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2D materials offer the ability to expose their electronic structure to manipulations by a proximity effect. This could be harnessed to craft properties of 2D interfaces and van der Waals heterostructures in devices and quantum materials. We explore the possibility to create an artificial spin polarized electrode from graphene through proximity interaction with a ferromagnetic insulator to be used in a magnetic tunnel junction (MTJ). Ferromagnetic insulator/graphene artificial electrodes were fabricated and integrated in MTJs based on spin analyzers. Evidence of the emergence of spin polarization in proximitized graphene layers was observed through the occurrence of tunnel magnetoresistance. We deduced a spin dependent splitting of graphene's Dirac band structure (â¼15 meV) induced by the proximity effect, potentially leading to full spin polarization and opening the way to gating. The extracted spin signals illustrate the potential of 2D quantum materials based on proximity effects to craft spintronics functionalities, from vertical MTJs memory cells to logic circuits.
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Magnetic 2D materials hold promise to change the miniaturization paradigm of unidirectional photonic components. However, the integration of these materials in devices hinges on the accurate determination of the optical properties down to the monolayer limit, which is still missing. By using hyperspectral wide-field imaging at room temperature, we reveal a nonmonotonic thickness dependence of the complex optical dielectric function in the archetypal magnetic 2D material CrI_{3} extending across different length scales: onsetting at the mesoscale, peaking at the nanoscale, and decreasing again down to the single layer. These results portray a modification of the electronic properties of the material and align with the layer-dependent magnetism in CrI_{3}, shedding light on the long-standing structural conundrum in this material. The unique modulation of the complex dielectric function from the monolayer up to more than 100 layers will be instrumental for understanding mesoscopic effects in layered materials and tuning light-matter interactions in magnetic 2D materials.
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Chirality-induced spin selectivity (CISS), whereby helical molecules polarize the spin of electrical current, is an intriguing effect with potential applications in nanospintronics. In this nascent field, the study of the CISS effect using paramagnetic chiral molecules, which could introduce another degree of freedom in controlling the spin transport, remains so far unexplored. To address this challenge, herein we propose the use of self-assembled monolayers (SAMs) of helical lanthanide-binding peptides. To elucidate the effect of the paramagnetic nuclei, monolayers of the peptide coordinating paramagnetic or diamagnetic ions are prepared. By means of spin-dependent electrochemistry, the CISS effect is demonstrated by cyclic voltammetry and electrochemical impedance measurements for both samples. Additionally, an implementation of the standard liquid-metal drop electron transport setup has been carried out, and this process helped to demonstrate the peptides' suitability for solid-state devices. Remarkably, the inclusion of a paramagnetic center in the peptide increases the spin polarization as was independently proved by different techniques. These findings permit the inclusion of magnetic biomolecules in the CISS field and pave the way to their implementation in a new generation of (bio)spintronic nanodevices.
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Compostos Organometálicos/química , Peptídeos/química , Sequência de Aminoácidos , Eletroquímica , Espectroscopia de Ressonância de Spin Eletrônica , Transporte de Elétrons , Ouro/química , Elementos da Série dos Lantanídeos/química , Modelos Químicos , Estereoisomerismo , Propriedades de Superfície , TemperaturaRESUMO
In Shwachman-Diamond syndrome (SDS), deletion of the long arm of chromosome 20, del(20)(q), often acquired in bone marrow (BM), may imply a lower risk of developing myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), due to the loss of the EIF6 gene. The genes L3MBTL1 and SGK2, also on chromosome 20, are in a cluster of imprinted genes, and their loss implies dysregulation of BM function. We report here the results of array comparative genomic hybridization (a-CGH) performed on BM DNA of six patients which confirmed the consistent loss of EIF6 gene. Interestingly, array single nucleotide polymorphisms (SNPs) showed copy neutral loss of heterozygosity for EIF6 region in cases without del(20)(q). No preferential parental origin of the deleted chromosome 20 was detected by microsatellite analysis in six SDS patients. Our patients showed a very mild haematological condition, and none evolved into BM aplasia or MDS/AML. We extend the benign prognostic significance of del(20)(q) and loss of EIF6 to the haematological features of these patients, consistently characterized by mild hypoplastic BM, no or mild neutropenia, anaemia and thrombocytopenia. Some odd results obtained in microsatellite and SNP-array analysis demonstrate a peculiar genomic instability, in an attempt to improve BM function through the acquisition of the del(20)(q).
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Cromossomos Humanos Par 20/genética , Instabilidade Genômica/genética , Síndrome de Shwachman-Diamond/genética , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Prognóstico , Síndrome de Shwachman-Diamond/patologia , Adulto JovemRESUMO
Metal-organic frameworks can be used as porous templates to exert control over polymerization reactions. Shown here are the possibilities offered by these crystalline, porous nanoreactors to capture highly-reactive intermediates for a better understanding of the mechanism of polymerization reactions. By using a cyclodextrin framework the polymerization of pyrrole is restricted, capturing the formation of terpyrrole cationic intermediates. Single-crystal X-ray diffraction is used to provide definite information on the supramolecular interactions that induce the formation and stabilization of a conductive array of cationic complexes.
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Conductive metal-organic frameworks are opening new perspectives for the use of these porous materials for applications traditionally limited to more classical inorganic materials, such as their integration into electronic devices. This has enabled the development of chemiresistive sensors capable of transducing the presence of specific guests into an electrical response with good selectivity and sensitivity. By combining experimental data with computational modelling, a possible origin for the underlying mechanism of this phenomenon in ultrathin films (ca. 30â nm) of Cu-CAT-1 is described.
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Acute lymphoblastic leukemia (ALL) is the major pediatric cancer. At diagnosis, the developmental timing of mutations contributing critically to clonal diversification and selection can be buried in the leukemia's covert natural history. Concordance of ALL in monozygotic, monochorionic twins is a consequence of intraplacental spread of an initiated preleukemic clone. Studying monozygotic twins with ALL provides a unique means of uncovering the timeline of mutations contributing to clonal evolution, pre- and postnatally. We sequenced the whole genomes of leukemic cells from two twin pairs with ALL to comprehensively characterize acquired somatic mutations in ALL, elucidating the developmental timing of all genetic lesions. Shared, prenatal, coding-region single-nucleotide variants were limited to the putative initiating lesions. All other nonsynonymous single-nucleotide variants were distinct between tumors and, therefore, secondary and postnatal. These changes occurred in a background of noncoding mutational changes that were almost entirely discordant in twin pairs and likely passenger mutations acquired during leukemic cell proliferation.
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Análise Mutacional de DNA , Genoma Humano/genética , Mutação/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Criança , Pré-Escolar , Humanos , Fatores de TempoRESUMO
Double-layer targets (DLTs), made of a low-density foam on top of a solid substrate, can efficiently convert the energy of a high-intensity laser to provide sources of photons and protons. We investigate a 30-fs pulse with a peak intensity of Iâ¼8.7×10^{20}W/cm^{2} and a peak power of â¼120 TW interacting with a DLT using three-dimensional (3D) particle-in-cell simulations. We focus on providing quantitative results in full 3D geometry on the foam thickness dependence; on the competition between two photon-generating processes in DLTs, i.e., nonlinear inverse Compton scattering (NICS) and bremsstrahlung (BS); and on the acceleration of protons via enhanced target-normal sheath acceleration. We discuss conversion efficiency, average energy, and angular distributions of such multiradiation sources. We find that NICS can prevail over BS if the DLT's substrate is thin enough (â¼µm) and that the optimal foam thickness that maximizes the conversion efficiency in NICS and BS photons and the proton cutoff energy, among those considered, is the same (15µm). These results show that DLTs constitute an excellent tool for developing relatively compact and optimized laser-driven multicomponent radiation sources.
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The interest in compact, cost-effective, and versatile accelerators is increasing for many applications of great societal relevance, ranging from nuclear medicine to agriculture, pollution control, and cultural heritage conservation. For instance, Particle Induced X-ray Emission (PIXE) is a non-destructive material characterization technique applied to environmental analysis that requires MeV-energy ions. In this context, superintense laser-driven ion sources represent a promising alternative to conventional accelerators. In particular, the optimization of the laser-target coupling by acting on target properties results in an enhancement of ion current and energy with reduced requirements on the laser system. Among the advanced target concepts that have been explored, one appealing option is given by double-layer targets (DLTs), where a very low-density layer, which acts as an enhanced laser absorber, is grown to a thin solid foil. Here we present some of the most recent results concerning the production with deposition techniques of advanced DLTs for laser-driven particle acceleration. We assess the potential of these targets for laser-driven ion acceleration with particle-in-cell simulations, as well as their application to PIXE analysis of aerosol samples with Monte Carlo simulations. Our investigation reports that MeV protons, accelerated with a â¼20 TW compact laser and optimized DLTs, can allow performing PIXE with comparable performances to conventional sources. We conclude that compact DLT-based laser-driven accelerators can be relevant for environmental monitoring.
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Children with Down syndrome have an augmented risk for B-cell acute lymphoblastic leukemia (DS-ALL), which is associated with lower survival than in non-DS-ALL. It is known that cytogenetic abnormalities common in childhood ALL are less frequent in DS-ALL, while other genetic aberrancies (ie, CRLF2 overexpression and IKZF1 deletions) are increased. A possible cause for the lower survival of DS-ALL that we herewith evaluated for the first time was the incidence and prognostic value of the Philadelphia-like (Ph-like) profile and the IKZF1plus pattern. These features have been associated with poor outcome in non-DS ALL and therefore introduced in current therapeutic protocols. Forty-six out of 70 DS-ALL patients treated in Italy from 2000 to 2014 displayed Ph-like signature, mostly characterized by CRLF2 (n = 33) and IKZF1 (n = 16) alterations; only 2 cases were positive for ABL-class or PAX5-fusion genes. Moreover, in an Italian and German joint cohort of 134 DS-ALL patients, we observed 18% patients positive for IKZF1plus feature. Ph-like signature and IKZF1 deletion were associated with poor outcome (cumulative incidence of relapse: 27.7 ± 6.8% versus 13 ± 7%; P = 0.04 and 35.2 ± 8.6% versus 17 ± 3.9%; P = 0.007, respectively), which further worsens when IKZF1 deletion was co-occurring with P2RY8::CRLF2, qualifying for the IKZF1plus definition (13/15 patients had an event of relapse or treatment-related death). Notably, ex vivo drug screening revealed sensitivity of IKZF1plus blasts for drugs active against Ph-like ALL such as Birinapant and histone deacetylase inhibitors. We provided data in a large setting of a rare condition (DS-ALL) supporting that these patients, not associated with other high-risk features, need tailored therapeutic strategies.
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We report on polariton condensation in photonic molecules formed by two coupled micropillars. We show that the condensation process is strongly affected by the interaction with the cloud of uncondensed excitons and thus strongly depends on the exact localization of these excitons within the molecule. Under symmetric excitation conditions, condensation is triggered on both binding and antibinding polariton states of the molecule. On the opposite, when the excitonic cloud is injected in one of the two pillars, condensation on a metastable state is observed and a total transfer of the condensate into one of the micropillars can be achieved. Our results highlight the crucial role played by relaxation kinetics in the condensation process.
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We report on large spin-filtering effects in epitaxial graphene-based spin valves, strongly enhanced in our specific multilayer case. Our results were obtained by the effective association of chemical vapor deposited (CVD) multilayer graphene with a high quality epitaxial Ni(111) ferromagnetic spin source. We highlight that the Ni(111) spin source electrode crystallinity and metallic state are preserved and stabilized by multilayer graphene CVD growth. Complete nanometric spin valve junctions are fabricated using a local probe indentation process, and spin properties are extracted from the graphene-protected ferromagnetic electrode through the use of a reference Al2O3/Co spin analyzer. Strikingly, spin-transport measurements in these structures give rise to large negative tunnel magneto-resistance TMR = -160%, pointing to a particularly large spin polarization for the Ni(111)/Gr interface PNi/Gr, evaluated up to -98%. We then discuss an emerging physical picture of graphene-ferromagnet systems, sustained both by experimental data and ab initio calculations, intimately combining efficient spin filtering effects arising (i) from the bulk band structure of the graphene layers purifying the extracted spin direction, (ii) from the hybridization effects modulating the amplitude of spin polarized scattering states over the first few graphene layers at the interface, and (iii) from the epitaxial interfacial matching of the graphene layers with the spin-polarized Ni surface selecting well-defined spin polarized channels. Importantly, these main spin selection effects are shown to be either cooperating or competing, explaining why our transport results were not observed before. Overall, this study unveils a path to harness the full potential of low Resitance.Area (RA) graphene interfaces in efficient spin-based devices.
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CBL syndrome is a Noonan-like RASopathy with heterogeneous clinical phenotype and predisposition to juvenile myelomonocytic leukemia (JMML). Here we describe two patients with identical germline CBL mutation and clinical and immune-hematological overlapping features with autoimmune lymphoproliferative syndrome (ALPS) and B-cell expansion with NF-κB and T-cell anergy (BENTA) syndrome. Increased immature/transitional B cells can be depicted in CBL syndrome, ALPS, and BENTA. Nonetheless, our patients here described showed peculiar B-cell phenotype due to increased immature/transitional CD34+ B cells. This feature differentiates CBL syndrome from BENTA, pointing toward an abnormal proliferation of B-cell early precursors.
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BACKGROUND: Despite intensive risk-based treatment protocols, 15% of paediatric patients with B-Cell Precursor Acute Lymphoblastic Leukaemia (BCP-ALL) experience relapse. There is urgent need of novel strategies to target poor prognosis subgroups, like PAX5 translocated. METHODS: We considered 289 childhood BCP-ALL cases consecutively enrolled in Italy in the AIEOP-BFM ALL2000/R2006 protocols and we performed extensive molecular profiling, integrating gene expression, copy number analyses and fusion genes discovery by target-capture NGS. We developed preclinical strategies to target PAX5 fusion genes. FINDINGS: We identified 135 cases without recurrent genetic rearrangements. Among them, 59 patients (43·7%) had a Ph-like signature; the remaining cases were identified as ERG-related (26%), High-Hyperdiploid-like (17%), ETV6::RUNX1-like (8·9%), MEF2D-rearranged (2·2%) or KMT2A-like (1·5%). A poor prognosis was associated with the Ph-like signature, independently from other high-risk features. Interestingly, PAX5 was altered in 54·4% of Ph-like compared to 16·2% of non-Ph-like cases, with 7 patients carrying PAX5 fusions (PAX5t), involving either novel (ALDH18A1, IKZF1, CDH13) or known (FBRSL1, AUTS2, DACH2) partner genes. PAX5t cases have a specific driver activity signature, extending to multiple pathways including LCK hyperactivation. Among FDA-approved drugs and inhibitors, we selected Dasatinib, Bosutinib and Foretinib, in addition to Nintedanib, known to be LCK ligands. We demonstrated the efficacy of the LCK-inhibitor BIBF1120/Nintedanib, as single agent or in combination with conventional chemotherapy, both ex vivo and in patient-derived xenograft model, showing a synergistic effect with dexamethasone. INTERPRETATION: This study provides new insights in high-risk Ph-like leukaemia and identifies a potential therapy for targeting PAX5-fusion poor risk group. FUNDING: Ricerca Finalizzata-Giovani Ricercatori (Italian Ministry of Health), AIRC, Transcall, Fondazione Cariparo.
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Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Subunidade alfa 2 de Fator de Ligação ao Core , Dasatinibe , Dexametasona , Humanos , Indóis , Recidiva Local de Neoplasia , Fator de Transcrição PAX5/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMO
In the past few years, the effect of strain on the optical and electronic properties of MoS2 layers has attracted particular attention as it can improve the performance of optoelectronic and spintronic devices. Although several approaches have been explored, strain is typically externally applied on the two-dimensional material. In this work, we describe the preparation of a reversible 'self-strainable' system in which the strain is generated at the molecular level by one component of a MoS2-based composite material. Spin-crossover nanoparticles were covalently grafted onto functionalized layers of semiconducting MoS2 to form a hybrid heterostructure. Their ability to switch between two spin states on applying an external stimulus (light irradiation or temperature change) serves to generate strain over the MoS2 layer. A volume change accompanies this spin crossover, and the created strain induces a substantial and reversible change of the electrical and optical properties of the heterostructure.
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We present a growth process relying on pulsed laser deposition for the elaboration of complex van der Waals heterostructures on large scales, at a 400 °C CMOS-compatible temperature. Illustratively, we define a multilayer quantum well geometry through successive in situ growths, leading to WSe2 being encapsulated into WS2 layers. The structural constitution of the quantum well geometry is confirmed by Raman spectroscopy combined with transmission electron microscopy. The large-scale high homogeneity of the resulting 2D van der Waals heterostructure is also validated by macro- and microscale Raman mappings. We illustrate the benefit of this integrative in situ approach by showing the structural preservation of even the most fragile 2D layers once encapsulated in a van der Waals heterostructure. Finally, we fabricate a vertical tunneling device based on these large-scale layers and discuss the clear signature of electronic transport controlled by the quantum well configuration with ab initio calculations in support. The flexibility of this direct growth approach, with multilayer stacks being built in a single run, allows for the definition of complex 2D heterostructures barely accessible with usual exfoliation or transfer techniques of 2D materials. Reminiscent of the III-V semiconductors' successful exploitation, our approach unlocks virtually infinite combinations of large 2D material families in any complex van der Waals heterostructure design.
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DOCK8 deficiency is a combined immunodeficiency due to biallelic variants in dedicator of cytokinesis 8 (DOCK8) gene. The disease has a wide clinical spectrum encompassing recurrent infections (candidiasis, viral and bacterial infections), virally driven malignancies and immune dysregulatory features, including autoimmune (cytopenia and vasculitis) as well as allergic disorders (eczema, asthma, and food allergy). Hypomorphic function and somatic reversion of DOCK8 has been reported to result in incomplete phenotype without IgE overproduction. Here we describe a case of DOCK8 deficiency in a 8-year-old Caucasian girl. The patient's disease was initially classified as autoimmune thrombocytopenia, which then evolved toward a combined immunodeficiency phenotype with recurrent infections, persistent EBV infection and lymphoproliferation. Two novel variants (one deletion and one premature stop codon) were characterized, resulting in markedly reduced, but not absent, DOCK8 expression. Somatic reversion of the DOCK8 deletion was identified in T cells. Hypomorphic function and somatic reversion were associated with restricted T cell repertoire, decreased STAT5 phosphorylation and impaired immune synapse functioning in T cells. Although the patient presented with incomplete phenotype (absence of markedly increase IgE and eosinophil count), sclerosing cholangitis was incidentally detected, thus indicating that hypomorphic function and somatic reversion of DOCK8 may delay disease progression but do not necessarily prevent from severe complications.
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Colangite Esclerosante/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Doenças da Imunodeficiência Primária/genética , Criança , Feminino , Humanos , MutaçãoAssuntos
Proteínas de Ciclo Celular/genética , Cromossomos Humanos/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Fator de Transcrição PAX5/genética , Proteínas/genética , Aberrações Cromossômicas , Proteínas do Citoesqueleto , Humanos , Hibridização in Situ Fluorescente , Proteínas de Ligação a Poli-ADP-Ribose , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Prognóstico , Fatores de Transcrição , Translocação Genética/genética , Ubiquitina-Proteína LigasesRESUMO
We report on spin transport in state-of-the-art epitaxial monolayer graphene based 2D-magnetic tunnel junctions (2D-MTJs). In our measurements, supported by ab-initio calculations, the strength of interaction between ferromagnetic electrodes and graphene monolayers is shown to fundamentally control the resulting spin signal. In particular, by switching the graphene/ferromagnet interaction, spin transport reveals magneto-resistance signal MR > 80% in junctions with low resistance × area products. Descriptions based only on a simple K-point filtering picture (i.e. MR increase with the number of layers) are not sufficient to predict the behavior of our devices. We emphasize that hybridization effects need to be taken into account to fully grasp the spin properties (such as spin dependent density of states) when 2D materials are used as ultimately thin interfaces. While this is only a first demonstration, we thus introduce the fruitful potential of spin manipulation by proximity effect at the hybridized 2D material / ferromagnet interface for 2D-MTJs.