Self-driven soft imaging in liquid by means of photothermal excitation

The use of a laser to induce oscillations of an atomic force microscopy cantilever provides a way to excite the dynamics of the system in a very controlled manner. This excitation scheme has been used to obtain reliable self-sustained oscillations, in air and in liquid environments, and to implement an additional control loop leading to a soft, low-interaction, working mode. The dynamics of the oscillating cantilever has been characterized, both theoretically and experimentally, and the effectiveness of the approach has been verified on a test sample. © 2011 American Institute of Physics.Peer Reviewe

Physics of nanomechanical spectrometry of viruses

There is an emerging need of nanotools able to quantify the mechanical properties of single biological entities. A promising approach is the measurement of the shifts of the resonant frequencies of ultrathin cantilevers induced by the adsorption of the studied biological systems. Here, we present a detailed theoretical analysis to calculate the resonance frequency shift induced by the mechanical stiffness of viral nanotubes. The model accounts for the high surface-to-volume ratio featured by single biological entities, the shape anisotropy and the interfacial adhesion. The model is applied to the case in which tobacco mosaic virus is randomly delivered to a silicon nitride cantilever. The theoretical framework opens the door to a novel paradigm for biological spectrometry as well as for measuring the Young's modulus of biological systems with minimal strains.We acknowledge financial support from the Spanish Science Ministry (MINECO) through projects MAT2012-36197 and from European Research Council through Starting Grant NANOFORCELLS (ERC-StG-2011-278860).Peer Reviewe

House Dust Mite Allergy and the Der p1 Conundrum: A Literature Review and Case Series

The house dustmite (HDM) is globally ubiquitous in human habitats. Thirty-two allergens for Dermatophagoides farinae and 21 for Dermatophagoides pteronyssinus have been detected so far. The present minireview summarizes information about the role of Der p 1 as a key coordinator of the HDM-induced allergic response and reports on a series of Italian patients who are allergic to HDMs. We studied the specific IgE profiles in a population of patients with allergic asthma and rhinitis screened for specific immunotherapy (SIT) for HDMallergies, with the aim of obtaining insights into the pathogenic role of Der p1. Patients co-sensitized to other airborne allergens showed a higher prevalence of asthma (9/12 (75%) vs. 2/7 (29%); p < 0.05) than did HDMmono-sensitized patients. The latter group showed higher Der p1 concentrations than that of the co-sensitized group (p = 0.0360), and a direct correlation between Der p1 and Der p2 (r = 0.93; p = 0.0003) was observed. In conclusion, our study offers insights into the role of Der p1 in a population of patients with allergic rhinitis and asthma who were candidates for SIT. Interestingly, Der p1 positivity was associated with bronchial asthma and co-sensitization

Spatially Multiplexed Micro-Spectrophotometry in Bright Field Mode for Thin Film Characterization

Thickness characterization of thin films is of primary importance in a variety of nanotechnology applications, either in the semiconductor industry, quality control in nanofabrication processes or engineering of nanoelectromechanical systems (NEMS) because small thickness variability can strongly compromise the device performance. Here, we present an alternative optical method in bright field mode called Spatially Multiplexed Micro-Spectrophotometry that allows rapid and non-destructive characterization of thin films over areas of mm2 and with 1 μm of lateral resolution. We demonstrate an accuracy of 0.1% in the thickness characterization through measurements performed on four microcantilevers that expand an area of 1.8 mm2 in one minute of analysis time. The measured thickness variation in the range of few tens of nm translates into a mechanical variability that produces an error of up to 2% in the response of the studied devices when they are used to measure surface stress variations.The authors acknowledge the financial support by European Research Council through Starting Grant NANOFORCELLS (ERC-StG-2011-278860). P. M. Kosaka acknowledges funding from the Fundación General CSIC ComFuturo program. We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI

Expanding the Clinical Spectrum of UBTF-Related Neurodevelopmental Disorder

Objectives: UBTF1 gene encodes for Upstream Binding Transcription Factor, an essential protein for RNA metabolism. A recurrent de novo variant (c.628G&gt;A; p.Glu210Lys) has recently been associated with a childhood-onset neurodegenerative disorder characterized by motor and language regression, ataxia, dystonia, and acquired microcephaly. In this study, we report the clinical, metabolic, molecular genetics and neuroimaging findings and histologic, histochemical, and electron microscopy studies in muscle samples of 2 patients from unrelated families with a neurodevelopmental disorder. Methods: Data were retrospectively analyzed by medical charts revision. Results: Patient 1, a 16-year-old boy, presented a childhood-onset slowly progressive neurodegenerative disorder mainly affecting language skills, behavior, and motor coordination. Patient 2, a 22-year-old woman, presented with a severe and rapidly progressive disease with dystonic tetra paresis, acquired microcephaly, and severe cognitive deficit complicated by pseudobulbar syndrome characterized by involuntary and uncontrollable outbursts of laughing, dysphagia requiring tube feeding, and nocturnal hypoventilation treated with noninvasive ventilation. Both patients carried the recurrent previously described UBTF1 de novo variant and had signs of mitochondrial dysfunction at muscle biopsy. The metabolic profile of patient 2 also revealed a decrease in CSF biopterin. Discussion: These case reports add new insights to the UBTF1 disease spectrum instrumental to improving the diagnostic rate in neurodevelopmental disorders

Silicon nanowires: where mechanics and optics meet at the nanoscale

Mechanical transducers based on nanowires promise revolutionary advances in biological sensing and force microscopy/spectroscopy. A crucial step is the development of simple and non-invasive techniques able to detect displacements with subpicometer sensitivity per unit bandwidth. Here, we design suspended tapered silicon nanowires supporting a range of optical resonances that confine and efficiently scatter light in the visible range. Then, we develop an optical method for efficiently coupling the evanescent field to the regular interference pattern generated by an incoming laser beam and the reflected beam from the substrate underneath the nanowire. This optomechanical coupling is here applied to measure the displacement of 50 nm wide nanowires with sensitivity on the verge of 1 fm/Hz1/2 at room temperature with a simple laser interferometry set-up. This method opens the door to the measurement of the Brownian motion of ultrashort nanowires for the detection of single biomolecular recognition events in liquids, and single molecule spectroscopy in vacuum.We acknowledge financial support from the Spanish Science Ministry (MINECO) through projects TEC2011-29120-C05-04; and from European Research Council through Starting Grant NANOFORCELLS (ERC-StG-2011-278860).Peer reviewe

Development of nanomechanical biosensors for the determination of cell mechanical properties

Póster presentado en el GEM4 Summer school, celebrado en Londres del 10 al 14 de septiembre de 2012.Peer Reviewe

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Theory, characterization and optomechanical effects of ultrathin nanomechanical resonators

Tesis llevada a cabo para conseguir el grado de Doctor por la Universidad Autónoma de de Madrid.--2016-04-20.--Sobresaliente Cum Laude. Premio extraordinarioLas nano-estructuras mecánicas que oscilan a altas frecuencias representan la base de una multitud de fascinantes aplicaciones en nanotecnología como el procesado de señales1-8 , sensores químicos 9-12 y biológicos 13-21 , y la observación de efectos cuánticos en sistemas mecánicos22-25 . Estos dispositivos, conocidos en la literatura como resonadores nanomecánicos pueden tener forma de palancas26-28, puentes4-7 y membranas29-32 o incluso pueden tener canales integrados para micro y nano-fluidica14,33-35 . El metódo más utilizado para mejorar el rendimiento de un resonador nanomecánico consiste en la miniaturización del dispositivo. La pequeña masa y las altas frecuencias de resonancia de estos dispositivos permiten alcanzar una sensibilidad en masa sin precedentes llegando hasta el yocto-gramo 36,37. Sin embargo, esta drástica miniaturización no es posible en una gran variedad de aplicaciones sensoras basadas en resonadores nanomecánicos, ya que, en muchos casos la sensibilidad no es la única cantidad que hay que maximizar. En aplicaciones que requieren medir pequeñas cantidades de analito ultradiluido27,38,39, hay que tener en cuenta también otro límite de detección determinado por el límite difusivo que escala con el área del sensor8 . Por lo tanto, en muchas aplicaciones el dispositivo ideal necesita tener una alta sensibilidad y, al mismo tiempo una gran área de captura; esta necesidad explica por qué hay tanto interés en el desarrollo de estructuras mecánicas ultradelgadas29,40-44 . Los resonadores nanomecánicos ultra-delgados representan el mejor compromiso para medir concentraciones ultra-bajas de analito con alta sensibilidad. Aunque estos dispositivos poseen un enorme potencial para el desarrollo de futuros sensores45, hay varias cuestiones abiertas que hay que resolver. En esta tesis voy a profundizar en algunos aspectos relevantes que surgen a la hora de utilizar los resonadores nanomecánicos ultra-delgadosPeer reviewe