Accurate detection of spherical objects in a complex background.

The automated detection of particles in microscopy images has become a routinely used method for quantitative image analysis in biology, physics, and other research fields. While the majority of particle detection algorithms have been developed for bulk materials, the detection of particles in a heterogenous environment due to surfaces or other objects in the studied material is of great interest. However, particle detection is hindered by a complex background due to the diffraction of light resulting in a decreased contrast and image noise. We present a new heuristic method for the reliable detection of spherical particles that suppresses false detections due to a heterogenous background without additional background measurements. Further, we discuss methods to obtain particle coordinates with improved accuracy and compare with other methods, in particular with that of Crocker and Grier.

Structure and component dynamics in binary mixtures of poly(2-(dimethylamino)ethyl methacrylate) with water and tetrahydrofuran: A diffraction, calorimetric, and dielectric spectroscopy study.

We have combined X-ray diffraction, neutron diffraction with polarization analysis, small angle neutron scattering,differential scanning calorimetry, and broad band dielectric spectroscopy to investigate the structure and dynamics of binary mixtures of poly(2-(dimethylamino)ethyl methacrylate) with either water or tetrahydrofuran (THF) at different concentrations. Aqueous mixtures are characterized by a highly heterogeneous structure where water clusters coexist with an underlying nano-segregation of main chains and side groups of the polymeric matrix. THF molecules are homogeneously distributed among the polymeric nano-domains for concentrations of one THF molecule/monomer or lower. A more heterogeneous situation is found for higher THF amounts, but without evidences for solvent clusters. In THF-mixtures, we observe a remarkable reduction of the glass-transition temperature which is enhanced with increasing amount of solvent but seems to reach saturation at high THF concentrations. Adding THF markedly reduces the activation energy of the polymer ß-relaxation. The presence of THF molecules seemingly hinders a slow component of this process which is active in the dry state. The aqueous mixtures present a strikingly broad glass-transition feature, revealing a highly heterogeneous behavior in agreement with the structural study. Regarding the solvent dynamics, deep in the glassy state all data can be described by an Arrhenius temperature dependence with a rather similar activation energy. However, the values of the characteristic times are about three orders of magnitude smaller for THF than for water. Water dynamics display a crossover toward increasingly higher apparent activation energies in the region of the onset of the glass transition, supporting its interpretation as a consequence of the freezing of the structuralrelaxation of the surrounding matrix. The absence of such a crossover (at least in the wide dynamic window here accessed) in THF is attributed to the lack of cooperativity effects in the relaxation of these molecules within the polymeric matrix.

The CONTIN algorithm and its application to determine the size distribution of microgel suspensions.

We review a powerful regularization method, known as CONTIN, for obtaining the size distribution of colloidal suspensions from dynamic light scattering data. We show that together with the so-called L-curve criterion for selecting the optimal regularization parameter, the method correctly describes the average size and size distribution of microgel suspensions independently characterized using small-angle neutron scattering. In contrast, we find that when using the default regularization process, where the regularizer is selected via the "probability to reject" method, the results are not as satisfactory.

Molecular scale dynamics of large ring polymers.

We present neutron scattering data on the structure and dynamics of melts from polyethylene oxide rings with molecular weights up to ten times the entanglement mass of the linear counterpart. The data reveal a very compact conformation displaying a structure approaching a mass fractal, as hypothesized by recent simulation work. The dynamics is characterized by a fast Rouse relaxation of subunits (loops) and a slower dynamics displaying a lattice animal-like loop displacement. The loop size is an intrinsic property of the ring architecture and is independent of molecular weight. This is the first experimental observation of the space-time evolution of segmental motion in ring polymers illustrating the dynamic consequences of their topology that is unique among all polymeric systems of any other known architecture.

Form factor of pNIPAM microgels in overpacked states.

We study the form factor of thermoresponsive microgels based on poly(N-isopropylacrylamide) at high generalized volume fractions, ζ, where the particles must shrink or interpenetrate to fit into the available space. Small-angle neutron scattering with contrast matching techniques is used to determine the particle form factor. We find that the particle size is constant up to a volume fraction roughly between random close packing and space filling. Beyond this point, the particle size decreases with increasing particle concentration; this decrease is found to occur with little interpenetration. Noteworthily, the suspensions remain liquid-like for ζ larger than 1, emphasizing the importance of particle softness in determining suspension behavior.

Effect and safety of duodenal levodopa infusion in advanced Parkinson's disease: a retrospective multicenter outcome assessment in patient routine care.

Duodenal levodopa infusion represents an effective strategy to manage motor and non-motor complications in patients with advanced Parkinson's disease (PD). However, most published clinical series regard small numbers of patients and do not exceed 1 year follow-up. In this multi-national observational cohort study conducted in seven specialised PD clinics and university hospitals we assessed long-term safety and outcome of chronic treatment with intra-duodenal levodopa infusions in a large population of patients with advanced PD. The starting population consisted of 98 treated patients (safety population). We report clinical outcomes of 73 patients with subsequent efficacy assessment(s) (efficacy population) over a follow-up period up to 2 years. Follow-up periods and collection of clinical observations varied based on individual routine care program. At last follow-up there was a significant (p ≤ 0.05) reduction in duration of "Off" periods as well as dyskinesia duration and severity that was associated with an improvement of quality of life. Twenty three patients (25.3 % of the safety population) withdraw, due to adverse drug reaction (5), procedure and device related events (7), compliance (3) and lack of efficacy (8). The mean duration for last value reported after baseline (LV) was 608 ± 292 days (median: 697 days). Our results demonstrate significant and sustained benefit over a long observation period in motor complications and in quality of life following a change from oral pulsatile to continuous levodopa delivery. The relatively large number of withdrawals reflects the current use of duodenal levodopa infusion in very advanced PD patients.

Poly(N-isopropylacrylamide) microgel swelling behavior and suspension structure studied with small-angle neutron scattering.

Microgels are of high interest for applications and as model systems due to their volume response to external stimuli. We use small-angle neutron scattering to measure the form and structure factors of poly(N-isopropylacrylamide) microgels in dilute and concentrated suspensions and find that microgels keep a constant size up to a concentration, above which they deswell. This happens before random-close packing. We emphasize suspension polydispersity must be considered to obtain accurate form and structure factors. Our results are compatible with microgel deswelling triggered by the osmotic pressure set by counterions associated to charged groups in the microgel periphery, which sharply increases when the counterion clouds surrounding the microgels percolate throughout the suspension volume.

A pilot iron substitution programme in female blood donors with iron deficiency without anaemia.

BACKGROUND AND OBJECTIVES: Blood donation can contribute to iron deficiency. The possibly resulting anaemia importantly affects donor return rate. The determination of serum ferritin levels revealed iron deficiency in many non-anaemic premenopausal female blood donors at our Institution. We started an iron substitution programme targeting this donor group to prevent anaemia and enhance donor retain. MATERIALS AND METHODS: Women aged≤50 with haemoglobin levels adequate for donation and serum ferritin≤10 ng/ml were offered iron supplementation. Substitution lasted 16 weeks and the donation interval was extended. History collection including iron deficiency-related symptoms, whole blood count and serum ferritin determination was performed at baseline and after 2 and 6 months. Data were recorded prospectively and compared with those of 108 female controls with iron deficiency not receiving iron substitution (retrospective data). RESULTS: Of the 116 participating subjects, 60% completed the programme. Significant results were serum ferritin increase (from a mean value of 7.12 to 25.2 ng/ml), resolution of prostration, fatigue, sleep disturbances, tension in the neck, hair loss and nail breakage. No case of anaemia occurred. Sixty per cent of the women completed the programme and donated blood again. CONCLUSIONS: Targeted iron substitution prevents the development of anaemia and enhances donation return in premenopausal female blood donors with iron deficiency.

Magnetic properties of silica coated spindle-type hematite particles.

Magnetic properties of particles are generally determined from randomly oriented ensembles and the influence of the particle orientation on the magnetic response is neglected. Here, we report on the magnetic characterization of anisotropic spindle-type hematite particles. The easy axis of magnetization is within the basal plane of hematite, which is oriented perpendicular to the spindle axis. Two standard synthesis routes are compared and the effects of silica coating and particle orientation on the magnetic properties are investigated. Depending on the synthesis route we find fundamentally different magnetic behavior compatible with either single domain particles or superparamagnetic sub-units. Furthermore, we show that silica coating reduces the mean blocking temperature to nearly room temperature. The mechanical stress induced by the silica coating appears to reduce the magnetic coupling between the sub-units.

Osmotic pressure of suspensions comprised of charged microgels.

We determine the osmotic pressure of microgel suspensions using membrane osmometry and dialysis, for microgels with different softnesses. Our measurements reveal that the osmotic pressure of solutions of both ionic and neutral microgels is determined by the free ions that leave the microgel periphery to maximize their entropy and not by the translational degrees of freedom of the microgels themselves. Furthermore, up to a given concentration it is energetically favorable for the microgels to maintain a constant volume without appreciable deswelling. The concentration where deswelling starts weakly depends on the crosslinker concentration, which affects the microgel dimension; we explain this by considering the dependence of the osmotic pressure and the microgel bulk modulus on the particle size.

Phonon-mediated back-action of a charge readout on a double quantum dot.

Quantum point contacts are in use as an on-chip capacitative readout for the charge state of quantum dot systems. Here we investigate experimentally the back-action of quantum point contacts (QPCs) on a nearby double quantum dot (DQD). Driving current through a QPC influences the DQD state and leads to a measurable current flow in the DQD circuit with no bias voltage applied. The responsible mechanism is an indirect back-action process due to ohmic heating of the phonon bath. The system behaves like a thermoelectric engine, where a temperature gradient between the phonon bath and the electronic bath generates work observable as a measurable current flowing through the DQD.

Structural changes of poly(N-isopropylacrylamide)-based microgels induced by hydrostatic pressure and temperature studied by small angle neutron scattering.

We study the structural properties of microgels made of poly(N-isopropylacrylamide) and acrylic acid as a function of hydrostatic pressure and temperature using small angle neutron scattering. Hydrostatic pressure induces particle deswelling by changing the mixing of the microgel with the solvent, similar to temperature. We extend this analogy to the structural properties of the particles and show that the form factor at a certain temperature is equal to the form factor at a certain hydrostatic pressure. We fit the results with an existent model for the microgel structure and carefully analyze the fitting procedure in order to obtain physically meaningful values of the free parameters in the model.

Real-space imaging of nucleation and growth in colloidal crystallization.

Crystallization of concentrated colloidal suspensions was studied in real space with laser scanning confocal microscopy. Direct imaging in three dimensions allowed identification and observation of both nucleation and growth of crystalline regions, providing an experimental measure of properties of the nucleating crystallites. By following their evolution, we identified critical nuclei, determined nucleation rates, and measured the average surface tension of the crystal-liquid interface. The structure of the nuclei was the same as the bulk solid phase, random hexagonal close-packed, and their average shape was rather nonspherical, with rough rather than faceted surfaces.

Crystal structure of highly concentrated, ionic microgel suspensions studied by neutron scattering.

We present a neutron-scattering investigation of the crystal structure formed by pH -sensitive poly(2-vinylpyridine) microgel particles with 5 wt % of cross-linker. We focus on highly swollen particles and explore concentrations ranging from below close packing to well above close packing, where the particles are forced to shrink and/or interpenetrate. The crystal structure is found to be random hexagonal close packed, similar to the structure typically found in hard-sphere systems.

Crystallization in three- and two-dimensional colloidal suspensions.

Despite progress in the understanding of crystal nucleation and crystal growth since the first theories for nucleation were developed, an exact quantitative prediction of the nucleation rates in most systems has remained an unsolved problem. Colloidal suspensions show a phase behavior that is analogous to atomic or molecular systems and serve accordingly as ideal model systems for studying crystal nucleation with an accuracy and depth on a microscopic scale that is hard to reach for atomic or molecular systems. Due to the mesoscopic size of colloidal particles they can be studied in detail on the single-particle level and their dynamics is strongly slowed down in comparison with atomic or molecular systems, such that the formation of a crystal nucleus can be followed in detail. In this review, recent progress in the study of homogeneous and heterogeneous crystal nucleation in colloids and the controlled growth of crystalline colloidal structures is reviewed. All this work has resulted in unprecedented insights into the early stage of nucleation and it is also relevant for a deeper understanding of soft matter materials in general as well as for possible applications based on colloidal suspensions.

Spontaneous deswelling of microgels controlled by counterion clouds.

Concentrated poly(N-isopropylacrylamide) (pNIPAM) microgel suspensions at a fixed temperature below the deswelling transition of pNIPAM exhibit spontaneous particle deswelling. The microgels deswell before they are in direct contact and in polydisperse suspensions this deswelling is most pronounced for the largest microgel particles; as a consequence, the polydispersity of the suspension is reduced. Recently, we presented a model for this spontaneous deswelling that is based on the presence of counterions originating from charged groups on the surface of the pNIPAM microgels [A. Scotti et al., Proc. Natl. Acad. Sci. USA 113, 5576 (2016)PNASA60027-842410.1073/pnas.1516011113]. Here we present numerical Poisson-Boltzmann calculations of the electrostatic potential and osmotic pressure inside and outside a pNIPAM microgel that could trigger the observed deswelling at high particle concentrations.

Phase behavior of binary and polydisperse suspensions of compressible microgels controlled by selective particle deswelling.

We investigate the phase behavior of suspensions of poly(N-isopropylacrylamide) (pNIPAM) microgels with either bimodal or polydisperse size distribution. We observe a shift of the fluid-crystal transition to higher concentrations depending on the polydispersity or the fraction of large particles in suspension. Crystallization is observed up to polydispersities as high as 18.5%, and up to a number fraction of large particles of 29% in bidisperse suspensions. The crystal structure is random hexagonal close-packed as in monodisperse pNIPAM microgel suspensions. We explain our experimental results by considering the effect of bound counterions. Above a critical particle concentration, these cause deswelling of the largest microgels, which are the softest, changing the size distribution of the suspension and enabling crystal formation in conditions where incompressible particles would not crystallize.

Anisotropic mean-square displacements in two-dimensional colloidal crystals of tilted dipoles.

Superparamagnetic colloidal particles confined to a flat horizontal air-water interface in an external magnetic field, which is tilted relative to the interface, form anisotropic two-dimensional crystals resulting from their mutual dipole-dipole interactions. Using real-space experiments and harmonic lattice theory we explore the mean-square displacements of the particles in the directions parallel and perpendicular to the in-plane component of the external magnetic field as a function of the tilt angle. We find that the anisotropy of the mean-square displacement behaves nonmonotonically as a function of the tilt angle and does not correlate with the structural anisotropy of the crystal.

Synthesis and secretion of Alzheimer amyloid beta A4 precursor protein by stimulated human peripheral blood leucocytes.

Alzheimer amyloid precursor proteins (APP) are actively secreted by stimulated human peripheral mononuclear blood leucocytes (PMBLs). Induction of APP transcription, translation and secretion was observed with several T cell mitogens but was highest with phytohemagglutinin. The time course of induction is similar to that reported for IL-2 and IL-2 receptor. We suggest that APP may play an important role in the construction of the immunological network and the differentiation of T cells.

Interleukin-6 and alpha-2-macroglobulin indicate an acute-phase state in Alzheimer's disease cortices.

Recent studies indicated that the formation of a major constituent of Alzheimer's disease (AD) senile plaques, called beta A4-peptide, does not result from normal processing of its precursor, amyloid precursor protein (APP). Since proteolytic cleavage of APP inside its beta A4 sequence was found to be part of APP processing the formation of the beta A4-peptide seems to be prevented under normal conditions. We considered whether in AD one of the endogenous proteinase inhibitors might interfere with APP processing. After we had recently found that cultured human neuronal cells synthesize the most potent of the known human proteinase inhibitors, alpha-2-macroglobulin (alpha 2M), upon stimulation with the inflammatory mediator interleukin-6 (IL-6) we now investigated whether alpha 2M and IL-6 could be detected in AD brains. Here we report that AD cortical senile plaques display strong alpha 2M and IL-6 immunoreactivity while no such immunoreactivity was found in age-matched control brains. Strong perinuclear alpha 2M immunoreactivity in hippocampal CA1 neurons of Alzheimer's disease brains indicates that neuronal cells are the site of alpha 2M synthesis in AD brains. We did not detect elevated IL-6 or alpha 2M levels in the cerebrospinal fluid of AD patients. Our data indicate that a sequence of immunological events which seem to be restricted to the local cortical environment is part of AD pathology.