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Spatial, momentum and energy separation of electronic spins in condensed-matter systems guides the development of new devices in which spin-polarized current is generated and manipulated1-3. Recent attention on a set of previously overlooked symmetry operations in magnetic materials4 leads to the emergence of a new type of spin splitting, enabling giant and momentum-dependent spin polarization of energy bands on selected antiferromagnets5-10. Despite the ever-growing theoretical predictions, the direct spectroscopic proof of such spin splitting is still lacking. Here we provide solid spectroscopic and computational evidence for the existence of such materials. In the noncoplanar antiferromagnet manganese ditelluride (MnTe2), the in-plane components of spin are found to be antisymmetric about the high-symmetry planes of the Brillouin zone, comprising a plaid-like spin texture in the antiferromagnetic (AFM) ground state. Such an unconventional spin pattern, further found to diminish at the high-temperature paramagnetic state, originates from the intrinsic AFM order instead of spin-orbit coupling (SOC). Our finding demonstrates a new type of quadratic spin texture induced by time-reversal breaking, placing AFM spintronics on a firm basis and paving the way for studying exotic quantum phenomena in related materials.
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Amorphous metal oxides with analog resistive switching functions (i.e., continuous controllability of the electrical resistance) are gaining emerging interest due to their neuromorphic functionalities promising for energy efficient electronics. The mechanisms are currently attributed to field-driven migration of the constituent ions, but the applications are being hindered by the limited understanding of the physical mechanisms due to the difficulty in analyzing the causal ion migration, which occurs on a nanometer or even atomic scale. Here, the direct electrical transport measurement of analog resistive switching and ångström scale imaging of the causal ion migration is demonstrated in amorphous TaOx (a-TaOx) by conductive atomic force microscopy. Atomically flat thin films of a-TaOx, which is a practical material for commercial resistive random access memory, are fabricated in this study, and the mechanisms of the three known types of analog resistive switching phenomena (current-dependent set, voltage-dependent reset, and time-dependent switching) are directly visualized on the surfaces. The observations indicate that highly analog type of resistive switching can be induced in a-TaOx by inducing the continuous redox reactions for 2.0 < x < 2.5, which are characteristic of a-TaOx. The measurements also demonstrate drastic control of the switching stochasticity, which is attributable to controlled segregation of a metastable a-TaO2 phase. The findings provide direct clues for tuning the analog resistive switching characteristics of amorphous metal oxides and developing new functions for future neuromorphic computing.
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Multidot single-electron devices (SEDs) can enable new types of computing technologies, such as those that are reconfigurable and reservoir-computing. A self-assembled metal nanodot array film that is attached to multiple gates is a candidate for use in such SEDs for achieving high functionality. However, the single-electron properties of such a film have not yet been investigated in conjunction with optimally controlled multiple gates because of the structural complexity of incorporating many nanodots. In this study, Fe nanodot-array-based double-gate SEDs were fabricated by vacuum deposition, and their single-electron properties (modulated by the top- and bottom-gate voltages; VT and VB, respectively) were investigated. The phase of the Coulomb blockade oscillation systematically shifted with VT, indicating that the charge state of the single dot was controlled by both the gate voltages despite the metallic random multidot structure. This result demonstrates that the Coulomb blockade oscillation (originating from the dot in the multidot array) can be modulated by the two gates. The top and bottom gates affected the electronic state of the dot unevenly owing to the geometrical effect caused by the following: (1) vertically asymmetric dot shape and (2) variation of the dot size (including the surrounding dots). This is a characteristic feature of a nanodot array that uses self-assembled metal dots; for example, prepared by vacuum deposition. Such variations derived from a randomly distributed nanodot array will be useful in enhancing the functionality of multidot devices.
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Dirac materials, which feature Dirac cones in the reciprocal space, have been one of the hottest topics in condensed matter physics in the past decade. To date, 2D and 3D Dirac Fermions have been extensively studied, while their 1D counterparts are rare. Recently, Si nanoribbons (SiNRs), which are composed of alternating pentagonal Si rings, have attracted intensive attention. However, the electronic structure and topological properties of SiNRs are still elusive. Here, by angle-resolved photoemission spectroscopy, scanning tunneling microscopy/spectroscopy measurements, first-principles calculations, and tight-binding model analysis, we demonstrate the existence of 1D Dirac Fermions in SiNRs. Our theoretical analysis shows that the Dirac cones derive from the armchairlike Si chain in the center of the nanoribbon and can be described by the Su-Schrieffer-Heeger model. These results establish SiNRs as a platform for studying the novel physical properties in 1D Dirac materials.
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Lymphodepleting cytotoxic regimens enhance the antitumor effects of adoptively transferred effector and naïve T cells. Although the mechanisms of antitumor immunity augmentation by lymphodepletion have been intensively investigated, the effects of lymphodepletion followed by T cell transfer on immune checkpoints in the tumor microenvironment remain unclear. The current study demonstrated that the expression of immune checkpoint molecules on transferred donor CD4+ and CD8+ T cells was significantly decreased in lymphodepleted tumor-bearing mice. In contrast, lymphodepletion did not reduce immune checkpoint molecule levels on recipient CD4+ and CD8+ T cells. Administration of anti-PD-1 antibodies after lymphodepletion and adoptive transfer of T cells significantly inhibited tumor progression. Further analysis revealed that transfer of both donor CD4+ and CD8+ T cells was responsible for the antitumor effects of a combination therapy consisting of lymphodepletion, T cell transfer and anti-PD-1 treatment. Our findings indicate that a possible mechanism underlying the antitumor effects of lymphodepletion followed by T cell transfer is the prevention of donor T cell exhaustion and dysfunction. PD-1 blockade may reinvigorate exhausted recipient T cells and augment the antitumor effects of lymphodepletion and adoptive T cell transfer.
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Linfócitos T CD8-Positivos , Neoplasias , Transferência Adotiva , Animais , Humanos , Imunoterapia Adotiva , Camundongos , Neoplasias/terapia , Receptor de Morte Celular Programada 1 , Microambiente TumoralRESUMO
Lateral heterojunctions of atomically precise graphene nanoribbons (GNRs) hold promise for applications in nanotechnology, yet their charge transport and most of the spectroscopic properties have not been investigated. Here, we synthesize a monolayer of multiple aligned heterojunctions consisting of quasi-metallic and wide-bandgap GNRs, and report characterization by scanning tunneling microscopy, angle-resolved photoemission, Raman spectroscopy, and charge transport. Comprehensive transport measurements as a function of bias and gate voltages, channel length, and temperature reveal that charge transport is dictated by tunneling through the potential barriers formed by wide-bandgap GNR segments. The current-voltage characteristics are in agreement with calculations of tunneling conductance through asymmetric barriers. We fabricate a GNR heterojunctions based sensor and demonstrate greatly improved sensitivity to adsorbates compared to graphene based sensors. This is achieved via modulation of the GNR heterojunction tunneling barriers by adsorbates.
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Cisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias do Colo/tratamento farmacológico , Insuficiência Renal/prevenção & controle , Animais , Apoptose , Proliferação de Células , Cilastatina/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Feminino , Taxa de Filtração Glomerular , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Endogâmicos NOD , Camundongos SCID , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Owing to the recent discovery of the current-induced metal-insulator transition and unprecedented electronic properties of the concomitant phases of calcium ruthenate Ca2RuO4, it is emerging as an important material. To further explore the properties, the growth of epitaxial thin films of Ca2RuO4 is receiving more attention, as high current densities can be applied to thin-film samples and the amount can be precisely controlled in an experimental environment. However, it is difficult to grow high-quality thin films of Ca2RuO4 due to the easy formation of the crystal defects originating from the sublimation of RuO4; therefore, the metal-insulator transition of Ca2RuO4 is typically not observed in the thin films. Herein, a stable current-induced metal-insulator transition is achieved in the high-quality thin films of Ca2RuO4 grown by solid-phase epitaxy under high growth temperatures and pressures. In the Ca2RuO4 thin films grown by ex situ annealing at >1200 °C and 1.0 atm, continuous changes in the resistance of over 2 orders of magnitude are induced by currents with a precise dependence of the resistance on the current amplitude. A hysteretic, abrupt resistive transition is also observed in the thin films from the resistance-temperature measurements conducted under constant-voltage (variable-current) conditions with controllability of the transition temperature. A clear resistive switching by the current-induced transition is demonstrated in the current-electric-field characteristics, and the switching currents and fields are shown to be very stable. These results represent a significant step toward understanding the high-current-density properties of Ca2RuO4 and the future development of Mott-electronic devices based on electricity-driven transitions.
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We investigated the electronic structures of mono- and few-layered Ru nanosheets (N layers (L) with N = 1, ~6, and ~9) on Si substrate by ultra-violet and x-ray photoemission spectroscopies. The spectral density of states (DOS) near EF of ~6 L and 1 L is suppressed as it approaches EF in contrast to that of ~9 L, which is consistent with the Ru 3 d core-level shift indicating the reduction of the metallic conductivity. A power law g(ε) â |ε - εF|α well reproduces the observed spectral DOS of ~6 L and 1 L. The evolution of the power factor α suggests that the transition from the metallic state of ~9 L to the 2-dimensional insulating state with the soft Coulomb gap of 1 L through the disordered 3-dimensional metallic state of ~6 L.
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Spin-orbit coupling (SOC) has gained much attention for its rich physical phenomena and highly promising applications in spintronic devices. The Rashba-type SOC in systems with inversion symmetry breaking is particularly attractive for spintronics applications since it allows for flexible manipulation of spin current by external electric fields. Here, we report the discovery of a giant anisotropic Rashba-like spin splitting along three momentum directions (3D Rashba-like spin splitting) with a helical spin polarization around the M points in the Brillouin zone of trigonal layered PtBi2. Due to its inversion asymmetry and reduced symmetry at the M point, Rashba-type as well as Dresselhaus-type SOC cooperatively yield a 3D spin splitting with αR ≈ 4.36 eV Å in PtBi2. The experimental realization of 3D Rashba-like spin splitting not only has fundamental interests but also paves the way to the future exploration of a new class of material with unprecedented functionalities for spintronics applications.
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Anisotropia , Bismuto/química , Eletrônica/métodos , Compostos de Platina/química , Platina/química , Algoritmos , Simulação por Computador , Cristalografia por Raios X , Eletricidade , Modelos Químicos , Modelos Moleculares , Nanoestruturas/química , Compostos de Platina/síntese químicaRESUMO
Although the blockade of programmed cell death 1 (PD-1)/PD-ligand (L) 1 has demonstrated promising and durable clinical responses for non-small-cell lung cancers (NSCLCs), NSCLC patients with epidermal growth factor receptor (EGFR) mutations responded poorly to PD-1/PD-L1 inhibitors. Previous studies have identified several predictive biomarkers, including the expression of PD-L1 on tumor cells, for PD-1/PD-L1 blockade therapies in NSCLC patients; however, the usefulness of these biomarkers in NSCLCs with EGFR mutations has not been elucidated. The present study was conducted to evaluate the predictive biomarkers for PD-1/PD-L1 inhibitors in EGFR-mutated NSCLCs. We retrospectively analyzed 9 patients treated with nivolumab for EGFR-mutated NSCLCs. All but one patient received EGFR-tyrosine kinase inhibitors before nivolumab treatment. The overall response rate and median progression-free survival were 11% and 33 days (95% confidence interval (CI); 7 to 51), respectively. Univariate analysis revealed that patients with a good performance status (P = 0.11; hazard ratio (HR) 0.183, 95% CI 0.0217 to 1.549), a high density of CD4+ T cells (P = 0.136; HR 0.313, 95% CI 0.045 to 1.417) and a high density of Foxp3+ cells (P = 0.09; HR 0.264, 95% CI 0.0372 to 1.222) in the tumor microenvironment tended to have longer progression-free survival with nivolumab. Multivariate analysis revealed that a high density of CD4+ T cells (P = 0.005; HR<0.001, 95% CI <0.001 to 0.28) and a high density of Foxp3+ cells (P = 0.003; HR<0.001, 95% CI NA) in tumor tissues were strongly correlated with better progression-free survival. In contrast to previous studies in wild type EGFR NSCLCs, PD-L1 expression was not associated with the clinical benefit of anti-PD-1 treatment in EGFR-mutated NSCLCs. The current study indicated that immune status in the tumor microenvironment may be important for the effectiveness of nivolumab in NSCLC patients with EGFR mutations.
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Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Nivolumabe/uso terapêutico , Adulto , Idoso , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/imunologia , Contagem de Linfócito CD4 , Carcinoma Pulmonar de Células não Pequenas/imunologia , Receptores ErbB/genética , Feminino , Fatores de Transcrição Forkhead/metabolismo , Genes erbB-1 , Humanos , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos , Microambiente Tumoral/imunologiaRESUMO
We demonstrate that the inclusion of a Ta interfacial layer is a remarkably effective strategy for forming interfacial oxygen defects at metal/oxide junctions. The insertion of an interfacial layer of a reactive metal, that is, a "scavenging" layer, has been recently proposed as a way to create a high concentration of oxygen defects at an interface in redox-based resistive switching devices, and growing interest has been given to the underlying mechanism. Through structural and chemical analyses of Pt/metal/SrTiO3/Pt structures, we reveal that the rate and amount of oxygen scavenging are not directly determined by the formation free energies in the oxidation reactions of the scavenging metal and unveil the important roles of oxygen diffusibility. Active oxygen scavenging and highly uniform oxidation via scavenging are revealed for a Ta interfacial layer with high oxygen diffusibility. In addition, the Ta scavenging layer is shown to exhibit a highly uniform structure and to form a very flat interface with SrTiO3, which are advantageous for the fabrication of a steep metal/oxide contact.
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2D anisotropic Dirac cones are observed in χ3 borophene, a monolayer boron sheet, using high-resolution angle-resolved photoemission spectroscopy. The Dirac cones are centered at the X and X' points. The data also reveal that the hybridization between borophene and Ag(111) is very weak, which explains the preservation of the Dirac cones. As χ3 borophene has been predicated to be a superconductor, the results may stimulate further research interest in the novel physics of borophene, such as the interplay between Cooper pairs and the massless Dirac fermions.
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Conventional Rashba spin polarization is caused by the combination of strong spin-orbit interaction and spatial inversion asymmetry. However, Rashba-Dresselhaus-type spin-split states are predicted in the centrosymmetric LaOBiS2 system by recent theory, which stem from the local inversion asymmetry of active BiS2 layer. By performing high-resolution spin- and angle-resolved photoemission spectroscopy, we have investigated the electronic band structure and spin texture of superconductor LaO0.55F0.45BiS2. Here we present direct spectroscopic evidence for the local spin polarization of both the valence band and the conduction band. In particular, the coexistence of Rashba-like and Dresselhaus-like spin textures has been observed in the conduction band. The finding is of key importance for fabrication of proposed dual-gated spin-field effect transistor. Moreover, the spin-split band leads to a spin-momentum locking Fermi surface from which superconductivity emerges. Our demonstration not only expands the scope of spintronic materials but also enhances the understanding of spin-orbit interaction-related superconductivity.
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Topological nodal line semimetals, a novel quantum state of materials, possess topologically nontrivial valence and conduction bands that touch at a line near the Fermi level. The exotic band structure can lead to various novel properties, such as long-range Coulomb interaction and flat Landau levels. Recently, topological nodal lines have been observed in several bulk materials, such as PtSn4, ZrSiS, TlTaSe2 and PbTaSe2. However, in two-dimensional materials, experimental research on nodal line fermions is still lacking. Here, we report the discovery of two-dimensional Dirac nodal line fermions in monolayer Cu2Si based on combined theoretical calculations and angle-resolved photoemission spectroscopy measurements. The Dirac nodal lines in Cu2Si form two concentric loops centred around the Γ point and are protected by mirror reflection symmetry. Our results establish Cu2Si as a platform to study the novel physical properties in two-dimensional Dirac materials and provide opportunities to realize high-speed low-dissipation devices.
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Electronic structures of ferromagnetic heavy fermion Yb compounds of YbPdSi, YbPdGe, and YbPtGe are studied by photoelectron spectroscopy around the Yb 4d-4f resonance, resonant x-ray emission spectroscopy at the Yb L 3 absorption edge, and density functional theory combined with dynamical mean field theory calculations. These compounds all have a temperature-independent intermediate Yb valence with large [Formula: see text] and small [Formula: see text] components. The magnitude of the Yb valence is evaluated to be YbPtGe [Formula: see text] YbPdGe [Formula: see text] YbPdSi, suggesting that YbPtGe is the closest to the quantum critical point among the three Yb compounds. Our results support the scenario of the coexistence of heavy fermion behavior and ferromagnetic ordering which is described by a magnetically-ordered Kondo lattice where the magnitude of the Kondo effect and the RKKY interaction are comparable.
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The adoptive transfer of effector T cells combined with lymphodepletion has demonstrated promising antitumor effects in mice and humans, although the availability of tumor-specific T cells is limited. We and others have also demonstrated that the transfer of polyclonal naïve T cells induces tumor-specific effector T cells and enhances antitumor immunity after lymphodepletion. Because tumors have been demonstrated to induce immunosuppressive networks and regulate the function of T cells, obtaining a sufficient number of fully functional naïve T cells that are able to differentiate into tumor-specific effector T cells remains difficult. To establish culture methods to obtain a large number of polyclonal T cells that are capable of differentiating into tumor-specific effector T cells, naïve T cells were activated with anti-CD3 mAbs in vitro. These cells were stimulated with IL-2 and IL-7 for the CD8 subset or with IL-7 and IL-23 for the CD4 subset. Transfer of these hyperexpanded T cells after lymphodepletion showed significant antitumor efficacy, and tumor-specific effector T cells were primed from these expanded T cells in tumor-bearing hosts. Moreover, these ex vivo-expanded T cells maintained T cell receptor diversity and showed long-term persistence of memory against specific tumors. Further analyses revealed that combination therapy consisting of vaccination with dendritic cells that were co-cultured with irradiated whole tumor cells and the transfer of ex vivo-expanded T cells significantly enhanced antitumor immunity. These results indicate that the transfer of ex vivo-expanded polyclonal T cells can be combined with other immunotherapies and augment antitumor effects.
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Transferência Adotiva/métodos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/transplante , Neoplasias/terapia , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Proliferação de Células , Células Cultivadas , Células Dendríticas/imunologia , Células Dendríticas/transplante , Feminino , Interleucina-2/imunologia , Interleucina-23/imunologia , Interleucina-7/imunologia , Ativação Linfocitária , Depleção Linfocítica , Camundongos Endogâmicos C57BL , Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T/imunologiaRESUMO
Topological semimetals have recently attracted extensive research interests as host materials to condensed matter physics counterparts of Dirac and Weyl fermions originally proposed in high energy physics. Although Lorentz invariance is required in high energy physics, it is not necessarily obeyed in condensed matter physics, and thus Lorentz-violating type-II Weyl/Dirac fermions could be realized in topological semimetals. The recent realization of type-II Weyl fermions raises the question whether their spin-degenerate counterpart-type-II Dirac fermions-can be experimentally realized too. Here, we report the experimental evidence of type-II Dirac fermions in bulk stoichiometric PtTe2 single crystal. Angle-resolved photoemission spectroscopy measurements and first-principles calculations reveal a pair of strongly tilted Dirac cones along the Γ-A direction, confirming PtTe2 as a type-II Dirac semimetal. Our results provide opportunities for investigating novel quantum phenomena (e.g., anisotropic magneto-transport) and topological phase transition.Whether the spin-degenerate counterpart of Lorentz-violating Weyl fermions, the Dirac fermions, can be realized remains as an open question. Here, Yan et al. report experimental evidence of such type-II Dirac fermions in bulk PtTe2 single crystal with a pair of strongly tilted Dirac cones.
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We have developed a laser-based scanning angle-resolved photoemission spectroscopy system (µ-ARPES) equipped with a high precision 6-axis control system, realizing not only high-resolution photoemission spectroscopy in energy and momentum, but also spatial resolution of a µm scale. This enables our µ-ARPES system to probe fine details of intrinsic electronic states near the Fermi level such as the superconducting gaps and lifetime broadening.
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We performed annealing and angle resolved photoemission spectroscopy studies on electron-doped cuprate Pr_{1-x}LaCe_{x}CuO_{4-δ} (PLCCO). It is found that the optimal annealing condition is dependent on the Ce content x. The electron number (n) is estimated from the experimentally obtained Fermi surface volume for x=0.10, 0.15 and 0.18 samples. It clearly shows a significant and annealing dependent deviation from the nominal x. In addition, we observe that the pseudo-gap at hot spots is also closely correlated with n; the pseudogap gradually closes as n increases. We established a new phase diagram of PLCCO as a function of n. Different from the x-based one, the new phase diagram shows similar antiferromagnetic and superconducting phases to those of hole doped ones. Our results raise a possibility for absence of disparity between the phase diagrams of electron- and hole-doped cuprates.