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For tumors to progress efficiently, cancer cells must overcome barriers of oxidative stress. Although dietary antioxidant supplementation or activation of endogenous antioxidants by NRF2 reduces oxidative stress and promotes early lung tumor progression, little is known about its effect on lung cancer metastasis. Here, we show that long-term supplementation with the antioxidants N-acetylcysteine and vitamin E promotes KRAS-driven lung cancer metastasis. The antioxidants stimulate metastasis by reducing levels of free heme and stabilizing the transcription factor BACH1. BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells. Targeting BACH1 normalized glycolysis and prevented antioxidant-induced metastasis, while increasing endogenous BACH1 expression stimulated glycolysis and promoted metastasis, also in the absence of antioxidants. We conclude that BACH1 stimulates glycolysis-dependent lung cancer metastasis and that BACH1 is activated under conditions of reduced oxidative stress.
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Antioxidantes/farmacología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Glucólisis/efectos de los fármacos , Neoplasias Pulmonares/patología , Animales , Antioxidantes/administración & dosificación , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Movimiento Celular/efectos de los fármacos , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante)/metabolismo , Hemo/metabolismo , Hexoquinasa/antagonistas & inhibidores , Hexoquinasa/genética , Hexoquinasa/metabolismo , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Ratones , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Factor 2 Relacionado con NF-E2/metabolismo , Metástasis de la Neoplasia , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The systematic structure modification of metal oxides is becoming more attractive, and effective strategies for structural tunning are highly desirable for improving their practical color-modulating energy storage performances. Here, the ability of a stoichiometrically tuned oxide-hydroxide complex of porous vanadium oxide, namely [V2O2+ξ(OH)3-ξ]ξ = 0:3 for multifunctional electrochromic supercapacitor application is demonstrated. Theoretically, the pre-optimized oxide complex is synthesized using a simple wet chemical etching technique in its optimized stoichiometry [V2O2+ξ(OH)3-ξ] with ξ = 0, providing more electroactive surface sites. The multifunctional electrode shows a high charge storage property of 610 Fg-1 at 1A g-1, as well as good electrochromic properties with high color contrast of 70% and 50% at 428 and 640 nm wavelengths, faster switching, and high coloration efficiency. When assembled in a solid-state symmetric electrochromic supercapacitor device, it exhibits an ultrahigh power density of 1066 mWcm-2, high energy density of 246 mWhcm-2, and high specific capacitance of 290 mFcm-2 at 0.2 mAcm-2. A prepared prototype device displays red when fully charged, green when half charged, and blue when fully discharged. A clear evidence of optimizing the multifunctional performance of electrochromic supercapacitor by stoichiometrical tuning is presented along with demonstrating a device prototype of a 25 cm2 large device for real-life applications.
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It is always interesting to understand how the interplay between two perturbations, affects any physical process and gets manifested in a semiconductor. Temperature- and wavelength-dependent Raman Spectromicroscopy was performed on heavily-doped Si to reveal an unusual anti-anharmonic effect. Additionally, the energy dispersive behaviour of Fano coupling strength was also studied and its possible interrelation with the observed anti-anharmonic effect was explored. A systematic study revealed that at the different excitation wavelengths, the strength of the Fano interaction was different, where the involved electron-phonon (Fano-Fano-interferon) bound states were counted together with different energies. By understanding how the interplay manifests in terms of the Raman line shape, a method to calculate the Fano-interferon dissociation energy was developed. The slope of the Raman linewidth at different excitation wavelengths with temperature showed a negative temperature coefficient and sign reversal on decreasing the doping concentration. A wavelength-dependent empirical relation is proposed to calculate the required thermal energy, required to dissociate the electron-phonon bound state.
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The Fermi energy is known to be dependent on doping and temperature, but finding its value and corresponding thermal Fermi shift experimentally is not only difficult but is virtually impossible if one attempts their simultaneous determination. We report that temperature dependent Raman spectromicroscopy solves the purpose easily and proves to be a powerful technique to determine the position and temperature associated Fermi shift in an extrinsic semiconductor as demonstrated for silicon in the present study. The typical asymmetrically broadened Raman spectral line-shape from sufficiently doped n- and p-type silicon contains the information about the Fermi level position through its known association with the Fano coupling strength. Thus, Raman line-shape parameters, the terms quantify the Fano-coupling, have been used as experimental observables to reveal the value of the Fermi energy and consequent thermal Fermi shift. A simple formula has been developed based on existing established theoretical frameworks that can be used to calculate the position of the Fermi level. The proposed Raman spectroscopy-based formulation applies well for n- and p-type silicon. The calculated Fermi level position and its temperature dependent variation are consistent with the existing reports.
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MicroRNAs of the miR-16 and miR-34 families have been reported to inhibit cell cycle progression, and their loss has been linked to oncogenic transformation. Utilizing a high-throughput, genome-wide screen for miRNAs and mRNAs that are differentially regulated in osteosarcoma (OS) cell lines, we report that miR-449a and miR-424, belonging to the miR-34 and miR-16 families, respectively, target the major S/G2 phase cyclin, cyclin A2 (CCNA2), in a bipartite manner. We found that the 3'-UTR of CCNA2 is recognized by miR-449a, whereas the CCNA2 coding region is targeted by miR-424. Of note, we observed loss of both miR-449a and miR-424 in OS, resulting in derepression of CCNA2 and appearance of aggressive cancer phenotypes. Ectopic expression of miR-449a and miR-424 significantly decreased cyclin A2 levels and inhibited proliferation rate, migratory potential, and colony-forming ability of OS cells. To further probe the roles of miR-449a and miR-424 in OS, we developed an OS mouse model by intraosseous injection of U2OS cells into the tibia bone of NOD-scid mice, which indicated that miR-449a and miR-424 co-expression suppresses tumor growth. On the basis of this discovery, we analyzed the gene expression of human OS biopsy samples, revealing that miR-449a and miR-424 are both down-regulated, whereas cyclin A2 is significantly up-regulated in these OS samples. In summary, the findings in our study highlight that cyclin A2 repression by miRNAs of the miR-16 and miR-34 families is lost in aggressive OS.
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Neoplasias Óseas/genética , Ciclina A2/metabolismo , MicroARNs/fisiología , Osteosarcoma/genética , Regiones no Traducidas 3' , Animales , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Línea Celular , Línea Celular Tumoral , Proliferación Celular , Replicación del ADN , Modelos Animales de Enfermedad , Regulación hacia Abajo , Fase G1 , Fase G2 , Redes Reguladoras de Genes , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID , MicroARNs/genética , Osteosarcoma/metabolismo , Osteosarcoma/patología , ARN Mensajero/genética , Fase SRESUMEN
Two colonies of Bacillus subtilis of identical strains growing adjacent to each other on an agar plate exhibit two distinct types of interactions: they either merge as they grow or demarcation occurs leading to formation of a line of demarcation at the colony fronts. The nature of this interaction depends on the agar concentration in the growth medium and the initial separation between the colonies. When the agar concentration was 0.67% or lower, the two sibling colonies were found to always merge. At 1% or higher concentrations, the colonies formed a demarcation line only when their initial separation was 20 mm or higher. Interactions of a colony with solid structures and liquid drops have indicated that biochemical factors rather than the presence of physical obstacles are responsible for the demarcation line formation. A reaction diffusion model has been formulated to predict if two sibling colonies will form a demarcation line under given agar concentration and initial separation. The model prediction agrees well with experimental findings and generates a dimensionless phase diagram containing merging and demarcation regimes. The phase diagram is in terms of a dimensionless initial separation, d[combining macron], and a dimensionless diffusion coefficient, D[combining macron], of the colonies. The phase boundary between the two interaction regimes can be described by a power law relation between d[combining macron] and D[combining macron].
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Agar/química , Bacillus subtilis/fisiología , Bacillus subtilis/clasificación , Técnicas Bacteriológicas , Medios de Cultivo , Difusión , Modelos Biológicos , MovimientoRESUMEN
The tumor microenvironment is characterized by nutrient-deprived conditions in which the cancer cells have to adapt for survival. Serum starvation resembles the growth factor deprivation characteristic of the poorly vascularized tumor microenvironment and has aided in the discovery of key growth regulatory genes and microRNAs (miRNAs) that have a role in the oncogenic transformation. We report here that miR-874 down-regulates the major G1/S phase cyclin, cyclin E1 (CCNE1), during serum starvation. Because the adaptation of cancer cells to the tumor microenvironment is vital for subsequent oncogenesis, we tested for miR-874 and CCNE1 interdependence in osteosarcoma cells. We observed that miR-874 inhibits CCNE1 expression in primary osteoblasts, but in aggressive osteosarcomas, miR-874 is down-regulated, leading to elevated CCNE1 expression and appearance of cancer-associated phenotypes. We established that loss of miR-874-mediated control of cyclin E1 is a general feature of osteosarcomas. The down-regulation of CCNE1 by miR-874 is independent of E2F transcription factors. Restoration of miR-874 expression impeded S phase progression, suppressing aggressive growth phenotypes, such as cell invasion, migration, and xenograft tumors, in nude mice. In summary, we report that miR-874 inhibits CCNE1 expression during growth factor deprivation and that miR-874 down-regulation in osteosarcomas leads to CCNE1 up-regulation and more aggressive growth phenotypes.
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Ciclina E/fisiología , MicroARNs/fisiología , Proteínas Oncogénicas/fisiología , Osteosarcoma/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular , Transformación Celular Neoplásica/genética , Ciclina E/genética , Ciclina G1/metabolismo , Regulación hacia Abajo , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Puntos de Control de la Fase G1 del Ciclo Celular/fisiología , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Ratones , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Oncogénicas/genética , Oncogenes , Osteosarcoma/genética , Fase SRESUMEN
The primary eukaryotic single-stranded DNA-binding protein, Replication protein A (RPA), binds to single-stranded DNA at the sites of DNA damage and recruits the apical checkpoint kinase, ATR via its partner protein, ATRIP. It has been demonstrated that absence of RPA incapacitates the ATR-mediated checkpoint response. We report that in the absence of RPA, human single-stranded DNA-binding protein 1 (hSSB1) and its partner protein INTS3 form sub-nuclear foci, associate with the ATR-ATRIP complex and recruit it to the sites of genomic stress. The ATRIP foci formed after RPA depletion are abrogated in the absence of INTS3, establishing that hSSB-INTS3 complex recruits the ATR-ATRIP checkpoint complex to the sites of genomic stress. Depletion of homologs hSSB1/2 and INTS3 in RPA-deficient cells attenuates Chk1 phosphorylation, indicating that the cells are debilitated in responding to stress. We have identified that TopBP1 and the Rad9-Rad1-Hus1 complex are essential for the alternate mode of ATR activation. In summation, we report that the single-stranded DNA-binding protein complex, hSSB1/2-INTS3 can recruit the checkpoint complex to initiate ATR signaling.
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Proteínas de Unión al ADN/metabolismo , Proteínas Mitocondriales/metabolismo , Proteína de Replicación A/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Línea Celular , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1) , ADN de Cadena Simple/metabolismo , Células HeLa , Humanos , Proteínas Quinasas/metabolismo , Interferencia de ARN , Proteína de Replicación A/genética , Transducción de Señal , Estrés Fisiológico/genéticaRESUMEN
Conventional ion-selective electrodes with a liquid junction have the disadvantage of potential drift. All-solid-state ion-selective electrodes with solid contact in between the metal electrode and the ion-selective membrane offer high capacitance or conductance to enhance potential stability. Solution-casted chitosan/Prussian blue nanocomposite (ChPBN) was employed as the solid contact layer for an all-solid-state sodium ion-selective electrode in a potentiometric sodium ion sensor. Morphological and chemical analyses confirmed that the ChPBN is a macroporous network of chitosan that contains abundant Prussian blue nanoparticles. Situated between a screen-printed carbon electrode and a sodium-ionophore-filled polyvinylchloride ion-selective membrane, the ChPBN layer exhibited high redox capacitance and fast charge transfer capability, which significantly enhanced the performance of the sodium ion-selective electrode. A good Nernstian response with a slope of 52.4 mV/decade in the linear range from 10-4-1 M of NaCl was observed. The stability of the electrical potential of the new solid contact was tested by chronopotentiometry, and the capacitance of the electrode was 154 ± 4 µF. The response stability in terms of potential drift was excellent (1.3 µV/h) for 20 h of continuous measurement. The ChPBN proved to be an efficient solid contact to enhance the potential stability of the all-solid-state ion-selective electrode.
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Sustainable development is the primary key to address global energy challenges. Though the scientific community is engaged in developing efficient ways to not only maximize energy production from natural resources like sun, wind, water, etc. but also to make all the electronic gadgets power efficient, despite all this, the materials used in most of the electronic devices are largely produced using various materials processing techniques and semiconductors, polymers, dielectrics, etc. which again increases the burden on energy and in turn affects the environment. While addressing these challenges, it is very important to explore the possibility to directly, or with minimum processing, utilize the potential of natural resources in the development of electronic devices. Recent articles are focused on the development of herbal electronic devices that essentially implement natural resources, like plants, leaves, etc., either in their raw or extracted form in the device assembly. This review encompasses the recent research developments around herbal electronic devices. Furthermore, herbal electronics has been discussed for several functional applications including electrochromism, energy storage, memresistor, LED, solar cell, water purification, pressure sensor, etc. Moreover, advantages, disadvantages, and challenges encountered in the realization of "herbal electronics" have been discussed at length.
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Electrónica , Materiales Biocompatibles/química , Ensayo de Materiales , Tamaño de la Partícula , Equipos y Suministros EléctricosRESUMEN
Eukaryotic ribosome assembly is an intricate process that involves four ribosomal RNAs, 80 ribosomal proteins, and over 200 biogenesis factors that take part in numerous interdependent steps. This complexity creates a large genetic space in which pathogenic mutations can occur. Dead-end ribosome intermediates that result from biogenesis errors are rapidly degraded, affirming the existence of quality control pathway(s) that monitor ribosome assembly. However, the factors that differentiate between on-path and dead-end intermediates are unknown. We engineered a system to perturb ribosome assembly in human cells and discovered that faulty ribosomes are degraded via the ubiquitin proteasome system. We identified ZNF574 as a key component of a novel quality control pathway, which we term the Ribosome Assembly Surveillance Pathway (RASP). Loss of ZNF574 results in the accumulation of faulty biogenesis intermediates that interfere with global ribosome production, further emphasizing the role of RASP in protein homeostasis and cellular health.
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Here, we report the design and synthesis of a redox-active multifunctional ionic porous organic polymer iPOP-Bpy with exchangeable Br- ions, incorporating viologen as a redox-active building block. The material shows not only excellent iodine uptake capacity in the vapor phase (540 wt %) but also in the organic (1009.77 mg g-1) and aqueous phases (3921.47 mg g-1) with very fast adsorption kinetics in all cases. The material also shows its utility in being used as a solid-state NH3 vapor sensor as it shows very fast color switching in the presence of NH3 vapor. Furthermore, the material found application as a p-type complementary electrochromic electrode and was fabricated into a bilayer device. Excellent coloration efficiency, high switching speed, and good color contrast were obtained as investigated using bias-dependent optical and spectroelectrochemical studies, paving the way for fabricating power-efficient solid-state electrochromic devices.
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BACKGROUND: Fetal midgut volvulus is an uncommon yet potentially life-threatening condition. Prenatal diagnosis may pose a challenge, due to the paucity of specific signs and symptoms. Timely prenatal diagnosis of this condition is imperative to prevent fetal mortality and morbidity. CASE PRESENTATION: We present a rare case report of fetal midgut volvulus, malrotation, and intestinal obstruction at 32 weeks of gestation in a 31-year-old multigravida Indian patient who presented with decreased fetal movements. Fetal ultrasound revealed midgut volvulus with proximal bowel obstruction and polyhydramnios. The patient underwent emergency surgery, which revealed intestinal malrotation and confirmed the diagnosis of midgut volvulus. Untwisting of the volvulus was done followed by Ladd's procedure. Follow-up postoperative ultrasound was unremarkable. CONCLUSIONS: Delay in the diagnosis of fetal midgut volvulus leads to poor fetal and maternal outcomes. Hence, it is vital for radiologists, sonologists, and obstetricians to be aware of this condition while performing fetal sonography. Prompt diagnosis and surgical intervention are vital to reduce the morbidity and mortality associated with this condition.
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Obstrucción Intestinal , Vólvulo Intestinal , Embarazo , Femenino , Humanos , Adulto , Vólvulo Intestinal/diagnóstico por imagen , Vólvulo Intestinal/cirugía , Vólvulo Intestinal/complicaciones , Diagnóstico Prenatal , Obstrucción Intestinal/etiología , Ultrasonografía Prenatal/efectos adversos , FetoRESUMEN
A nonlinear Fano interaction has been reported here which is manifest in terms of a parabolic temperature-dependent phonon decay process observable in terms of a Raman spectral parameter. Temperature-dependent Raman spectroscopic studies have been carried out on heavily and moderately doped crystalline silicon to investigate the behavior of anharmonic phonon decay in semiconductor systems where Fano interactions are present inherently. Systematic study reveals that in heavily doped systems an interferon-mediated decay route exists for cold phonons present at lower temperatures (<475 K) where Fano coupling is stronger and dominates over the typical multiple-phonon decay process. On the other hand, the anharmonic phonon decay remains the predominant process at higher temperatures irrespective of the doping level. Temperature-dependent phonon self-energy has been calculated using experimentally observed Raman line-shape parameters to validate the fact that the nonlinear decay of phonons through interferon mediation is a thermodynamically favorable process at low temperatures.
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A dual purpose solid state electrochromic diode has been fabricated using polythiophene (P3HT) and ethyl Viologen (EV), predoped with multiwalled carbon nanotubes (MWCNTs) and MoS2. The device has been designed by considering two important aspects, first, the complementary redox activity of P3HT and EV and second, the electron holding properties of MoS2 and MWCNTs. The latter is found to enhance the electrochromic performance of the solid state device. On the other hand, the complementary redox nature gives the asymmetric diodic I-V characteristic to the device which has been exploited to use the electrochromic device for rectification application. The MoS2 nanoflower and MWCNTs are synthesized by one-step hydrothermal and pyrolysis techniques and well characterized by scanning electron microscopy (SEM), X-ray analysis (XRD), and Raman spectroscopy. Electrochromic properties of the device have been studied in detail to reveal an improvement in device performance in terms of faster speed and high coloration efficiency and color contrast. In situ bias-dependent Raman spectroscopy has been performed to understand the operation mechanism of the electrochromic diode which reveals (bi-)polaron formation as a result of dynamic doping eventually leading to color change. A half-wave rectifier has been realized from the electrochromic diode which rectifies an AC voltage of frequency 1 Hz or less making it suitable for low frequency operation. The study opens a new possibility to design and fabricate multipurpose frequency selective electrochromic rectifiers.
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Excitation wavelength-dependent Raman spectroscopy has been carried out to study electron-phonon interaction (Fano resonance) in multi-layered bulk 2H-MoS2 nano-flakes. The electron-phonon coupling is proposed to be caused due to interaction between energy of an excitonic quasi-electronic continuum and the discrete one phonon, first-order Raman modes of MoS2. It is proposed that an asymmetrically broadened Raman line shape obtained by 633 nm laser excitation is due to electron-phonon interaction whose electronic continuum is provided by the well-known A and B excitons. Typical wavelength-dependent Raman line shape has been observed, which validates and quantifies the Fano interaction present in the samples. The experimentally obtained Raman scattering data show very good agreement with the theoretical Fano-Raman line-shape functions and help in estimating the coupling strength. Values of the electron-phonon interaction parameter obtained, through line-shape fitting, for the two excitation wavelengths have been compared and shown to have generic Fano-type dependence on the excitation wavelength.
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Optical and electrochemical properties from Cassia and Giloy leaves' raw extract have been studied, and they show similar properties as UV absorber but different emission properties, under UV excitation, even though they appear the same in natural light. Giloy and Cassia extracts show red and green luminescence, respectively, under UV excitation. Like the appearance, their redox properties are also similar, which shows that both can act as antioxidants. Raman spectroscopy and excitation wavelength dependent photoluminescence data have been compared. The difference in relative emission intensities have been explained based on the presence of corresponding color centers in different ratios in the two leaves.
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Cassia , Senna , Tinospora , Cassia/química , Luminiscencia , Extractos Vegetales/análisis , Hojas de la Planta/química , Tinospora/químicaRESUMEN
We report on a new class of core-shell electrocatalysts for the oxygen-reduction reaction. These electrocatalysts comprise a Pt monolayer shell and ordered intermetallic compounds cores and have enhanced activity and stability compared with conventional ones. These advantages are derived from combining the unique properties of Pt monolayer catalysts (high activity, low metal content) and of the intermetallic compounds (high stability and, possibly, low price). This method holds excellent potential for creating efficient fuel cell electrocatalysts.
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Membranas Artificiales , Nanopartículas del Metal/química , Oxígeno/química , Platino (Metal)/química , Catálisis , Electroquímica , Electrodos , Oxidación-ReducciónRESUMEN
High quality single crystal PtM (M = Bi or Pb) (100) and (001) surfaces have been generated from solid state bulk materials. The specific orientation was determined via X-ray Laue back-reflection and the miscut angles of the single crystal surfaces were â¼0.3° which was limited by instrumental resolution. The PtM (001) electrode had a Pt termination based on cyclic voltammetric (CV) profiles. The surface structure and composition of single crystal PtM surfaces have been studied by synchrotron-based in situ X-ray grazing incidence diffraction (GID) under active electrochemical control. Cycling of the potential to increasingly high values resulted in dramatic changes to the surface crystalline structure and composition of these single crystal electrodes. Well-defined Pt nano-domains in a hexagonal pattern with a 23° offset angle to the substrate were formed on the PtM (001) surface after electrochemical pretreatment in supporting electrolyte (0.1M H(2)SO(4)), especially for E(ulp) (E(ulp) = upper limit potential) of +0.80 V or beyond. From an analysis of the diffraction peaks, the size of the Pt domains was estimated to be â¼15 nm. The Pt domain formation on the single crystal surfaces, similar to results on polycrystalline intermetallic phases, was due to leaching of the less-noble elements (Bi or Pb) from the intermetallic matrix and sintering of the Pt atoms on the surfaces. On the other hand, Pt domains with a preferential direction but no offset angle to the substrate were formed on PtM (100) surface after similar electrochemical pretreatment. PtBi and PtPb single crystal surfaces exhibited different anisotropic electrocatalytic activities towards the electrooxidation of formic acid and other potential fuels for fuel cell applications. The reactivities of these single crystal electrodes towards the oxidation of small organic molecules were a function of E(ulp) values and maximal activities were around +0.60 V for PtBi(001) surface which might be due to formation of partially oxidized surfaces but around +1.20 V for PtPb(100) and (001) surfaces which might be due to the increasing boundary lines of Pt and PtPb grains.