AXL Receptor in Breast Cancer: Molecular Involvement and Therapeutic Limitations

Breast cancer was one of the first malignancies to benefit from targeted therapy, i.e., treatments directed against specific markers. Inhibitors against HER2 are a significant example and they improved the life expectancy of a large cohort of patients. Research on new biomarkers, therefore, is always current and important. AXL, a member of the TYRO-3, AXL and MER (TAM) subfamily, is, today, considered a predictive and prognostic biomarker in many tumor contexts, primarily breast cancer. Its oncogenic implications make it an ideal target for the development of new pharmacological agents; moreover, its recent role as immune-modulator makes AXL particularly attractive to researchers involved in the study of interactions between cancer and the tumor microenvironment (TME). All these peculiarities characterize AXL as compared to other members of the TAM family. In this review, we will illustrate the biological role played by AXL in breast tumor cells, highlighting its molecular and biological features, its involvement in tumor progression and its implication as a target in ongoing clinical trials.     

Radial junctions formed by conformal chemical doping for innovative hole-based solar cells

In this paper an innovative approach for Si solar cells based on radial junctions is presented. It consists of fabricating the junction in quasi one-dimensional structures like holes. The hole-based architecture, while maintaining the decoupling between the light absorption and the electrical collection typical of the more common wires and rods, ensures more robustness, numerous waveguide coupling modes and possibility to form non-conformal top contact. Nanosizes also provide the possibility to tune the band gap by quantum effects. Doping of the nanoholes, like in the case of nanowires, presents critical issues like conformality and control of the dopant dose and junction depth at nanometric level. We propose to dope the nanoholes by using a chemical method based on the use of a dopant containing molecules dispersed in solution. We apply the procedure on an array of holes of micrometric sizes fabricated to test and study the method and to properly scale it down and implement it on the nanostructures. Results show that the method provides junction depths in the nm scale with dopant peak concentrations as high as 10¹⁹ cm^?3 and that the doping is conformal on the vertical surfaces of the hole.     

Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.     

Lactate as a Metabolite and a Regulator in the Central Nervous System

More than two hundred years after its discovery, lactate still remains an intriguing molecule. Considered for a long time as a waste product of metabolism and the culprit behind muscular fatigue, it was then recognized as an important fuel for many cells. In particular, in the nervous system, it has been proposed that lactate, released by astrocytes in response to neuronal activation, is taken up by neurons, oxidized to pyruvate and used for synthesizing acetyl-CoA to be used for the tricarboxylic acid cycle. More recently, in addition to this metabolic role, the discovery of a specific receptor prompted a reconsideration of its role, and lactate is now seen as a sort of hormone, even involved in processes as complex as memory formation and neuroprotection. As a matter of fact, exercise offers many benefits for our organisms, and seems to delay brain aging and neurodegeneration. Now, exercise induces the production and release of lactate into the blood which can reach the liver, the heart, and also the brain. Can lactate be a beneficial molecule produced during exercise, and offer neuroprotection? In this review, we summarize what we have known on lactate, discussing the roles that have been attributed to this molecule over time.     

Design methodology for the optimization of transformer-loaded RF circuits

In this paper, a design methodology for the optimization of transformer-loaded RF circuits is presented. The optimization procedure is based on a novel figure of merit for the integrated transformer (namely the transformer characteristic resistance), which was introduced to quantify its performance when operated as a tuned load. Using the proposed approach, a highly linear up-converter for 5-GHz wireless LAN applications was implemented in a 45-GHz-f/sub T/ SiGe HBT technology. The circuit achieved an output 1-dB compression point of 4.5 dBm and a power gain of 18 dB, while drawing only 34 mA from a 3-V power supply.     

A 5-GHz highly integrated receiver front-end

In this paper a radio front-end for a IEEE 802.11a and HIPERLAN2 sliding-IF receiver is presented. The circuit, implemented in a low-cost 46-GHz-f _T silicon bipolar process, includes a variable-gain low noise amplifier and a double-balanced mixer. Thanks to monolithic LC filters and on-chip single-ended-to-differential conversion of the RF signal, the proposed solution does not require the expensive image rejection filter and an external input balun. The receiver front-end exhibits a 4.3-dB noise figure and a power gain of 21 dB, providing an image rejection ratio higher than 50 dB. By using a 1-bit gain control, it achieves an input 1-dB compression point of −11 dBm, while drawing only 22 mA from a 3-V supply voltage.     

Low-power broadband quadrature signal generator based on phase-tunable dividers

This paper presents the design and experimental results of a low-power 300–960 MHz I/Q signal generator for low-IF receivers. The circuit is based on phase-tunable dividers and uses delay-locked loops, which provide phase accuracy for the quadrature signals as well as low-sensitivity of the phase error against temperature and power supply variations. Thanks to the adopted technique, the phase error can be further reduced by trimming the reference voltage of the delay-locked loops through a calibration digital word, which can be stored in a non-volatile memory during manufacturing. The I/Q generator exhibits an absolute phase error before calibration that is lower than 1.5°. The I/Q phase drift due to temperature variations from ?40 to 85 °C and power supply variations from 1.1 to 1.3 V is 0.3° and 0.2°, respectively. By dividing the overall frequency range into four 165-MHz wide sub-bands and using only four 5-bit calibration words, the I/Q phase variation with respect to frequency, temperature, and power supply is lower than 1° in the 300–960 MHz operating band. The I/Q generator is implemented in a 90-nm CMOS technology and exhibits a current consumption as low as 0.5 mA.     

Digitally controlled linear-in-dB variable-gain amplifier for high-frequency applications

A design technique to implement a digitally controlled dB-linear variable-gain amplifier (VGA) for high-frequency applications is presented. The design approach is applicable to current-steering VGAs and is based on a digital gain control circuit that operates as a nonlinear digital-to-analogue converter to achieve a digitally controlled dB-linear gain control characteristic. Using the proposed approach, a variable-gain up-converter for 5-GHz wireless LAN applications has been fabricated with a low-cost 46-GHz-f_rceil silicon bipolar technology. The adopted VGA, operating at a frequency of 1 GHz, provides a linear-in-dB gain control characteristic over a 30-dB dynamic range with a 2-dB step and a +0.8-dB gain error.     

An iterative method for the computation of the solutions of nonlinear equations

In this paper, we present new iterative methods for the computation of zeros of C ¹ functions. The idea is mainly based on a new asymptotic expansion (the Bernoulli expansion) for regular functions. Just as the Newton method is derived from the linear part of the Taylor polynomial, the new methods are analogously derived from the quadratic part of the Bernoulli expansion. We prove that the proposed procedures combine the assured convergence of bisection-like algorithms with a superlinear convergence speed which characterizes Newton-like methods. We show that the order of this new procedure is p= 2 and that the cost per iteration is completely equivalent to that of the Newton method. Finally some numerical experiments are performed. The related results seem to indicate that at least one of the proposed techniques works better than the Newton method. Moreover, the given method used in connection with an enclosing-interval procedure [2], is competitive with the ones recently proposed by Alefeld and Potra [2]. Received: July 1997 / Accepted: January 1998     

A silicon bipolar transmitter front-end for 802.11a and HIPERLAN2 wireless LANs

A 5-GHz transmitter front-end for 802.11a and HIPERLAN2 wireless local area networks was implemented in a low-cost 46-GHz-f/sub T/ silicon bipolar technology. The transmitter includes a digitally controlled linear-in-dB variable-gain up-converter and a three-stage linear power amplifier. At a 3-V supply voltage, the front-end exhibits a 23.5-dBm output 1-dB compression point, 35-dB maximum power gain, and 30-dB dynamic range. The dB-linear gain error is lower than /spl plusmn/0.8 dB. The transmitter is able to comply with the stringent error vector magnitude requirement of the standard up to a 19-dBm output power level.