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Background: Neoadjuvant chemotherapy (NACT) is an increasingly used approach for treatment of breast cancer. The pathological complete response (pCR) is considered a good predictor of disease-specific survival. This study investigated whether circulating exosomal microRNAs could predict pCR in breast cancer patients treated with NACT. Method: Plasma samples of 20 breast cancer patients treated with NACT were collected prior to and after the first cycle. RNA sequencing was used to determine microRNA profiling. The Cancer Genome Atlas (TCGA) was used to explore the expression patterns and survivability of the candidate miRNAs, and their potential targets based on the expression levels and copy number variation (CNV) data. Results: Three miRNAs before that NACT (miR-30b, miR-328 and miR-423) predicted pCR in all of the analyzed samples. Upregulation of miR-127 correlated with pCR in triple-negative breast cancer (TNBC). After the first NACT dose, pCR was predicted by exo-miR-141, while miR-34a, exo-miR182, and exo-miR-183 predicted non-pCR. A significant correlation between the candidate miRNAs and the overall survival, subtype, and metastasis in breast cancer, suggesting their potential role as predictive biomarkers of pCR. Conclusions: If the miRNAs identified in this study are validated in a large cohort of patients, they might serve as predictive non-invasive liquidmore »biopsy biomarkers for monitoring pCR to NACT in breast cancer.« less

The Ruby Mountains, East Humboldt Range and Wood Hills (REHW) of Elko County Nevada, one of the classic metamorphic core complexes of the Cordillera, preserves a protracted and episodic record of both ancient and modern crustal extension that has only recently been unraveled based on its thermochronometrically constrained cooling history. Extension began during the Late Eocene synchronously with a major pulse of intermediate to felsic magmatism preserved locally by plutonic rocks intruded into the REHW and regionally by widespread Late Eocene to early Oligocene volcanism (“the ignimbrite flare-up”). The Eocene-Oligocene event accommodated at least 15 km of extension concentrated in the northern half of the complex and associated with deposition in the Elko Basin to the west, a relatively thin (~1 km), broad sequence of Late Eocene lacustrine and related strata that contrasts with the younger sedimentation patterns represented by the narrower, thicker (up to 4+km), coarse clastics of the Miocene Humboldt Basin. Though locally significant, the Eocene-Oligocene extensional phase appears not to have been associated with broadly distributed regional extension, again contrasting with Miocene and younger events. The initial phase of extension slowed or halted by the mid-Oligocene, after which extension re-accelerated in the latest Oligocene to early Miocenemore »(~25 – 21 Ma), correlative with deposition of a coarse clastic and lacustrine sequence known as the Clover Formation. This extensional phase propagated farther south than the earlier phase along the full length of the REHW. Extension likely slowed again between ~21 Ma and ~17.5 Ma, after which it abruptly re-accelerated through the Middle Miocene to ~10 Ma, synchronous with deposition of the thick, coarse clastics of the Humboldt Formation. Middle Miocene extension likely initiated with crustal-scale heating marking the impingement of the Yellowstone hot spot in NW Nevada. Sometime after 10 Ma, the interior of the core complex was transected by east-dipping normal faults that today define the steep eastern face of the Ruby Mountains and East Humboldt Range; these face west-dipping normal faults along the west flank of the Pequop Mountains and Spruce Mountains. Extension continues today at a rate of ~1 mm/yr as represented by the 2008 MW 6.0 Wells Earthquake.« less

Previous high-resolution angle-resolved photoemission (ARPES) studies of URu₂Si₂have characterized the temperature-dependent behavior of narrow-band states close to the Fermi level (E_F) at low photon energies near the zone center, with an emphasis on electronic reconstruction due to Brillouin zone folding. A substantial challenge to a proper description is that these states interact with other hole-band states that are generally absent from bulk-sensitive soft x-ray ARPES measurements. Here we provide a more globalk-space context for the presence of such states and their relation to the bulk Fermi surface (FS) topology using synchrotron-based wide-angle and photon energy-dependent ARPES mapping of the electronic structure using photon energies intermediate between the low-energy regime and the high-energy soft x-ray regime. Small-spot spatial dependence,f-resonant photoemission, Si 2pcore-levels, x-ray polarization, surface-dosing modification, and theoretical surface slab calculations are employed to assist identification of bulk versus surface state character of theE_F-crossing bands and their relation to specific U- or Si-terminations of the cleaved surface. The bulk FS topology is critically compared to density functional theory (DFT) and to dynamical mean field theory calculations. In addition to clarifying some aspects of the previously measured high symmetry Γ,ZandXpoints, incommensurate 0.6a* nested Fermi-edge states located alongZ–N–Zare found to be distinctlymore »different from the DFT FS prediction. The temperature evolution of these states aboveT_HO, combined with a more detailed theoretical investigation of this region, suggests a key role of theN-point in the hidden order transition.

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Rhyolitic melt that fuels explosive eruptions often originates in the upper crust via extraction from crystal-rich sources, implying an evolutionary link between volcanism and residual plutonism. However, the time scales over which these systems evolve are mainly understood through erupted deposits, limiting confirmation of this connection. Exhumed plutons that preserve a record of high-silica melt segregation provide a critical subvolcanic perspective on rhyolite generation, permitting comparison between time scales of long-term assembly and transient melt extraction events. Here, U-Pb zircon petrochronology and 40 Ar/ 39 Ar thermochronology constrain silicic melt segregation and residual cumulate formation in a ~7 to 6 Ma, shallow (3 to 7 km depth) Andean pluton. Thermo-petrological simulations linked to a zircon saturation model map spatiotemporal melt flux distributions. Our findings suggest that ~50 km 3 of rhyolitic melt was extracted in ~130 ka, transient pluton assembly that indicates the thermal viability of advanced magma differentiation in the upper crust.

Consensus is viewed as a proxy for truth in many discussions of science. When a consensus is formed by the independent and free deliberations of many, it is indeed a strong indicator of truth. Yet not all consensuses are independent and freely formed. We investigate the role of dependence and pressure in the formation of consensus, showing that strong polarization, external pressure, and dependence among individuals can force consensus around an issue, regardless of the underlying truth of the affirmed position. Dependence breaks consensus, often rendering it meaningless; a consensus can only be trusted to the extent that individuals are free to disagree with it.