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We present the design and the preliminary experimental characterization of a novel lab-on-a-chip platform for high-sensitivity impedimetric detection of single magnetic beads employed as magnetic cargos with molecular payload for accurate drug delivery. The real-time impedimetric detection of these superparamagnetic microbeads in saline solution is here experimentally demonstrated (20 nS conductance variation for a single 1μm bead), validating the insulating-sphere model and the finite-element simulations employed for optimal electrode design. A custom electronic front-end for impedance tracking in the 1-10 MHz range, required to compensate the impact of the large parasitic impedance due to the silicon substrate, is also presented. Thanks to introduction of an ad-hoc noise cancelling network based on a dummy circuit and a phase shifter for low-frequency phase noise counteraction by active subtraction, slow fluctuations are significantly reduced (by a factor 10), allowing a SNR > 10.

Concrete is the second most used material in the world, after water. More than 10,000 million cubic meters are globally produced every year, with the consumption of more than 19,000 million tons of natural aggregates (coarse aggregates and sand). About 200 million cubic meters of concrete (2 per cent of the global production) are not placed at the jobsite and are returned to readymixed plant where, in most cases, are disposed as waste material. Recently, a new technology to treat returned concrete has been developed. By the new technology, one cubic meter of returned concrete is transformed into 2.3 tons of aggregates, without any waste production. New concrete materials, made by 100 % aggregates produced with the new technology, have been developed in Japan and used in many construction sites. In the present paper, the aggregate production process from returned concrete is reviewed, the composition and design of the new concrete materials are discussed and the mechanical performance and durability tests of the new concrete are presented. These new concrete materials represents an important contribution to concrete sustainability, in terms of natural resources protection, waste disposal and economical benefit both for the ready-mixed plant and the general contractor.

In this paper we provide a complete theoretical analysis of a two-dimensional degenerate non convex singular stochastic control problem. The optimisation is motivated by a storage-consumption model in an electricity market, and features a stochastic real-valued spot price modelled by Brownian motion. We find analytical expressions for the value function, the optimal control and the boundaries of the action and inaction regions. The optimal policy is characterised in terms of two monotone and discontinuous repelling free boundaries, although part of one boundary is constant and and the smooth fit condition holds there.

We derive a new equation for the optimal investment boundary of a general irreversible investment problem under exponential Levy uncertainty. The problem is set as an infinite time-horizon, two-dimensional degenerate singular stochastic control problem. In line with the results recently obtained in a diffusive setting, we show that the optimal boundary is intimately linked to the unique optional solution of an appropriate Bank-El Karoui representation problem. Such a relation and the Wiener-Hopf factorization allow us to derive an integral equation for the optimal investment boundary. In case the underlying Levy process hits any point in R with positive probability we show that the integral equation for the investment boundary is uniquely satisfied by the unique solution of another equation which is easier to handle. As a remarkable by-product we prove the continuity of the optimal investment boundary. The paper is concluded with explicit results for profit functions of (i) Cobb-Douglas type and (ii) CES type. In the first case the function is separable and in the second case non-separable.

In this paper we present an innovative on-chip platform suitable for the simultaneous manipulation and detection of the transit of a single magnetic bead. This system is based on the controlled displacement of constrained magnetic domain walls (DWs) that are used to move and sense particles in suspension over the chip. To this scope, the high stray field from the transverse DWs created at the corners of ferromagnetic zig-zag structures is used for particles manipulation, while electrical contacts flanking a single corner are employed to simultaneously monitor the DW passage through that corner, via anisotropic magneto resistance (AMR) measurements. A single DW carrying a magnetic particle is nucleated and manipulated within the zig-zag shaped magnetic conduit, trough the action of external magnetic fields. At the same time, the variation of the voltage drop across a corner flanked by a pair of electrical leads is measured, allowing to detect the transit of the DW thanks to the change of the relative orientation of current and spins at the corner related to the peculiar micromagnetic configuration of the DW (AMR). Work is in progress in order to selectively distinguish the transit of a naked DW from that of a DW bound to a magnetic particle. This work paves the way to the development of a closed-loop microlfuidic platform for on-chip bead manipulation, where single bead can be finely moved and their motion continuously checked, via AMR electrical detection and without need of optical monitoring, in a fully integrated closed-loop system.

A novel microsensor for capacitive detection of particulate matter (PM) directly in air is presented. The feasibility of detecting single PM 10 particles (calibrated 10 μm polystyrene beads) by means of ad-hoc designed coplanar microelectrodes (4 μm gap), a PDMS air deposition system, and a low-noise (∼2 aF capacitive resolution) readout electronics is experimentally demonstrated. Finite element numerical simulations have been performed to optimize the design of the microelectrodes, investigate the detection limit and validate the experimental results. The real-time deposition on the sensor surface of sequences of single industrial talc particles (average diameter of ∼8 μm, corresponding to a signal of ∼12 aF) has been successfully tracked with 10 ms temporal resolution and, subsequently, validated by microscope inspection. This CMOS- and MEMS-compatible capacitance detection technique enables radical miniaturization of next generation air quality monitors, paving the ways to their embedment in personal portable devices for pervasive mapping of air pollution.

The ability of the VCCTL microstructural model to predict the hydration kinetics and elastic moduli of cement materials was tested by coupling a series of computer simulations and laboratory experiments, using different cements. The novel aspects of this study included the fact that the simulated hydration kinetics were benchmarked using real-time measurements of the early-age phase composition during hydration by in situ X-ray diffraction. Elastic moduli are measured both by strain gauges (static approach) and by P-wave propagation (dynamic approach). Compressive strengths were measured by loading mortar prisms until rupture. Virtual samples were generated by VCCTL, using particle size distribution and phase composition as input. The hydration kinetics and elastic moduli were simulated and the numerical results were compared with the experimental observations. The compressive strength of the virtual mortars were obtained from the elastic moduli, using a power-law relation. Experimentally measured and simulated time-dependence of the major cement clinker phases and hydration product phases typically agreed to within 5%. Also, refinement of the input values of the intrinsic elastic moduli of the various phases enabled predictions of effective moduli, at different ages and different water-to-cement mass ratios, that are within the 10% uncertainty in the measured values. These results suggest that the VCCTL model can be successfully used as a predictive tool, which can reproduce the early age hydration kinetics, elastic moduli and mechanical strength of cement-based materials, using different mix designs.

A non-invasive technique is presented for tracking the intensity of light propagating in Si waveguides whose conductivity, increasing due to surface defects-mediated sub-bandgap photon absorption, is monitored through a ContactLess Integrated Photonic Probe (CLIPP). A dynamic range of 40 dB is demonstrated, with a minimum detection level of -30 dBm (local optical power), without perturbing light propagation. A custom-designed multichannel and low-noise integrated front-end allows miniaturized and high resolution sensing (2 pS noise floor), thanks to a significant parasitics reduction. Beyond power monitoring, this novel technique is suitable for tuning and control of key optical devices such as ring resonators.

We show wavelength tuning, locking, and swapping of thermally tuned silicon microrings assisted by a non-invasive light monitor integrated in the resonator. Closed-loop wavelength stabilization is achieved in a 150 ms time scale.

This paper examines a Markovian model for the optimal irreversible investment problem of a firm aiming at minimizing total expected costs of production. We model market uncertainty and the cost of investment per unit of production capacity as two independent one-dimensional regular diffusions, and we consider a general convex running cost function. The optimization problem is set as a three-dimensional degenerate singular stochastic control problem. We provide the optimal control as the solution of a Skorohod reflection problem at a suitable free-boundary surface. Such boundary arises from the analysis of a family of two-dimensional parameter-dependent optimal stopping problems and it is characterized in terms of the family of unique continuous solutions to parameter-dependent nonlinear integral equations of Fredholm type.

The paper presents the possibilities offered by the Correlation Spectrum Analyzer in the characterisation of semiconductor materials and microelectronic devices. The instrument performs noise analysis in a frequency range from a few mHz to 1 MHz with an extraordinary sensitivity of 1fA/√Hz in current noise measurements and of 20 pV/√Hz in voltage noise measurements. Noise spectra taken in these conditions can be used as a non-destructive-sensitive probe to investigate physical properties of semiconductor materials as well as quantify the noise produced by new devices. As an example of these applications, the text reports on the extraction of noise parameters from a MOSFET operated in strong sub-threshold regime to be inserted in noise models for circuit simulation and on the determination of carrier mobility in single-crystal cadmium telluride (CdTe) samples.

Nanopore sensors are a new class of single-molecule biosensors that allow for the detection of DNA, RNA, proteins, their complexes, as well as non-biological polymers, nanoparticles and small molecules. In their simplest form, such sensors feature a thin membrane that separates an electrolyte-filled cell into two compartments with one electrode each. A nanometre-scale pore connects the two parts of the cell for the transport of liquid, ions, and analyte molecules. Since the pore is so small - diameters range from 1 to about 100 nm - it typically represents the largest source of resistance in the cell (MΩ to GΩ). Application of a bias voltage between the two electrodes results in an ion current through the cell, which to a first approximation depends on the dimensions of the pore; the bias voltage applied; and the conductivity of the electrolyte. Transport of, say DNA through the pore (“translocation”), changes the pore conductance and hence the ion current - which can be detected with fast low-current detection electronics. The duration, magnitude and details of the modulation event may then be related back to the identity of the analyte molecule. For example, the longer the DNA, the longer the translocation event; the larger its magnitude, the larger the relative pore volume temporarily blocked by the DNA; the more feature-rich the current modulation, the more complex the structure of the analyte (e.g. due to specific binding of proteins to the DNA) and so forth

CD40 signaling induces B cell proliferative and differentiation responses that can be modulated by many different cytokines. Cytokines in the IL-2 receptor gamma chain (gammac)-common family are known to play an integral role in B cell development. Therefore, we investigated the possibility that CD40 signaling induced B cell responsiveness to multiple gammac-common cytokines and that individual gammac-common cytokines induced distinct B cell responses. B cells were isolated from lymphoid follicles of sheep Peyer's patches (PP) and co-cultured with murine CD40 ligand (mCD40L). CD40 signaling induced PP B cell responsiveness to recombinant human IL-2, IL-4, IL-7 and IL-15. mCD40L-induced B cell growth was enhanced by combining IL-4 with a second gammac-common cytokine and sustained B cell growth required co-stimulation with IL-4 plus IL-2, IL-7 and IL-15. gammac-common cytokine responsiveness remained dependent upon CD40 signaling, and removal of mCD40L resulted in B cell differentiation and cell death. Similar proliferative responses to mCD40L and gammac-common cytokines were observed for both immature (ileal) and mature (jejunal) PP B cells. Finally, the capacity of CD40-activated B cells to respond to multiple gammac-common cytokines was analyzed with individual PP B cell clones. All B cell clones displayed similar proliferative responses to IL-2 but quantitatively different responses to IL-4, IL-7 and IL-15. The biological significance of B cell responsiveness to multiple gammac-common cytokines is discussed.

A spectrum analyzer with a sensitivity better than few pV/Hz in voltage noise measurements and better than 1 fA/Hz in current noise measurements is presented. It has two distinct and independent input amplifiers in parallel, connected to the same device under test (DUT) and is based on the suppression of their uncorrelated noises. The instrument is modular with different front-end amplifiers conceived to optimize the measurement of low impedance or high impedance DUTs. The instrument can cover 8 decades of frequency span, from 10 mHz to 1 MHz. The improvement of sensitivity with respect to a traditional system and the simplicity in the connection and biasing of the DUT makes it perfectly suited to measure ultralow noise levels in semiconductor devices, like trapping noise, shot noise associated with tunneling in fractional quantum Hall systems, 1/f and channel noise in metal–oxide–semiconductor field effect transistors operated below threshold.

Lecture Notes on Impedance Spectroscopy (LNIS) is a book series covering new advances in the field of impedance spectroscopy including theory, fundamentals, and applications. In every volume it releases a selection of scientific contributions as extended chapters with detailed information about recent scientific research results.

A new sensing configuration based on the direct use of the metal input pad of a dedicated CMOS amplifier as a conductive substrate electrode for nanoscale high-performance electrical measurement with a standard conductive AFM is proposed and experimentally validated. Combining the state-of-the-art performance of an integrated current preamplifier (5MHz bandwidth, 14fA/sqrt(Hz) noise at 1MHz) with pad and setup optimization, it has been possible to straightforwardly achieve 14zF total capacitive rms resolution (0.5V applied at 1MHz with 1s averaging time) that corresponds to 75pm resolution in tracking the piezo vertical movement (allowing the detection of 6nm steps of the cantilever with a SNR of ~40dB).

A theoretical and experimental comparison between vertical and coplanar interdigitated sensing configurations for impedimetric cell growth tracking is presented. These widely-adopted approaches are quantitatively compared on the same cell populations and on the same 10 μm interdigitated microelectrodes using a versatile custom-made monitoring platform including a 24-channel miniaturized potentiostat. The characterization of bare microelectrodes in buffer and tracking experiments with HeLa cells over 16 hours demonstrate that the coplanar configuration provides a higher sensitivity to cell adhesion and spreading (Cell Index = 1.6 vs. 0.4) albeit at a higher frequency of maximum sensitivity (100 kHz vs. 24 kHz) shifting over time.

A compact platform for nanopore-based detection is presented. The system is tailored for high-capacitance (hundreds of pF) solid-state nanopores with integrated tunneling electrodes for DNA detection and label-free sequencing. This platform includes two low-noise current sensing channels and auxiliary biasing and selectable filtering circuits. In order to overcome the noise/bandwidth trade-off of the standard transimpedance configuration, an improved integrator-differentiator topology is adopted. The use of a discrete couple of matched JFETs at the differential input allows achieving very low equivalent input voltage noise (1.5nV/√Hz) critical with high input capacitance. Thus, the transimpedance amplifiers provide 100MO gain, 75kHz bandwidth and 11pArms noise, comparable with the state-of-the-art performance. The system design, its characterization and λ-DNA detection with a sub-20nm pore are reported.

We study a continuous-time problem of public good contribution under uncertainty for an economy with a finite number of agents. Each agent aims to maximize his expected utility allocating his initial wealth over a given time period between private consumption and repeated but irreversible contributions to increase the stock of some public good. We study the corresponding social planner problem and the case of strategic interaction between the agents. These problems are set up as stochastic control problems with both monotone and classical controls representing the cumulative contribution into the public good and the consumption of the private good, respectively. We characterize the optimal investment policies by a set of necessary and sufficient stochastic Kuhn-Tucker conditions, which in turn allow to identify a universal signal process that triggers the public good investments. Further we show that our model exhibits a dynamic free rider effect. We explicitly evaluate it in a symmetric Black-Scholes setting with Cobb-Douglas utilities and we show that uncertainty and irreversibility of public good provisions need not affect the degree of free-riding.

Poly(ethylenimine)s (PEIs) are able to condense DNA and RNA into stable toroidal and globular nanostructures (polyplexes) and are among the most efficient and promising synthetic transfectants, but they induce severe cytotoxicity. The mechanisms of PEI-mediated cytotoxicity have not been fully delineated but PEI toxicity appears to predominantly depend on membrane perturbing effects in cellular compartments in which they accumulate. Electrochemical Impedance Spectroscopy (EIS) is used as a non-invasive biophysical approach for the investigation of the electrical properties of biological materials according to their physiological and morphological changes. In this work, EIS has been used to evaluate impedance changes due to the polycation perturbations on a cell population. HeLa cells have been cultured on laminin-coated gold interdigitated electrode arrays integrated into a tailor-made microfluidic cell culture platform. Multiplexed EIS data from each sensor element were acquired using a 24-channel miniaturized potentiostat (30 points between 100 Hz and 100k-Hz). Two alternative sensing configuration approaches (the standard “vertical” configuration (a single working electrode (WE) versus a large, distant counter electrode (CE)), and the interdigitated configuration (WEa comb versus WEb comb) ) have been used and compared on the same cell population, providing optimal detection conditions. The experiments have been performed by initially seeding about 103 cells into each chamber, continuously perfused with fresh culture medium. The platform was incubated in a humidified atmosphere. After 24 hours, different concentrations of PEIs have been introduced in the culture medium and the incubation continued for other 24 hours. Cell adhesion, growth and PEI-cytotoxicity have been detected in real-time by following impedance changes. Microscopic imaging and MTS assays have been combined to the electrochemical detection. Complementary ongoing experiments aim to monitor in real-time gene transfection in order to detect the cytotoxic effects (apoptosis and necrosis) induced by different cationic polyplexes. This approach can contributes to a clearer and detailed mechanistic understanding of polycation-modulated cellular functions and cell death and could initiate rational approaches for design and engineering of safer vectors for nucleic acid transfection.

The assessment of marine environmental health is a complex but fundamental task both for ecosystem conservation and food safety related to the human consumption of marine products. Manila clams inhabiting the Venice Lagoon constitute an excellent case study for evaluating the effects of complex mixtures of industrial and urban effluents on aquatic organisms. Clams were collected in different seasons at four locations within the Venice Lagoon. The sampling sites were characterized by a range of pollutant concentrations and included Porto Marghera, a highly polluted industrial area where clam harvesting for human consumption is strictly forbidden. Pooled soft tissues were subjected to mass spectroscopy analysis to measure the concentrations of PCDDs/PCDFs/PCBs-DL, PCBs, PBDEs, HCB and PAHs, and pooled digestive gland samples were used for gene expression profiling. While seasonal variation was found to be responsible for the largest proportion of transcriptional changes, significance analysis of microarrays quantitative correlation analysis identified 162 transcripts that were correlated with at least one class of chemicals measured in the samples from the four different sampling sites. Prediction Analysis of Microarrays (PAM) identified a minimal set of seven genes that correctly assigned samples collected in the restricted polluted area (Porto Marghera), independent of the season in which they were collected. An integrated approach combining transcriptomics and chemical analyses of the Manila clam provided a global picture of how Manila clams respond to complex mixtures of xenobiotics and their interplay with other biotic and abiotic factors. We were also able to identify gene expression signatures for different classes of chemicals and a set of robust biomarkers of exposure to these chemicals.

We study a continuous-time, finite-horizon optimal stochastic reversible investment problem for a firm producing a single good. The production capacity is modeled as a one-dimensional, time-homogeneous, linear diff usion controlled by a bounded variation process which represents the cumulative investment-disinvestment strategy. We associate to the investment-disinvestment problem a zero-sum optimal stopping game and characterize its value function through a free boundary problem with two moving boundaries. These are continuous, bounded and monotone curves that solve a system of non-linear integral equations of Volterra type. The optimal investment-disinvestment strategy is then shown to be a di ffusion reflected at the two boundaries.

In this article, we present a technique to sort out in a multielectrode device a vanishing small noise component between two electrodes affected by a much larger overall noise. The technique is based on the use of a correlation spectrum analyzer and has proven to detect a current noise of interest as low as 1 fA/Hz in the presence of undesirable noise of 50 fA/Hz. The possibility offered by this technique is useful in a number of applications, ranging from gate current investigation in metal-oxide-semiconductor field effect transistors to the study of leakage currents in nanodevices.

The incidence and prevalence of end-stage renal disease increased steadily for 35 years in the population of Italy's Mantua province until the end of 2007, when they started to decrease. We describe the results of providing information and raising awareness among residents of the province's capital, Mantua, and of direct teaching and short training courses in hospital wards for general practitioners over a period of 3 years. During this period there was also more consultation activity for all kidney outpatients, from the first to the last stages of chronic kidney disease. Clinical data collected by the local NHS section (ASL) showed an increase in age and comorbidities (mainly type 2 diabetes) in kidney patients. As a result of the preventive measures, there has been an effective reduction of the yearly incidence and prevalence for all kinds of treatment, with the exception of kidney transplants, which have increased progressively during the last years.

In this paper, we derive a new handy integral equation for the free-boundary of infinite time horizon, continuous time, stochastic, irreversible investment problems with uncertainty modeled as a one-dimensional, regular diffusion $X$. The new integral equation allows to explicitly find the free-boundary $b(\cdot)$ in some so far unsolved cases, as when the operating profit function is not multiplicatively separable and $X$ is a three-dimensional Bessel process or a CEV process. Our result follows from purely probabilistic arguments. Indeed, we first show that $b(X(t))=l^*(t)$, with $l^*$ the unique optional solution of a representation problem in the spirit of Bank-El Karoui [Ann. Probab. 32 (2004) 1030-1067]; then, thanks to such an identification and the fact that $l^*$ uniquely solves a backward stochastic equation, we find the integral problem for the free-boundary., Published in at http://dx.doi.org/10.1214/13-AAP991 the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org)

A novel mixed-signal generation, acquisition and elaboration motherboard for electrochemical sensing is presented. This compact USB-controlled instrument is based on a FPGA for fast real-time execution of multiple measurement families: amperometry, voltammetry and impedance spectroscopy in particular. A digital dual-phase lock-in demodulator based on an internal DDS/PLL has been embedded with a custom analog front-end to provide an extended frequency range up to 10MHz. The design and experimental characterization of the full instrument encompassing fast (14bit, 80MSa/s) and auxiliary precise (18bit, 100kSa/s) channels are here discussed.

We report on the charge transfer dynamics between a silicon quantum dot and an individual phosphorous donor extracted from the current through the quantum dot as a probe for the donor ionization state. We employ a silicon n-metal-oxide-semiconductor field-effect transistor (MOSFET) with two side gates at a single metallization level to control both the device conductance and the donor charge. The elastic nature of the process is demonstrated by temperature and magnetic field independent tunneling times. The Fano factor approaches 1/2 revealing that the process is sub-poissonian. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4721433]

Dopant atoms are used to control the properties of semiconductors in most electronic devices. Recent advances such as single-ion implantation(1-5) have allowed the precise positioning of single dopants in semiconductors as well as the fabrication of single-atom transistors(6-9), representing steps forward in the realization of quantum circuits(10-14). However, the interactions between dopant atoms have only been studied in systems containing large numbers of dopants, so it has not been possible to explore fundamental phenomena such as the Anderson-Mott transition between conduction by sequential tunnelling through isolated dopant atoms, and conduction through thermally activated impurity Hubbard bands(15-18). Here, we observe the Anderson-Mott transition at low temperatures in silicon transistors containing arrays of two, four or six arsenic dopant atoms that have been deterministically implanted along the channel of the device. The transition is induced by controlling the spacing between dopant atoms. Furthermore, at the critical density between tunnelling and band transport regimes, we are able to change the phase of the electron system from a frozen Wigner-like phase to a Fermi glass by increasing the temperature. Our results open up new approaches for the investigation of coherent transport, band engineering and strongly correlated systems in condensed-matter physics.

A novel potentiostat containing 54 current amplifiers matched to an array of custom-fabricated 5μm microelectrodes for electrochemical imaging of released neurotransmitters is presented. The board is integrated with a programmable microfluidic cell culture system and the whole assembly is thin and compact enough to be placed under the objective of a standard microscope for simultaneous optical and electrochemical monitoring. Each channel, scanned every 54μs, features 3pA current resolution over a 5kHz bandwidth, suitable for detecting single exocytotic events. The design and electrical characterization of the system are reported together with its functionality, certified by a 54-pixel electrochemical imaging of the diffusion of a 10μl droplet of a target analyte inside the cell culture chamber.

An electrochemical detection system specifically designed for multi-parameter real-time monitoring of stem cell culturing/differentiation in a microfluidic system is presented. It is composed of a very compact 24-channel electronic board, compatible with arrays of microelectrodes and coupled to a microfluidic cell culture system. A versatile data acquisition software enables performing amperometry, cyclic voltammetry and impedance spectroscopy in each of the 12 independent chambers over a 100 kHz bandwidth with current resolution down to 5 pA for 100 ms measuring time. The design of the platform, its realization and experimental characterization are reported, with emphasis on the analysis of impact of input capacitance (i.e., microelectrode size) and microfluidic pump operation on current noise. Programmable sequences of successive injections of analytes (ferricyanide and dopamine) and rinsing buffer solution as well as the impedimetric continuous tracking for seven days of the proliferation of a colony of PC12 cells are successfully demonstrated.

We fabricated silicon transistors containing two and six arsenic ions implanted in one dimensional array along the channel by single-ion implantation method. The quantum transport was measured through the D0 and D− states of the arsenic ions at low temperature. We observed two different quantum transport regimes from the individual donor regime to the intermediate doping regime in which Hubbard bands are formed in agreement with the theoretical models. These results indicate that our deterministic single-ion doping method is more effective and reliable for single-dopant transistor development and pave the way towards single atom electronics for extended CMOS applications [12].

The electrical properties of a Single Hole Field Effect Transistor (SH-FET) based on CMOS technology are analyzed in a cryogenic environment. Few electron–hole Coulomb diamonds are observed using quantum transport spectroscopy measurements, down to the limit of single hole transport. Controlling the hole filling of the SH-FET is made possible by biasing the top gate, while the bulk contact is employed as a back gate that tunes the hole state coupling with the contacts and their distance from the interface. We compare the cryogenic Coulomb blockade regime with the room temperature regime, where the device operation is similar to that of a standard p-MOSFET.

Lymphoid follicles of the ileal Peyer's patch (PP) of young sheep function as the major source of B cells and a site of immunoglobulin (Ig) receptor diversification. However, extensive cell death in culture has restricted investigations of ileal PP follicular (iPf)B cell biology. We investigated the possibility that sustained iPfB cell proliferation may require an interaction with mesenchymal stromal cells (SC). Four SC lines, cloned from lymphoid follicles of the ileal PP, and various sheep and xenogeneic mesenchymal cells were used to characterize the nature of iPfB cell-SC interactions. A sustained proliferative response was unique to iPfB cells, required iPfB cell-SC contact, and SC membranes functioned as intact SC to either enhance or inhibit iPfB cell proliferative responses. The iPfB cell proliferation in SC co-cultures was accompanied by extensive cell death and a slow decline in viable cell number. Flow cytometric analysis confirmed that viable lymphocytes, present in SC co-cultures, were immature B cells that expressed surface IgM, with either lambda or kappa. Ig light chain, and that SC co-culture inhibited iPfB cell differentiation. Finally, addition of soluble anti-sheep Ig to iPfB cell-SC co-cultures did not inhibit SC-dependent iPfB cell proliferation or iPfB cell binding to SC. These data indicate that an interaction between specific SC membrane molecules and non-Ig molecules of iPfB cells either supported or inhibited a self-renewing proliferative response by immature (sIgMLo, BAQ44A-) iPfB cells. Finally, SC-dependent iPfB cell proliferation was independent of T cells and extrinsic antigen which further suggests that a functionally distinct B cell population resides in lymphoid follicles of the ileal PP.

Si transistors with deterministically implanted donors were fabricated by single-ion implantation method and their quantum transport was investigated. By placing donors in one dimensional array, we observed the transport characteristics categorized into two regimes: single-electron tunneling through isolated D0 and D− states; Hubbard band formation due to the inter-donor coupling.

In this paper we present a compact system for impedance measurement in the kHz-MHz frequency range with attoFarad resolution. It has been designed to address micro- and nano-scale bio-sensing applications, such as impedimetric flow cytometry or molecular affinity bio-sensors. The core of the detection system is an integrated circuit that features a low noise current amplifier, a two-phase square waveform lock-in detector and two ΣΔ analog-to-digital converters. The CMOS chip is complemented by all the blocks needed to perform spectroscopy measurements, including versatile signal generation, digital processing and PC data transmission. The whole stand-alone system is USB powered and can reach sub-fF resolution in capacitive tracking on a sub-millisecond time scale.

Lab-on-a-chip systems have been attracting a growing attention for the perspective of miniaturization and portability of bio-chemical assays. Here we present a the design and characterization of a miniaturized, USB-powered, self-contained, 2-channel instrument for impedance sensing, suitable for label-free tracking and real-time detection of cells flowing in microfluidic channels. This original circuit features a signal generator based on a direct digital synthesizer, a transimpedance amplifier, an integrated square-wave lock-in coupled to a Σu ADC converter, and a digital processing platform. Real-time automatic peak detection on two channels is implemented in a FPGA. System functionality has been tested with an electronic resistance modulator to simulate 1% impedance variation produced by cells, reaching a time resolution of 50μs (enabling a count rate of 2000 events/s) with an applied voltage as low as 200mV. Biological experiments have been carried out counting yeast cells. Statistical analysis of events is in agreement with the expected amplitude and time distributions. 2-channel yeast counting has been performed with concomitant dielectrophoretic cell separation, showing that this novel and ultra compact sensing system, thanks to the selectivity of the lock-in detector, is compatible with other AC electrical fields applied to the device.

We study a stochastic, continuous time model on a finite horizon for a firm that produces a single good. We model the production capacity as an Ito diffusion controlled by a nondecreasing process representing the cumulative investment. The firm aims to maximize its expected total net profit by choosing the optimal investment process. That is a singular stochastic control problem. We derive some first order conditions for optimality and we characterize the optimal solution in terms of the base capacity process, i.e. the unique solution of a representation problem in the spirit of Bank and El Karoui (2004). We show that the base capacity is deterministic and it is identified with the free boundary of the associated optimal stopping problem, when the coefficients of the controlled diffusion are deterministic functions of time. This is a novelty in the literature on finite horizon singular stochastic control problems. As a subproduct this result allows us to obtain an integral equation for the free boundary, which we explicitly solve in the infinite horizon case for a Cobb-Douglas production function and constant coefficients in the controlled capacity process., Comment: 23 pages

The increase in the understanding of the physical and functional properties of the biological material, from the cellular level down to single molecules, owes its success to the development of suitable high-sensitivity platforms to image the biomaterial and analyze its response to specific stimuli. Imaging has indeed reached molecular capabilities, thanks to optical or magnetic markers [1], to the atomic force microscopy (AFM) in surface reconstruction [2], and is nearing success in three-dimensional (3-D) reconstruction thanks to X-ray holography [3].

SUMMARYIn recent years,Salmonella enteritidishas become an increasingly important public health problem in Italy. In some parts of the country, the fraction of total human salmonella isolates accounted for byS. enteritidishas risen from 3–4% in the mid-1980s to more than 30% in 1990. Between 1090 and 1991. the number of reportedS. enteritidisoutbreaks increased more than sixfold. The 33 outbreaks reported in 1991 occurred in seven contiguous regions in northern and central Italy and were clustered in time between June and October: in the majority, products containing raw or undercooked shell eggs were implicated. Five of the egg-related outbreaks that occurred within a 30 kilometre radius over a 7-week period were investigated in detail. A phage type 1 strain containing a 38·9 MDa plasmid appeared responsible for three of the outbreaks, while in the remaining two a phage type 4 strain, also with a 38·9 MDa plasmid was isolated. Efforts are being made to enhance epidemiological surveillance and laboratory evaluation, and the use of pasteurized eggs has been recommended for high-risk populations.

The aim of this study was to report the frequency of kidney diseases related to gender, age, clinical presentation and renal function at the time of kidney biopsy in the population of Mantua province (400,000 residents). We collected the results of 132 real-time ultrasound-guided fine-needle (18 G) kidney biopsies by optical and immunofluorescence microscopy. The clinical presentation at the time of biopsy was nephrotic syndrome in 57%, nephritic syndrome in 22%, and urinary abnormalities in 21% of cases. Serum creatinine was-1.5 mg/dL in 48% of patients. Membranous nephropathy was the most frequent histological finding (21.4%), followed by IgA nephropathy (14.5%), focal glomerulosclerosis (11.5%), diabetic nephropathy (8.4%), and chronic interstitial nephritis (6.9%). Primary glomerulonephritis including membranous glomerulonephritis and IgA nephropathy showed a male predominance. The pathological correlations in native biopsy-proven renal disease provided useful information for clinical practice. The histological findings in our patient series are similar to those recorded in Italian and European registries. A less invasive policy in the case of isolated urinary abnormalities and a normal eGFR resulted in a lower incidence of IgA nephropathy in our series than was recorded in the national Italian registry.

The design and experimental characterization of a novel electronic control unit for fly-by-wire aircraft actuators are presented. Thanks to a carefully-engineered compact volume, it is embedded in the actuator body, providing local closed-loop control. Various digital control laws can be implemented in the easily reconfigurable digital platform. After system modeling and tuning, a variable-gain controller has been selected. Beyond reduction of weight (900g), power dissipation (7W) and cabling connections (required only for power supply and digital communication bus), the advantages provided by this smart unit are both in terms of performance and safety improvement. In fact, fast (1Hz) and precise (1mm resolution, 2mm accuracy, no overshoot) closed-loop linear displacement regulation is here demonstrated. Furthermore, this robust and rugged unit is endowed with self-diagnostic capabilities: fault detection of all critical electronic and electro/mechanical sections is implemented by dedicated analog circuits. It is suitable for fully-electrical and hybrid electro-hydraulic actuators. Extensive thermal characterization has confirmed the fulfillment of specifications over the whole −40°C ÷ +70°C operating range.

A multiphysics model for Phase Change Memory (PCM) is calibrated on a large set of experimental data. Critical material and interface properties such as electrical and thermal resistivities and their dependence on temperature are extracted from data or fitting electrical characteristics with numerical simulations. The model is shown to match with a unique set of parameters experimental data from 90nm and 45nm technology nodes. The calibrated model is then exploited to perform a sensitivity analysis of key cell characteristics to geometry and material properties variations. Furthermore, the model is used to predict performance of a scaled down cell suitable for the 32nm technology node and the results demonstrate the consistent scalability of PCM with respect to the technology node.

A recently developed synchrotron-based imaging technique, X-ray diffraction microtomography (XRD-CT), has been applied here for the first time to a complex system, the hydrating Portland cement paste, in order to monitor the evolution of microstructure and phase formation with a 3D non-invasive imaging approach. The ettringite-XRD-peak-based image reconstructions, combined with transmission microtomography (X-microCT) images, allowed to assess the ubiquitous distribution of this phase, which appears early in the hydration process and showed its preferential concentration in the relatively less compact regions of the paste. The comparison of greyscale histograms for cement pastes after 9 and 58 h from hydration showed an increase of ettringite content with age, in agreement with the quantitative Rietveld analysis of the sum patterns. By renormalizing the greyscale histograms to the relative weight fraction, as obtained from Rietveld refinements, a new technique which allows estimation of phase contents with spatial resolution has been developed. The results achievable by combining XRD-CT, X-microCT and Rietveld appear very promising to provide experimental snapshots of the cement hydration process to be compared with results obtained from computer simulations.

Millions of cubic meters of sediments are dredged every year in the world. About 10–20% on weight basis of this material is contaminated by organic and/or inorganic pollutants. This work presents the laboratory tests performed to study a system for the remediation and reuse of mercury-contaminated sediments. The treatment is based on a cement-based granulation step (solidification/stabilization (S/S)), followed by a thermal process under vacuum during which volatile and semi-volatile compounds are removed. The experiments focused on: (1) cement hydration reactions; (2) pollutant removal efficiencies; and (3) leaching behavior, in relation to temperature and duration of the thermal process. Mercury speciation was also investigated. Dredged at the marine harbor of Augusta (SR, Italy), the sediments used in the experiments were highly polluted by mercury (200 mg kg−1 dry weight (d.w.)). The recipe applied in the S/S step was based on the particle size distribution of the resulting granulates. An indirectly–heated batch system operated under vacuum (2.6 ± 1.3 103 Pa) at: (1) 150°C for 16 h; (2) 200°C for 6 h; (3) 250°C for 4 h; or (4) 280°C for 4 h. X-ray diffraction spectroscopy and scanning electron microscopy were used to study cement hydration reactions. Total mercury concentration and leaching tests were carried out to assess the effects of the different treatment conditions. The best results were obtained by treating the granulate at 250°C for 4 h. Under these conditions, mercury final concentration was 49 mg kg−1 d.w., resulting in a removal efficiency of 63% referred to the granular material before thermal treatment, and 75% referred to the sediment. The concentrations measured in the leachate were compatible with the Italian requirements for reuse, with some exceptions (pH, chlorides, nickel, copper, and COD) ascribed to the specific nature of the sediment. Mercury speciation analyses pointed out changes after both the treatment steps. The final granulates accomplish most Italian requirements for reuse, even though an improvement in the S/S step or an additional washing step would help for the exceptions mentioned above. Different reuse options in civil engineering (e.g., filling material, road material, concrete aggregates, etc.) will be evaluated also taking into consideration the mechanical properties. Further studies will be carried out to assess the long-term leaching behavior and leaching under different pH conditions.

We measure the temperature of a mesoscopic system consisting of an ultra-dilute two dimensional electron gas at the $Si/SiO_2$ interface in a metal-oxide-semiconductor field effect transistor (MOSFET) quantum dot by means of the capture and emission of an electron in a point defect close to the interface. Contrarily to previous reports, we show that the capture and emission by point defects in Si n-MOSFETs can be temperature dependent down to 800 mK. As the finite quantum grand canonical ensemble model applies, the time domain charge fluctuation in the defect is used to determine the temperature of the few electron gas in the channel., Comment: 4 Figures (color)

By using a correlation spectrum analyzer, we succeeded in performing direct measurements of the current noise spectra of cadmium telluride (CdTe) diodes, commonly used in γ-ray spectrometers. The current noise spectra have been measured over a wide range of frequencies, from below 1 Hz up to 100 kHz, and for diode operating points from 0 up to 150 V. The device showed linear I–V characteristics in all the bias range with a dynamic resistance of about 2 GΩ. Around the equilibrium condition (0–0.5 V), the white component of the noise spectrum is in agreement with the Johnson noise associated to the device resistance. As the bias is increased up to 150 V, the white noise level is shown to slowly approach the shot noise behavior. The white noise shows a cut-off frequency consistent with the carriers transit time across the device. In all the nonequilibrium conditions, the noise spectra also show a significant 1/f component whose power density increases with the square of the device current.