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1.
Nano Lett ; 22(8): 3245-3251, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35416679

RESUMO

For multiband superconductors, the orbital multiplicity yields orbital differentiation in normal-state properties and can lead to orbital-selective spin-fluctuation Cooper pairing. The orbital-selective phenomenon has become increasingly pivotal in clarifying the pairing "enigma", particularly for multiband high-temperature superconductors. Meanwhile, in one-unit-cell (1-UC) FeSe/SrTiO3, since the standard electron-hole Fermi pocket nesting scenario is inapplicable, the actual pairing mechanism is subject to intense debate. Here, by measuring high-resolution Bogoliubov quasiparticle interference, we report observations of highly anisotropic magnetic Cooper pairing in 1-UC FeSe. Theoretically, it is important to incorporate orbitally selective effects of electronic correlations within a spin-fluctuation pairing calculation, where the dxy orbital becomes coherence-suppressed. The resulting pairing gap is compatible with the experimental findings, which suggests that high-Tc Cooper pairing with orbital selectivity applies to 2D-limit 1-UC FeSe. Our findings imply the general existence of orbital selectivity in iron-based superconductors and the universal significance of electron correlations in high-Tc superconductors.

2.
Nat Rev Cancer ; 21(12): 786-802, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34584243

RESUMO

Brain cancers carry bleak prognoses, with therapeutic advances helping only a minority of patients over the past decade. The brain tumour microenvironment (TME) is highly immunosuppressive and differs from that of other malignancies as a result of the glial, neural and immune cell populations that constitute it. Until recently, the study of the brain TME was limited by the lack of methods to de-convolute this complex system at the single-cell level. However, novel technical approaches have begun to reveal the immunosuppressive and tumour-promoting properties of distinct glial and myeloid cell populations in the TME, identifying new therapeutic opportunities. Here, we discuss the immune modulatory functions of microglia, monocyte-derived macrophages and astrocytes in brain metastases and glioma, highlighting their disease-associated heterogeneity and drawing from the insights gained by studying these malignancies and other neurological disorders. Lastly, we consider potential approaches for the therapeutic modulation of the brain TME.


Assuntos
Neoplasias Encefálicas , Glioma , Encéfalo , Neoplasias Encefálicas/patologia , Glioma/patologia , Humanos , Microglia/patologia , Microambiente Tumoral
3.
J Neurooncol ; 152(3): 515-522, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33646525

RESUMO

PURPOSE: Although uncommon, detection of BRAF V600E mutations in adult patients with glioblastoma has become increasingly relevant given the widespread application of molecular diagnostics and encouraging therapeutic activity of BRAF/MEK inhibitors. METHODS: We performed a retrospective study of adult glioblastoma patients treated at Dana-Farber Cancer Institute/Brigham and Women's Hospital or Massachusetts General Hospital from January 2011 to July 2019 with an identified BRAF V600E mutation by either immunohistochemistry or molecular testing. Patient characteristics, molecular genomics, and preoperative MRI were analyzed. RESULTS: Nineteen glioblastoma patients were included, with median age at diagnosis of 41-years-old (range 22-69). Only 1/18 was IDH1/2-mutant; 10/17 had MGMT unmethylated tumors. The most common additional molecular alterations were CDKN2A/2B biallelic loss/loss-of-function (10/13, 76.9%), polysomy 7 (8/12, 66.7%), monosomy 10 (5/12, 41.7%), PTEN biallelic loss/loss-of-function (5/13, 38.5%) and TERT promoter mutations (5/15, 33.3%). Most tumors were well-circumscribed (11/14) and all were contrast-enhancing on MRI. Twelve patients eventually developed subependymal or leptomeningeal dissemination. Six patients were treated with BRAF/MEK inhibition following disease progression after standard of care therapy, with 4/6 patients showing partial response or stable disease as best response. Median time to progression after BRAF/MEK inhibition was 6.0 months (95% CI 1.2-11.8). Grade 1 skin rash was present in 2 patients, but no other adverse events were reported. Median OS for the entire cohort was 24.1 months (95% CI 15.7-38.9). CONCLUSION: Understanding the natural history and features of BRAF V600E glioblastoma may help better identify patients for BRAF/MEK inhibition and select therapeutic strategies.


Assuntos
Glioblastoma , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Feminino , Genômica , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/radioterapia , Humanos , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno , Mutação , Inibidores de Proteínas Quinases , Estudos Retrospectivos , Adulto Jovem
4.
Nat Commun ; 12(1): 298, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436594

RESUMO

By using scanning tunneling microscopy (STM) we find and characterize dispersive, energy-symmetric in-gap states in the iron-based superconductor FeTe0.55Se0.45, a material that exhibits signatures of topological superconductivity, and Majorana bound states at vortex cores or at impurity locations. We use a superconducting STM tip for enhanced energy resolution, which enables us to show that impurity states can be tuned through the Fermi level with varying tip-sample distance. We find that the impurity state is of the Yu-Shiba-Rusinov (YSR) type, and argue that the energy shift is caused by the low superfluid density in FeTe0.55Se0.45, which allows the electric field of the tip to slightly penetrate the sample. We model the newly introduced tip-gating scenario within the single-impurity Anderson model and find good agreement to the experimental data.

5.
Nat Commun ; 11(1): 4415, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887890

RESUMO

Quantum states induced by single-atomic impurities are at the frontier of physics and material science. While such states have been reported in high-temperature superconductors and dilute magnetic semiconductors, they are unexplored in topological magnets which can feature spin-orbit tunability. Here we use spin-polarized scanning tunneling microscopy/spectroscopy (STM/S) to study the engineered quantum impurity in a topological magnet Co3Sn2S2. We find that each substituted In impurity introduces a striking localized bound state. Our systematic magnetization-polarized probe reveals that this bound state is spin-down polarized, in lock with a negative orbital magnetization. Moreover, the magnetic bound states of neighboring impurities interact to form quantized orbitals, exhibiting an intriguing spin-orbit splitting, analogous to the splitting of the topological fermion line. Our work collectively demonstrates the strong spin-orbit effect of the single-atomic impurity at the quantum level, suggesting that a nonmagnetic impurity can introduce spin-orbit coupled magnetic resonance in topological magnets.

6.
Phys Rev Lett ; 123(21): 217004, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31809171

RESUMO

The interplay between unconventional Cooper pairing and quantum states associated with atomic scale defects is a frontier of research with many open questions. So far, only a few of the high-temperature superconductors allow this intricate physics to be studied in a widely tunable way. We use scanning tunneling microscopy to image the electronic impact of Co atoms on the ground state of the LiFe_{1-x}Co_{x}As system. We observe that impurities progressively suppress the global superconducting gap and introduce low energy states near the gap edge, with the superconductivity remaining in the strong-coupling limit. Unexpectedly, the fully opened gap evolves into a nodal state before the Cooper pair coherence is fully destroyed. Our systematic theoretical analysis shows that these new observations can be quantitatively understood by the nonmagnetic Born-limit scattering effect in an s±-wave superconductor, unveiling the driving force of the superconductor to metal quantum phase transition.

7.
Nat Mater ; 18(7): 709-716, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31110345

RESUMO

Superconductivity in FeSe emerges from a nematic phase that breaks four-fold rotational symmetry in the iron plane. This phase may arise from orbital ordering, spin fluctuations or hidden magnetic quadrupolar order. Here we use inelastic neutron scattering on a mosaic of single crystals of FeSe, detwinned by mounting on a BaFe2As2 substrate to demonstrate that spin excitations are most intense at the antiferromagnetic wave vectors QAF = (±1, 0) at low energies E = 6-11 meV in the normal state. This two-fold (C2) anisotropy is reduced at lower energies, 3-5 meV, indicating a gapped four-fold (C4) mode. In the superconducting state, however, the strong nematic anisotropy is again reflected in the spin resonance (E = 3.6 meV) at QAF with incommensurate scattering around 5-6 meV. Our results highlight the extreme electronic anisotropy of the nematic phase of FeSe and are consistent with a highly anisotropic superconducting gap driven by spin fluctuations.

8.
Neurology ; 92(21): e2483-e2491, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31019097

RESUMO

OBJECTIVE: To perform a retrospective analysis examining the incidence and prognosis of glioma patients with leptomeningeal disease (LMD) at Memorial Sloan Kettering Cancer Center over a 15-year period and correlate these findings with clinicopathologic characteristics. METHODS: We conducted a retrospective review of glioma patients with LMD at Memorial Sloan Kettering Cancer Center diagnosed from 2001 to 2016. Patients were identified through a keyword search of their electronic medical record and by ICD-9 codes. RESULTS: One hundred three patients were identified with disseminated LMD and 85 patients with subependymal spread of disease, 4.7% of all patients with glioma. These cohorts were analyzed separately for time to development of disseminated LMD/subependymal LMD, median overall survival, and survival from LMD diagnosis. Patients were pooled for subsequent analyses (n = 188) because of comparable clinical behavior. LMD was present at glioma diagnosis in 10% of patients. In the remaining 90% of patients diagnosed at recurrence, time to LMD diagnosis, survival after LMD diagnosis, and overall survival varied by original histology. Patients with oligodendroglioma had a median survival of 10.8 (range 1.8-67.7) months, astrocytoma 6.5 (0.1-28.5) months, and glioblastoma 3.8 (0.1-32.6) months after LMD diagnosis. In addition, we found that treatment of LMD was associated with superior performance status and increased survival. CONCLUSION: Patients with LMD diagnosed at relapse may not have decreased overall survival as compared to historical controls with parenchymal relapse and may benefit from treatment.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/secundário , Neoplasias Meníngeas/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/epidemiologia , Astrocitoma/secundário , Feminino , Glioblastoma/epidemiologia , Glioblastoma/secundário , Glioma/epidemiologia , Glioma/terapia , Humanos , Incidência , Masculino , Neoplasias Meníngeas/epidemiologia , Neoplasias Meníngeas/terapia , Pessoa de Meia-Idade , Oligodendroglioma/epidemiologia , Oligodendroglioma/secundário , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
9.
Phys Rev Lett ; 121(2): 027002, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-30085763

RESUMO

We propose a mechanism whereby disorder can enhance the transition temperature T_{c} of an unconventional superconductor with pairing driven by exchange of spin fluctuations. The theory is based on a self-consistent real space treatment of pairing in the disordered one-band Hubbard model. It has been demonstrated before that impurities can enhance pairing by softening the spin fluctuations locally; here, we consider the competing effect of pair breaking by the screened Coulomb potential also present. We show that, depending on the impurity potential strength and proximity to magnetic order, this mechanism results in a weakening of the disorder-dependent T_{c}-suppression rate expected from Abrikosov-Gor'kov theory, or even in disorder-generated T_{c} enhancements.

10.
Phys Rev Lett ; 121(3): 037205, 2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-30085777

RESUMO

We determine theoretically the effect of spin-orbit coupling on the magnetic excitation spectrum of itinerant multiorbital systems, with specific application to iron-based superconductors. Our microscopic model includes a realistic ten-band kinetic Hamiltonian, atomic spin-orbit coupling, and multiorbital Hubbard interactions. Our results highlight the remarkable variability of the resulting magnetic anisotropy despite constant spin-orbit coupling. At the same time, the magnetic anisotropy exhibits robust universal behavior upon changes in the band structure corresponding to different materials of iron-based superconductors. A natural explanation of the observed universality emerges when considering optimal nesting as a resonance phenomenon. Our theory is also of relevance to other itinerant systems with spin-orbit coupling and nesting tendencies in the band structure.

11.
Phys Rev Lett ; 121(6): 067002, 2018 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-30141678

RESUMO

Understanding magnetic interactions in the parent compounds of high-temperature superconductors forms the basis for determining their role for the mechanism of superconductivity. For parent compounds of iron pnictide superconductors such as AFe_{2}As_{2} (A=Ba, Ca, Sr), although spin excitations have been mapped out throughout the entire Brillouin zone, the respective measurements were carried out on twinned samples and did not allow for a conclusive determination of the spin dynamics. Here we use inelastic neutron scattering to completely map out spin excitations of ∼100% detwinned BaFe_{2}As_{2}. By comparing observed spectra with theoretical calculations, we conclude that the spin excitations can be well described by an itinerant model when taking into account moderate electronic correlation effects.

12.
Phys Rev Lett ; 121(5): 057001, 2018 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-30118255

RESUMO

Recent experiments in iron pnictide superconductors reveal that, as the putative magnetic quantum critical point is approached, different types of magnetic order coexist over a narrow region of the phase diagram. Although these magnetic configurations share the same wave vectors, they break distinct symmetries of the lattice. Importantly, the highest superconducting transition temperature takes place close to this proliferation of near-degenerate magnetic states. In this Letter, we employ a renormalization group calculation to show that such a behavior naturally arises due to the effects of spin-orbit coupling on the quantum magnetic fluctuations. Formally, the enhanced magnetic degeneracy near the quantum critical point is manifested as a stable Gaussian fixed point with a large basin of attraction. Implications of our findings to the superconductivity of the iron pnictides are also discussed.

13.
Nat Commun ; 8: 15996, 2017 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-28660875

RESUMO

Spin fluctuations are a leading candidate for the pairing mechanism in high temperature superconductors, supported by the common appearance of a distinct resonance in the spin susceptibility across the cuprates, iron-based superconductors and many heavy fermion materials. The information we have about the spin resonance comes almost exclusively from neutron scattering. Here we demonstrate that by using low-temperature scanning tunnelling microscopy and spectroscopy we can characterize the spin resonance in real space. We show that inelastic tunnelling leads to the characteristic dip-hump feature seen in tunnelling spectra in high temperature superconductors and that this feature arises from excitations of the spin fluctuations. Spatial mapping of this feature near defects allows us to probe non-local properties of the spin susceptibility and to image its real space structure.

14.
Nat Commun ; 8: 14317, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-28176779

RESUMO

The combination of electronic correlations and Fermi surfaces with multiple nesting vectors can lead to the appearance of complex multi-Q magnetic ground states, hosting unusual states such as chiral density waves and quantum Hall insulators. Distinguishing single-Q and multi-Q magnetic phases is however a notoriously difficult experimental problem. Here we propose theoretically that the local density of states (LDOS) near a magnetic impurity, whose orientation may be controlled by an external magnetic field, can be used to map out the detailed magnetic configuration of an itinerant system and distinguish unambiguously between single-Q and multi-Q phases. We demonstrate this concept by computing and contrasting the LDOS near a magnetic impurity embedded in three different magnetic ground states relevant to iron-based superconductors-one single-Q and two double-Q phases. Our results open a promising avenue to investigate the complex magnetic configurations in itinerant systems via standard scanning tunnelling spectroscopy, without requiring spin-resolved capability.

16.
Phys Rev Lett ; 117(25): 257002, 2016 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-28036210

RESUMO

We study the effects of disorder on unconventional superconductors in the presence of correlations, and explore a novel correlated disorder paradigm dominated by strong deviations from standard Abrikosov-Gor'kov theory due to generation of local bound states and cooperative impurity behavior driven by Coulomb interactions. Specifically we explain under which circumstances magnetic disorder acts as a strong poison destroying high-T_{c} superconductivity at the sub-1% level, and when nonmagnetic disorder, counterintuitively, hardly affects the unconventional superconducting state while concomitantly inducing an inhomogeneous full-volume magnetic phase. Recent experimental studies of Fe-based superconductors have discovered that such unusual disorder behavior seems to be indeed present in those systems.

17.
Phys Rev Lett ; 116(16): 167001, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-27152819

RESUMO

Pair-density-wave superconductivity constitutes a novel electronic condensate proposed to be realized in certain unconventional superconductors. Establishing its potential existence is important for our fundamental understanding of superconductivity in correlated materials. Here we compute the dynamical magnetic susceptibility in the presence of a pair-density-wave ordered state and study its fingerprints on the spin-wave spectrum including the neutron resonance. In contrast to the standard case of d-wave superconductivity, we show that the pair-density-wave phase exhibits neither a spin gap nor a magnetic resonance peak, in agreement with a recent neutron scattering experiment on underdoped La_{1.905}Ba_{0.095}CuO_{4} [Z. Xu et al., Phys. Rev. Lett. 113, 177002 (2014)].

18.
J Immunother Cancer ; 4: 11, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26885373

RESUMO

BACKGROUND: Annexin A2 (ANXA2) is a pleiotropic, calcium-dependent, phospholipid-binding protein with a broad tissue distribution. It can be intracellular, membrane-bound, or secreted, and it exists as a monomer or heterotetramer. The secreted ANXA2 heterotetramer signals human and murine macrophages to produce IL-1, IL-6, and TNF-α through TLR4/MyD88- and TRIF-dependent pathways. METHODS: GL261 glioma cells were cultured in 5 % or 20 % O2. Monomeric ANXA2 (ANXA2m) was identified as a TLR2-binding protein enriched in 5 % O2 by mass spectrometry. Purified ANXA2m and ANXA2-derived peptides were added to TLR2-expressing reporter cells and immature dendritic cells (DCs) cells in vitro. ANXA2m was then mixed with chicken ovalbumin (OVA) for vaccination of TLR2 (+/+) and TLR2 (-/-) mice for subsequent quantification of antigen-specific CD8(+) T cell responses. The TLR2-binding region of ANXA2m was determined using various peptides derived from the ANXA2 amino terminus on TLR2 reporter cells and in vaccinated mice. RESULTS: ANXA2m is overexpressed by murine glioblastoma GL261 cells grown under 5 % O2, but not atmospheric 20 % O2, and acts as an adjuvant by inducing murine and human DC maturation through TLR2. ANXA2m upregulates CD80 and CD86 expression, enhances antigen cross-presentation, and induces the secretion of IL-12p70, TNF-α, and IFN-γ. The amino-terminal 15 amino acids of ANXA2m are necessary and sufficient for TLR2 binding and DC activation. CONCLUSION: This novel finding adds to the known functions of ANXA2 and suggests ways to exploit it as a vaccine adjuvant. ANXA2-antigen fusion peptides could be developed for patients as "off-the-shelf" agents containing common tumor antigens. Alternatively, they could be "personalized" and synthesized after tumor sequencing to identify immunogenic tumor-specific neo-antigens. As the amino terminal 15 amino acids of ANXA2 are required to stimulate TLR2 activity, a fusion peptide could be as short as 30 amino acids if one or two CD8 T cell epitopes are fused to the ANXA2 amino terminal portion. Future work will address the efficacy of ANXA2 peptide fusions alone and in combination with established TLR agonists to induce synergy in preclinical models of glioma as observed in other vaccines.

19.
Phys Rev Lett ; 115(2): 026402, 2015 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-26207487

RESUMO

We provide a band structure with low-energy properties consistent with recent photoemission and quantum oscillation measurements on FeSe, assuming mean-field-like site- and/or bond-centered ferro-orbital ordering at the structural transition. We show how the resulting model provides a consistent explanation of the temperature dependence of the measured Knight shift and the spin-relaxation rate. Furthermore, the superconducting gap structure obtained from spin-fluctuation theory exhibits nodes on the electron pockets, consistent with the V-shaped density of states obtained by tunneling spectroscopy on this material, and the temperature dependence of the London penetration depth.

20.
Phys Rev Lett ; 114(9): 097003, 2015 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-25793844

RESUMO

The unusual temperature dependence of the resistivity and its in-plane anisotropy observed in the Fe-based superconducting materials, particularly Ba(Fe_{1-x}Co_{x})_{2}As_{2}, has been a long-standing puzzle. Here, we consider the effect of impurity scattering on the temperature dependence of the average resistivity within a simple two-band model of a dirty spin density wave metal. The sharp drop in resistivity below the Néel temperature T_{N} in the parent compound can only be understood in terms of a Lifshitz transition following Fermi surface reconstruction upon magnetic ordering. We show that the observed resistivity anisotropy in this phase, arising from nematic defect structures, is affected by the Lifshitz transition as well.

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