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Suppression of 1/f noise in tunnel magnetoresistance (TMR) sensors is a central issue in the realization of magnetic field sensors with ultrafine magnetic field detectivity. Although AC modulation with an external magnetic field has been proposed as a method to shift the operating frequency of a sensor to a high frequency and substantially suppress 1/f noise, its effects on the two types of 1/f noise, that is, magnetic and electrical 1/f noise, are not well understood. In this study, we investigated the noise characteristics and signal detection performance of TMR sensors with an even-function resistance-magnetic field curve operated by the AC modulation method. For one TMR device in which the magnetic 1/f noise was dominant, AC modulation degraded the magnetic field detectivity owing to the additional noise induced by the AC modulation field. However, in another TMR device, in which the electrical 1/f noise was artificially enhanced by introducing lattice defects in the MgO tunnel barrier, AC modulation effectively suppressed the 1/f noise and improved the magnetic field detectivity by one order. This demonstrates that the AC modulation method using an external magnetic field is effective for magnetic field sensors in which electrical 1/f noise is dominant. [ABSTRACT FROM AUTHOR]

Magnetic stabilization of the ferromagnetic layers of magnetoresistive elements is a key technological requirement for fabricating highly sensitive and accurate magnetic sensors. Here, we report on a tunnel magnetoresistive (TMR) sensor wherein the free layer (FL) magnetization is stabilized by combining exchange bias, noncollinear interlayer exchange coupling through a RuFe spacer, and orange-peel ferromagnetic coupling. This method facilitates stabilization of the FL magnetization over a wide range of noncollinear angles with respect to the pinning direction by controlling the composition of the RuFe spacer. Moreover, the uniaxial anisotropy induced in the FL by annealing plays an important role in the resistance–magnetic field (R–H) curve, which was studied both experimentally and through simulation. The TMR devices exhibited negligible hysteresis even in the major R–H loops, which is promising for magnetic field-sensing applications. [ABSTRACT FROM AUTHOR]

We report on tunnel magnetoresistance (TMR) sensors with two ferromagnetic free layers (FLs) on both sides of a MgO tunnel barrier. The magnetizations of these FLs are weakly (softly) pinned in an anti-parallel configuration by the exchange bias of IrMn antiferromagnetic layers through ferromagnetic and/or antiferromagnetic interlayer couplings of non-magnetic spacer layers. These dual soft-pinned FL (SPFL) sensors show a symmetric resistance (R) change with respect to the polarity of the external magnetic field (H) applied to the hard axis (HA) of the SPFLs and TMR ratios of over 200%, which is much higher than those of the single-SPFL sensors, where one side of the ferromagnetic layers is an SPFL and the other side is a strongly pinned reference layer. When the applied H exhibits an angular misalignment from the HA, dual-SPFL sensors show much-reduced asymmetry in the R–H curves than single-SPFL sensors. Macrospin simulations of the magnetization behavior and R–H curve for both dual- and single-SPFL sensors revealed that the small asymmetry in the R–H curves of dual-SPFL sensors was owing to their significantly smaller dependence of relative magnetization angle between the SPFLs on the magnetic field misalignment from the HA. These results suggest that dual-SPFL TMR sensors are promising for use in magnetic sensors such as encoder sensors for position and rotation detections. [ABSTRACT FROM AUTHOR]

Recent advances in the study of materials with topological electronic band structures have revealed magnetic materials exhibiting giant anomalous Hall effects (AHEs). The giant AHE has not only attracted the research interest in its mechanism but also opened up the possibility of practical application in magnetic sensors. In this article, we describe simulation-based investigations of AHE magnetic sensors for applications to read head sensors (readers) of hard disk drives. With the shrinking of magnetic recording patterns, the reader technology, which currently uses multilayer-based tunnel magnetoresistance (TMR) devices, is associated with fundamental challenges, such as insufficient spatial resolution and signal-to-noise ratio (SNR) in sensors with dimensions below 20 nm. The structure of an AHE-based device composed of a single ferromagnetic material is advantageous for magnetic sensors with nanoscale dimensions. We found that AHE readers using topological ferromagnets with giant AHE, such as Co2MnGa, can achieve a higher SNR than current TMR readers. The higher SNR originates from the large output signal of the giant AHE as well as from the reduced thermal magnetic noise, which is the dominant noise in TMR readers. We highlight a major challenge in the development of AHE readers: the reduction in the output signal due to the shunting of the bias current and the leakage of the Hall voltage through the soft magnetic shields surrounding the AHE reader. We propose reader structures that overcome this challenge. Finally, we discuss the scope for future research to realize AHE readers. [ABSTRACT FROM AUTHOR]

To utilize highly spin-polarized Heusler alloys in practical spintronic devices, the realization of highly textured and structurally ordered polycrystalline thin films under limited annealing temperatures (TA) is critical. Compared to the natural [110]-texture of Heusler alloys, the [001]-texture is considered to be favorable for current-perpendicular-to-plane giant magnetoresistance devices due to the reduced lattice misfit with the face-centered-cubic Ag spacer layers. In this study, we fabricated [001]-oriented polycrystalline Co2FeGa0.5Ge0.5 (CFGG) Heusler alloy films epitaxially grown on a [001]-oriented polycrystalline Ag buffer layer on a thermally oxidized Si substrate, and the microstructure of the [001]-oriented Ag/CFGG bilayer film was investigated in detail. The [001]-oriented Ag films were obtained by introducing N2 into Ar during the sputtering process. The [001]-oriented CFGG films exhibited smooth interfaces, B2 ordering, and a high saturation magnetization close to the theoretical value under relatively low annealing at TA = 300 °C, which are critical for industrial applications such as read heads of hard disk drives. [ABSTRACT FROM AUTHOR]

We studied the effect of the (Ni0.8Fe0.2)100−xCrx seed layer on the current-in-plane giant magnetoresistance (CIP-GMR) in Fe16Co66Ni18/Cu multilayer films. Both the GMR ratio (ΔR/R) and interlayer exchange coupling (IEC) between the FeCoNi layers showed strong dependences on the Cr concentration x in the seed layer. The highest ΔR/R of ∼30% was obtained for x = 38 (at. %) due to a comparatively strong antiparallel IEC resulting from a strong [111]-out-of-plane-texture of the [FeCoNi/Cu] multilayer. This confirms that a strong [111] texture is essential for the GMR in antiferromagnetically coupled multilayers as reported in previous works. However, we found that the strong [111] texture is not sufficient to obtain large ΔR/R. For x = 48, the [FeCoNi/Cu] multilayer showed a strong [111] texture as that for x = 38; however, the observed ΔR/R and antiparallel IEC for x = 48 were much smaller than those for x = 38. Detailed microstructural and chemical analyses by scanning transmission electron microscopy revealed that the fluctuation of the thickness of the Cu spacer layer can explain the reduction of antiparallel IEC that gave rise to the decrease in ΔR/R in the case of x = 48. We also discuss the effect of IEC energies on the sensitivity of GMR sensors. [ABSTRACT FROM AUTHOR]

Magnetoresistance (MR) devices with symmetric (even-function) resistance change to an external magnetic field is useful for various magnetic sensor applications, such as encoders for position and rotation detection and ultra-sensitive magnetic field sensors, when combined with a frequency modulation method. In this study, we developed tunnel magnetoresistance (TMR) sensors with even-function resistance–field (R–H) responses and investigated their noise properties. The developed TMR sensors achieved a higher MR ratio (∼120%) than those of conventional giant magnetoresistive multilayers exhibiting even-function R–H responses. The TMR sensors were realized by stabilizing the magnetization of the magnetic free layer (FL) in an anti-parallel configuration with respect to that of the reference layer. Orange-peel ferromagnetic coupling between the FL and a pinned layer through an AgSn spacer layer was used to control the strength of the unidirectional magnetic anisotropy of the FL, by which even-function R–H responses with negligible hysteresis were obtained. The sensors enabled us to study the intrinsic noise properties of TMR devices, particularly under an external AC modulation magnetic field. We found that the magnetic 1/f noise originating from thermal magnetization fluctuation was the dominant noise of the TMR sensors at low frequencies. We observed that the application of an AC modulation field to the TMR sensors increased the noise owing to the magnetic domain fluctuation and the transfer of magnetic 1/f noise to the modulation frequency. [ABSTRACT FROM AUTHOR]

Magnetic field sensors using the tunnel magnetoresistance (TMR) effect require linear resistance–magnetic field (R–H) response curves with small hysteresis, for which the soft magnetic property of the free layer (FL) is critical. In this work, we investigated amorphous CoFeBTa (CFBT) as a soft magnetic layer of the FL of CoFeB/MgO/CoFeB-based magnetic tunnel junctions in view of magnetic, TMR, and low-frequency noise properties. A two-step annealing process enabled an orthogonal magnetization configuration between the FL and the reference layer, by which linear R–H curves with small hysteresis were realized. The change in the shape of the R–H curve depending on annealing temperature is explained by the Stoner–Wohlfarth model. The highest TMR ratio of ∼160% and sensitivity of ∼70%/mT were obtained with a CFBT (20 nm)/Ta (0.3 nm)/CoFeB (3 nm) FL. The noise of the TMR devices are dominated by 1/f noise below ∼10 kHz in frequency, which limits the detectivity (D) of the magnetic field of the sensor. The sensor devices patterned to 50 µm diameter circular shapes showed a minimum D of ∼2 nT/ at 10 Hz, which is superior to the previously reported values for the TMR sensors with NiFe soft magnetic layers. [ABSTRACT FROM AUTHOR]

We investigated the degree of B2 order (S B2) of 4-10 nm-thick polycrystalline Co 2 (Mn 0.6 Fe 0.4)Ge (CMFG) Heusler alloy films using anomalous X-ray diffraction (AXRD) and its correlation to the magnitude of current-perpendicular-to-plane giant magnetoresistive (CPP-GMR) effect. We found that S B2 of the CMFG films is degraded for the film thickness below 6 nm, which is an issue for practical applications of CPP-GMR devices such as read head sensors of hard disk drives. Since S B2 has a thickness-dependence, the bulk spin polarization (β) of the CMFG layers is also expected to vary depending on the thickness; thus, the deduction of β using the Valet-Fert model, where β is assumed to be thickness-independent, is not valid for these CPP-GMR devices. Image, graphical abstract [ABSTRACT FROM AUTHOR]

We report on the direct observation of the magneto-Peltier effect in a current-in-plane giant magnetoresistive (CIP-GMR) spin valve. By means of the recently developed thermoelectric imaging technique based on lock-in thermography, we demonstrate that thermoelectric cooling and heating are generated by applying a local magnetic field to the CIP-GMR spin-valve film, confirming the different Peltier coefficients of the spin valve between the parallel and antiparallel magnetization configurations. The cooling and heating positions are found to be tuned simply by changing the magnitude of the local magnetic field. This versatile and reconfigurable thermoelectric conversion functionality may provide a thermal management method for CIP-GMR magnetic sensors. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the role of the fractalkine (FKN)/CX3CR1 pathway in joint destruction in rheumatoid arthritis. Methods: We examined the effect of treatment with anti–mouse FKN (anti‐mFKN) monoclonal antibody (mAb) on joint destruction and the migration of osteoclast precursors (OCPs) into the joint, using the collagen‐induced arthritis (CIA) model. DBA/1 mice were immunized with bovine type II collagen to induce arthritis, and then treated with anti‐mFKN mAb. Disease severity was monitored by arthritis score, and joint destruction was evaluated by soft x‐ray and histologic analyses. Plasma levels of joint destruction markers were assessed by enzyme‐linked immunosorbent assay. FKN expression on endothelial cells was detected by immunohistochemistry. Bone marrow–derived OCPs were labeled with fluorescein and transferred to mice with CIA, and the migration of the OCPs to the joints was then analyzed. Results: Both prophylactic and therapeutic treatment with anti‐mFKN mAb significantly decreased the arthritis and soft x‐ray scores. Plasma levels of cartilage oligomeric matrix protein and matrix metalloproteinase 3 decreased after treatment with anti‐mFKN mAb. Histologic analysis revealed that anti‐mFKN mAb inhibited synovitis, pannus formation, and cartilage destruction, as well as suppressed bone damage, with a marked reduction in the number of tartrate‐resistant acid phosphatase–positive osteoclasts. Anti‐mFKN mAb strongly inhibited the migration of bone marrow–derived OCPs into the affected synovium. Conclusion: Anti‐mFKN mAb notably ameliorates arthritis and joint destruction in the CIA model, as well as inhibits migration of OCPs into the synovium. These results suggest that inhibition of the FKN/CX3CR1 pathway could be a novel strategy for treatment of both synovitis and joint destruction in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

The near-future ultra-high-density magnetic recording with an assist recording technology requires a substantial evolution of the read-head technology. A read sensor with a small sensor resistance-area product ( $RA$ ), a large magnetoresistance ratio ( \Delta R/R$ ), and a thin total sensor thickness is required for the low bit error rate and high-spatial resolution of reading. We developed current-perpendicular-to-plane giant magnetoresistance sensors using highly spin-polarized Heusler alloy ferromagnetic layers with the spin polarization of the conducting electron \beta \sim 0.8$ . A reasonably large \Delta R/R$ up to 14% was obtained by a practical bottom-pinned spin-valve structure with a conventional metallic spacer layer of an Ag90Sn10 (AgSn) alloy. By replacing the spacer layer with a conductive oxide-based AgSn/InZnO bilayer, a large \Delta R/R , which is optimal for the read sensor application. A large voltage output up to 6 mV was obtained for a sensor utilization of ~33% at a bias voltage of 100 mV. [ABSTRACT FROM PUBLISHER]

• Study on the effect of the composition of NiFeCr seed layer on the interlayer exchange coupling (IEC) and giant magnetoresistance (GMR) in FeCoNi/Cu multilayer films. • Optimal composition of (Ni 0.55 Cr 0.45) 100- y Fe y with 0 ≤ y ≤ 47 at. % for seed layer to obtain the largest GMR ratio of 35%. This is due to a strong [1 1 1]-texture and a coarse grain size of the FeCoNi/Cu multilayer. • We found that not only the crystallographic texture and grain size but also the roughness of FeCoNi/Cu interface influence IEC and GMR. • This paper provides a guideline for development of GMR magnetic sensors. We present a systematic study on the giant magnetoresistance (GMR) and interlayer exchange couplings (IEC) in polycrystalline [Fe 16 Co 66 Ni 18 /Cu] 5 /Fe 16 Co 66 Ni 18 multilayer films deposited on NiFeCr seed layers with various compositions. We observed that the GMR ratio (Δ R / R) depends on bilinear and biquadratic IEC coefficients, J 1 and J 2 , and varies linearly with their ratio, J 1 / J 2. The maximum Δ R / R of 35 ± 2.5% and strong antiparallel IEC (J 1 / J 2 > 1) were observed for the seed layers with a particular Ni:Fe ratio of (Ni 0.55 Cr 0.45) 100- y Fe y with 0 ≤ y ≤ 47 at. %. Structural studies confirm that the high Δ R / R and J 1 / J 2 for these NiFeCr compositions are related to a strong fcc [1 1 1] crystallographic texture and a coarse grain size of the FeCoNi/Cu mutilayers. In addition, we observed that the film deposited on a Ni 32 Fe 33 Cr 35 seed layer showed a stronger [1 1 1] texture, but a lower Δ R / R (17%) than those deposited on a Ni 36 Fe 51 Cr 13 seed layer (Δ R / R = 28%). Detailed microstructural analysis indicated an increased arithmetic average roughness (R a) of the interfaces between FeCoNi and Cu layers for the films with the Ni 32 Fe 33 Cr 35 seed layer. We argue that the lower Δ R / R in the film despite the relatively strong [1 1 1] texture is due to its higher R a which causes a reduction in antiparallel IEC. This indicates that two conditions of (i) a strong [1 1 1] crystallographic texture and (ii) small interface roughness must be satisfied in the FeCoNi/Cu multilayer to achieve a strong antiparallel IEC and thus large Δ R / R. [ABSTRACT FROM AUTHOR]

• Sputter-deposited FeCr thin film in the Fe-rich composition range is studied using first-principles calculations and experimental techniques for a spintronic material with negative spin polarization. • First-principles calculations predict high negative spin polarization of disordered FeCr and reveal that it originates from the high conductance of the minority-spin band electrons due to the band matching of Fe and Cr and resultant weak scattering. • Magnetoresistance device measurements show negative spin polarization, which is estimated to be −0.28, which is smaller than that predicted by the calculations. • X-ray magnetic circular dichroism measurements showed the ferrimagnetic configuration of the Fe and Cr magnetic moments, supporting the calculation results. Fe moment shows a large moment over the wide composition range, whereas the Cr moment decreased with the Cr concentration. • Mössbauer spectroscopy measurements indicated the inhomogeneity of the FeCr, which reflects the phase separation nature of the Fe-Cr system. However, the inhomogeneity was not considered in the calculation and could be the origin of the smaller spin polarization observed in the experiment. Negative spin polarization materials generate a spin current whose spin direction is opposite to the magnetization direction. This characteristic is technologically important because it increases the freedom in the design of spintronic devices. In this paper, we studied FeCr from the viewpoints of band structure, atomic magnetic moments, and local atomic arrangement to explore its potentiality as a negative spin polarization material. First-principles calculations on the disordered FeCr alloy predicted a high negative spin polarization, which was attributed to the band matching of the minority spin. We experimentally fabricated Fe 1- x Cr x thin films in the Cr concentration (x) range from 0.2 to 0.4 by sputter deposition and demonstrated inverse magnetoresistance using current-perpendicular-to-plane giant magnetoresistance (GMR) devices, which provided evidence of negative spin polarization. The spin polarization of Fe 0.7 Cr 0.3 estimated from the GMR device measurements was −0.28 and fell below the calculated value. Synchrotron X-ray magnetic circular dichroism measurements showed a ferrimagnetic configuration of the Fe and Cr magnetic moments. The Fe moment showed a large moment over a wide Cr concentration range, whereas the Cr moment decreased with the Cr concentration, which agreed with the calculation result. Synchrotron Mössbauer spectroscopy measurements indicated the inhomogeneity of the FeCr composition even in the as-deposited state. Fe-rich regions were formed after annealing, reflecting the phase separation nature of the Fe-Cr system. Inhomogeneity was not considered in the calculation and could be the origin of the smaller negative spin polarization observed in the experiment. [ABSTRACT FROM AUTHOR]

Abstract: Purkinje cells (PCs) provide the primary output from the cerebellar cortex, which controls movement and posture, and loss of PCs causes severe cerebellar dysfunction. The mechanisms underlying cell fate determination and early differentiation of PC remain largely unknown. Here we show that the c-Ski family member and transcriptional regulator Corl2 is required for correct differentiation of PCs. In Corl2 knock-out embryos, initial PC specification appeared largely normal, but in a subset of presumptive PCs generated near the ventral border of the PC domain, cell fate choice was compromised and cells showed a mixed identity expressing the interneuron marker Pax2 as well. Additionally, selection and maintenance of the transmitter phenotype was compromised in most developing PCs in the mutants. During later differentiation steps, induction of PC marker genes was significantly suppressed, suggesting that maturation was delayed in the absence of Corl2. Consistently, defects in migration, cell polarization and dendrite formation were observed in mutant PCs, although their axonal trajectories appeared normal. These phenotypes closely resembled those of mutants for Rora, an essential regulator of PC differentiation. However, Rora expression was not significantly changed in the Corl2 mutants, indicating that Corl2 does not simply act upstream of Rora to promote PC differentiation. ChIP experiments revealed that Corl2 bound to the promoter regions of several PC-selective genes, which are also known to be direct downstream targets of RORα. Altogether, our results identified a novel regulatory program of PC differentiation involving Corl2, which might cooperate with the RORα pathway. [Copyright &y& Elsevier]

Abstract: Mesencephalic dopaminergic (mesDA) neurons control movement and behavior, and their loss causes severe neurological disorders, such as Parkinson''s disease. Recent studies have revealed that mesDA neurons originate from mesencephalic floor plate (FP) cells, which had been thought of as non-neurogenic organizer cells regulating regional patterning and axonal projections. Otx2 and its FP-specific downstream factor Lmx1a have been shown to be sufficient to confer neurogenic activity on FP cells and determine a mesDA fate. However, the mechanism underlying how these factors control mesDA development and how FP cells and mesDA neurons are coordinately specified are still largely unknown. In the present study, we obtained evidence that Lmx1a and Lmx1b cooperate with Foxa2 to specify mesDA neuron identity by gain-of-function approaches using transgenic mice. Lmx1a/b appeared to select a mesDA fate by suppressing red nucleus fate in the context of Foxa2-positive progenitors, at least in part, through repressing the Sim1-Lhx1 and Ngn1 pathways that inhibit proper mesDA differentiation. We also found that, in the mesencephalon, FP cell fate is primarily determined by Foxa2 with a supportive action of Lmx1a/b through repressing Nkx6.1, which inhibits FP cell differentiation. Thus, FP and mesDA identities are determined by distinct specification pathways, both of which are controlled by the same combination of transcription factors, Lmx1a/b and Foxa2, and, as a consequence, mesDA neurons are generated from mesencephalic FP cells. [Copyright &y& Elsevier]

Abstract: The developmental origin of cerebellar Purkinje cells (PCs) has not been precisely mapped and the genetic program of the specification of this neuronal subtype is largely unknown. Here, we report the isolation of a novel mouse gene encoding a transcriptional corepressor, Corl2, and its expression pattern. Corl2 expression was restricted to the central nervous system in both adult and embryonic stages. In situ hybridization and immunohistochemistry using a polyclonal antibody against Corl2 revealed that Corl2 is selectively expressed at high levels in the developing cerebellum, ventral metencephalon and myelencephalon at E12.5. In these brain regions, neural progenitors did not express Corl2 during the proliferative state but started to express it shortly after exit from the cell cycle. In the cerebellum, Corl2 was specifically expressed in PCs at the adult stage, and consistently, most Corl2+ cells expressed PC markers, such as RORα and calbindin, at the late embryonic stage. At E12.5, when PCs are emerging, GABAergic neurons generated from the dorsal part of the Ptf1a+ progenitor domain selectively expressed Corl2. Importantly, Corl2+ cells in the cerebellum did not express the GABAergic interneuron marker Pax2 at any of the developmental stages. Collectively, these results strongly suggest that Corl2 is a specific marker for PCs in the cerebellum from their emergence until the adult stage. Furthermore, this marker was useful for unmasking the precise origin of PCs and delineating the domain map within the ventricular zone that generates cerebellar GABAergic neurons. [Copyright &y& Elsevier]

Delta-Notch signaling plays an essential role in cell fate determination in many tissue types, including the central nervous system. Although the signaling mechanism of Notch has been extensively studied, the behaviors of its ligands are not well understood. In the present study, we found that, in the developing neural tube, Dll1(Delta-like 1) was mainly localized on the processes extending from nascent neurons toward both the pia and the ventricle and accumulated at apical termini, where adherens junctions (AJs) were formed. To understand the mechanism of Dll1 localization, we searched for binding proteins for Dll1 and identified a scaffolding molecule, MAGI1. In the developing spinal cord, MAGI1 mRNA was highly expressed in the ventricular zone, where Dll1 mRNA was expressed. MAGI1 protein accumulated at the AJs formed around the termini of apically extending processes and was partially colocalized with Dll1. MAGI1 bound not only to Dll1 but also to N-cadherin-β-catenin complexes. In cultured AJ-forming fibroblasts, MAGI1 was localized at AJs, and Dll1 was recruited to these AJs through binding to MAGI1. In addition, Dll1 was stabilized on the cell surface by MAGI1. Taken together, these results suggest that Dll1 is presented on the surface of AJs formed at the apical termini of processes through interaction with MAGI1 to activate Notch on neighboring cells in the developing central nervous system. [ABSTRACT FROM AUTHOR]

During development, neuronal identity is determined by a combination of numerous transcription factors. However, the mechanisms of synergistic action of these factors in transcriptional regulation and subsequent cell fate specification are largely unknown. In this study, we identified a novel gene, Corl1, encoding a nuclear protein with homology to the Ski oncoprotein. Corl1 was highly selectively expressed in the central nervous system (CNS). In the embryonic CNS, Corl1 was expressed in a certain subset of postmitotic neurons generated posterior to the midbrain-hindbrain border. In the developing spinal cord, Corl1 was selectively expressed in the dorsal horn interneurons where a homeodomain transcription factor, Lbx1, is required for proper specification. Corl1 was localized in a nuclear dot-like structure and interacted with general transcriptional corepressors. In addition, Corl1 showed transcriptional repression activity in the GAL4-fusion system, indicating its involvement in the regulation of transcriptional repression. Furthermore, Corl1 interacted with Lbx1 and cooperatively repressed transcription, suggesting that it acts as a transcriptional corepressor for Lbx1 in regulating cell fate determination in the dorsal spinal cord. Corl1 corepressor activity did not depend on Gro/TLE activity, and Gro/TLE also functioned as a corepressor for Lbx1. Thus, Lbx1 can select two independent partners, Corl1 and Gro/TLE, as corepressors. Identification of a novel transcriptional corepressor with neuronal subtype-restricted expression might provide insights into the mechanisms of cell fate determination in neurons. [ABSTRACT FROM AUTHOR]

Neuronal differentiation is regulated by many basic-helix-loop-helix (bHLH) family transcriptional activators and repressors, and the balance of activity between these factors is important for the differentiation process. Here, we report the identification of a novel transcriptional repressor, designated Helt. Helt encoded a Hey-related bHLH protein containing the bHLH and Orange domains. Helt could homodimerize, and heterodimerize with Hes5 or Hey2. Both the bHLH and Orange domains were involved in the homodimerization. In contrast, only the bHLH domain was required for the heterodimerization with Hey2, whereas only the Orange domain mediated the interaction between Helt and Hes5. Thus, Helt has two dimerization domains, and these domains independently select a partner. Identification of preferred recognition sequences by CASTing experiments revealed that Helt bound to the E box, which was distinct from the Hes1 optimal sequence around the E box core. Not only the core sequence but also sequences flanking the E box were essential for the recognition by Helt and Hes1. Furthermore, Helt repressed transcription from an artificial promoter through binding to the optimal E box elements, as well as transcription from its own promoter. Using in situ hybridization and immunohistochemistry, Helt expression in embryos was investigated. Helt was mainly expressed in undifferentiated neural progenitors in some of the developing brain regions, including the mesencephalon and diencephalon, at the neurogenesis stage. These results suggest that Helt acts as a transcriptional repressor to regulate neuronal differentiation and/or identity. [ABSTRACT FROM AUTHOR]

The combination of magnetoresistive (MR) element and magnetic flux concentrators (MFCs) offers highly sensitive magnetic field sensors. To maximize the effect of MFC, the geometrical design between the MR element and MFCs is critical. In this paper, we present simulation and experimental studies on the effect of the geometrical relationship between current-in-plane giant magnetoresistive (GMR) element and MFCs made of a NiFeCuMo film. Finite element method (FEM) simulations showed that although an overlap between the MFCs and GMR element enhances their magneto-static coupling, it can lead to a loss of magnetoresistance ratio due to a magnetic shielding effect by the MFCs. Therefore, we propose a comb-shaped GMR element with alternate notches and fins. The FEM simulations showed that the fins of the comb-shaped GMR element provide a strong magneto-static coupling with the MFCs, whereas the electric current is confined within the main body of the comb-shaped GMR element, resulting in improved sensitivity. We experimentally demonstrated a higher sensitivity of the comb-shaped GMR sensor (36.5 %/mT) than that of a conventional rectangular GMR sensor (28 %/mT). [ABSTRACT FROM AUTHOR]

Current-perpendicular-to-plane magnetoresistance (CPP-MR) devices using a Co2Fe(Ga0.5Ge0.5) Heusler alloy as ferromagnetic electrodes and a Ag/Mg-Ti-O (MTO)/Ag tri-layer as a spacer are studied. A large voltage output of 16 mV with a magnetoresistance ratio of 46% and resistance-area product RpA in the parallel magnetization state of approximately 200 mΩ μm2 are obtained. The microstructure characterization reveals that upon annealing at 550 °C, nanoscale Ag channels are formed penetrating the MTO layer, which are responsible for the large MR output. At room temperature, for all the devices, RpA decreases with increasing the bias voltage Vb, which is contradictory to the conventional CPP-giant magnetoresistance devices with a current-confined-path structure, in which the RpA increases with increasing Vb. Such a Vb dependence of RpA is in accordance with the temperature dependence of RpA. These results suggest that the magneto-transport channels comprise semiconducting current confined paths, bringing new perspectives for the design and engineering of CPP-MR devices with conductive oxides-based multilayer spacers. [ABSTRACT FROM AUTHOR]

We investigate the effects of off-stoichiometric compositional variations from the Co2Fe(Ga0.5Ge0.5) (CFGG) full-Heusler alloy on its half-metallic electronic structure. First-principles calculations predict that the Co antisite defects that occupy Fe-sites (CoFe) lead to a finite DOS in the half-metallic gap of CFGG. Fe antisites defects in Co-sites (FeCo) introduced by excessing Fe composition, which could suppress the formation of CoFe, preserves the half-metallic gap but reduces spin polarization because the Fermi level shifts to the lower energy. We found that, in Fe-excess CFGG, Ge-excess has an important role to enhance the spin polarization by lifting up the Fermi level position and suppressing the formation of CoFe. To confirm the effect of the Fe and Ge-excess off-stoichiometric composition on spin polarization and phase-purity experimentally, we fabricated CFGG epitaxial thin films with various composition ratios (Co2−αFe1+α) (Ga1−βGeβ)1+γ with small positive γ (=0.09–0.29). It turns out that Co1.75Ge or Fe1.7Ge secondary phase often forms in the films for β ≥ 0.69 in Fe-deficient (α ≤ 0.21) and excess (α ≥ 0.49) compositions. This secondary phase can be suppressed by tuning the Ge and Fe compositions, and the L21-phase pure film was found in Co39.4Fe29.3Ga13.4Ge17.9 (α = 0.28 , β = 0.57 , γ = 0.25). The measurements of conventional magnetoresistance effects qualitatively indicate higher spin polarization in the Co39.4Fe29.3Ga13.4Ge17.9 film compared to other Co-excess and Ge-deficient films, which evidences the benefit to make Fe- and Ge-excess off-stoichiometric CFGG for obtaining the half-metallic nature of CFGG. [ABSTRACT FROM AUTHOR]

Floor plate (FP) cells, the ventral midline cells of the developing neural tube, have long been thought to be non-neurogenic organizer cells that control neuronal patterning and axonal guidance. Recent studies have revealed that mesencephalic FP (mesFP) cells have neurogenic activity and generate dopaminergic neurons. However, the mechanisms underlying the control of neurogenic potential in FP cells are not yet fully understood. Here we identified the bHLH factor Nato3 as an FP-specific transcription factor. In Nato3-null mutant mice, FP cells in the spinal cord were correctly specified, but could not properly mature. By contrast, in the developing mesencephalon, loss of Nato3 did not affect FP differentiation, but led to loss of neurogenic activity in the medial subpopulation of mesFP cells by suppressing proneural gene expression and inducing cell cycle arrest. As a consequence, the number of midbrain dopaminergic neurons generated was decreased in mutants. We also found that Hes1, which is known to be required for non-dividing organizer cell development in the neural tube, was aberrantly upregulated in the mesFP cells of Nato3 mutants. Consistently, forced expression of Nato3 repressed Hes1 expression and consequently induced premature neurogenesis. Finally, we showed that forced expression of Hes1 in mesFP cells induced cell cycle arrest and downregulation of proneural factors. Taken together, these results suggest that Nato3 confers neurogenic potential on mesFP cells by suppressing classical non-neurogenic FP cell differentiation, at least in part, through repressing Hes1. [ABSTRACT FROM AUTHOR]

Directed differentiation and purification of mesencephalic dopaminergic (mesDA) neurons from stem cells are crucial issues for realizing safe and efficient cell transplantation therapies for Parkinson's disease. Although recent studies have identified the factors that regulate mesDA neuron development, the mechanisms underlying mesDA neuron specification are not fully understood. Recently, it has been suggested that mesencephalic floor plate (FP) cells acquire neural progenitor characteristics to generate mesDA neurons. Here, we directly examined this in a fate mapping experiment using fluorescence-activated cell sorting (FACS) with an FP cell-specific surface marker, and demonstrate that mesencephalic FP cells have neurogenic activity and generate mesDA neurons in vitro. By contrast, sorted caudal FP cells have no neurogenic potential, as previously thought. Analysis of dreher mutant mice carrying a mutation in the Lmx1a locus and transgenic mice ectopically expressing Otx2 in caudal FP cells demonstrated that Otx2 determines anterior identity that confers neurogenic activity to FP cells and specifies a mesDA fate, at least in part through the induction of Lmx1a. We further show that FACS can isolate mesDA progenitors, a suitable transplantation material, from embryonic stem cell-derived neural cells. Our data provide insights into the mechanisms of specification and generation of mesDA neurons, and illustrate a useful cell replacement approach for Parkinson's disease. [ABSTRACT FROM AUTHOR]

The mechanism underlying the determination of neurotransmitter phenotype in the developing mesencephalon, particularly GABAergic versus glutamatergic fate, remains largely unknown. Here, we show in mice that the basic helix-loop-helix transcriptional repressor gene Helt (also known as Megane and Heslike) functions as a selector gene that determines GABAergic over glutamatergic fate in the mesencephalon. Helt was coincidently expressed in all the progenitor domains for mesencephalic GABAergic neurons. In the mesencephalon of Helt-deficient embryos, GABAergic neurons were mostly absent and glutamatergic neurons emerged instead. Conversely, ectopically expressed Helt suppressed glutamatergic formation and induced GABAergic neurogenesis. However, the Helt mutants showed normal progenitor domain formation. In consequence, postmitotic expression of the homeodomain factor Nkx2.2, which was specifically expressed by GABAergic populations in wild-type embryos, was maintained despite the transmitter phenotype conversion from GABAergic to glutamatergic in the Helt mutants, suggesting that Helt is not involved in neuronal identity specification. Furthermore, we identified proneural genes Ngn1 and Ngn2, which were selectively expressed in glutamatergic progenitors in the developing mesencephalon and had the ability to confer the glutamatergic fate, as downstream target genes of Helt. These results suggest that Helt determines GABAergic over glutamatergic fate, at least in part, by repressing Ngn (Neurog) genes and that basic helix-loop-helix transcription factor networks involving Helt and Ngns are commonly used in the mesencephalon for determination of the GABAergic versus glutamatergic transmitter phenotype. [ABSTRACT FROM AUTHOR]

• Epitaxial CoFe/bcc-Cu/CoFe CIP-GMR spin-valve devices were fabricated on industrially viable Si(0 0 1) substrate by using an epitaxial NiAl buffer layer. • Microstructural analysis by scanning transmission electron microscopy revealed the mechanisms that influence the CIP-GMR properties. • CIP-GMR is hindered by the formation of the fcc-Cu phase in addition to the metastable bcc-Cu preferred for large GMR effect. Following the high magnetoresistance (MR) ratio reported for fully epitaxial CoFe/bcc-Cu/CoFe current-in-plane giant magnetoresistance (CIP-GMR) grown on MgO(0 0 1) single crystalline substrate, we attempted to grow epitaxial CoFe/bcc-Cu/CoFe CIP-GMR devices on industrially viable Si(0 0 1) substrate through an epitaxial NiAl buffer layer. We found that the deposition of MgO insulation layer on the NiAl buffer layer is crucial to prevent current shunting in the NiAl layer which reduces MR ratio. The epitaxial CIP-GMR device grown on Si(0 0 1) exhibited sufficiently high MR ratio up to 15.9(±0.1)% at room temperature; however, it is somehow lower than that grown on the MgO(0 0 1) substrate, 20.6(±0.1)%. Detailed microstructural analysis revealed that fcc phase of Cu presented in the bcc-Cu spacer, which is considered to be the reason for the lower MR ratio of the device grown on Si(0 0 1) substrate. [ABSTRACT FROM AUTHOR]

LL5β has been identified as a microtubule-anchoring factor that attaches EB1/CLIP-associating protein (CLASP)-bound microtubule plus ends to the cell cortex. In this study, we show that LL5β and its homologue LL5α (LL5s) colocalize with autocrine laminin-5 and its receptors, integrins α3β1 and α6β4, at the basal side of fully polarized epithelial sheets. Depletion of both laminin receptor integrins abolishes the cortical localization of LL5s, whereas LL5 depletion reduces the amount of integrin α3 at the basal cell cortex. Activation of integrin α3 is sufficient to initiate LL5 accumulation at the cell cortex. LL5s form a complex with the cytoplasmic tails of these integrins, but their interaction might be indirect. Analysis of the three-dimensional distribution of microtubule growth by visualizing EB1-GFP in epithelial sheets in combination with RNA interference reveals that LL5s are required to maintain the density of growing microtubules selectively at the basal cortex. These findings reveal that signaling from laminin-integrin associations attaches microtubule plus ends to the epithelial basal cell cortex. [ABSTRACT FROM AUTHOR]

Abstract: GABAergic Purkinje cells (PCs) provide the primary output from the cerebellar cortex, which controls movement and posture. Although the mechanisms of PC differentiation have been well studied, the precise origin and initial specification mechanism of PCs remain to be clarified. Here, we identified a cerebellar and spinal cord GABAergic progenitor-selective cell surface marker, Neph3, which is a direct downstream target gene of Ptf1a, an essential regulator of GABAergic neuron development. Using FACS, Neph3+ GABAergic progenitors were sorted from the embryonic cerebellum, and the cell fate of this population was mapped by culturing in vitro. We found that most of the Neph3+ populations sorted from the mouse E12.5 cerebellum were fated to differentiate into PCs while the remaining small fraction of Neph3+ cells were progenitors for Pax2+ interneurons, which are likely to be deep cerebellar nuclei GABAergic neurons. These results were confirmed by short-term in vivo lineage-tracing experiments using transgenic mice expressing Neph3 promoter-driven GFP. In addition, we identified E-cadherin as a marker selectively expressed by a dorsally localized subset of cerebellar Neph3+ cells. Sorting experiments revealed that the Neph3+ E-cadherinhigh population in the embryonic cerebellum defined PC progenitors while progenitors for Pax2+ interneurons were enriched in the Neph3+ E-cadherinlow population. Taken together, our results identify two spatially demarcated subregions that generate distinct cerebellar GABAergic subtypes and reveal the origin of PCs in the ventricular zone of the cerebellar primordium. [Copyright &y& Elsevier]

Spin torque oscillators (STOs) that generate a persistent magnetization oscillation by spin-transfer torque are promising spintronic devices for various applications. In this study, we propose and experimentally demonstrate a method to characterize the magnetization dynamics of STOs using injection locking. By placing the STO near an antenna that generates a microwave magnetic field of a variable frequency ( f M W ), injection locking of the STO to the microwave field occurs when f M W is in the locking range around the intrinsic oscillation frequency. During injection locking, the dc resistance of the STO exhibits a peak-and-valley dependence on f M W , which originates from the modification of the magnetization trajectory induced by injection locking. Based on this principle, the oscillation frequency can be estimated by measuring the dc resistance change. Because this method does not require measuring the high-frequency magnetoresistance signal from the STO, which is used in the conventional method, it is advantageous in cases where the high-frequency magnetoresistance signal is undetectable or exhibits additional frequency components different from the oscillation frequency. [ABSTRACT FROM AUTHOR]

Large magnetoresistance (MR) with a linear response to the magnetic field is an important feature in MR devices for magnetic sensor applications. Following the largest MR ratio realized in a current-in-plane (CIP) giant magnetoresistance (GMR) device using a metastable body-centered cubic (bcc)-Cu spacer, we developed a new CIP-GMR device with a combination of two spacer materials, i.e. CoFe/Rh/CoFe (sensing layer)/bcc-Cu/CoFe asymmetric structure and realized a large linear sensitivity due to large MR ratio (21%) and linear response through a biquadratic coupling, high sensitivity of 0.047% mT−1, reduced nonlinearity of 0.98% full scale along with a substantially wider operation field range of 220 mT. Our numerical simulation analyses of magnetization curves clearly establish that the middle CoFe sensing layer is well-controlled by interlayer exchange coupling through the Rh spacer, giving rise to a linear response without losing the high MR ratio through the bcc-Cu spacer. These findings demonstrate that CIP-GMR devices are promising for wide dynamic range magnetic sensors. [ABSTRACT FROM AUTHOR]

Current-perpendicular-to-plane giant-magnetoresistance effect in a ferromagnetic/nonmagnetic multilayer is studied theoretically by solving the diffusion equation of the spin accumulation without assuming the periodic boundary condition. We show that the Valet and Fert theory underestimates spin asymmetries with decreasing the number of layers. [ABSTRACT FROM AUTHOR]

Chemokine systems modulate inflammatory and immune responses in inflammatory bowel disease (IBD). The colons of IBD patients show increased levels of fractalkine (FKN) and high numbers of FKN receptor-positive (CX3CR1+) cells; however, the FKN–CX3CR1 axis's role in intestinal inflammation, especially in intravascular leukocyte behaviors, still remains unclear. Here, we show that interruption of the FKN–CX3CR1 axis by anti-FKN monoclonal antibody (mAb) ameliorates murine colitis through regulation of intravascular monocyte behaviors in murine colitis models. FKN expression was detectable in vascular endothelium and CX3CR1+ macrophages accumulated in the mucosal lamina propria and submucosa of the inflamed colons. CD115+ monocytes tethered to the venous endothelium and expressed pro-inflammatory mediators. The anti-FKN mAb improved colitis symptoms, markedly reduced pro-inflammatory factors in the colon, maintained blood vessel integrity and reduced tethered monocytes in the inflamed veins. Intravital imaging revealed that CD115+Gr-1low/− monocytes crawled on the apical surfaces of venous endothelium, and anti-FKN mAb rapidly dislodged the crawling monocytes and inhibited their patrolling behavior. These findings suggest that the FKN–CX3CR1 axis triggers the patrolling behavior of crawling monocytes on the venous endothelium of inflamed colons, and accelerates the subsequent leukocyte activation and infiltration by locally producing inflammatory cytokines and chemokines. The mAb also ameliorated symptoms in another IBD model, T-cell-transferred colitis. Blocking the FKN–CX3CR1 axis with an anti-FKN mAb considerably inhibits the colitis-triggered inflammatory cascades, which may be an alternative strategy to treat IBD. [ABSTRACT FROM AUTHOR]

Abstract: The neuronal network is tightly regulated by a large variety of locally connected GABAergic neurons. Neuregulin1 (Nrg1) and its receptor ErbB4 are master regulators in the morphological and functional development of excitatory synapses in GABAergic neurons. We previously showed that the immunoglobulin-like cell adhesion molecule, nectin-like molecule-2 (Necl-2)/CADM1, interacts with the ErbB3 and ErbB4 receptors, and that the interaction of Necl-2 with ErbB3 inhibits the Nrg1-induced ErbB3/ErbB2 signaling in epithelial cells. Here, we examined the role of the interaction of Necl-2 with ErbB4 in GABAergic neurons. Necl-2 was co-expressed with ErbB4 in parvalbumin-positive GABAergic neurons in the mouse hippocampus and co-localized with ErbB4 at excitatory synapses. Necl-2 knockdown enhanced the Nrg1-induced phosphorylation of ErbB4. Moreover, overexpression of PTPN13, which is a tyrosine phosphatase bound to the cytoplasmic tail of Necl-2, suppressed the Nrg1-induced development of excitatory synapses in GABAergic neurons through the inhibition of ErbB4 activity. These results indicate that Necl-2 interacts with ErbB4 and regulates the development of excitatory synapses via the regulation of ErbB4 activity in GABAergic neurons. [Copyright &y& Elsevier]

Abstract: Postmitotic neural precursors are generated in the ventricular zone (VZ) of the developing neural tube and immediately migrate to the mantle layer (ML) where they differentiate into mature neurons. Although the regulation of neuronal differentiation and migration has extensively been studied, the behavior of the early postmitotic precursors migrating toward the ML is largely unknown. In this study, we have identified Neph3 as a specific marker for early postmitotic neural precursors in the VZ of the developing spinal cord. Analysis of Neph3 localization by immunofluorescence and immunoelectron microscopy revealed that early neural precursors in the VZ possessed not only pia-connected processes but also ones that reached the ventricle. This apical extension of processes was confirmed by analyzing another early postmitotic marker, Dll1 mRNA, which was actively transported toward the ventricle and accumulated at the termini of the processes. Furthermore, adherens junctions (AJs) were formed around the apical end of processes extending from Neph3- and Dll1 mRNA-positive postmitotic precursors. Taken together, these observations suggest that migrating early postmitotic neural precursors in the VZ of the developing spinal cord form a neuroepithelial cell-like bipolar morphology and communicate with their neighboring cells through AJs. [Copyright &y& Elsevier]

• CoFe/Rh/CoFe/bcc-Cu/CoFe based epitaxial current-in-plane -GMR devices were fabricated. • The effect of CoFe and Rh thicknesses on the nature of magnetic couplings was studied. • Numerical simulation confirmed both biquadratic and bilinear couplings, offering linear MR. • CIP-GMR devices with the asymmetric structure are promising for the next generation linear magnetic sensors. Giant magnetoresistance (GMR) devices known for their widespread application as magnetic field sensors face challenges owing to their nonlinear resistance response with the magnetic field. Here, we have developed CoFe(3 nm)/Rh(t R h nm)/CoFe(t m i d C o F e nm)/bcc Cu(1.6 nm)/CoFe(t t o p C o F e nm)/MgO(2 nm) based current in plane (CIP)-GMR devices and demonstrated linear MR curves with tunable characteristics. The MR ratio and saturating magnetic field were tunable between 3.9% and 23.5%, and 0.013 T and 1.5 T. The numerical simulation modeling confirmed biquadratic coupling between the bottom and middle CoFe layers through Rh and antiferromagnetic coupling between the middle and top CoFe layers through a Cu spacer, providing the linear MR. The fine-tuning of thicknesses of the middle and top CoFe layers provides supplementary routes for optimizing the sensitivity and operation field range of the CIP-GMR devices to specific magnetic sensor applications in the low and medium magnetic field range. The above results demonstrate that CIP-GMR devices with the asymmetric structure demonstrated in this study are promising for the next generation linear magnetic sensors. [ABSTRACT FROM AUTHOR]