanding which protein levels are impacted by copy-number alterations, and how mutations impact protein expression and pathway activity, provides deeper insights into cancer biology. 

"Often those insights hint at unexplored therapeutic options, or at specific subpopulations that might benefit from specific treatments," he added. "This is especially important with a disease like LSCC, where so many clinical trials have failed." 

Immune explorations

Even though immunotherapy represents the greatest advance in LSCC therapy in decades, patient outcomes lag behind those seen with LUAD; only a minority of patients with LSCC exhibit long-term responses. Based on their proteogenomic data, the team presented a detailed picture of the immune landscape of LSCC, highlighting several immune regulation pathways that could serve as targetable points. In particular, their analysis highlighted a subset of tumors that exhibit markers associated with response to immune checkpoint inhibitors (such as PD-1/PD-L1 blockers), and with immune evasion, providing some clues as to why immunotherapy outcomes are so uneven across patients with LSCC.

“A deeper understanding of the immune landscape of LSCC tumors could eventually lead to more effective immunotherapies and markers for patient stratification,” said Zhang, a professor in the Lester and Sue Smith Breast Center and the Department of Molecular and Human Genetics at Baylor.

Metabolic dysregulation and crosstalk revealed

Ubiquitylation is a process by which the cell flags proteins with another small protein called ubiquitin (or its biochemical relatives) to target them for destruction. While this process is important in normal function, when dysregulated it can contribute or lead to disease. The Broad team previously developed UbiFast, a technology that enables deep-scale, high-throughput analysis of ubiquitylation in patient tissue samples. Applied to LSCC, UbiFast revealed complex regulation of metabolic pathways such as glycolysis and oxidative stress-driven by molecular crosstalk based on ubiquitylation (or ubiquitin-like modifications) and two other forms of protein modification, phosphorylation (which changes a protein's enzymatic or catalytic activity) and acetylation (which can affect a protein's structure, activity, localization, and stability).

A new subtype emerges

Prior efforts have identified four molecular subtypes of LSCC using genomics, corresponding to distinct cell types and processes. With their proteomic perspective, the research team not only gained a deeper understanding of immune, metabolic and proliferative signals associated with these subtypes but also uncovered a new epithelial-to-mesenchymal transition subtype. The cells of this new type, they noted, may have greater potential for metastasis, but also feature active, kinase-driven molecular pathways that could be targeted therapeutically. 

“This is remarkable because LSCC tumors generally lack the types of kinase alterations present in LUAD that have been the basis for the development of a broad spectrum of therapeutic inhibitors,” said Ana Robles, program director in NCI’s Office of Cancer Clinical Proteomics Research.

The study collaborators performed their work under the auspices of CPTAC, an NCI-sponsored, multidisciplinary/multi-institutional effort to accelerate the understanding of the molecular basis of cancer through the application of large-scale proteogenomic analysis. This work builds on prior studies by CPTAC and the International Cancer Proteogenomics Consortium on LUAD. All datasets generated by CPTAC are available to the research community as a unique public resource that provides an exceptional foundation to guide further research and support the development of therapeutic modalities in LSCC and other cancers.

“Studies like ours and others from the CPTAC network and beyond are increasingly demonstrating the importance of undertaking multi-omic, integrative analyses of tumors to provide a more detailed and nuanced understanding of cancer," said Carr, senior director of Proteomics at Broad. "These studies have already revealed new, previously unrecognized targets for therapeutic intervention."