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1.
Blood ; 144(6): 615-628, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-38657201

RESUMO

ABSTRACT: Teclistamab, an off-the-shelf B-cell maturation antigen (BCMA) × CD3 bispecific antibody that mediates T-cell activation and subsequent lysis of BCMA-expressing myeloma cells, is approved for the treatment of patients with relapsed/refractory multiple myeloma (R/RMM). As a T-cell redirection therapy, clinical outcomes with teclistamab may be influenced by patient immune fitness and tumor antigen expression. We correlated tumor characteristics and baseline immune profiles with clinical response and disease burden in patients with R/RMM from the pivotal phase 1/2 MajesTEC-1 study, focusing on patients treated with 1.5 mg/kg of teclistamab (N = 165). Peripheral blood samples were collected at screening, and bone marrow samples were collected at screening and cycle 3. Better clinical outcomes to teclistamab correlated with higher baseline total T-cell counts in the periphery. In addition, responders (partial response or better) had a lower proportion of immunosuppressive regulatory T cells (Tregs), T cells expressing coinhibitory receptors (CD38, PD-1, and PD-1/TIM-3), and soluble BCMA and a T-cell profile suggestive of a more cytolytic potential, compared with nonresponders. Neither frequency of baseline bone marrow BCMA expression nor BCMA-receptor density was associated with clinical response to teclistamab. Improved progression-free survival was observed in patients with a lower frequency of T cells expressing exhaustion markers and immunosuppressive Tregs. Overall, response to teclistamab was associated with baseline immune fitness; nonresponders had immune profiles suggestive of immune suppression and T-cell dysfunction. These findings illustrate the importance of the contribution of the immune landscape to T-cell redirection therapy response. This trial was registered at www.ClinicalTrials.gov as #NCT03145181/NCT04557098.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Masculino , Anticorpos Biespecíficos/uso terapêutico , Feminino , Antígeno de Maturação de Linfócitos B/imunologia , Pessoa de Meia-Idade , Idoso
2.
Ann Hematol ; 103(6): 1989-2001, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38233570

RESUMO

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive, heterogeneous non-Hodgkin lymphoma resulting from malignant proliferation of cytotoxic natural killer (NK) or T cells. Previous studies demonstrated variable expression of CD38 on NKTCL tumors. Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, was hypothesized to be a novel therapeutic option for patients with relapsed or refractory (R/R) NKTCL. In the phase 2 NKT2001 study (ClinicalTrials.gov Identifier: NCT02927925) assessing the safety and efficacy of daratumumab, a suboptimal overall response rate was seen in R/R NKTCL patients. One patient, whose tumors did not express CD38, responded to treatment, suggesting that the immunomodulatory activities of daratumumab may be sufficient to confer clinical benefit. To understand the suboptimal response rate and short duration of response, we investigated the immune profile of NKTCL patients from NKT2001 in the context of daratumumab anti-tumor activity. Tumor tissue and whole blood were, respectively, analyzed for CD38 expression and patient immune landscapes, which were assessed via cytometry by time-of-flight (CyTOF), multiparameter flow cytometry (MPFC), clonal sequencing, and plasma Epstein-Barr virus (EBV)-DNA level measurements. Changes observed in the immune profiles of NKTCL patients from NKT2001, including differences in B and T cell populations between responders and nonresponders, suggest that modulation of the immune environment is crucial for daratumumab anti-tumor activities in NKTCL. In conclusion, these findings highlight that the clinical benefit of daratumumab in NKTCL may be enriched by B/T cell-related biomarkers.


Assuntos
Anticorpos Monoclonais , Linfoma Extranodal de Células T-NK , Humanos , Anticorpos Monoclonais/uso terapêutico , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/imunologia , Masculino , Feminino , ADP-Ribosil Ciclase 1 , Pessoa de Meia-Idade , Idoso , Adulto , Glicoproteínas de Membrana
3.
Small ; 15(48): e1902081, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31210002

RESUMO

Metal-free carbon electrodes with well-defined composition and smooth topography are prepared via sputter deposition followed by thermal treatment with inert and reactive gases. X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy show that three carbons of similar N/C content that differ in N-site composition are thus prepared: an electrode consisting of almost exclusively graphitic-N (NG ), an electrode with predominantly pyridinic-N (NP ), and one with ≈1:1 NG :NP composition. These materials are used as model systems to investigate the activity of N-doped carbons in the oxygen reduction reaction (ORR) using voltammetry. Results show that selectivity toward 4e-reduction of O2 is strongly influenced by the NG /NP site composition, with the material possessing nearly uniform NG /NP composition being the only one yielding a 4e-reduction. Computational studies on model graphene clusters are carried out to elucidate the effect of N-site homogeneity on the reaction pathway. Calculations show that for pure NG -doping or NP -doping of model graphene clusters, adsorption of hydroperoxide and hydroperoxyl radical intermediates, respectively, is weak, thus favoring desorption prior to complete 4e-reduction to hydroxide. Clusters with mixed NG /NP sites display synergistic effects, suggesting that co-presence of these sites improves activity and selectivity by achieving high theoretical reduction potentials while facilitating retention of intermediates.

4.
Blood ; 119(24): 5621-31, 2012 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-22490804

RESUMO

To detect targeted antileukemia agents we have designed a novel, high-content in vivo screen using genetically engineered, T-cell reporting zebrafish. We exploited the developmental similarities between normal and malignant T lymphoblasts to screen a small molecule library for activity against immature T cells with a simple visual readout in zebrafish larvae. After screening 26 400 molecules, we identified Lenaldekar (LDK), a compound that eliminates immature T cells in developing zebrafish without affecting the cell cycle in other cell types. LDK is well tolerated in vertebrates and induces long-term remission in adult zebrafish with cMYC-induced T-cell acute lymphoblastic leukemia (T-ALL). LDK causes dephosphorylation of members of the PI3 kinase/AKT/mTOR pathway and delays sensitive cells in late mitosis. Among human cancers, LDK selectively affects survival of hematopoietic malignancy lines and primary leukemias, including therapy-refractory B-ALL and chronic myelogenous leukemia samples, and inhibits growth of human T-ALL xenografts. This work demonstrates the utility of our method using zebrafish for antineoplastic candidate drug identification and suggests a new approach for targeted leukemia therapy. Although our efforts focused on leukemia therapy, this screening approach has broad implications as it can be translated to other cancer types involving malignant degeneration of developmentally arrested cells.


Assuntos
Antineoplásicos/toxicidade , Hidrazonas/toxicidade , Leucemia/patologia , Quinolinas/toxicidade , Peixe-Zebra/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Crise Blástica/patologia , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Humanos , Hidrazonas/química , Hidrazonas/farmacocinética , Hidrazonas/uso terapêutico , Leucemia/tratamento farmacológico , Camundongos , Mitose/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinolinas/química , Quinolinas/farmacocinética , Quinolinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Phys Chem Chem Phys ; 16(44): 24536-48, 2014 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-25310112

RESUMO

In this paper we investigate the possibility to apply the concepts of non-specific intermolecular interactions and dispersive local field effect approach for study of the influence of interactions of metal nanoparticles with matrix molecules on the spectral characteristics of composites. The effect of intermolecular (interparticle) interactions and the influence of the dielectric environment on the peak position of the plasmon resonance band of colloidal solutions and thin films formed from noble metal nanostructures is determined. Simulated and experimental absorption spectra obtained for a colloidal solution of silver and gold nanoparticles, of various shapes and sizes in water and glycerol, are in good agreement.

6.
Materials (Basel) ; 16(6)2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36984290

RESUMO

In this study, new composite materials comprising zeolitic imidazolate framework (ZIF) structures and microchannel glass (MCG) plates were fabricated using the hydrothermal method and their morphological and spectral properties were investigated using XRD, SEM, FTIR, and Raman spectroscopy. XRD studies of powder samples revealed the presence of an additional phase for a ZIF-8 sample, whereas ZIF-67 samples, which were prepared through two different chemical routes, showed no additional phases. A detailed analysis of the FTIR and micro-Raman spectra of the composite samples revealed the formation of stable ZIF structures inside the macropores of the MCG substrate. The hydrophilic nature of the MCG substrate and its interaction with the ZIF structure resulted in the formation of stable ZIF-MCG composites. We believe that these composite materials may find a wide range of important applications in the field of sensors, molecular sieving.

7.
Materials (Basel) ; 15(15)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35897629

RESUMO

Surface-enhanced Raman spectroscopy (SERS) is regarded as a versatile tool for studying the composition and structure of matter. This work has studied the preparation of a SERS substrate based on a self-assembling plasmonic nanoparticle film (SPF) in a polymer matrix. Several synthesis parameters for the SPF are investigated, including the size of the particles making up the film and the concentration and type of the self-assembling agent. The result of testing systems with different characteristics is discussed using a model substance (pseudoisocyanin iodide). These models can be useful in the study of biology and chemistry. Research results contain the optimal parameters for SPF synthesis, maximizing the SERS signal. The optimal procedure for SPF assembly is determined and used for the synthesis of composite SPFs within different polymer matrices. SPF in a polymer matrix is necessary for the routine use of the SERS substrate for various types of analytes, including solid samples or those sensitive to contamination. Polystyrene, polyvinyl alcohol (PVA), and polyethylene are investigated to obtain a polymer matrix for SPF, and various methods of incorporating SPF into a polymer matrix are being explored. It is found that films with the best signal enhancement and reproducibility were obtained in polystyrene. The minimum detectable concentration for the SERS substrate obtained is equal to 10-10 M. We prepared a SERS substrate with an analytical enhancement factor of 2.7 × 104, allowing an increase in the detection sensitivity of analyte solutions of five orders of magnitude.

8.
Opt Lett ; 36(10): 1854-6, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21593913

RESUMO

We report on what is believed to be the first example of an ultrawide, bandpass filter, based on a high-contrast multicomponent one-dimensional Si photonic crystal (PC). The effect of the disappearance of a limited number of flat stopbands and their replacement with extended passbands is demonstrated over a wide IR range. The passbands obtained exhibit a high transmission of 92% to 96% and a substantial bandwidth of 1800 nm, which is spectrally flat within the passband. The multicomponent PC model suggested can be applied to the design of any micro- or nanostructured semiconductor or dielectric material for application across a wide spectral range.

9.
Bipolar Disord ; 13(1): 41-51, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21320251

RESUMO

OBJECTIVES: Disrupted intracellular calcium (Ca(2+) ) homeostasis (ICH) related to mitochondrial and/or endoplasmic reticulum (ER) dysfunction has been implicated in bipolar disorder (BD). The anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl-2), encoded in a putative BD susceptibility locus, modulates ER-Ca(2+) dynamics. Recently, an intronic single-nucleotide polymorphism (SNP) in the Bcl-2 gene, rs956572, was suggested as a functionally active SNP that influences its messenger RNA (mRNA) and protein level as well as human gray matter volume. We sought to evaluate the impact of this variant on ICH in BD. METHODS: Basal intracellular Ca(2+) concentrations ([Ca(2+) ](B) ) and rs956572 genotypes were determined in B lymphoblast cell lines (BLCLs) from bipolar I disorder (BD-I) (n=150), bipolar II disorder (BD-II) (n=65), and major depressive disorder (n=30) patients, and from healthy subjects (n=70). Bcl-2 mRNA and protein levels were determined by quantitative reverse transcriptase polymerase chain reaction and immunoblotting, respectively. Functional interactions of rs956572 with ICH were assessed by thapsigargin- and lysophosphatidic acid (LPA)-stimulated Ca(2+) responses. RESULTS: Although rs956572 variation was not significantly associated with BD, BD-I, or BD-II, BLCL [Ca(2+) ](B) was significantly higher in BD-I G/G patients compared with other genotypes and with healthy subjects. Bcl-2 mRNA and protein levels were lowest in BD-I G/G patients. Compared with A carriers, BD-I patients with G/G variants showed a modest enhancing effect on thapsigargin- and LPA-stimulated Ca(2+) responses. CONCLUSIONS: These findings support the notion that genetic variation in Bcl-2 affecting its expression impacts ICH in BD. Moreover, we show here for the first time that this interactive effect is diagnostically specific to BD-I.


Assuntos
Transtorno Bipolar/genética , Cálcio/metabolismo , Transtorno Depressivo Maior/genética , Retículo Endoplasmático/metabolismo , Genes bcl-2/genética , Homeostase , RNA Mensageiro/genética , Adulto , Linfócitos B/metabolismo , Transtorno Bipolar/metabolismo , Estudos de Casos e Controles , Transtorno Depressivo Maior/metabolismo , Retículo Endoplasmático/genética , Feminino , Genes bcl-2/fisiologia , Genótipo , Humanos , Immunoblotting , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
10.
Int J Neuropsychopharmacol ; 13(6): 693-702, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19400980

RESUMO

Irregularities of intracellular calcium (Ca2+) homeostasis have been implicated in the pathophysiology of bipolar disorder (BD). Findings that chronic ex-vivo treatment with lithium modifies lysophosphatidic acid (LPA)-stimulated Ca2+ responses in B lymphoblast cell lines (BLCLs) from BD-I patients and healthy controls, and differentially decreases levels of the type-3 canonical transient receptor potential Ca2+-permeable channel in BLCLs from BD-I patients, support the view that the amelioration of these abnormalities is important in the therapeutic action of lithium. To determine whether other clinically efficacious mood stabilizers share these effects, LPA (100 mum)- and thapsigargin (TG, 200 nm)-stimulated Ca2+ responses were determined in BLCLs from BD-I patients and healthy controls treated acutely (24 h) and chronically (7 d) ex vivo with therapeutically relevant concentrations of lithium (0.75 mm), valproate (0.5 mm), lamotrigine (15 mum) or respective vehicles. Chronic treatment with valproate significantly attenuated LPA-stimulated Ca2+ responses ([downward arrow]8%: F's=9.1-9.4, d.f.=1, 9, p's<0.05) compared to vehicle in BLCLs from BD-I patients and healthy controls, similar to chronic lithium treatment ([downward arrow]8%: F=6.2, d.f.=1, 21, p<0.05), but also attenuated TG-evoked Ca2+ responses ([downward arrow]10% to [downward arrow]19%: F's=5.5-15.5, d.f.=1, 12, p's<0.05). However, chronic lamotrigine treatment did not affect LPA- or TG-stimulated Ca2+ responses. These results suggest that chronic lithium and valproate treatments act differently from lamotrigine in respect of modulation of receptor- and/or capacitance-mediated Ca2+ flux. These differential effects on Ca2+ responses may be relevant to the distinctive clinical profiles of these mood stabilizers.


Assuntos
Antimaníacos/farmacologia , Linfócitos B/efeitos dos fármacos , Cálcio/metabolismo , Líquido Intracelular/efeitos dos fármacos , Cloreto de Lítio/farmacologia , Adulto , Linfócitos B/metabolismo , Linfócitos B/patologia , Transtorno Bipolar/patologia , Linhagem Celular Transformada , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Líquido Intracelular/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Tapsigargina/farmacologia , Ácido Valproico/farmacologia
11.
Materials (Basel) ; 13(22)2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33233341

RESUMO

Market pressures have placed new demands on modern photonic and opto-electronic materials, including requirements for miniaturization, higher efficiency, tunable and controllable optical and electrical properties, and consistent performance [...].

12.
Materials (Basel) ; 13(3)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32023870

RESUMO

The optical constant of bulk metal is used to determine the dispersion of the local field under one-dimensional (1D), two-dimensional (2D) and three-dimensional (3D) confinement. 3D confinement, expressed as ε 2 m i c ( ω 3 D ) , corresponds to the dielectric loss spectra of spherical particles with a diameter, d, much less than the wavelength of the beam used to measure the spectrum (d << λ). Excellent agreement with the results of Mie theory and experimental data for solid colloids within alkali halide crystals was observed. The function expressed as ε 2 m i c ( ω 1 D ) allows the measurement of spectral micro-characteristics in the frequency range of the longitudinal collective motion of the free electrons. This corresponds to the spectrum of dielectric losses of bulk plasma oscillations. The function ε 2 m i c ( ω 2 D ) describes the spectra of the dielectric losses of surface plasma oscillations in thin metal films. It is shown that the peak positions of ε 2 m i c ( ω 3 D ) , ε 2 m i c ( ω 2 D ) and ε 2 m i c ( ω 1 D ) spectra for simple metals, viz. alkali metals as well as Al, Be, Mg, Ga, In, Sn and Si, are in agreement with experimental results from electron-energy-loss spectroscopy and various optical techniques.

13.
Front Chem ; 8: 593932, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240854

RESUMO

Nitrogen-free amorphous carbon thin films prepared via sputtering followed by graphitization, were used as precursor materials for the creation of N-doped carbon electrodes with varying degrees of amorphization. Incorporation of N-sites was achieved via nitrogen plasma treatments which resulted in both surface functionalization and amorphization of the carbon electrode materials. X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy were used to monitor composition and carbon organization: results indicate incorporation of predominantly pyrrolic-N sites after relatively short treatment cycles (5 min or less), accompanied by an initial etching of amorphous regions followed by a slower process of amorphization of graphitized clusters. By leveraging the difference in the rate of these two processes it was possible to investigate the effects of chemical N-sites and C-defect sites on their electrochemical response. The materials were tested as metal-free electrocatalysts in the oxygen reduction reaction (ORR) in alkaline conditions. We find that the introduction of predominantly pyrrolic-N sites via plasma modification results in improvements in selectivity in the ORR, relative to the nitrogen-free precursor material. Introduction of defects through prolonged plasma exposure has a more pronounced and beneficial effect on ORR descriptors than introduction of N-sites alone, leading to both increased onset potentials, and reduced hydroperoxide yields relative to the nitrogen-free carbon material. Our results suggest that increased structural disorder/heterogeneity results in the introduction of carbon sites that might either serve as main activity sites, or that enhance the effects of N-functionalities in the ORR via synergistic effects.

14.
RSC Adv ; 9(7): 4063-4071, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35518062

RESUMO

Nitrogen incorporated carbon materials play an important role in electrochemical energy conversion technologies from fuel cells to capacitive storage devices. This work investigates the effects of nitrogen incorporation on capacitance, work function and semiconductor properties of amorphous carbon thin film electrodes. Nitrogenated electrodes (a-C:N) electrodes were synthesized via magnetron sputtering and characterized using X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy (UPS), Raman spectroscopy, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). EIS was carried in both aqueous (0.1 M KCl) and organic (0.1 M TBAPF6/acetonitrile) electrolytes to discriminate between pseudocapacitive contributions and changes to semiconductor properties of the materials arising from structural and chemical disruption of the graphitic carbon scaffold. Raman and UPS spectroscopy both suggest that nitrogen incorporation increases the metallic character of the disordered carbon matrix at low-intermediate concentrations, whereas further nitrogen incorporation results in significantly more defective carbon with small graphitic cluster size. EIS studies in 0.1 M KCl indicate that the capacitance of a-C:N electrodes increases relative to nitrogen-free a-C electrodes due to a combination of microroughness and pseudocapacitive contributions in parallel to those of the double layer capacitance. Results in 0.1 M TBAPF6 in acetonitrile which are dominated by the interfacial capacitance, show that initial nitrogen incorporation into the disordered carbon scaffold compensates for p-type properties in the disordered carbon matrix, resulting in an increase in metallic character. Greater levels of nitrogenation, are instead disruptive and increase defect density while decreasing the double layer capacitance.

15.
Materials (Basel) ; 12(21)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31689939

RESUMO

Over recent years, quantum dots (QDs) based on ternary metal dichalcogenides have attracted a lot of attention due to their unique properties and a range of potential applications. Here, we review the latest studies on the optical properties of AgInS2/ZnS QDs with emphasis on their theoretical modeling, and present our investigations of electronic transitions invisible in unstructured absorption spectra of AgInS2/ZnS QDs. The analysis of the absorption, photoluminescence excitation (PLE), and magnetic circular dichroism (MCD) spectra of hydrophobic and hydrophilic AgInS2/ZnS QDs of different sizes enables us to determine positions of electron transitions in these QDs. We demonstrate that the use of the second derivative of PLE spectra provides more unequivocal data on the position of the energy transitions compared with the second derivative of absorption spectra. Analysis of the MCD spectra reveals that the magnetic field induces energy level mixing in AgInS2/ZnS QDs in contrast to the traditional Cd-based QDs, where MCD is associated only with removing degeneracy of the excited energy level.

16.
ACS Nano ; 12(2): 954-964, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29338193

RESUMO

Two-dimensional (2D) nanomaterials have been intensively investigated due to their interesting properties and range of potential applications. Although most research has focused on graphene, atomic layered transition metal dichalcogenides (TMDs) and particularly MoS2 have gathered much deserved attention recently. Here, we report the induction of chirality into 2D chiral nanomaterials by carrying out liquid exfoliation of MoS2 in the presence of chiral ligands (cysteine and penicillamine) in water. This processing resulted in exfoliated chiral 2D MoS2 nanosheets showing strong circular dichroism signals, which were far past the onset of the original chiral ligand signals. Using theoretical modeling, we demonstrated that the chiral nature of MoS2 nanosheets is related to the presence of chiral ligands causing preferential folding of the MoS2 sheets. There was an excellent match between the theoretically calculated and experimental spectra. We believe that, due to their high aspect ratio planar morphology, chiral 2D nanomaterials could offer great opportunities for the development of chiroptical sensors, materials, and devices for valleytronics and other potential applications. In addition, chirality plays a key role in many chemical and biological systems, with chiral molecules and materials critical for the further development of biopharmaceuticals and fine chemicals, and this research therefore should have a strong impact on relevant areas of science and technology such as nanobiotechnology, nanomedicine, and nanotoxicology.

17.
Sci Rep ; 7: 42120, 2017 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-28186118

RESUMO

In this work, we propose a novel approach for wafer-scale integration of 2D materials on CMOS photonic chip utilising methods of synthetic chemistry and microfluidics technology. We have successfully demonstrated that this approach can be used for integration of any fluid-dispersed 2D nano-objects on silicon-on-insulator photonics platform. We demonstrate for the first time that the design of an optofluidic waveguide system can be optimised to enable simultaneous in-situ Raman spectroscopy monitoring of 2D dispersed flakes during the device operation. Moreover, for the first time, we have successfully demonstrated the possibility of label-free 2D flake detection via selective enhancement of the Stokes Raman signal at specific wavelengths. We discovered an ultra-high signal sensitivity to the xyz alignment of 2D flakes within the optofluidic waveguide. This in turn enables precise in-situ alignment detection, for the first practicable realisation of 3D photonic microstructure shaping based on 2D-fluid composites and CMOS photonics platform, while also representing a useful technological tool for the control of liquid phase deposition of 2D materials.

18.
J Phys Chem B ; 109(20): 9885-91, 2005 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-16852195

RESUMO

The spectral properties of composite materials based on small particles under 1D, 2D, and 3D size confinement are described using a combination of dispersive internal field and effective media theory approaches. Calculations performed for a number of crystalline materials have shown that the peak position and intensity of the vibrational band of the material under conditions of 1D, 2D, and 3D size confinement are changed, whereas the bandwidth of the band remains the same. In the case of 3D confinement, the peak position of the spectrum of isolated "mesoparticles" (epsilon(meso)(2)) appears to be very close to the intrinsic frequency of the lattice vibrations, calculated from the elastic constants of this crystal, as well as to the Fröhlich's frequency. The largest shift (Deltanu) of the peak frequency, nu(max), from the bulk value is obtained in the case of 1D confinement when the peak position is practically coincident with the frequency of the longitudinal optical phonon (nu(LO)). These shifts are the result of intermolecular interactions, including both resonant and induced resonant dipole-dipole interactions.

19.
Sci Transl Med ; 6(236): 236ra62, 2014 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-24828076

RESUMO

Intensified and central nervous system (CNS)-directed chemotherapy has improved outcomes for pediatric B cell acute lymphoblastic leukemia (B-ALL) but confers treatment-related morbidities. Moreover, many patients suffer relapses, underscoring the need to develop new molecular targeted B-ALL therapies. Using a mouse model, we show that leukemic B cells require pre-B cell receptor (pre-BCR)-independent spleen tyrosine kinase (SYK) signaling in vivo for survival and proliferation. In diagnostic samples from human pediatric and adult B-ALL patients, SYK and downstream targets were phosphorylated regardless of pre-BCR expression or genetic subtype. Two small-molecule SYK inhibitors, fostamatinib and BAY61-3606, attenuated the growth of 69 B-ALL samples in vitro, including high-risk (HR) subtypes. Orally administered fostamatinib reduced heavy disease burden after xenotransplantation of HR B-ALL samples into immunodeficient mice and decreased leukemia dissemination into spleen, liver, kidneys, and the CNS of recipient mice. Thus, SYK activation sustains the growth of multiple HR B-ALL subtypes, suggesting that SYK inhibitors may improve outcomes for HR and relapsed B-ALL.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Células Precursoras de Linfócitos B/citologia , Inibidores de Proteínas Quinases/química , Proteínas Tirosina Quinases/metabolismo , Baço/enzimologia , Administração Oral , Adulto , Aminopiridinas , Animais , Proliferação de Células , Sobrevivência Celular , Criança , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Leucemia/tratamento farmacológico , Masculino , Camundongos , Camundongos SCID , Morfolinas , Mutação , Transplante de Neoplasias , Niacinamida/análogos & derivados , Niacinamida/química , Análise de Sequência com Séries de Oligonucleotídeos , Oxazinas/química , Fosforilação , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/química , Piridinas/química , Pirimidinas/química , Recidiva , Transdução de Sinais , Quinase Syk , Resultado do Tratamento
20.
Sci Rep ; 4: 6917, 2014 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-25369911

RESUMO

The size dependence of the quantized energies of elementary excitations is an essential feature of quantum nanostructures, underlying most of their applications in science and technology. Here we report on a fundamental property of impurity states in semiconductor nanocrystals that appears to have been overlooked--the anticrossing of energy levels exhibiting different size dependencies. We show that this property is inherent to the energy spectra of charge carriers whose spatial motion is simultaneously affected by the Coulomb potential of the impurity ion and the confining potential of the nanocrystal. The coupling of impurity states, which leads to the anticrossing, can be induced by interactions with elementary excitations residing inside the nanocrystal or an external electromagnetic field. We formulate physical conditions that allow a straightforward interpretation of level anticrossings in the nanocrystal energy spectrum and an accurate estimation of the states' coupling strength.

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