RESUMEN

Cavity optomechanics has demonstrated remarkable capabilities, such as measurement and control of mechanical motion at the quantum level. Yet many compelling applications of optomechanics-such as microwave-to-telecom wavelength conversion, quantum memories, materials studies, and sensing applications-require hybrid devices, where the optomechanical system is coupled to a separate, typically condensed matter, system. Here, we demonstrate such a hybrid optomechanical system, in which a mesoscopic ferromagnetic needle is integrated with an optomechanical torsional resonator. Using this system we quantitatively extract the magnetization of the needle, not known a priori, demonstrating the potential of this system for studies of nanomagnetism. Furthermore, we show that we can magnetically dampen its torsional mode from room-temperature to 11.6 K-improving its mechanical response time without sacrificing torque sensitivity. Future extensions will enable studies of high-frequency spin dynamics and broadband wavelength conversion via torque mixing.

RESUMEN

Scanning tunnelling microscopy observations resolve the structure and dynamics of metallic glass Cu100-xHfx films and demonstrate scanning tunnelling microscopy control of aging at a metallic glass surface. Surface clusters exhibit heterogeneous hopping dynamics. Low Hf concentration films feature an aged surface of larger, slower clusters. Argon ion-sputtering destroys the aged configuration, yielding a surface in constant fluctuation. Scanning tunnelling microscopy can locally restore the relaxed state, allowing for nanoscale lithographic definition of aged sections.

RESUMEN

A universal, torque-mixing method for magnetic resonance spectroscopy is presented. In analogy to resonance detection by magnetic induction, the transverse component of a precessing dipole moment can be measured in sensitive broadband spectroscopy, here using a resonant mechanical torque sensor. Unlike induction, the torque amplitude allows equilibrium magnetic properties to be monitored simultaneously with the spin dynamics. Comprehensive electron spin resonance spectra of a single-crystal, mesoscopic yttrium iron garnet disk at room temperature reveal assisted switching between magnetization states and mode-dependent spin resonance interactions with nanoscale surface imperfections. The rich detail allows analysis of even complex three-dimensional spin textures. The flexibility of microelectromechanical and optomechanical devices combined with broad generality and capabilities of torque-mixing magnetic resonance spectroscopy offers great opportunities for development of integrated devices.

RESUMEN

Optomechanical transduction has demonstrated its supremacy in probing nanomechanical displacements. In order to apply nano-optomechanical systems (NOMS) as force and mass sensors, knowledge about the transduction responsivity (i.e. the change in measured optical transmission with nanomechanical displacement) and its tradeoffs with system design is paramount. We compare the measured responsivities of NOMS devices with varying length, optomechanical coupling strength gom, and optical cavity properties. Cantilever beams 1.5 to 5 µm long are fabricated 70 to 160 nm from a racetrack resonator optical cavity and their thermomechanical (TM) noise signals are measured. We derive a generic expression for the transduction responsivity of the NOMS in terms of optical and mechanical system parameters such as finesse, optomechanical coupling constant, and interaction length. The form of the expression holds direct insight as to how these parameters affect the responsivity. With this expression, we obtain the optomechanical coupling constants using only measurements of the TM noise power spectra and optical cavity transmission slopes. All optical pump/probe operation is also demonstrated in our side-coupled cantilever-racetrack NOMS. Finally, to assess potential operation in a gas sensing environment, the TM noise signal of a device is measured at atmospheric pressure.

RESUMEN

The androgen receptor (AR) is a transcription factor that employs many diverse interactions with coregulatory proteins in normal physiology and in prostate cancer (PCa). The AR mediates cellular responses in association with chromatin complexes and kinase cascades. Here we report that the nuclear matrix protein, scaffold attachment factor B1 (SAFB1), regulates AR activity and AR levels in a manner that suggests its involvement in PCa. SAFB1 mRNA expression was lower in PCa in comparison with normal prostate tissue in a majority of publicly available RNA expression data sets. SAFB1 protein levels were also reduced with disease progression in a cohort of human PCa that included metastatic tumors. SAFB1 bound to AR and was phosphorylated by the MST1 (Hippo homolog) serine-threonine kinase, previously shown to be an AR repressor, and MST1 localization to AR-dependent promoters was inhibited by SAFB1 depletion. Knockdown of SAFB1 in androgen-dependent LNCaP PCa cells increased AR and prostate-specific antigen (PSA) levels, stimulated growth of cultured cells and subcutaneous xenografts and promoted a more aggressive phenotype, consistent with a repressive AR regulatory function. SAFB1 formed a complex with the histone methyltransferase EZH2 at AR-interacting chromatin sites in association with other polycomb repressive complex 2 (PRC2) proteins. We conclude that SAFB1 acts as a novel AR co-regulator at gene loci where signals from the MST1/Hippo and EZH2 pathways converge.

Asunto(s)

Factor de Crecimiento de Hepatocito/metabolismo , Proteínas de Unión a la Región de Fijación a la Matriz/metabolismo , Proteínas Asociadas a Matriz Nuclear/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Receptores Androgénicos/metabolismo , Receptores de Estrógenos/metabolismo , Animales , Línea Celular Tumoral , Proteína Potenciadora del Homólogo Zeste 2 , Regulación Neoplásica de la Expresión Génica , Factor de Crecimiento de Hepatocito/genética , Histona Metiltransferasas , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/genética , Histonas/metabolismo , Humanos , Masculino , Proteínas de Unión a la Región de Fijación a la Matriz/genética , Ratones , Ratones Desnudos , Proteínas Asociadas a Matriz Nuclear/genética , Complejo Represivo Polycomb 2/genética , Complejo Represivo Polycomb 2/metabolismo , Regiones Promotoras Genéticas , Antígeno Prostático Específico/genética , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/enzimología , Neoplasias de la Próstata Resistentes a la Castración/genética , Proteínas Proto-Oncogénicas/genética , Receptores Androgénicos/genética , Receptores de Estrógenos/genética , Transcripción Genética

RESUMEN

After neuronal injury or death glial cells become reactive, exhibiting dramatic changes in morphology and patterns of gene expression and ultimately engulfing neuronal debris. Rapid clearance of degenerating neuronal material is thought to be crucial for suppression of inflammation and promotion of functional recovery. Here we demonstrate that Drosophila c-Jun N-terminal kinase (dJNK) signaling is a critical in vivo mediator of glial engulfment activity. In response to axotomy, we find glial dJNK signals through a cascade involving the upstream mitogen-activated protein kinase kinase kinases Slipper and Tak1, the mitogen-activated protein kinase kinase MKK4, and ultimately the Drosophila activator protein 1 (AP-1) transcriptional complex composed of Jra and Kayak to initiate glial phagocytosis of degenerating axons. Interestingly, loss of dJNK also blocked injury-induced upregulation of Draper levels in glia, and glial-specific overexpression of Draper was sufficient to rescue engulfment defects associated with loss of dJNK signaling. This work identifies that the dJNK pathway is a novel mediator of glial engulfment activity and a primary role for the glial Slipper/Tak1 →MKK4 →dJNK →dAP-1 signaling cascade appears to be activation of draper expression after axon injury.

Asunto(s)

Proteínas de Drosophila/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas de la Membrana/metabolismo , Neuroglía/metabolismo , Fagocitosis/genética , Animales , Apoptosis , Axones/metabolismo , Axotomía , Encéfalo/metabolismo , Lesiones Encefálicas/genética , Lesiones Encefálicas/metabolismo , Drosophila , Proteínas de Drosophila/biosíntesis , Proteínas de Drosophila/genética , Proteínas Quinasas JNK Activadas por Mitógenos/genética , MAP Quinasa Quinasa 4/genética , MAP Quinasa Quinasa 4/metabolismo , Quinasas Quinasa Quinasa PAM/genética , Quinasas Quinasa Quinasa PAM/metabolismo , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/genética , Neuroglía/citología , Interferencia de ARN , ARN Interferente Pequeño , Transducción de Señal/genética , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo

RESUMEN

Prostate cancer is a major health concern as it has the second highest incidence rate among cancers in men. Despite progress in tumor diagnostics and therapeutic approaches, prognosis for men with advanced disease remains poor. In this review we provide insight into the changes of the intermediary metabolism in normal prostate and prostate cancer. In contrast to normal cells, prostate cancer cells are reprogrammed for optimal energy-efficiency with a functional Krebs cycle and minimal apoptosis rates. A key element in this relationship is the uniquely high zinc level of normal prostate epithelial cells. Zinc is transported by the SLC30 and SLC39 families of zinc transporters. However, in prostate cancer the intracellular zinc content is remarkably reduced and expression levels of certain zinc transporters are altered. Here, we summarize the role of different zinc transporters in the development of prostate cancer.

Asunto(s)

Proteínas de Transporte de Catión/metabolismo , Ciclo del Ácido Cítrico/fisiología , Metabolismo Energético/fisiología , Regulación Neoplásica de la Expresión Génica/fisiología , Neoplasias de la Próstata/metabolismo , Zinc/metabolismo , Humanos , Masculino , Modelos Biológicos

RESUMEN

Quantitative characterization of intrinsic and artificial defects in ferromagnetic structures is critical to future magnetic storage based on vortices or domain walls moving through nanostructured devices. Using torsional magnetometry, we observe finite size modifications to the Barkhausen effect in the limiting case of a single vortex core interacting with individual pointlike pinning sites in a magnetic thin film. The Barkhausen effect in this limit becomes a quantitative two-dimensional nanoscale probe of local energetics in the film. Tailoring the pinning potential using single-point focused ion beam implantation demonstrates control of the effect and points the way to integrated magneto-mechanical devices incorporating quantum pinning effects.

RESUMEN

Ubiquitination of epidermal growth factor receptor (EGFR) is required for downregulation of the receptor by endocytosis. Impairment of this pathway results in constitutively active EGFR, which is associated with carcinogenesis, particularly in lung cancer. We previously demonstrated that the deubiquitinating enzyme ubiquitin-specific protease 2a (USP2a) has oncogenic properties. Here, we show a new role for USP2a as a regulator of EGFR endocytosis. USP2a localizes to early endosomes and associates with EGFR, stabilizing the receptor, which retains active downstream signaling. HeLa cells transiently expressing catalytically active, but not mutant (MUT), USP2a show increased plasma membrane-localized EGFR, as well as decreased internalized and ubiquitinated EGFR. Conversely, USP2a silencing reverses this phenotype. Importantly, USP2a prevents the degradation of MUT in addition to wild-type EGFR. Finally, we observed that USP2a and EGFR proteins are coordinately overexpressed in non-small cell lung cancers. Taken together, our data indicate that USP2a antagonizes EGFR endocytosis and thus amplifies signaling activity from the receptor. Our findings suggest that regulation of deubiquitination could be exploited therapeutically in cancers overexpressing EGFR.

Asunto(s)

Endocitosis/fisiología , Endopeptidasas/fisiología , Receptores ErbB/metabolismo , Proteolisis , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Regulación hacia Abajo/genética , Endocitosis/genética , Endopeptidasas/genética , Endopeptidasas/metabolismo , Receptores ErbB/genética , Regulación Neoplásica de la Expresión Génica , Células HeLa , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Estabilidad Proteica , Ubiquitina Tiolesterasa , Proteasas Ubiquitina-Específicas , Ubiquitinación/genética

RESUMEN

The addition of minute amounts of chemically inert polyacrylamide polymer to liquids results in large instabilities under steady electro-osmotic pumping through 2 : 1 constrictions, demonstrating that laminar flow conditions can be broken in electro-osmotic flow of viscoelastic material. By excluding shear and imposing symmetry we create a platform where only elongational viscoelastic instabilities, and diffusion, affect mixing. In contrast to earlier studies with significant shear that found up to orders of magnitude increase in mixing we find that inclusion of polymers excites large viscoelastic instabilities yet mixing is reduced relative to polymer-free liquids. The absolute decrease in mixing we find is consistent with the understanding that adding polymer increases viscosity while viscoelastic flows progress towards elastic turbulence, a type of mild (Batchelor) turbulence, and indicates that electro-osmotic pumped devices are an ideal platform for studying viscoelastic instabilities without supplementary factors.

Asunto(s)

Mezclas Complejas/química , Microfluídica/métodos , Modelos Químicos , Soluciones/química , Simulación por Computador , Módulo de Elasticidad , Resistencia al Corte , Viscosidad

RESUMEN

In this issue of Oncogene, Mollinedo and co-workers present promising evidence that cholesterol-sensitive signaling pathways involving lipid rafts can be therapeutically targeted in multiple myeloma. Because the pathways considered in their study are used by other types of tumor cells, one implication of this report is that cholesterol-targeting approaches may be applicable to other malignancies.

Asunto(s)

Colesterol/metabolismo , Mieloma Múltiple/terapia , Humanos , Mieloma Múltiple/metabolismo , Transducción de Señal

RESUMEN

Fluid transport in microfluidic systems typically is laminar due to the low Reynolds number characteristic of the flow. The inclusion of suspended polymers imparts elasticity to fluids, allowing instabilities to be excited when substantial polymer stretching occurs. For high molecular weight polymer chains we find that flow velocities achievable by standard electro-osmotic pumping are sufficient to excite extensional instabilities in dilute polymer solutions. We observe a dependence in measured fluctuations on polymer concentration which plateaus at a threshold corresponding to the onset of significant molecular crowding in macromolecular solutions; plateauing occurs well below the overlap concentration. Our results show that electro-osmotic flows of complex fluids are disturbed from the steady regime, suggesting potential for enhanced mixing and requiring care in modeling the flow of complex liquids such as biopolymer suspensions.

RESUMEN

We present details of an apparatus for capacitive detection of biomaterials in microfluidic channels operating at microwave frequencies where dielectric effects due to interfacial polarization are minimal. A circuit model is presented, which can be used to adapt this detection system for use in other microfluidic applications and to identify ones where it would not be suitable. The detection system is based on a microwave coupled transmission line resonator integrated into an interferometer. At 1.5 GHz the system is capable of detecting changes in capacitance of 650 zF with a 50 Hz bandwidth. This system is well suited to the detection of biomaterials in a variety of suspending fluids, including phosphate-buffered saline. Applications involving both model particles (polystyrene microspheres) and living cells-baker's yeast (Saccharomyces cerevisiae) and Chinese hamster ovary cells-are presented.

RESUMEN

Nanoelectromechanical systems could have applications in fields as diverse as ultrasensitive mass detection and mechanical computation, and can also be used to explore fundamental phenomena such as quantized heat conductance and quantum-limited displacement. Most nanomechanical studies to date have been performed in the frequency domain. However, applications in computation and information storage will require transient excitation and high-speed time-domain operation of nanomechanical systems. Here we show a time-resolved optical approach to the transduction of ultrahigh-frequency nanoelectromechanical systems, and demonstrate that coherent control of nanomechanical oscillation is possible through appropriate pulse programming. A series of cantilevers with resonant frequencies ranging from less than 10 MHz to over 1 GHz are characterized using the same pulse parameters.

Asunto(s)

Electrónica/instrumentación , Microondas , Nanotecnología/instrumentación , Algoritmos , Diseño de Equipo , Fenómenos Mecánicos , Nanoestructuras , Oscilometría , Transductores

RESUMEN

The mechanical behavior of cells offers insight into many aspects of their properties. We propose an approach to the mechanical analysis of cells that uses a combination of electromanipulation for stimulus and capacitance for sensing. To demonstrate this approach, polystyrene spheres and yeast cells flowing in a 25 mumx100 mum microfluidic channel were detected by a perpendicular pair of gold thin film electrodes in the channel, spaced 25 mum apart. The presence of cells was detected by capacitance changes between the gold electrodes. The capacitance sensor was a resonant coaxial radio frequency cavity (2.3 GHz) coupled to the electrodes. The presence of yeast cells (Saccharomyces cerevisiae) and polystyrene spheres resulted in capacitance changes of approximately 10 and 100 attoFarad (aF), respectively, with an achieved capacitance resolution of less than 2 aF in a 30 Hz bandwidth. The resolution is better than previously reported in the literature, and the capacitance changes are in agreement with values estimated by finite element simulations. Yeast cells were trapped using dielectrophoretic forces by applying a 3 V signal at 1 MHz between the electrodes. After trapping, the cells were displaced using amplitude and frequency modulated voltages to produce modulated dielectrophoretic forces. Repetitive displacement and relaxation of these cells was observed using both capacitance and video microscopy.

RESUMEN

An extension of the classical Ising model to a situation including a source of spin-flip excitations localized on the scale of individual spins is considered. The scenario is realized by scanning tunneling microscopy of the Si(100) surface at low temperatures. Remarkable details, corresponding to the passage of phasons through the tunnel junction, are detected by the STM within the short span between two atoms comprising an individual Si dimer.

RESUMEN

The dynamic behavior in the evolving pattern of thermally assisted, nonequilibrium domains in magnetic thin-film elements undergoing ultrafast 180 degrees magnetization reversal was studied. Magnetization reversal enters a fully dynamic regime when the external field conditions are changed much faster than the sample is able to respond. The dynamic pathway develops a complexity not seen in quasistatic reversal but still retains a high level of order with well-developed dynamic domain patterns formed in response to subnanosecond transitions of the external applied magnetic field.

RESUMEN

Physical forces play a critical role in the survival and proliferation of many cell types, including fibroblasts. Gingival fibroblasts are exposed to mechanical stress during mastication, orthodontic tooth movement, and wound healing following periodontal surgery. The aim of this study was to examine the effect of mechanical strain on human gingival fibroblasts (hGF). Cells were subjected to short-term (up to 60 min) and long-term (up to 48 hrs) 20% average elongation at 0.1 Hz. We monitored survival signaling by evaluating the phosphorylation status and localization of Forkhead box (FoxO) family members, which are mediators of apoptosis. We also examined strain-induced proliferation by measuring the level of proliferating cell nuclear antigen (PCNA). We observed that cyclic strain caused the phosphorylation and retention in the cytoplasm of FoxO family members. Moreover, mechanical strain resulted in increased ERK kinase phosphorylation and PCNA expression. In conclusion, cyclic strain delivers anti-apoptotic and proliferative stimuli to hGF.

Asunto(s)

Proteínas de Unión al ADN/metabolismo , Fibroblastos/metabolismo , Encía/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Transducción de Señal/fisiología , Factores de Transcripción/metabolismo , Apoptosis/fisiología , División Celular/fisiología , Tamaño de la Célula/fisiología , Células Cultivadas , Proteína Forkhead Box O1 , Factores de Transcripción Forkhead , Encía/citología , Humanos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Estrés Mecánico , Factores de Tiempo , Translocación Genética

RESUMEN

OBJECTIVES: To determine the diagnostic accuracy of the sperm penetration assay (SPA) and standard semen parameters for subsequent fertilization in in vitro fertilization-embryo transfer (IVF-ET). DESIGN: Prospective study. SETTING: Andrology Laboratory, and university research laboratory. PATIENTS: Two hundred sixteen couples undergoing male-partner screening before IVF-ET (265 cycles). INTERVENTION(S): Male-partner screening (semen analyses [SA] and SPA), standard IVF-ET procedures, follow-up of fertilization in IVF-ET. MAIN OUTCOME MEASURE(S): Diagnostic accuracy of SA and SPA for prediction of fertilization in IVF-ET. RESULT(S): The SPA predicted IVF fertilization with high negative (84%) and positive (98%) predictive rates, and correct prediction in 88% of cycles. In contrast, sperm concentration, motility, morphology, and complete SA showed poor diagnostic accuracy, with correct prediction of IVF fertilization in 64%, 65%, 45%, and 68% of cycles, respectively. CONCLUSION(S): Very low sperm concentration and/or motility were good predictors of poor IVF fertilization, however, low to normal semen parameters were not predictive of successful IVF fertilization. The SPA is a useful screening tool that predicts IVF fertilization with high diagnostic accuracy. The SPA may be useful to discriminate between those couples with a high probability of normal fertilization in IVF and those with a low probability of normal fertilization that may benefit from assisted fertilization by intracytoplasmic sperm injection (ICSI).

Asunto(s)

Transferencia de Embrión , Inyecciones de Esperma Intracitoplasmáticas/métodos , Interacciones Espermatozoide-Óvulo/fisiología , Animales , Cricetinae , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Fertilización/fisiología , Humanos , Masculino , Mesocricetus , Valor Predictivo de las Pruebas , Embarazo , Estudios Prospectivos , Análisis de Regresión , Sensibilidad y Especificidad , Recuento de Espermatozoides , Motilidad Espermática

RESUMEN

A recent study identifies a novel nonautonomous signaling pathway that regulates cell migration and differentiation in early Drosophila mesodermal tissues.

Asunto(s)

Proteínas de Drosophila/metabolismo , Drosophila/embriología , Mesodermo/citología , Transducción de Señal , Animales , Diferenciación Celular , Movimiento Celular , Drosophila/citología , Proteínas de Drosophila/genética , Mesodermo/metabolismo , Morfogénesis