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Biomedical subjects

M Pappalardo

Publications and source records attributed to M Pappalardo.

17 recordsLinked to original sources

A molecular dynamics approach to the structural characterization of amyloid aggregation.

A novel computational approach to the structural analysis of ordered beta-aggregation is presented and validated on three known amyloidogenic polypeptides. The strategy is based on the decomposition of the sequence into overlapping stretches and equilibrium implicit solvent molecular dynamics (MD) simulations of an oligomeric system for each stretch. The structural stability of the in-register parallel aggregates sampled in the implicit solvent runs is further evaluated using explicit water simulations for a subset of the stretches. The beta-aggregation propensity along the sequence of the Alzheimer's amyloid-beta peptide (Abeta(42)) is found to be highly heterogeneous with a maximum in the segment V(12)HHQKLVFFAE(22) and minima at S(8)G(9), G(25)S(26), G(29)A(30), and G(38)V(39), which are turn-like segments. The simulation results suggest that these sites may play a crucial role in determining the aggregation tendency and the fibrillar structure of Abeta(42). Similar findings are obtained for the human amylin, a 37-residue peptide that displays a maximal beta-aggregation propensity at Q(10)RLANFLVHSSNN(22) and two turn-like sites at G(24)A(25) and G(33)S(34). In the third application, the MD approach is used to identify beta-aggregation "hot-spots" within the N-terminal domain of the yeast prion Ure2p (Ure2p(1-94)) and to design a double-point mutant (Ure2p-N4748S(1-94)) with lower beta-aggregation propensity. The change in the aggregation propensity of Ure2p-N4748S(1-94) is verified in vitro using the thioflavin T binding assay.

Amino Acid Sequence↗

Propagation-independent fields.

Nondiffracting beams are solutions of the wave equation which keep their shape during free propagation. Because of this property, they are widely studied, both as mechanical and electromagnetic waves. Another scheme, however, can be devised in order to find beams that, even if do not maintain their shape upon propagation, are independent on the propagation distance, apart from a phase factor. In this sense it can be said that these beams are also nondiffracting. In this work, the scheme leading to this different kind of nondiffracting fields, which we term propagation-independent beams, is presented. Closed-form expressions for a few of these fields, for 1-D sources, are found. A method, which in principle is able to produce beams of this type, is given. This also clarifies some of their properties. Finally, the item of finite realizations of these beams, which in principle require infinite-dimension sources, is analyzed through numerical simulations. It is also shown that the practical feasibility of these fields poses some limitations on the bandwidth they can present.

Journal Article↗

PSpice modeling of capacitive microfabricated ultrasonic transducers.

Capacitive microfabricated ultrasonic transducers (cMUTs) are the newest and potentially the most promising devices to convert electrical into acoustic signals and vice-versa. These devices are based on the capacitance modulation of a microcondenser which is obtained by microfabrication onto a silicon substrate. The aim of this paper is to describe a PSpice model of the cMUT, based on an analytical distributed model previously reported (IEEE Trans. UFFC 49 (2) (2002) 159-168), which can be used to simulate the performances of a general ultrasound system, either in frequency or time domain. The PSpice model consists of a capacitor with a parallel resistor, which represent the static capacitance and the loss and bias resistances of the transducer, respectively, plus two quadrupoles (GLAPLACE) modeling the mechanical impedance of the membranes and the radiation impedance of the medium. The usefulness of a PSpice model is the possibility to simulate and optimize the cMUT transducers in transmission and reception, along with driving and receiving electronics, in a general ultrasound system. Experimental measurements on a 5 MHz cMUT operating in pulse-echo are in good agreement with model predictions.

Journal Article↗

An allele associated with a non-detectable amount of alpha s2 casein in goat milk.

The goat CSN1S2 locus is characterized by the presence of three alleles, A, B and C, all associated with about 2.5 g/l of protein per allele. The SDS-PAGE analysis of 441 individual milk samples obtained from goats belonging to a population reared in Southern Italy showed that the milk produced by three goats did not apparently contain alpha s2-casein, whereas milk produced by 37 goats showed a less intense electrophoretic band of this casein fraction (about 50%). These results can be explained by hypothesizing the presence of another allele at this locus, CSN1S2o, associated with a 'null' content of alpha s2-casein. Southern blot, PCR and PCR-RFLP analyses of the DNA region containing the CSN1S2 gene of individuals producing milk with and without alpha s2-casein did not show differences between the two groups. As a consequence, goats producing milk without alpha s2-casein carry an apparently intact gene. The first results obtained by sequencing part of the CSN1S2o allele revealed a G-->A transition at nucleotide 80 of the 11th exon which creates a stop codon and could be responsible for the absence of the alpha s2-casein in goat milk. This mutation eliminates a NcoI restriction site. A test based on this polymorphism has been established in order to identify carriers of the CSN1S2o allele.

Alleles↗

Characterization of two new alleles at the goat CSN1S2 locus.

Two novel alleles at the goat CSN1S2 locus have been identified: CSN1S2(F) and CSN1S2(D). Sequence analyses revealed that the CSN1S2(F) allele is characterized by a G --> A transition at the 13th nucleotide in exon 3 changing the seventh amino acid of the mature protein from Val to Ile. The CSN1S2(D) allele, apparently associated with a decreased synthesis of alpha s2-casein, is characterized by a 106-bp deletion, involving the last 11 bp of the exon 11 and the first 95 bp of the following intron. Methods (PCR-RFLP and PCR) for identification of carriers of these alleles have been developed.

Alleles↗

Frequency decomposition and compounding of ultrasound medical images with wavelet packets.

Ultrasound beams propagating in biological tissues undergo distortions due to local inhomogeneities of the acoustic parameters and the nonlinearity of the medium. The spectral analysis of the radio-frequency (RF) backscattered signals may yield important clinical information in the field of tissue characterization, as well as enhancing the detectability of tissue parenchymal diseases. In this paper, we propose a new tissue spectral imaging technique based on the wavelet packets (WP) decomposition. In a conventional ultrasound imaging system, the received echo-signals are generally decimated to generate a medical image, with a loss of information. With the proposed approach, all the RF data are processed to generate a set of frequency subband images. The ultrasound echo signals are simultaneously frequency decomposed and decimated, by using two quadrature mirror filters, followed by a dyadic subsampling. In addition, to enhance the lesion detectability and the image quality, we apply a nonlinear filter to reduce noise in each subband image. The proposed method requires simple additional signal processing and it can be implemented on any real-time imaging system. The frequency subband images, which are available simultaneously, can be either used in a multispectral display or summed up together to reduce speckle noise. To localize the different frequency response in the tissues, we propose a multifrequency display method where three different subband images, chosen among those available, are encoded as red, green, and blue intensities (RGB) to create a false-colored RGB image. According to the clinical application, different choices can evidence different spectral proprieties in the biological tissue under investigation. To enhance the lesion contrast in a grey-level image, one of the possible methods is the summation of the images obtained from narrow frequency subbands, according to the frequency compounding technique. We show that by adding the denoised subband images created with the WP decomposition, the contrast-to-noise ratio in two phantom images is largely increased.

Image Processing, Computer-Assisted↗

Optimization of wide-band linear arrays.

An optimization method is proposed for linear arrays to be used in ultrasound systems under wide-band operation. A fast algorithm, the threshold accepting, has been utilized to determine the element positions and weight coefficients of a linear array that generates a desired beam pattern. To reduce the computational burden in the optimization procedure, an efficient numerical routine for the beam pattern evaluation has been implemented. We address the optimization problem of both dense and sparse wide-band arrays. In the first case, the goal is to minimize the side-lobe energy by varying the element weights; we compare the optimized beam pattern with that obtained with classical shading functions, showing that better results can be achieved with a wide-band optimization. We also consider the optimization of the layout (positions and weights) of a sparse linear array to achieve a desired beam pattern with a fixed or minimum number of array elements. The comparison of the proposed method with a narrow-band optimization algorithm is presented, showing that better performances (about -7 dB further reduction of the side-lobe level) can be achieved with a wide-band sparse array optimization. Further numerical simulations are given, showing that the proposed method yields better results than wide-band sparse random arrays and periodic arrays with the same aperture width.

Journal Article↗

A novel approach to the aperture windowing in medical imaging.

A new technique is proposed to improve the lateral resolution in the conventional B-mode imaging systems, which enables a simple array aperture windowing in the transmitting mode. Amplitude shaping is performed without modifying the transmitting voltage of the array elements, but only varying the excitation pulse length from one element to another. This method presents some attractive practical advantages, and the reduction of the sidelobe energy is comparable to that attainable with a conventional aperture windowing. Parametric plots are given, which transform an amplitude apodization into a 'time apodization' for any type of transducer array.

Ultrasonography↗

A new beamforming technique for ultrasonic imaging systems

We propose a simple, versatile and inexpensive beamforming method that performs the aperture windowing of an ultrasonic transducer array in the transmit mode, without modifying the driver voltage, but simply controlling the length of the electric pulse driving the array elements. A conversion formula has been determined that permits us to compute, for a desired emitted pulse amplitude, the corresponding driving pulse length to be applied. Any shading function can be implemented over any type of transducer array, using very low-cost hardware. Computer simulations and experimental measurements, with a 3.8 MHz convex array, confirm the effectiveness of this approach in enhancing the contrast resolution, since the off-axis intensity in the radiated beam pattern is largely reduced.

Journal Article↗

A matrix model of the axle vibration of a piezoelectric motor

In this work, a matrix model of the axle vibration of a piezoelectric motor is proposed. The stator of this motor is composed of a thin piezoelectric membrane and a steel axle fitted at the center of the membrane. The rotor consists of a cylinder-shaped permanent magnet, pressed in contact with the other end of the axle by means of the magnetic forces. A travelling wave is excited in the membrane by using four electrodes and four, properly delayed, driving signals. The rotating flexural displacement of the membrane produces a wide precessional motion of the axle. In this way, a continuous slipping takes place between the axle and the rotor, and therefore, a torque is transmitted to the rotor. In this paper, the precessional motion of the axle is modeled as the composition of two transverse vibrations belonging to two perpendicular planes passing through the axle. The axle, vibrating in its transverse mode, is modeled as a two-port system: the input is the bending moment supplied by the membrane, and the output is the transverse force at the terminal end of the axle. With this model, we have computed the trasmission transfer function as a function of frequency, and the transversal displacement along the axle at its resonance frequency. The computed results are in reasonable agreement with experimental interferometric measurements carried out on a prototype.

Journal Article↗

Synthesis of some derivatives of 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(piperazin-1-yl)-3-quino linecarbo xylic acid (norfloxacin) as potential antibacterial agents.

Twelve new fluoroquinolones, structurally related to norfloxacin, have been synthesized in order to investigate the effect of substituents at the secondary nitrogen of the piperazine ring on antimicrobial activity. The new substances (carbamates, isoureas, guanidines, ureas and cyanamides) tested on a variety of gram-positive and gram-negative organisms showed lower activity than the model compound.

Anti-Bacterial Agents↗

Synthesis and calcium antagonistic activity of a new class of 1,4-dihydropyridines having an alkoxyimino group in position 3.

The synthesis of new 1,4-dihydropyridines having an alkoxyimino group in position 3 is described. Pharmacological evaluation included calcium antagonistic activity in the guinea pig Taenia coli test, acute toxicity and oral antihypertensive activity in SHR. The compounds had a remarkable calcium antagonistic activity in vitro and low toxicity, but no antihypertensive activity in vivo, probably due to an unfavourable pharmacokinetic profile.

Animals↗

Echographic imaging with dynamically focused insonification.

This work describes a real-time echographic imaging device with lateral scanning and a new process for dynamic focusing. While, in reception, a time varying focus is a well-established process, the system that we propose is able to perform dynamic focusing also in transmission. This is carried out by emitting several acoustic pulses focused in different regions. This process, which we call dynamic focused insonification, gives good results and can be used either alone or in connection with dynamic focusing in reception.

Image Enhancement↗

Specific kappa opioid receptor agonists.

The results of studies on the design of a heterocyclic scaffold for the dynorphin A pharmacophore and on structure-affinity relationships in the MPCB/CCB series are described. The representative ligands provide insights to binding modes of benzomorphan derivatives to the kappa opioid receptor.

Analgesics, Opioid↗