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Advancements in stem cell technology together with an improved understanding of in vitro organogenesis have enabled new routes that exploit cell-autonomous self-organization responses of adult stem cells (ASCs) and homogenous pluripotent stem cells (PSCs) to grow complex, three-dimensional (3D), mini-organ like structures on demand, the so-called organoids. Conventional optical and electrical neurophysiological techniques to acquire functional data from brain organoids, however, are not adequate for chronic recordings of neural activity from these model systems, and are not ideal approaches for throughput screenings applied to drug discovery. To overcome these issues, new emerging approaches aim at fusing sensing mechanisms and/or actuating artificial devices within organoids. Here we introduce and develop the concept of the Lab-in-Organoid (LIO) technology for in-tissue sensing and actuation within 3D cell aggregates. This challenging technology grounds on the self-aggregation of brain cells and on integrated bioelectronic micro-scale devices to provide an advanced tool for generating 3D biological brain models with in-tissue artificial functionalities adapted for routine, label-free functional measurements and for assay's development. We complete previously reported results on the implementation of the integrated self-standing wireless silicon micro-devices with experiments aiming at investigating the impact on neuronal spheroids of sinusoidal electro-magnetic fields as those required for wireless power and data transmission. Finally, we discuss the technology headway and future perspectives. [ABSTRACT FROM AUTHOR]

FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of miRNAs (MIR) as modulators of chemosensitivity to identify potential biomarkers of response. We find that 41 and 84 microRNA inhibitors enhance the sensitivity of Capan1 and MiaPaCa2 PDAC cells respectively. These include a MIR1307-inhibitor that we validate in further PDAC cell lines. Chemotherapy-induced apoptosis and DNA damage accumulation are higher in MIR1307 knock-out (MIR1307KO) versus control PDAC cells, while re-expression of MIR1307 in MIR1307KO cells rescues these effects. We identify binding of MIR1307 to CLIC5 mRNA through covalent ligation of endogenous Argonaute-bound RNAs cross-linking immunoprecipitation assay. We validate these findings in an in vivo model with MIR1307 disruption. In a pilot cohort of PDAC patients undergoing FOLFIRONX chemotherapy, circulating MIR1307 correlates with clinical outcome. Understanding which patients will respond to FOLFIRINOX therapy is important for clinical outcome. Here, the authors show that the MIR1307 is increased pancreatic cancer cell lines and inhibition of the microRNA sensitises cells to treatment.' stratifying patients to achieve the best clinical outcome. Here, the authors show that the MIR1307 is increased in a subgroup of human pancreatic cancers and inhibition of the microRNA in in vitro and in vivo models of pancreatic cancer sensitises cells to treatment. [ABSTRACT FROM AUTHOR]

This letter describes a single-transistor oscillator implemented on a paper substrate at the operating frequency of 24 GHz, based on a design procedure that makes it possible to overcome the limitations caused by thin high-loss substrates and package parasitics of commercial components. The commercial transistor adopted in the oscillator is led to instability by exploiting its parasitic gate inductance. The drain network compensates for the parasitic inductance of the transistor package and connects the oscillator circuit to a 50- $\Omega $ load resistance. Finally, an external inductor at the source terminal is used to resonate out the capacitive contribution of the circuit at the oscillation frequency. Overall, the active device appears in a quasi-common-drain stage. Experimental results on prototype show that the oscillator exhibits an output power of +6.2 dBm at 24 GHz, with a dc power consumption of 72.5 mW. [ABSTRACT FROM AUTHOR]

River discharge is an important variable to measure in order to predict droughts and flood occurrences. Once the cross-sectional geometry of the river is known, discharge can be inferred from water level and surface flow velocity measurements. Since river discharges are of particular interest during extreme weather events, when river sites cannot be safely accessed, noncontact sensing technologies are particularly appealing. To this purpose, this work proposes a prototype of a low-cost continuous wave (CW) Doppler radar sensor, which is able to monitor the surface flow velocity of rivers. The prototype is tested at two gauged sites in central Italy, along the Tiber River. The surface flow velocity distribution across the river is monitored by means of the analysis of received Doppler signal. The surface velocity statistics are then extracted using a novel algorithm that is optimized to run on a microprocessor platform with minimal computing power (ArduinoUNO). In particular, the radar measurements are used to initialize a 2-D entropy-based velocity model (EVM) that is able to estimate river discharges in any flow condition. Finally, the results concerning the observed discharge provided by the EVM prove to be comparable with those obtained with more expensive commercial solutions. The results are important since the described methodology can be extended to small-size Doppler radar sensors onboard unmanned aerial vehicles (UAVs), the latter providing a method for mapping surface velocity of rivers. [ABSTRACT FROM AUTHOR]

Summary: We propose a novel CMOS differential voltage‐controlled equivalent active resistor based on a modified common‐source cross‐coupled pair. The equivalent resistance exhibited by the circuit can be tuned to be either positive or negative through the tail current, which is controlled by a bias voltage. The complete cell comprises four transistors, two resistors in addition to the bias voltage, and tail current source. Application to the design of oscillators is demonstrated by theoretical analysis, circuit simulations, and verified experimentally through measurements on prototypes implemented using discrete transistors. In this work, we propose a novel tunable negative or positive differential resistance implemented using four transistors, which offers an advantage over the conventional cross‐coupled differential pair. The advantage being that the equivalent resistance exhibited by the circuit can be tuned to be either negative or positive through a tail current as well as via a bias voltage. Its linearity and range of operation are examined, and applications to oscillators are demonstrated through simulations and experiments. [ABSTRACT FROM AUTHOR]

This paper reports the analyses of the inductive degeneration, noise filter, and optimum current density techniques for phase noise reduction in the CMOS Hartley oscillator circuit topology. The design of the circuit topology is carried out in 28 nm bulk CMOS technology in a range of common conditions adopted also for a previous study on the Colpitts topology, so complementing the previous study on Colpitts topology and allowing a direct comparison between the Hartley and Colpitts topologies. The theoretical analyses of the three techniques are carried out and verified by means of circuit simulations. The results obtained for the inductive degeneration and noise filter show the existence of an optimum inductance for minimum phase noise. Moreover, the results obtained for the optimum bias current density technique applied to a Hartley oscillator circuit topology incorporating either inductive degeneration or noise filter provide the demonstration of the existence of an optimum bias current density for minimum phase noise. Moreover, we will go beyond this important result, by investigating for the first time the relationship with the optimum current density for transistor minimum noise figure and other general results reported in the literature. Overall, the analyses show that the adoption of these techniques may lead to a potential phase noise reduction up to 16 dB at a 1 MHz frequency offset for an oscillation frequency of 10 GHz, with respect to the traditional Hartley topology. Lastly, we report a comparison under common conditions between Colpitts and Hartley topologies implementing the aforementioned techniques, which could, from a designer perspective, be useful to acquiring a few key insights about the circuit design opportunities and focus the design efforts toward specific directions for performance optimizations. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A 50 GHz cross-coupled differential-pair oscillator with a high-Q active inductor in the LC tank has been designed and fabricated in 65 nm bulk complementary metal-oxide semiconductor (CMOS) technology. The principle of operation is explained and a complete theoretical study is carried out. The analytical expressions for the open loop transfer function, oscillation frequency, start-up condition, tank impedance, and phase noise are derived. The results of the analytical study are compared with those obtained by SpectreRF simulations in the Cadence design environment. Measurement results of the stand-alone mm-wave active inductor show an equivalent inductance of 133 pH with a quality factor exceeding 400 at 50 GHz, demonstrating experimentally the implementation of high-Q active inductors operating at the millimeter waves in CMOS technology. The measurement results of the oscillator show a phase noise of −85 dBc/Hz at 1 MHz frequency offset from the carrier when the active inductor is switched off and −91 dBc/Hz when it is switched on, leading to a phased noise reduction of 6 dB. [ABSTRACT FROM AUTHOR]

This paper reports a novel oscillator circuit topology based on a transformer-coupled p-network. As a case study, the proposed oscillator topology has been designed and studied for 60 GHz applications in the frame of the emerging fifth generation wireless communications. The analytical expression of the oscillation frequency is derived and validated through circuit simulations. The root-locus analysis shows that oscillations occur only at that resonant frequency of the LC tank. Moreover, a closed-form expression for the quality factor (Q) of the LC tank is derived which shows the enhancement of the equivalent quality factor of the LC tank due to the transformer-coupling. Last, a phase noise analysis is reported and the analytical expressions of phase noise due to flicker and thermal noise sources are derived and validated by the results obtained through SpectreRF simulations in the Cadence design environment with a 28 nm CMOS process design kit commercially available. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is an aggressive cancer of the digestive system, which is becoming a serious health problem worldwide. Overall survival for patients with pancreatic cancer is poor, mainly due to a lack of biomarkers to enable early diagnosis and a lack of prognostic markers that can inform decision-making, facilitating personalized treatment and an optimal clinical outcome. ncRNAs play an important role in pancreatic carcinogenesis. Here we review the literature on the role of ncRNAs as biomarkers in pancreatic cancer. We focus on the significance of ncRNAs as markers for early diagnosis, as prognostic biomarkers able to inform clinical management and as targets for novel therapeutics for patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

This paper presents two 4-bit (16-phase) mm-wave vector modulator phase shifters exploiting a novel in-phase and quadrature signal generator that consists of a single-input double-output cascode amplifier incorporating a lumped-element coupled-line quadrature coupler. The two circuit implementations have been designed and fabricated in a 28 nm fully depleted silicon-on-insulator CMOS. The first (PS1) achieves a higher gain and the second (PS2) has a more compact area (reduced to about 50%). Each consumes 18 mA from a 1.2 V supply. PS1 exhibits an average gain of 2.3 dB at 87.4 GHz and B3\text {dB} from 78.8 to 92.8 GHz; rms gain error of 1.68 dB at 87.4 GHz and <2 dB in the B3\text {dB} ; rms phase error of 9.4° at 87.4 GHz and <11.9° in B3\text {dB} ; S11 <-10.5 dB in B3\text {dB} ; average P1\text {dB} of −7 dBm; and average noise figure (NF) equal to 10.8 dB at 87 GHz. PS2 exhibits an average gain of 0.83 dB at 89.2 GHz and B3\text {dB} from 80.2 to 96.8 GHz; rms gain error of 1.46 dB at 89.2 GHz and <2 dB in B3\text {dB} ; rms phase error of 11.2° at 89.2 GHz and <11.9° in B3\text {dB} ; S11 <-11.5 dB in B3\text {dB} ; average P1\text {dB} of −6 dBm; and average NF of 11.9 dB at 89 GHz. [ABSTRACT FROM AUTHOR]

This paper presents a 67GHz LC oscillator exploiting a three-spiral transformer and implemented in 65nm bulk complementary metal-oxide-semiconductor technology by STMicroelectronics. The three-spiral transformer allows operating with a lower voltage supply, still obtaining good phase noise performance, and achieving a compact design. Measured performances when supplied with 1.2 V are: oscillation frequency of 67 GHz, phase noise ( PN) equal to −96 dBc/Hz at 1 MHz frequency offset from the carrier, power consumption ( PC) equal to 19.2 mW and figure of merit ( FOM) equal to −179.7 dB/Hz. Measured performances when supplied with 0.6 V are: oscillation frequency of 67 GHz; PN equal to −88.7 dBc/Hz at a 1 MHz frequency offset from the carrier; PC equal to 3.6 mW and FOM equal to −179.7 dB/Hz. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This paper reports a phase noise analysis in a differential Armstrong oscillator circuit topology in CMOS technology. The analytical expressions of phase noise due to flicker and thermal noise sources are derived and validated by the results obtained through SpectreRF simulations for oscillation frequencies of 1, 10, and 100 GHz. The analysis captures well the phase noise of the oscillator topology and shows the impact of flicker noise contribution as the major effect leading to phase noise degradation in nano-scale CMOS LC oscillators. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) in microRNA genes have been associated with colorectal cancer (CRC) risk, survival and response to treatment. Conflicting results are available on the association between rs4919510, a SNP in mature miR-608 and clinical outcome in CRC. Here, we analyzed the association between rs4919510 and benefit from perioperative treatment in a randomised phase II trial of neoadjuvant Capecitabine and Oxaliplatin (CAPOX) followed by chemo-radiotherapy, surgery and adjuvant CAPOX ± Cetuximab in high-risk locally advanced rectal cancer (LARC). A total of 155/164 (94.5%) patients were assessable. 95 (61.3%) were homozygous for CC, 55 (35.5%) heterozygous (CG) and 5 (3.2%) homozygous for GG. Median follow-up was 64.9 months. In the CAPOX arm the 5-year progression-free survival (PFS) and overall survival (OS) rates were 54.6% and 60.7% for CC and 82.0% and 82.1% for CG/GG, respectively (HR PFS 0.13, 95% CI: 0.12-0.83, P = 0.02; HR OS 0.38, 95% CI: 0.14-1.01, P = 0.05). In the CAPOX-C arm PFS and OS were 73.2 and 82.2%, respectively for CC carriers and 64.6 and 73.1% for CG/GG carriers (HR PFS 1.38, 95% CI: 0.61-3.13, P = 0.44; HR OS 1.34, 95% CI: 0.52-3.48, P = 0.55). An interaction was found between study treatment and rs4919510 genotype for both PFS (P = 0.02) and OS (P = 0.07). This is the first study investigating rs4919510 in LARC. The CC genotype appeared to be associated with worse prognosis compared to the CG/GG genotype in patients treated with chemotherapy and chemo-radiotherapy alone. Addition of Cetuximab to chemotherapy and chemo-radiotherapy in CC carriers appeared to improve clinical outcome. [ABSTRACT FROM AUTHOR]

This paper reports the results of the on-body experimental tests of a set of four planar differential antennas, originated by design variations of radiating elements with the same shape and characterized by the potential for covering wide and narrow bands. All the antenna designs have been implemented on low-cost FR4 substrate and characterized experimentally through on-body measurements. The results show the impact of the proximity to the human body on antenna performance and the opportunities in terms of potential coverage of wide and narrow bands for future ad hoc designs and implementations through wearable substrates targeting on-body and off-body communication and sensing applications. [ABSTRACT FROM AUTHOR]

This paper reports the analyses of three techniques for phase noise reduction in the complementary metal-oxide semiconductor (CMOS) Colpitts oscillator circuit topology. Namely, the three techniques are inductive degeneration, noise filter, and optimum current density. The design of the circuit topology is carried out in 28-nm bulk CMOS technology. The analytical expression of the oscillation frequency is derived and validated through circuit simulations. Moreover, the theoretical analyses of the three techniques are carried out and verified by means of circuit simulations within a commercial design environment. The results obtained for the inductive degeneration and noise filter show the existence of an optimum inductance for minimum phase noise. The results obtained for the optimum bias current density technique applied to a Colpitts oscillator circuit topology incorporating either inductive degeneration or noise filter show the existence of an optimum bias current density for minimum phase noise. Overall, the analyses show that the adoption of these techniques may lead to a potential phase noise reduction up to 19 dB at a 1-MHz frequency offset for an oscillation frequency of 10 GHz. © 2015 The Authors International Journal of Circuit Theory and Applications Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

This paper addresses the extension of the on-chip cold-source noise figure (NF) measurement methodology to millimeter-wave (mm-wave) integrated circuits by using the PNA-X. The proposed methodology has been successfully applied to the on-chip NF measurements of mm-wave building blocks on silicon such as a 4-b programmable 16-phase active phase shifter. The results show how the cold-source method can be extended up to the mm-wave frequency range by using the PNA-X with frequency extenders and an active frequency down-converter, so allowing satisfactory NF measurements of mm-wave integrated circuits. [ABSTRACT FROM AUTHOR]

The potential of active inductors (AIs) has been often reduced by lack of accurate design methodologies and limitations due to the inherent noise sources. This paper deals with these two open issues for a high-frequency CMOS AI characterized by high-quality factor, low-power consumption, and low noise. First, it reports an effective design methodology for the implementation of high-frequency CMOS AIs with a high-quality factor. In particular, it shows how, through an advanced small-signal circuit model, to carry out an accurate and reliable design at high frequency (over 10 GHz) in modern nanoscale CMOS process. The design methodology is validated through cases of study at 13 GHz implemented in a standard 90-nm CMOS process and characterized experimentally. The results show that the AI exhibits an equivalent inductance close to 3.2 nH with an associated quality factor close to 200. After, it reports a noise analysis. It shows that the AI exhibits a very low level of noise, enabling its application to the implementation of high-quality factor low-noise LC tank in high-frequency building blocks of radio frequency front-ends. The results show that the AI exhibits a noise power spectral density lower than −150 dBm/Hz. [ABSTRACT FROM AUTHOR]

This paper presents three practical antenna implementations based on variations of one general planar differential antenna topology originally proposed for ultrawideband (UWB) applications. All designs were implemented on a low-cost FR4 substrate and experimentally characterized in an anechoic chamber. The results show how the proposed design variations lead to the required antenna performances and how they give rise to new opportunities in terms of coverage of wide, narrow, and multiple frequency bands for communication and sensing applications below 5 GHz. In particular, the results show how a significant enhancement in bandwidth performance is achieved by folding the differential radiating elements. Moreover, they show how an agile design strategy enables adaption of the antenna design to different requirements for covering wide, narrow, and multiple bands, making the proposed class of antennas suitable for different wireless applications. In detail, the proposed class of antennas covers multiple frequency bands, ranging from the 868 MHz and 915 MHz bands to 2.4 GHz industrial scientific and medical (ISM) bands, including the 1.2 GHz L band for Global Positioning and Navigation Satellite Systems (GNSS) and the lower portion of the UWB band. [ABSTRACT FROM AUTHOR]

Comparative Phase Noise analyses of common-source cross-coupled pair, Colpitts, Hartley and Armstrong differential oscillator circuit topologies, designed in 28 nm bulk CMOS technology in a set of common conditions for operating frequencies in the range from 1 GHz to 100 GHz, are carried out in order to identify their relative performance. The impulse sensitivity function (ISF) is used to carry out qualitative and quantitative analyses of the noise contributions exhibited by each circuit component in each topology, allowing an understanding of their impact on phase noise. The comparative analyses show the existence of five distinct frequency regions in which the four topologies rank unevenly in terms of best phase noise performance. Moreover, the results obtained from the ISF show the impact of flicker noise contribution as the major effect leading to phase noise degradation in nanoscale CMOS LC oscillators. [ABSTRACT FROM AUTHOR]