Low temperature sensitivity CMOS transconductor based on GZTC MOSFET condition

Complementary Metal Oxide Semiconductor (CMOS) Transconductors, or Gm cells, are key building blocks to implement a large variety of analog circuits such as adjustable filters, multipliers, controlled oscillators and amplifiers. Usually temperature stability is a must in such applications, and herein we define all required conditions to design low thermal sensitivity Gm cells by biasing MOSFETs at Transconductance Zero Temperature Condition (GZTC). This special bias condition is analyzed using a MOSFET model which is continuous from weak to strong inversion, and it is proved that this condition always occurs from moderate to strong inversion operation in any CMOS fabrication process. Additionally, a few example circuits are designed using this technique: a single-ended resistor emulator, an impedance inverter, a first order and a second order filter. These circuits have been simulated in a 130 nm CMOS commercial process, resulting in improved thermal stability in the main performance parameters, in the range from 27 to 53 ppm/ºC

MOSFET ZTC condition analysis for a self-biased current reference design

In this paper a self-biased current reference based on Metal-Oxide-Semiconductor Field Effect Transistor (MOSFET) Zero Temperature Coefficient (ZTC) condition is proposed. It can be imple mented in any Complementary Metal-Oxide-Semiconductor (CMOS) fabrication process and pro vides another alternative to design current references. In order to support the circuit design, ZTC condition is analyzed using a MOSFET model that is continuous from weak to strong inversion, show ing that this condition always occurs from moderate to strong inversion in any CMOS process. The proposed topology was designed in a 180 nm process, operates with a supply voltage from 1.4V to 1.8 V and occupies around 0.010mm2 of silicon area. From circuit simulations our reference showed a temperature coefficient (TC) of 15 ppm/o C from -40 to +85o C, and a fabrication process sensitivity of σ/μ = 4.5% for the current reference, including average process and local mismatch variability analysis. The simulated power supply sensitivity is estimated around 1%/V

X-ray fluorescence from the element with atomic number Z = 120

Accepted for publication in Physical Review LettersAn atomic clock based on X-ray fluorescence yields has been used to estimate the mean characteristic time for fusion followed by fission in reactions 238U + 64Ni at 6.6 MeV/A. Inner shell vacancies are created during the collisions in the electronic structure of the possibly formed Z=120 compound nuclei. The filling of these vacancies accompanied by X-ray emission with energies characteristic of Z=120 can take place only if the atomic transitions occur before nuclear fission. Therefore, the X-ray yield characteristic of the united atom with 120 protons is strongly related to the fission time and to the vacancy lifetimes. K X-rays from the element with Z = 120 have been unambiguously identified from a coupled analysis of the involved nuclear reaction mechanisms and of the measured photon spectra. A minimum mean fission time $\tau$_f$ = 2.5×10−18s has been deduced for Z=120 from the measured X-ray multiplicity

Ultrafast Radiographic Imaging and Tracking: An overview of instruments, methods, data, and applications

Ultrafast radiographic imaging and tracking (U-RadIT) use state-of-the-art ionizing particle and light sources to experimentally study sub-nanosecond dynamic processes in physics, chemistry, biology, geology, materials science and other fields. These processes, fundamental to nuclear fusion energy, advanced manufacturing, green transportation and others, often involve one mole or more atoms, and thus are challenging to compute by using the first principles of quantum physics or other forward models. One of the central problems in U-RadIT is to optimize information yield through, e.g. high-luminosity X-ray and particle sources, efficient imaging and tracking detectors, novel methods to collect data, and large-bandwidth online and offline data processing, regulated by the underlying physics, statistics, and computing power. We review and highlight recent progress in: a.) Detectors; b.) U-RadIT modalities; c.) Data and algorithms; and d.) Applications. Hardware-centric approaches to U-RadIT optimization are constrained by detector material properties, low signal-to-noise ratio, high cost and long development cycles of critical hardware components such as ASICs. Interpretation of experimental data, including comparisons with forward models, is frequently hindered by sparse measurements, model and measurement uncertainties, and noise. Alternatively, U-RadIT makes increasing use of data science and machine learning algorithms, including experimental implementations of compressed sensing. Machine learning and artificial intelligence approaches, refined by physics and materials information, may also contribute significantly to data interpretation, uncertainty quantification and U-RadIT optimization.Comment: 51 pages, 31 figures; Overview of ultrafast radiographic imaging and tracking as a part of ULITIMA 2023 conference, Mar. 13-16,2023, Menlo Park, CA, US

MiR-543 regulates the epigenetic landscape of myelofibrosis by targeting TET1 and TET2

Myelofibros is (MF) is a myeloproliferative neoplasm characterized by cytopenia and extramedullary hematopoiesis, resulting in splenomegaly. Multiple pathological mechanisms (e.g., circulating cytokines and genetic alterations, such as JAK(V617F) mutation) have been implicated in the etiology of MF, but the molecular mechanism causing resistance to JAK(V617F) inhibitor therapy remains unknown. Among MF patients who were treated with the JAK inhibitor ruxolitinib, we compared noncoding RNA profiles of ruxolitinib therapy responders versus nonresponders and found miR-S43 was significantly upregulated in non responders. We validated these findings by reverse transcription-quantitative PCR. in this same cohort, in 2 additional independent MF patient cohorts from the United States and Romania, and in a JAK2(V617F) mouse model of MF. Both in vitro and in vivo models were used to determine the underlying molecular mechanism of miR-543 in MF. Here, we demonstrate that miR-543 targets the dioxygenases ten-eleven translocation 1 (TET1) and 2 (TET2) in patients and in vitro, causing increased levels of global 5-methylcytosine, while decreasing the acetylation of histone 3, STAT3, and tumor protein p53. Mechanistically, we found that activation of STAT3 by JAKs epigenetically controls miR-543 expression via binding the promoter region of miR-543. Furthermore, miR-543 upregulation promotes the expression of genes related to drug metabolism, including CYP3A4, which is involved in ruxolitinib metabolism. Our findings suggest miR-543 as a potentially novel biomarker for the prognosis of MF patients with a high risk of treatment resistance and as a potentially new target for the development of new treatment options

Age, gender, and cancer but not neurodegenerative and cardiovascular diseases strongly modulate systemic effect of the Apolipoprotein E4 allele on lifespan

Enduring interest in the Apolipoprotein E (ApoE) polymorphism is ensured by its evolutionary-driven uniqueness in humans and its prominent role in geriatrics and gerontology. We use large samples of longitudinally followed populations from the Framingham Heart Study (FHS) original and offspring cohorts and the Long Life Family Study (LLFS) to investigate gender-specific effects of the ApoE4 allele on human survival in a wide range of ages from midlife to extreme old ages, and the sensitivity of these effects to cardiovascular disease (CVD), cancer, and neurodegenerative disorders (ND). The analyses show that women's lifespan is more sensitive to the e4 allele than men's in all these populations. A highly significant adverse effect of the e4 allele is limited to women with moderate lifespan of about 70 to 95 years in two FHS cohorts and the LLFS with relative risk of death RR = 1.48 (p = 3.6×10(−6)) in the FHS cohorts. Major human diseases including CVD, ND, and cancer, whose risks can be sensitive to the e4 allele, do not mediate the association of this allele with lifespan in large FHS samples. Non-skin cancer non-additively increases mortality of the FHS women with moderate lifespans increasing the risks of death of the e4 carriers with cancer two-fold compared to the non-e4 carriers, i.e., RR = 2.07 (p = 5.0×10(−7)). The results suggest a pivotal role of non-sex-specific cancer as a nonlinear modulator of survival in this sample that increases the risk of death of the ApoE4 carriers by 150% (p = 5.3×10(−8)) compared to the non-carriers. This risk explains the 4.2 year shorter life expectancy of the e4 carriers compared to the non-carriers in this sample. The analyses suggest the existence of age- and gender-sensitive systemic mechanisms linking the e4 allele to lifespan which can non-additively interfere with cancer-related mechanisms

Present and Future of Surface-Enhanced Raman Scattering.

The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist