Bayesian modeling reveals metabolite‐dependent ultrasensitivity in the cyanobacterial circadian clock
Not Available
59 BASIC BIOLOGICAL SCIENCES↗
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Unraveling Vulnerabilities in Endocrine Therapy-Resistant HER2+/ER+ Breast Cancer
Abstract Breast tumors overexpressing human epidermal growth factor receptor (HER2) confer intrinsic resistance to endocrine therapy (ET), and patients with HER2/estrogen receptor–positive (HER2+/ER+) breast cancer (BCa) are less responsive to ET than HER2–/ER+. However, real-world evidence reveals that a large subset of patients with HER2+/ER+ receive ET as monotherapy, positioning this treatment pattern as a clinical challenge. In the present study, we developed and characterized 2 in vitro models of ET-resistant (ETR) HER2+/ER+ BCa to identify possible therapeutic vulnerabilities. To mimic ETR to aromatase inhibitors (AIs), we developed 2 long-term estrogen deprivation (LTED) cell lines from BT-474 (BT474) and MDA-MB-361 (MM361). Growth assays, PAM50 subtyping, and genomic and transcriptomic analyses, followed by validation and functional studies, were used to identify targetable differences between ET-responsive parental and ETR-LTED HER2+/ER+ cells. Compared to their parental cells, MM361 LTEDs grew faster, lost ER, and increased HER2 expression, whereas BT474 LTEDs grew slower and maintained ER and HER2 expression. Both LTED variants had reduced responsiveness to fulvestrant. Whole-genome sequencing of aggressive MM361 LTEDs identified mutations in genes encoding transcription factors and chromatin modifiers. Single-cell RNA sequencing demonstrated a shift towards non-luminal phenotypes, and revealed metabolic remodeling of MM361 LTEDs, with upregulated lipid metabolism and ferroptosis-associated antioxidant genes, including GPX4. Combining a GPX4 inhibitor with anti-HER2 agents induced significant cell death in both MM361 and BT474 LTEDs. The BT474 and MM361 AI-resistant models capture distinct phenotypes of HER2+/ER+ BCa and identify altered lipid metabolism and ferroptosis remodeling as vulnerabilities of this type of ETR BCa.
60 APPLIED LIFE SCIENCES↗
Expanding the landscape of $ \mathcal{N} $ = 2 rank 1 SCFTs
Here, we refine our previous proposal [1-3] for systematically classifying 4d rank-1 N = 2 SCFTs by constructing their possible Coulomb branch geometries. Four new recently discussed rank-1 theories [4, 5], including novel N = 3 SCFTs, sit beautifully in our refined classification framework. By arguing for the consistency of their RG flows we can make a strong case for the existence of at least four additional rank-1 SCFTs, nearly doubling the number of known rank-1 SCFTs. The refinement consists of relaxing the assumption that the flavor symmetries of the SCFTs have no discrete factors. This results in an enlarged (but finite) set of possible rank-1 SCFTs. Their existence can be further constrained using consistency of their central charges and RG flows.
72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
Phase-controlled improvement of photon lifetime in coupled superconducting cavities
High-quality cavities are crucial for various fundamental physical studies and applications. Here we find that by coupling two cavities directly or via a phase-tunable coupling channel, the photon lifetime of the local field can exceed that of the bare cavities. The cavity photon lifetime is modified by the phases of the initial states and the phase accumulation on the coupling channel, which affect the interference between cavities. In experiments, by coupling superconducting radio-frequency cavities via phase-tunable cables, we realize a factor of 2 improvement in the cavity photon lifetime. The results can bring rich revenue to quantum information science, sensing, and high-energy physics.
43 PARTICLE ACCELERATORS↗
Interpolating Low Time-Resolution Forecast Data
Methodology that interpolates low time-resolution data (e.g., hourly) to high time-resolution (e.g., minutely) with variability patterns extracted from historical records. Magnitude of the variability inserted into the low time resolution data can be adjusted according to the installed capacity represented by the low time-resolution data compared to that by historical records. This approach enables detailed analysis of the impacts from wind and solar on power system intra-hour operations and balancing reserve requirements even with only hourly data. It also allows convenient creation of high resolution wind or solar generation data with various degree of variability to investigate their operational impacts. The methodology comprises of the following steps: 1. Smooth the historical data (set A) with an appropriate window length l to get its trend (set B); l can be a fraction of an hour (e.g., 15 minutes) or longer than an hour, of which the length of the variability patterns will be; 2. Extract the variable component (set C) of historical data by subtracting the smooth trend from it, i.e. set C = set A - set B 3. For each window length l of the variable component data set, find the average value x (will call it base component) of the corresponding window of the historical data set; 4. Define a series of segments (set D) that the values of data will be grouped into, e.g. (0, 0.1), (0.1, 0.2), ..., (0.9, 1.0) after normalization; Link each variability pattern to a data segment based on its corresponding base component x; after this step, each data segment should be linked to multiple variability patterns after this step; 5. Use spline function to interpolate the low time-resolution forecast data (set E) to become a high time-resolution smooth curve (set F); 6. Based on the window length l , calculate the average value y in each window length of set F; find the data segment that y belongs to; then randomly select one of the variability patterns linked to this data segment; 7. Add the selected variability pattern in each window to set F to get the high time-resolution data (set G) with variability observed from historical data set A; a coefficient k can be multiplied to the selected variability pattern to reflect the potential difference in variability between forecast set E and historical data set A caused by installation capacity and other factors. 8. After set G is constructed, variability statistics can be checked for set A and set G for comparison. Adjust the coefficient k if necessary to achieve desired variability in the reconstructed data.
Lu, Shuai↗
In-plane g factor of low-density two-dimensional holes in a Ge quantum well.
High-mobility two-dimensional (2D) holes residing in a Ge quantum well are a new electronic system with potentials in quantum computing and spintronics. Since for any electronic material, the effective mass and the g factor are two fundamental material parameters that determine the material response to electric and magnetic fields, measuring these two parameters in this material system is thus an important task that needs to be completed urgently. Because of the quantum confinement in the crystal growth direction (z), the biaxial strain of epitaxial Ge on SiGe, and the valance band nature, both the effective mass and the g factor can show very strong anisotropy. In particular, the in-plane g factor (g ip ) can be vanishingly small while the perpendicular g factor (g z ) can be much larger than 2. Here we report the measurement of g ip at very low hole densities using in-plane magneto-resistance measurement performed at the NHMFL.
36 MATERIALS SCIENCE↗
Measurement of Neutral Current Elastic Cross Section in MicroBooNE
The MicroBooNE experiment is an 85 ton active volume liquid-argon time projection chamber located in the Fermilab Booster Neutrino Beamline. MicroBooNE’s ability to detect low-energy protons allows us to study single proton events with a four-momentum transfer squared, Q$^2$, as low as 0.10 GeV$^2$. We present a measurement of the flux-averaged neutral-current elastic differential cross sections for neutrinos scattering on argon as a function of Q$^2$, proton momentum and proton angle with respect to the direction of the neutrino beam. This is our first step towards extracting the strange quark contribution to the axial form factor, which is not only the least-constrained contribution to the neutral-current elastic scattering cross section but is also crucial for understanding the strange quark contribution to the proton spin.
72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
CCAR1 is required for Ngn3-mediated endocrine differentiation
Highlights: Black-Right-Pointing-Pointer We identify CCAR1 to directly interact with Ngn3. Black-Right-Pointing-Pointer CCAR1 is co-localized with Ngn3 in the nucleus. Black-Right-Pointing-Pointer CCAR1 cooperates with Ngn3 in activating NeuroD expression. Black-Right-Pointing-Pointer CCAR1 is required for Ngn3-mediated PANC-1 transdifferentiation. -- Abstract: Neurogenin3 (Ngn3) is a basic helix-loop-helix transcription factor that specifies pancreatic endocrine cell fates during pancreas development. It can also initiate a transdifferentiation program when expressed in pancreatic exocrine and ductal cells. However, how Ngn3 initiates a transcriptional cascade to achieve endocrine differentiation is still poorly understood. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1), which is a transcriptional coactivator for nuclear receptors, also interacts with Ngn3. The association between Ngn3 and CCAR1 was verified by pull-down assays and co-immunoprecipitation analyses. Using gene reporter assays, we found that CCAR1 is essential for Ngn3 to activate the expression of the reporter genes containing the NeuroD promoter. Moreover, down-regulation of endogenous CCAR1 in the PANC-1 pancreatic ductal cell line inhibits the transdifferentiation program initiated by Ngn3. CCAR1 is, therefore, a novel partner of Ngn3 in mediating endocrine differentiation.
60 APPLIED LIFE SCIENCES↗
Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease
Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids are observed in NASH. ► Hepatic bile acid synthesis shifts toward the alternative pathway in NASH.
60 APPLIED LIFE SCIENCES↗
Phase control of light propagation via Fano interference in asymmetric double quantum wells
We investigate the light propagation and dynamical control of a weak pulsed probe field in asymmetric double quantum wells via Fano interference, which is caused by tunneling from the excited subbands to the same continuum. Our results show that the system can produce anomalous and normal dispersion regions with negligible absorption by choosing appropriate coupling strength of the tunneling and the Fano interference. Interesting enough, the dispersion can be switched between normal and anomalous by adjusting the relative phase between the pulsed probe and coherent control fields owing to the existence of the perfectly Fano interference. Thus, the relative phase can be regarded as a switch to manipulate light propagation with subluminal or superluminal. The temporal and spatial dynamics of the pulsed probe field with hyperbolic secant envelope are analyzed.
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
Apelin-13-induced proliferation and migration induced of rat vascular smooth muscle cells is mediated by the upregulation of Egr-1
Highlights: •The mechanism underlying the effects of Apelin-13 on VSMC was investigated. •Apelin-13 induced VSMC migration, proliferation and Egr-1 and OPN upregulation. •These effects were inhibited by the Egr-1 specific deoxyribozyme, ED5. •The effects of Apelin-13 on VSMC are mediated via Egr-1 upregulation. •These data will help in attempts to prevent and treat vascular remodeling diseases. -- Abstract: Apelin-13 plays an important role in the migration and proliferation of vascular smooth muscle cells (VSMCs); however, the underlying mechanisms are still unclear. Egr-1 is a nuclear transcription factor, which is considered to be the critical initiating factor of the processes of VSMC proliferation and migration. Egr-1 is known to regulate the expression of osteopontin (OPN), which is a marker of the phenotypic modulation that is a necessary condition of VSMC proliferation and migration. We hypothesized that the role of Apelin-13 is mediated via upregulation of Egr-1. To test this hypothesis, we analyzed the effects of Apelin-13 treatment on Egr-1 mRNA and protein expression in A10 rat aortic VSMCs by RT-PCR and Western blotting, respectively. Results showed that, Apelin-13 upregulated the expression of Egr-1. Furthermore, treatment with the extracellular-regulated protein kinase (ERK) inhibitor, PD98059, inhibited the upregulation of Egr-1 by Apelin-13. In addition, this upregulation was inhibited by treatment of VSMCs with the Egr-1 specific deoxyribozyme ED5 (DNAenzyme/10-23 DRz). Furthermore, ED5 treatment was found to significantly inhibit Apelin-13-induced migration and proliferation of VSMCs using transwell and MTT assays, respectively. The evaluation of OPN mRNA and protein expression levels by RT-PCR and Western blot analyses revealed that ED5 treatment also inhibited Apelin-13-induced OPN upregulation. The results of this study indicated that Apelin-13 upregulates Egr-1 via ERK. Furthermore, Apelin-13 induced the proliferation and migration of VSMCs as well as the upregulation of OPN via the upregulation of Egr-1. These results will provide an important theoretical and experimental basis for the control of inappropriate remodeling of vessel walls, and will hopefully lead to the prevention and treatment of vascular remodeling diseases.
60 APPLIED LIFE SCIENCES↗
A Review on Organic Polymer-Based Thermoelectric Materials
Converting heat energy directly into useable electricity by harvesting low-cost energy resources, such as solar energy and the waste heat, has attracted great interest recent years. Thermoelectricity offers a promising technology to convert heat from solar energy and to recover waste heat from industrial sectors and automobile exhausts. Classically, a number of inorganic compounds have been considered as the best thermoelectric materials. Organic materials in particular intrinsically conducting polymers had been considered as competitors of classical thermoelectric since their figure of merit has been improved several orders of magnitude in last year. In addition, the applications of thermoelectric polymers at low temperatures have shown various advantages such as easy and low cost of fabrication, light weight, and flexibility. Therefore, organic thermoelectric materials will be the best candidates to compete with inorganic materials in the future. In this review, we focused on exploring different types of organic thermoelectric materials and the factors affecting their thermoelectric properties, and discussed various strategies to improve the performance of thermoelectric materials. In addition, a review on theoretical studies of thermoelectric transport in polymers is also given.
36 MATERIALS SCIENCE↗
Electrochemical performance and stability of SrTi 0.3 Fe 0.6 Co 0.1 O 3-δ infiltrated La 0.8 Sr 0.2 MnO 3 Zr 0.92 Y 0.16 O 2-δ oxygen electrodes for intermediate-temperature solid oxide electrochemical cells
We report that the La 0.8 Sr 0.2 MnO 3 -Zr 0.92 Y 0.16 O 2-δ (LSM-YSZ) composite is the most widely used oxygen electrode for solid oxide electrochemical cells (SOCs). However, operating temperatures > 700 degrees C are required for good performance since oxygen reactions are limitied to three-phase boundaries (TPBs) because of poor ionic conductivity of LSM. Furthermore, LSM-YSZ electrodes typically delaminate during electrolysis operation leading to cell degradation. One strategy to improve SOCs with LSM-YSZ electrodes is to infiltrate a mixed ionically and electronically conducting (MIEC) material that promotes oxygen exchange. However, infiltrated materials have a nano-scale structure that may not be stable under SOC operating temperatures. Here, we report results on the infiltration of SrTi 0.3 Fe 0.6 Co 0.1 O 3-δ (STFC), a recently reported high performance MIEC, into LSM-YSZ to improve its electrochemical performance and stability at intermediate temperatures. The infiltrated STFC enhances LSM-YSZ and cell performance, typically yielding a decrease in electrode polarization resistance by a factor > 3 times, resulting in an increase in fuel cell maximum power density and electrolysis current density (at 1.3 V) by a factor > 2 times. Perhaps more significantly, the infiltrated electrodes show good performance stability, with suppression of electrode delamination during electrolysis and no evidence of coarsening or segregation induced degradation.
36 MATERIALS SCIENCE↗
Effect of thermal aging on oxide film of stainless steel weld overlay cladding exposed to high temperature water
Highlights: • Oxide film of aged cladding material in high temperature water was studied. • Thermal aging contributed to high corrosion susceptibility of the ferrite phase. • Highly corrosion of aged ferrite phase was caused by spinodal decomposition. • Carbides along phase boundary facilitated the corrosion of the cladding material. - Abstract: Characteristics of the oxide film formed on stainless steel weld overlay cladding aged at 400 °C for different times in high temperature water were studied. The results showed that thermal aging showed no obvious effect on the volume fraction of ferrite phase but resulted in high corrosion susceptibility of the aged ferrite phase mainly. The oxide film formed on the unaged cladding material consisted of 100-nm-thick inner oxide layer (FeCr{sub 2}O{sub 4} and Cr{sub 2}O{sub 3}) and Fe-rich outer oxide particles (Fe{sub 3}O{sub 4}) with a size of 2 O4, Cr{sub 2}O{sub 3} and Fe{sub 3}O{sub 4}) and outer oxide particles (Fe{sub 3}O{sub 4} and FeCr{sub 2}O{sub 4}) with a size of <700 nm formed on the aged ferrite phase. Spinodal decomposition was considered as the main factor to promote the corrosion of the aged ferrite phase, and existence of carbides along phase boundary facilitated corrosion of the cladding material in high temperature water.
36 MATERIALS SCIENCE↗
Accurate optimization of amino acid form factors for computing small-angle X-ray scattering intensity of atomistic protein structures
Structure modelling via small-angle X-ray scattering (SAXS) data generally requires intensive computations of scattering intensity from any given biomolecular structure, where the accurate evaluation of SAXS profiles using coarse-grained (CG) methods is vital to improve computational efficiency. To date, most CG SAXS computing methods have been based on a single-bead-per-residue approximation but have neglected structural correlations between amino acids. To improve the accuracy of scattering calculations, accurate CG form factors of amino acids are now derived using a rigorous optimization strategy, termed electron-density matching (EDM), to best fit electron-density distributions of protein structures. This EDM method is compared with and tested against other CG SAXS computing methods, and the resulting CG SAXS profiles from EDM agree better with all-atom theoretical SAXS data. By including the protein hydration shell represented by explicit CG water molecules and the correction of protein excluded volume, the developed CG form factors also reproduce the selected experimental SAXS profiles with very small deviations. Taken together, these EDM-derived CG form factors present an accurate and efficient computational approach for SAXS computing, especially when higher molecular details (represented by the q range of the SAXS data) become necessary for effective structure modelling.
Tong, Dudu↗
Lignin-Derived Thioacidolysis Dimers: Reevaluation, New Products, Authentication, and Quantification
Not Available
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Balancing global water availability and use at basin scale in an integrated assessment model
Water is essential for the world’s food supply, for energy production, including bioenergy and hydroelectric power, and for power system cooling. Water is already scarce in many regions of the world and could present a critical constraint as society attempts simultaneously to mitigate climate forcing and adapt to climate change, and to provide for a larger and more prosperous human population. Numerous studies have pointed to growing pressures on the world’s scarce fresh water resources from population and economic growth, and climate change. This study goes further. We use the Global Change Assessment Model to analyze interactions between population, economic growth, energy, land and water resources simultaneously in a dynamically evolving system where competing claims on water resources from all claimants—energy, land, and economy—are reconciled with water resource availability—from renewable water, non-renewable groundwater sources and desalinated water—across 14 geopolitical regions, 151 agriculture-ecological zones, and 235 major river basins. We find that previous estimates of global water withdrawal projections are overestimated. Model simulations show that it is more economical in some basins to alter agricultural and energy activities rather than utilize non-renewable groundwater or desalinated water. This study highlights the importance of accounting for water as a binding factor in agriculture, energy and land use decisions in IAMs and implications for global responses to water scarcity, particularly in the trade of agricultural commodities and land-use decisions.
basin↗