Giner (United States)

Detecting ovarian cancer (OC) early using existing biomarkers, for example, cancer antigen 125 (CA125), is challenging due to its ubiquitous expression in many tissues. Doppel, a prion‐like protein, expresses in the male reproductive organ but is absent in female reproductive systems and healthy tissues, but plays an important role in neo‐angiogenesis. Here, we have shown two platforms, soluble Doppel in sera/ascites and Doppel expressed in circulating tumor cells (Dpl+CTC) in the whole blood, to detect subsets of epithelial OC (EOC). Increased levels of Doppel in the sera of OC patients, in three different cohorts, confirm Doppel as an OC‐specific biomarker. Serum Doppel levels can distinguish OC with high sensitivity and specificity (sensitivity = 0.91 and specificity = 0.89) and can also detect early‐stage HGSOCs (FIGO stages I and II) from non‐cancerous conditions with high sensitivity and specificity (sensitivity = 0.94 and specificity = 0.83). Moreover, significantly higher Doppel expression is observed in all EOC subtypes except clear cell OC. Stratifying the EOCs based on Doppel levels, we categorized them into Doppel‐high (Dplhi) and Doppel‐low (Dpllow) groups. Using ascites‐derived organoids, made from Dplhi and Dpllow patients, we identify that Doppel induces epithelial–mesenchymal transition (EMT). Doppel levels in the sera/ascites correlate with the changes in Dpl+CTC number in whole blood, highlighting the association of Doppel‐induced EMT with CTC dissemination in the circulation. Thus, Doppel‐based detection of EOC subtypes could be a promising platform as a clinical biomarker and link the Doppel axis with OC dissemination.

Achieving cost-effective and durable water electrolysis using widely available, minimally purified water is a central challenge for large-scale hydrogen production. A major bottleneck lies in developing robust oxygen evolution reaction (OER) catalysts that can maintain high activity and stability while operating in water containing dissolved salts and other contaminants. To address this, we have designed and synthesized non-platinum group metal (PGM) OER electrodes—including novel monolithic metal oxides deposited on stainless-steel or Hastelloy substrates—tailored to withstand harsh electrolyzer conditions without significant performance loss. By optimizing catalyst composition, ionomer content, and mass transport within the electrode, we aim to achieve current densities exceeding 2 A cm⁻² at 1.8 V or less while ensuring minimal degradation rates in alkaline environments with salt concentrations of at least 1000 ppm.Full-cell tests conducted in 5 cm² anion-exchange membrane electrolyzers demonstrate that these advanced OER catalysts, when paired with PGM-free cathodes, deliver stable performance across multiple impurity levels (e.g., up to 1000 ppm NaCl) in 0.1 M KOH at 80 °C. Notably, current densities exceeding 1.5 A cm⁻² at 2 V have been achieved under both tap-water and brinier feeds, validating the feasibility of durable, high-performance operation on low-grade water. Ongoing work focuses on optimizing catalyst-layer morphology, catalyst-ionomer interactions, and active-area scale-up to improve electrolyzer resiliency and cost-effectiveness, paving the way for commercially viable hydrogen production from impure water streams.

Lithium-sulfur (Li–S) batteries promise ultra-high energy densities but suffer from sluggish sulfur reduction reaction (SRR) kinetics and polysulfide shuttling. Here, we demonstrate that bis(4-nitrophenyl) carbonate (BNC), a previously overlooked carbonate additive, exhibits concentration-dependent bifunctionality in practical Li–S cells (4 mg cm-2 sulfur loading, E/S = 8 µL mg-1). At an optimized concentration of 0.01 M, BNC simultaneously modifies the Li+ solvation environment and anchors soluble polysulfides, thereby enhancing SRR kinetics and suppressing shuttle effects.We validate these dual mechanisms through an integrated suite of molecular simulations and operando techniques. Ab initio molecular dynamics (AIMD) and 7Li NMR spectroscopy reveal that BNC induces a redistribution of solvent molecules in the Li+ solvation shell, weakening DME coordination and facilitating desolvation for faster reaction kinetics. Operando Raman spectroscopy indicates that middle- and long-chain polysulfide peaks diminish earlier in BNC-containing cells, while operando X-ray absorption spectroscopy (XAS) captures the formation and transformation of short-chain polysulfides (Li2Sx, x<4), culminating in enhanced Li2S formation. Quantitative deconvolution using MCR-ALS confirms a more complete 16-electron conversion under BNC regulation.Electrochemical studies further corroborate these findings. Randles–Sevcik analysis and potentiostatic Li2S nucleation tests show a 46% increase in Li-ion diffusion and a 30 mAh gs -1 enhancement in Li2S nucleation capacity. In situ EIS reveals that BNC lowers the SRR activation energy by 40.6%, particularly at the most kinetically hindered stages. Galvanostatic cycling achieves 650.93 mAh gs -1 with 93% coulombic efficiency over 200 cycles at C/2. Meanwhile, XRF mapping and shuttle current measurements confirm reduced sulfur deposition on the Li anode, directly linking BNC’s function to suppressed parasitic reactions.This work not only reveals BNC’s unique ability to simultaneously optimize solvation structure and immobilize polysulfides but also sets a blueprint for additive design in high-loading, lean-electrolyte Li–S systems, advancing their viability for commercial applications. Figure 1

Detecting ovarian cancer (OC) early using existing biomarkers, e.g., cancer antigen 125 (CA125), is challenging due to its ubiquitous expression in many tissues. Doppel, a prion-like protein, expresses in male reproductive organ but absent in female reproductive systems and healthy tissues, but plays an important role in neoangiogenesis. Here, we have shown two platforms, soluble Doppel in sera/ascites and Doppel expressed circulating tumor cells ( Dpl+ CTC) in the whole blood, to detect subsets of epithelial OC (EOC). Increased level of Doppel in the sera of OC patients, in three different cohorts, confirm Doppel as OC specific biomarker. Serum Doppel level distinguishes EOC subtypes and early stages HGSOCs from non-cancerous conditions with high sensitivity and specificity. Stratifying the EOCs based on Doppel level, we categorized them into Doppel-high (Dpl hi ) and Doppel-low (Dpl low ) groups. Using ascites-derived organoids and single cell sequencing of whole ascites of Dpl hi and Dpl low patients, we identify that Doppel induces epithelial-mesenchymal transition (EMT) and creates an immunosuppressive microenvironment, respectively. Doppel levels in the sera/ascites correlate with the changes of Dpl+ CTC number in whole blood, highlighting the association of Doppel-induced EMT with CTC dissemination in circulation. Thus, Doppel-based detection of EOC subtypes could be a promising platform as clinical biomarker and link Doppel-axis with OC dissemination.

The use of Machine Learning (ML) tools has grown a lot in several areas, including in the civil construction space. Part one of this study tried to use ML to estimate results for sound insulation of floor systems and had concluded that ML is not applicable to those situations. Part two tried some adjustments to the ML script and used an on-site vertical partition system test database as input with ML tools used to estimate new results based on the input data. The conclusion of this new study is that the tool is now more applicable to floor systems but it is not the best form to predict the results, given the complexity of sound propagation between rooms, which is not considered in the statistical analysis of the machine.

As the large-scale commercialization of proton exchange membrane fuel cells (PEMFC) for numerous applications, including heavy-duty trucks draws nearer, there is increasing interest in optimizing fuel cell membranes for both improved efficiency and durability. One of the major membrane attributes being considered for optimization is thickness. The current range of (perfluorosulfonic acid) PFSA membrane thicknesses employed for commercial applications range from 8 -25 µm. As with most adjustable materials parameters, there are a host of properties (cost, gas permeability, proton conductivity, etc.) that require co-optimization to provide the overall preferred position. For example, thin membranes will minimize proton resistance, facilitating high power densities, but will simultaneously allow increased gas crossover fluxes that can contribute to both reduced fuel efficiency and increased oxidative stress. On the other end of the spectrum, thick membranes will decrease gas crossover fluxes, offering improved fuel efficiency while simultaneously decreasing power density. A major question surrounding the tradeoffs of membrane thickness involves the chemical durability impact. Here, we report our investigations of PFSA membrane chemical durability as a function of thickness. For the studies reported here, a thickness series (8, 12 and 20 µm) of ePTFE reinforced Nafion®-like PFSA standalone membranes (SAMs) were prepared.A two-pronged approach was taken for this study. The first involves investigation of intrinsic chemical stability of the ionomer as a function of membrane thickness using an ex-situ H2O2 vapor test. The second investigative mode, which targets the oxidative stress generated by crossover gas flux, employs OCV durability tests of full MEAs. In addition to membrane thickness, gas crossover rates are known to be functions of membrane hydration and gas pressures.1,2 Accordingly, a 3(4-1) fractional factorial experimental design was executed to probe the role of membrane thickness as well as the other factors known to affect gas crossover. The fractional factorial design allows all main effects to be determined and further allows estimation of two factor interactions, if present.References T. Sakai, H. Tanenaka, E, Torikai, “Gas Diffusion in Dried and Hydrated Nations” J. Electrochem. Soc., 1986, 133, 88-92R. Jiang, T. Fuller, S. Brawn, C. Gittleman, “Perfluorocyclobutane and poly(vinylidene fluoride) blend membranes for fuel cells” Electrochimica, Acta, 2013, 110, 306-315

This proposed project aims to develop and evaluate novel manganese based, nitrogen-derived, PGM-free electrocatalysts (denoted as Mn-N-C) to fully address the membrane electrolyte assemblies (MEA)’s ionomer degradation issue resulting from iron. Four thrusts will be pursed in this proposed project. First, advanced first-principles computation methods will be employed to accelerate the rational catalyst design and synthesis. Second, an effective hydro-gel method will be used to maximize atomic Mn active sites embedded in carbon matrix. Next, state-of-the art methods in fuel cell companies will be used to fabricate MEAs containing the Mn-N-C catalysts. Finally, industry standards will be rigorously followed to evaluate fuel cell performance and durability of the Mn-N-C catalysts. With successful completion of the project, it is expected that the following outcomes will be achieved. (1) A set of MEAs containing the Mn-N-C catalysts and with active area large than 50 cm2 for independent testing, (2) testing results demonstrating that the MEAs of Mn-N-C catalysts have mass activity of 0.044 A/cm2 at 0.9 VIR-free and H2/air performance of 0.50 V at 1.0 A/cm2; (3) fundamental understanding of the composition-structure-property relation of the PGM-free Mn- N-C catalysts, and (4) computational data, measurement data, and publications deposited into the database of ElectroCat Consortium.

The proper integration of materials to enable high performing low temperature fuel cell operation has never been more crucial to realizing the isolated (e.g. half-cell or ex-situ) improvements of advanced electrocatalysts, supports and ionomers in an effort to maximize efficiency. The integration pathway for oxygen reduction electrocatalysts, from initial testing in a rotating disk electrode (RDE) to their apex form as porous electrodes in a membrane electrode assembly (MEA) is replete with potential pitfalls. Along the route to improving MEA level electrocatalyst kinetics and electrode transport properties are numerous choices relating to ink formulation (i.e. solvents and solvent ratios), ink processing and deposition methodology, ionomer content and chemistry and electrochemical MEA conditioning. Combined with carbon morphology/porosity, such variables can alter the final electrode morphology, influencing active site accessibility and ORR activity as well as oxygen transport resistance and electrode proton conductivity.[1–5]Here, the development and utilization of in situ diagnostics designed to probe specific phenomena (e.g. catalyst/ionomer interactions, molecular and Knudsen diffusion, electrochemical active site accessibility and catalyst layer proton resistance) will be presented as tools to contrast the ink, processing and fabrication methods necessary to achieve high performance PGM (e.g. Pt/C and Pt alloy/C) and PGM-free (e.g. FeNx/C) electrocatalysts based electrodes. For PGM based MEAs, the dynamic effects of electrochemical conditioning will be examined in an effort to both baseline MEA level performance and decouple the contributions of simultaneous electrocatalyst particle growth and the removal of system impurities.[6] The prerequisite understanding gleaned from the application of electrochemical diagnostics and MEA conditioning procedures will be combined with the development of a novel sulfonated ionic liquid block copolymer ionomer and tailored integration methodology to illustrate a pathway towards improved MEA level performance.[7] Lastly, alterations in ionomer interactions as a function of accelerated stress tests will be discussed, providing insight into the evolving electrode structure as the community targets more robust systems capable of efficient operation for 25,000 hrs.[8]References[1] A. Orfanidi, P.J. Rheinlander, N. Schulte, H.A. Gasteiger, Ink Solvent Dependence of the Ionomer Distribution in the Catalyst Layer of a PEMFC, Journal of The Electrochemical Society. (2018) 11.[2] S. Khandavalli, J.H. Park, N.N. Kariuki, D.J. Myers, J.J. Stickel, K. Hurst, K.C. Neyerlin, M. Ulsh, S.A. Mauger, Rheological Investigation on the Microstructure of Fuel Cell Catalyst Inks, ACS Appl. Mater. Interfaces. (2018) 13.[3] D.A. Cullen, R. Koestner, R.S. Kukreja, Z.Y. Liu, S. Minko, O. Trotsenko, A. Tokarev, L. Guetaz, H.M. Meyer, C.M. Parish, K.L. More, Imaging and Microanalysis of Thin Ionomer Layers by Scanning Transmission Electron Microscopy, J. Electrochem. Soc. 161 (2014) F1111–F1117. https://doi.org/10.1149/2.1091410jes.[4] T. Van Cleve, S. Khandavalli, A. Chowdhury, S. Medina, S. Pylypenko, M. Wang, K.L. More, N. Kariuki, D.J. Myers, A.Z. Weber, S.A. Mauger, M. Ulsh, K.C. Neyerlin, Dictating Pt-Based Electrocatalyst Performance in Polymer Electrolyte Fuel Cells, from Formulation to Application, ACS Appl. Mater. Interfaces. 11 (2019) 46953–46964. https://doi.org/10.1021/acsami.9b17614.[5] G. Wang, L. Osmieri, A.G. Star, J. Pfeilsticker, K.C. Neyerlin, Elucidating the Role of Ionomer in the Performance of Platinum Group Metal-free Catalyst Layer via in situ Electrochemical Diagnostics, J. Electrochem. Soc. 167 (2020) 044519. https://doi.org/10.1149/1945-7111/ab7aa1.[6] S. Kabir, D.J. Myers, N. Kariuki, J. Park, G. Wang, A. Baker, N. Macauley, R. Mukundan, K.L. More, K.C. Neyerlin, Elucidating the Dynamic Nature of Fuel Cell Electrodes as a Function of Conditioning: An ex Situ Material Characterization and in Situ Electrochemical Diagnostic Study, ACS Appl. Mater. Interfaces. 11 (2019) 45016–45030. https://doi.org/10.1021/acsami.9b11365.[7] Y. Li, T.V. Cleve, R. Sun, R. Gawas, G. Wang, M. Tang, Y.A. Elabd, J. Snyder, K.C. Neyerlin, Modifying the Electrocatalyst−Ionomer Interface via Sulfonated Poly(ionic liquid) Block Copolymers to Enable High- Performance Polymer Electrolyte Fuel Cells, ACS Energy Letters. (2020) 6.[8] D.A. Cullen, K.C. Neyerlin, R.K. Ahluwalia, R. Mukundan, K.L. More, R.L. Borup, A.Z. Weber, D.J. Myers, A. Kusoglu, New roads and challenges for fuel cells in heavy-duty transportation, Nature Energy. (2021) 1–13. https://doi.org/10.1038/s41560-021-00775-z.

BACKGROUND Psychological resilience has been extensively studied by developmental researchers, and there is a growing body of literature regarding its role in psychiatry and psychopathology research and practice. This study contributes to this growing literature by providing real-world evidence on the relationship between resilience and clinical symptoms among a large sample of employed Americans. OBJECTIVE This study aimed to describe resilience levels in individuals accessing Ginger, a virtual mental health system, in addition to the association of resilience with demographic characteristics, baseline depression, and anxiety symptoms. METHODS We conducted a retrospective observational study of 9165 members who signed up for Ginger and completed a baseline survey between January 1 and August 5, 2021. We used multivariate regression models to test for associations between baseline resilience and other member characteristics. RESULTS Baseline resilience scores centered on a mean of 23.84 (SD 6.56) and median of 24 (IQR 8) out of 40, with 81.0% (7424/9165) of the sample having low resilience at baseline. Despite having relatively higher resilience scores, members with no or mild depression or anxiety still had low resilience scores on average. Self-reported suicidal ideation was associated with lower resilience. CONCLUSIONS Overall, members had low baseline resilience, similar to resilience levels observed in trauma survivors in prior studies. Younger members and those with higher levels of depression and anxiety at intake reported lower levels of resilience at baseline. Notably, members with no or mild depression or anxiety still had low resilience scores on average, suggesting a need for mental health support among individuals who might not typically be recommended for treatment based on traditional clinical assessments, such as the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder scale (GAD-7). Two suggestions for topics of future research are to develop treatment recommendations based on the Connor-Davidson Resilience Scale and to understand the interaction between resilience levels and symptom-based outcome measures, such as the PHQ-9 and the GAD-7.

Proton exchange membrane fuel cells (PEMFCs) have drawn increasing attention in automotive and residential applications. To significantly reduce the cost of the PEMFC stacks, current platinum-group metal (PGM) catalysts must be replaced by PGM-free catalysts. Although Fe-based PGM-free catalysts (Fe-N-C) have exhibited promisingly high activity for the oxygen reduction reaction (ORR)1, they suffer from insufficient stability. Additionally, a major issue associated with Fe-containing catalysts is that dissolved iron ions can facilitate Fenton’s reaction thus forming a strong radical known to degrade the ionomer and membrane2.Mn-based catalysts have recently been developed, aiming to improve the catalyst durability and mitigate the Fenton’s reaction3. However, the catalyst stability and integration into membrane electrode assemblies (MEAs) have yet to be studied. In this work, density function theory (DFT) has been applied to study the active sites and their degradation mechanism. Computational fluid dynamic (CFD) modeling was also applied to study water, oxygen and proton transport in the electrode. Electrode fabrication optimizations were conducted based on the guidance from the CFD results. The optimizations include ionomer content, electrode porosity and MEA fabrication approaches It has been found that Mn-based catalysts showed improved MEA durability compared to Fe-based catalysts due to the higher carbon graphitization degree, reduced de-metallization and mitigation of peroxide radical formation. However, there is still a significant performance degradation compared to PGM-based MEAs. X-ray absorption has been applied to examine the catalyst and corresponding MEAs before and after durability. The degradation is primarily attributed to the oxidation and agglomeration of active sites. Acknowledgement: The project is financially supported by the Department of Energy’s HFTO under the Grant DE-EE0008075. Reference:1. Wu, K.L. More, C.M. Johnston, P. Zelenay, Science, 332, 443, 2011.2. F Coms, H Xu, T. McCallum, C. Mittelsteadt, ECS Trans. 64, 389, 2014.3. Li, J.; Chen, M.; Cullen, D. A.; Hwang, S.; Wang, M.; Li, B.; Liu, K.; Karakalos, S.; Lucero, M.; Zhang, H.; Lei, C.; Xu, H.; Sterbinsky, G. E.; Feng, Z.; Su, D.; More, K. L.; Wang, G.; Wang, Z.; Wu, G., Atomically dispersed manganese catalysts for oxygen reduction in proton-exchange membrane fuel cells. Nature Catalysis 2018, 1 (12), 935-945.