Predicting the size and morphology of nanoparticle clusters driven by biomolecular recognition.

Nanoparticle aggregation is a driving principle of innovative materials and biosensing methodologies, improving transduction capabilities displayed by optical, electrical or magnetic measurements. This aggregation can be driven by the biomolecular recognition between target biomolecules (analytes) and receptors bound onto nanoparticle surface. Despite theoretical advances on modelling the entropic interaction in similar systems, predictions of the fractal morphologies of the nanoclusters of bioconjugated nanoparticles are lacking. The morphology of resulting nanoclusters is sensitive to the location, size, flexibility, average number of receptors per particle f̄, and the analyte-particle concentration ratio. Here we considered bioconjugated iron oxide nanoparticles (IONPs) where bonds are mediated by a divalent protein that binds two receptors attached onto different IONPs. We developed a protocol combining analytical expressions for receptors and linker distributions, and Brownian dynamics simulations for bond formation, and validated it against experiments. As more bonds become available (e.g., by adding analytes), the aggregation deviates from the ideal Bethe's lattice scenario due to multivalence, loop formation, and steric hindrance. Generalizing Bethe's lattice theory with a (not-integer) effective functionality feff leads to analytical expressions for the cluster size distributions in excellent agreement with simulations. At high analyte concentration steric impediment imposes an accessible limit value facc to feff, which is bounded by facc < feff < f̄. A transition to gel phase, is correctly captured by the derived theory. Our findings offer new insights into quantifying analyte amounts by assessing nanocluster size, and predicting nanoassembly morphologies accurately is a first step towards understanding variations of physical properties in clusters formed after biomolecular recognition.

Introduction to Nanomaterials Applied to Life Sciences.

A. Espinosa, F. J. Teran and D. Ortega introduce the Nanoscale Advances themed collection on Nanomaterials Applied to Life Sciences.

Emergency electroencephalogram: Usefulness in the diagnosis of nonconvulsive status epilepticus by the on-call neurologist. / Uso de la electroencefalografía urgente por el neurólogo de guardia: utilidad en el diagnóstico del estatus epiléptico no convulsivo.

INTRODUCTION: We aim to describe the use of emergency electroencephalogram (EmEEG) by the on-call neurologist when nonconvulsive status epilepticus (NCSE) is suspected, and in other indications, in a tertiary hospital. SUBJECTS AND METHODS: Observational retrospective cohort study of emergency EEG (EmEEG) recordings with 8-channel systems performed and analysed by the on-call neurologist in the emergency department and in-hospital wards between July 2013 and May 2015. Variables recorded were sex, age, symptoms, first diagnosis, previous seizure and cause, previous stroke, cancer, brain computed tomography, diagnosis after EEG, treatment, patient progress, routine control EEG (rEEG), and final diagnosis. We analysed frequency data, sensitivity, and specificity in the diagnosis of NCSE. RESULTS: The study included 135 EEG recordings performed in 129 patients; 51.4% were men and their median age was 69 years. In 112 cases (83%), doctors ruled out suspected NCSE because of altered level of consciousness in 42 (37.5%), behavioural abnormalities in 38 (33.9%), and aphasia in 32 (28.5%). The EmEEG diagnosis was NCSE in 37 patients (33%), and this was confirmed in 35 (94.6%) as the final diagnosis. In 3 other cases, NCSE was the diagnosis on discharge as confirmed by rEEG although the EmEEG missed this condition at first. EmEEG performed to rule out NCSE showed 92.1% sensitivity, 97.2% specificity, a positive predictive value of 94.6%, and a negative predictive value of 96%. CONCLUSIONS: Our experience finds that, in an appropriate clinical context, EmEEG performed by the on-call neurologist is a sensitive and specific tool for diagnosing NCSE.

Unraveling viscosity effects on the hysteresis losses of magnetic nanocubes.

Hysteresis losses in magnetic nanoparticles constitute the basis of magnetic hyperthermia for delivering a local thermal stress. Nevertheless, this therapeutic modality is only to be realised through a careful appraisal of the best possible intrinsic and extrinsic conditions to the nanoparticles for which they maximise and preserve their heating capabilities. Low frequency (100 kHz) hysteresis loops accurately probe the dynamical magnetic response of magnetic nanoparticles in a more reliable manner than calorimetry measurements, providing conclusive quantitative data under different experimental conditions. We consider here a set of iron oxide or cobalt ferrite nanocubes of different sizes, through which we experimentally and theoretically study the influence of the viscosity of the medium on the low frequency hysteresis loops of magnetic colloids, and hence their ability to produce and dissipate heat to the surroundings. We analyse the role of nanoparticle size, size distribution, chemical composition, and field intensity in making the magnetisation dynamics sensitive to viscosity. Numerical simulations using the stochastic Landau-Lifshitz-Gilbert equation model the experimental observations in excellent agreement. These results represent an important contribution towards predicting viscosity effects and hence to maximise heat dissipation from magnetic nanoparticles regardless of the environment.

Effects of inter- and intra-aggregate magnetic dipolar interactions on the magnetic heating efficiency of iron oxide nanoparticles.

Iron oxide nanoparticles have found an increasing number of biomedical applications as sensing or trapping platforms and therapeutic and/or diagnostic agents. Most of these applications are based on their magnetic properties, which may vary depending on the nanoparticle aggregation state and/or concentration. In this work, we assess the effect of the inter- and intra-aggregate magnetic dipolar interactions on the heat dissipation power and AC hysteresis loops upon increasing the nanoparticle concentration and the hydrodynamic aggregate size. We observe different effects produced by inter- (long distance) and intra-aggregate (short distance) interactions, resulting in magnetizing and demagnetizing effects, respectively. Consequently, the heat dissipation power under alternating magnetic fields strongly reflects such different interacting phenomena. The intra-aggregate interaction results were successfully modeled by numerical simulations. A better understanding of magnetic dipolar interactions is mandatory for achieving a reliable magnetic hyperthermia response when nanoparticles are located into biological matrices.

Collective character of spin excitations in a system of Mn2+ spins coupled to a two-dimensional electron gas.

We have studied the low energy spin excitations in n-type CdMnTe based dilute magnetic semiconductor quantum wells. For magnetic fields for which the energies for the excitation of free carriers and Mn spins are almost identical, an anomalously large Knight shift is observed. Our findings suggest the existence of a magnetic-field-induced ferromagnetic order in these structures, which is in agreement with recent theoretical predictions [Phys. Rev. Lett. 91, 077202 (2003)]].

Pauli paramagnetism and Landau level crossing in a modulation doped CdMnTe/CdMgTe quantum well.

Electrical transport measurements are reported on a 2DEG in a CdMnTe quantum well structure. The amplitude of the Shubnikov-de Haas oscillations show a distinct beating pattern with nodes corresponding to coincidences between the spin splitting and a half integer multiple of the cyclotron energy. The observed pattern of nodes is a direct consequence of the large Pauli paramagnetism induced by the s-d exchange interaction between the spins of electronic states and the localized magnetic moments.

Cloning, sequencing, and use as a molecular probe of a gene encoding an aminoglycoside 6'-N-acetyltransferase of broad substrate profile.

A gene coding for an aminoglycoside 6'-N-acetyltransferase that was able to modify amikacin was cloned from a plasmid isolated from a clinical strain of Enterobacter cloacae. Sequencing of a 955-bp segment which mediates the modifying activity revealed a single open reading frame of 432 nucleotides that predicted a polypeptide of 144 amino acid residues with a molecular weight of 16,021. Putative ribosomal binding sites and -10 and -35 sequences were located at the 5' end of the gene. The size of the polypeptide was confirmed through minicell analysis of the expression products of plasmids containing the sequence. The use of the gene as a molecular probe revealed its specificity toward strains harboring genes coding for related enzymes. This probe is therefore useful for epidemiological studies.

Molecular relationship among fosfomycin-resistant plasmids and clinical impact of fosfomycin resistance.

We have been carrying out a surveillance programme on plasmid-mediated fosfomycin resistance in our community over the last decade and have isolated and characterized several varieties of conjugative plasmids from different enterobacteriae. In this work we show that seven varieties of plasmids are related with the Inc M group, and carry the same For determinant which encodes a modifying enzyme. The comparative study on their R-phenotype, restriction analysis and DNA-DNA hybridization showed different degrees of molecular relationship among them. The spread of For-plasmids as well as the fosfomycin resistance by other mechanisms seems to be low in spite of the great For-plasmid diversity found.