We report on the design and performance of an on-chip microwave circulator with a widely (GHz) tunable operation frequency. Nonreciprocity is created with a combination of frequency conversion and ...delay, and requires neither permanent magnets nor microwave bias tones, allowing on-chip integration with other superconducting circuits without the need for high-bandwidth control lines. Isolation in the device exceeds 20 dB over a bandwidth of tens of MHz, and its insertion loss is small, reaching as low as 0.9 dB at select operation frequencies. Furthermore, the device is linear with respect to input power for signal powers up to hundreds of fW (≈103 circulating photons), and the direction of circulation can be dynamically reconfigured. We demonstrate its operation at a selection of frequencies between 4 and 6 GHz.
Plant foods are not only a main source of nutrients, but they are also rich in physiologically bioactive bionutrients or phytochemicals. Consumption of fruit and vegetables is associated with a ...decreased risk of pathological status, including cancer. Reactive oxygen species play a key role in the genesis and development of cancer. Therefore, antioxidant functions of phytonutrients have been thoroughly investigated in the last years in relation to their crucial effect in the pathophysiology associated with neoplasia. This review discusses current knowledge on phytochemicals in relation to their potential as chemopreventive and/or chemotherapeutic molecule against human cancers. Finally, we will outline the use of bioactive phytochemicals on synergistic actions involved in the prevention and treatment of cancer as well as its future prospects.
Time-division multiplexing (TDM) is a mature scheme for the readout of arrays of transition-edge sensors (TESs). TDM is based on superconducting-quantum-interference-device (SQUID) current ...amplifiers. Multiple spectrometers based on gamma-ray and X-ray microcalorimeters have been operated with TDM readout, each at the scale of 200 sensors per spectrometer, as have several astronomical cameras with thousands of sub-mm or microwave bolometers. Here we present the details of two different versions of our TDM system designed to read out X-ray TESs. The first has been field-deployed in two 160-sensor (8 columns
×
20 rows) spectrometers and four 240-sensor (8 columns
×
30 rows) spectrometers. It has a three-SQUID-stage architecture, switches rows every 320 ns, and has total readout noise of 0.41
μ
Φ
0
/
√
Hz. The second, which is presently under development, has a two-SQUID-stage architecture, switches rows every 160 ns, and has total readout noise of 0.19
μ
Φ
0
/
√
Hz. Both quoted noise values are non-multiplexed and referred to the first-stage SQUID. In a demonstration of this new architecture, a multiplexed 1-column
×
32-row array of NIST TESs achieved average energy resolution of
2.55
±
0.01
eV at 6 keV.
Cancer cells require a robust supply of reduced nitrogen to produce nucleotides, non-essential amino acids and a high cellular redox activity. Glutamine provides a major substrate for respiration as ...well as nitrogen for the production of proteins, hexosamines, and macromolecules. Therefore, glutamine is one of key molecules in cancer metabolism during cell proliferation. The notion of targeting glutamine metabolism in cancer, originally rationalized by the number of pathways fed by this nutrient, has been reinforced by more recent studies demonstrating that its metabolism is regulated by oncogenes. Glutamine can exert its effects by modulating redox homeostasis, bioenergetics, nitrogen balance or other functions, including by being a precursor of glutathione, the major nonenzymatic cellular antioxidant. Glutaminase (GA) is the first enzyme that converts glutamine to glutamate, which is in turn converted to alpha-ketoglutarate for further metabolism in the tricarboxylic acid cycle. Different GA isoforms in mammals are encoded by two genes, Gls and Gls2. As each enzymatic form of GA has distinct kinetic and molecular characteristics, it has been speculated that the differential regulation of GA isoforms may reflect distinct functions or requirements in different tissues or cell states. GA encoded by Gls gene (GLS) has been demonstrated to be regulated by oncogenes and to support tumor cell growth. GA encoded by Gls2 gene (GLS2) reduces cellular sensitivity to reactive oxygen species associated apoptosis possibly through glutathione-dependent antioxidant defense, and therefore to behave more like a tumor suppressor. Thus, modulation of GA function may be a new therapeutic target for cancer treatment.
Reactive Oxygen Species (ROS) are produced during normal cellular function. ROS include hydroxyl radicals, superoxide anion, hydrogen peroxide and nitric oxide. They are very transient species due to ...their high chemical reactivity that leads to lipid peroxidation and oxidation of DNA and proteins. Under normal conditions, antioxidant systems of the cell minimize the perturbations caused by ROS. When ROS generation is increased to an extent that overcomes the cellular antioxidants, the result is oxidative stress. It is now clear that several biological molecules, which are involved in cell signaling and gene regulation systems are very sensitive to redox statue of the cell. Antioxidants are substances that delay or prevent the oxidation of cellular oxidizable substrates. The various antioxidants exert their effect by scavenging superoxide, or by activating of a battery of detoxifying/defensive proteins. The prevention of oxidation is an essential process in all the aerobic organisms, as decreased antioxidant protection may lead to cytotoxicity, mutagenicity and/or carcinogenicity. This article also focuses on the mechanisms by which antioxidants and xenobiotics induce the gene expression of detoxifying enzymes. On the other hand, small molecules that mimic antioxidant enzymes are becoming new tools for the treatment of many diseases.
We present the first performance results obtained with microwave multiplexed Transition Edge Sensors prototypes specifically designed for the HOLMES experiment, a project aimed at directly measuring ...the electron neutrino mass through the calorimetric measurement of the
163
Ho electron capture spectrum. The detectors required for such an experiment feature a high energy resolution at the
Q
–value of the transition, around
∼
2.8 keV, and a fast response time combined with the compatibility to be multiplexed in large arrays in order to collect a large statistics while keeping the pile-up contribution as small as possible. In addition, the design has to be suitable for future ion-implantation of
163
Ho. The results obtained in these tests allowed us to identify the optimal detector design among several prototypes. The chosen detector achieved an energy resolution of (4.5 ± 0.3) eV on the chlorine K
α
line, at
∼
2.6 keV, obtained with an exponential rise time of 14
μ
s. The achievements described in this paper pose a milestone for the HOLMES detectors, setting a baseline for the subsequent developments, aiming to the actual ion-implantation of the
163
Ho nuclei. In the first section the HOLMES experiment is outlined along with its physics goal, while in the second section the HOLMES detectors are described; the experimental set-up and the calibration source used for the measurements described in this paper are reported in Sects.
3
and
4
, respectively; finally, the details of the data analysis and the results obtained are reported in Sect.
6
.
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