Time-resolved CARS measurements of vibrational decoherence of I₂ isolated in matrix Ar

Time-resolved coherent anti-Stokes Raman scattering is applied to prepare and interrogate vibrational coherences on the ground electronic surface of molecular iodine isolated in Ar matrices. The coherence decay time shows a linear dependence on vibrational quantum numbers, for v = 3–15. The temperature dependence of decoherence rates is negligible for v < 7, in the experimental range T = 18–32 K. For a v = 13, 14 superposition, the temperature dependence indicates dephasing by a 66 cm–¹ pseudo-local phonon, just outside the Debye edge of the solid. The accuracy of the data is limited due to two-photon induced dissociation of the molecule, which process is characterized using polarized fields. The T → 0 limit of dephasing is discussed

NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence

Senescent cells interact with the surrounding microenvironment achieving diverse functional outcomes. We have recently identified that NOTCH1 can drive ‘lateral induction’ of a unique senescence phenotype in adjacent cells by specifically upregulating the NOTCH ligand JAG1. Here we show that NOTCH signalling can modulate chromatin structure autonomously and non-autonomously. In addition to senescence-associated heterochromatic foci (SAHF), oncogenic RAS-induced senescent (RIS) cells exhibit a massive increase in chromatin accessibility. NOTCH signalling suppresses SAHF and increased chromatin accessibility in this context. Strikingly, NOTCH-induced senescent cells, or cancer cells with high JAG1 expression, drive similar chromatin architectural changes in adjacent cells through cell–cell contact. Mechanistically, we show that NOTCH signalling represses the chromatin architectural protein HMGA1, an association found in multiple human cancers. Thus, HMGA1 is involved not only in SAHFs but also in RIS-driven chromatin accessibility. In conclusion, this study identifies that the JAG1–NOTCH–HMGA1 axis mediates the juxtacrine regulation of chromatin architecture

‘G’ followed by ‘H’-gout follows homoeopathy

Currently in modern medicine, it is seen that taking a uric acid reducing drug during an attack of gout actually prolongs the pain and discomfort. So, the learning is that one need not worry about high uric acid levels during an acute flair of gout. What actually someone needs is an anti-inflammatory that reduces the inflammation caused by the crystals of uric acid that build up in the joints when someone has gout. This anti-inflammatory drug is ‘colchicine’. Homoeopathy has been using the drug ‘colchicum autumnale’ for last 233 years since its discovery in 1790 by Dr. Samuel Hahnemann (1755-1843). It also uses its active principle ‘colchicine’ for the last 233 years. It is quite striking to see that the modern medicine is realizing the importance of ‘colchicine’ currently. The same ‘colchicine’ was advised to be used as an anti-inflammatory to reduce the markers like C-reactive protein, LDH, D-dimer and homocysteine. During the COVID-19 peak, again the homoeopathic Colchicine came to the rescue. The current article examines the use of homoeopathy in gout and uric acid problems and again at a larger issue with the protein metabolism and the kidney heath. Integration of homoeopathy at large scale will help the nation to protect its members from protein metabolism disorders, kidney health and gout as well

A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma.

Transcriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis remain poorly understood. Here we report that Kruppel like factor 6 (KLF6), a transcription factor of the zinc finger family, regulates lipid homeostasis in clear cell renal cell carcinoma (ccRCC). We show that KLF6 supports the expression of lipid metabolism genes and promotes the expression of PDGFB, which activates mTOR signalling and the downstream lipid metabolism regulators SREBF1 and SREBF2. KLF6 expression is driven by a robust super enhancer that integrates signals from multiple pathways, including the ccRCC-initiating VHL-HIF2A pathway. These results suggest an underlying mechanism for high mTOR activity in ccRCC cells. More generally, the link between super enhancer-driven transcriptional networks and essential metabolic pathways may provide clues to the mechanisms that maintain the stability of cell identity-defining transcriptional programmes in cancer.CRU

SPIDER: a balloon-borne CMB polarimeter for large angular scales

We describe SPIDER, a balloon-borne instrument to map the polarization of the millimeter-wave sky with degree angular resolution. Spider consists of six monochromatic refracting telescopes, each illuminating a focal plane of large-format antenna-coupled bolometer arrays. A total of 2,624 superconducting transition-edge sensors are distributed among three observing bands centered at 90, 150, and 280 GHz. A cold half-wave plate at the aperture of each telescope modulates the polarization of incoming light to control systematics. Spider's first flight will be a 20-30-day Antarctic balloon campaign in December 2011. This flight will map \sim8% of the sky to achieve unprecedented sensitivity to the polarization signature of the gravitational wave background predicted by inflationary cosmology. The Spider mission will also serve as a proving ground for these detector technologies in preparation for a future satellite mission.Comment: 12 pages, 6 figures; as published in the conference proceedings for SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy V (2010

Spider Optimization: Probing the Systematics of a Large Scale B-Mode Experiment

Spider is a long-duration, balloon-borne polarimeter designed to measure large scale Cosmic Microwave Background (CMB) polarization with very high sensitivity and control of systematics. The instrument will map over half the sky with degree angular resolution in I, Q and U Stokes parameters, in four frequency bands from 96 to 275 GHz. Spider's ultimate goal is to detect the primordial gravity wave signal imprinted on the CMB B-mode polarization. One of the challenges in achieving this goal is the minimization of the contamination of B-modes by systematic effects. This paper explores a number of instrument systematics and observing strategies in order to optimize B-mode sensitivity. This is done by injecting realistic-amplitude, time-varying systematics in a set of simulated time-streams. Tests of the impact of detector noise characteristics, pointing jitter, payload pendulations, polarization angle offsets, beam systematics and receiver gain drifts are shown. Spider's default observing strategy is to spin continuously in azimuth, with polarization modulation achieved by either a rapidly spinning half-wave plate or a rapidly spinning gondola and a slowly stepped half-wave plate. Although the latter is more susceptible to systematics, results shown here indicate that either mode of operation can be used by Spider.Comment: 15 pages, 12 figs, version with full resolution figs available here http://www.astro.caltech.edu/~lgg/spider_front.ht

Modeling and characterization of the SPIDER half-wave plate

Spider is a balloon-borne array of six telescopes that will observe the Cosmic Microwave Background. The 2624 antenna-coupled bolometers in the instrument will make a polarization map of the CMB with approximately one-half degree resolution at 145 GHz. Polarization modulation is achieved via a cryogenic sapphire half-wave plate (HWP) skyward of the primary optic. We have measured millimeter-wave transmission spectra of the sapphire at room and cryogenic temperatures. The spectra are consistent with our physical optics model, and the data gives excellent measurements of the indices of A-cut sapphire. We have also taken preliminary spectra of the integrated HWP, optical system, and detectors in the prototype Spider receiver. We calculate the variation in response of the HWP between observing the CMB and foreground spectra, and estimate that it should not limit the Spider constraints on inflation

The renal lineage factor PAX8 controls oncogenic signalling in kidney cancer

Large-scale human genetic data(1-3) have shown that cancer mutations display strong tissue-selectivity, but how this selectivity arises remains unclear. Here, using experimental models, functional genomics and analyses of patient samples, we demonstrate that the lineage transcription factor paired box 8 (PAX8) is required for oncogenic signalling by two common genetic alterations that cause clear cell renal cell carcinoma (ccRCC) in humans: the germline variant rs7948643 at 11q13.3 and somatic inactivation of the von Hippel-Lindau tumour suppressor (VHL)(4-6). VHL loss, which is observed in about 90% of ccRCCs, can lead to hypoxia-inducible factor 2 alpha (HIF2A) stabilization(6,7). We show that HIF2A is preferentially recruited to PAX8-bound transcriptional enhancers, including a pro-tumorigenic cyclin D1 (CCND1) enhancer that is controlled by PAX8 and HIF2A. The ccRCC-protective allele Cat rs7948643 inhibits PAX8 binding at this enhancer and downstream activation of CCND1 expression. Co-option of a PAX8-dependent physiological programme that supports the proliferation of normal renal epithelial cells is also required for MYC expression from the ccRCC metastasis-associated amplicons at 8q21.3-q24.3 (ref. (8)). These results demonstrate that transcriptional lineage factors are essential for oncogenic signalling and that they mediate tissue-specific cancer risk associated with somatic and inherited genetic variants.Peer reviewe

A cryogenic rotation stage with a large clear aperture for the half-wave plates in the Spider instrument

We describe the cryogenic half-wave plate rotation mechanisms built for and used in Spider, a polarization-sensitive balloon-borne telescope array that observed the Cosmic Microwave Background at 95 GHz and 150 GHz during a stratospheric balloon flight from Antarctica in January 2015. The mechanisms operate at liquid helium temperature in flight. A three-point contact design keeps the mechanical bearings relatively small but allows for a large (305 mm) diameter clear aperture. A worm gear driven by a cryogenic stepper motor allows for precise positioning and prevents undesired rotation when the motors are depowered. A custom-built optical encoder system monitors the bearing angle to an absolute accuracy of +/- 0.1 degrees. The system performed well in Spider during its successful 16 day flight