The Apoptosis Regulation Mechanisms in Hypothalamic Neurons in Physiological and Pathological (Overexpression of Oncogene HER-2/Neu) Aging

This study reveals the molecular regulation mechanisms of neurosecretory cell apoptosis in physiological and pathological (oncogene human epidermal growth factor receptor (HER)-2/Neu overexpression) aging. As we have shown previously, apoptosis level in hypothalamic neurosecretory centers increases in aging, and a low level of apoptosis in aged HER-2/Neu transgenic mice is associated with p53-dependent cascade suppression. In this chapter, we consider the participation of p53-regulating genes and p53 target genes in activation of this cascade during physiological aging, as well as suppression under HER-2/Neu overexpression. However, cell resistance to apoptosis may also be due to the activity of cytokine-dependent STAT-signaling pathway, including the high expression of survivin belonging to the family of inhibitors of apoptosis proteins (IAP). Also, another cytokine-dependent signaling, an extrinsic apoptosis pathway associated with the family of tumor necrosis factor (TNF) receptors, has been investigated. Thus, in the present work, three signaling cascades are considered: p53-dependent (the expression and interaction of apoptosis-associated proteins p53, WRN, pin1, p21, and caspase-3), STAT-mediated (STAT1, 3, 5, 6, and survivin), and TNF-dependent (CD95 (FAS), Fas-associated death domain (FADD), TNF receptor–associated death domain (TRADD), and caspase-8). These cascades are involved in both the activation of apoptosis and its suppression. This will reveal the general trends of regulation of neurosecretory cell apoptosis during aging

ADRENO- AND CHOLINOREACTIVITY OF ERYTHROCYTES AND ESTIMATION OF THEIR CONJUGATION WITH PARAMETERS OF FREE RADICAL BALANCE OF BLOOD IN NON-LINEAR RATS

The values of the β-adrenoreactivity of erythrocytes (β-ARE, 40.6 ± 2.3 rel. units) and the M-cholinoreactivity of erythrocytes (M-ChRE, 7.9 ± 0.3 rel. units), concentration of hemoglobin, the parameters of free radical balance: the level of TBA-reactive products (TBA-RP) and catalase activity in erythrocytes and plasma were determined in male non-linear rats. Sample grouping by clustering largest β-ARE showed that rats with a high β-ARE (>50 rel. units) have a greater concentration of hemoglobin, TBA-RP and CAT in erythrocytes, than rats with an average (30 to 50 rel. units) and low (<30 rel. units) β-ARE. According to the results of the correlation and factor analysis, M-ChRE is predominantly conjugated with erythrocyte (Factor 1), and β-ARE – with plasma characteristics of free radical balance in blood (Factor 3). The introduction of β-adrenergic blocker anapriline (2 mg/kg bw) decreases β-ARE and potentiates the accumulation of TBA-RP in the erythrocytes and plasma, the administration of the blocker of M-cholinergic receptors atropine (1 mg/kg bw) reduces not only M-ChRE, but also β-ARE and promotes the growth of erythrocyte catalase activity. Thus, in the intact state, under the conditions of blockade of adrenergic receptor and cholinergic receptors, dependences have been revealed that make it possible to treat β-ARE and M-ChRE as a link between regulatory influences on erythrocytes and biochemical, including free radical processes in the «erythrocyte – blood plasma»

BICEP2 II: Experiment and Three-Year Data Set

We report on the design and performance of the BICEP2 instrument and on its three-year data set. BICEP2 was designed to measure the polarization of the cosmic microwave background (CMB) on angular scales of 1 to 5 degrees ($\ell$=40-200), near the expected peak of the B-mode polarization signature of primordial gravitational waves from cosmic inflation. Measuring B-modes requires dramatic improvements in sensitivity combined with exquisite control of systematics. The BICEP2 telescope observed from the South Pole with a 26~cm aperture and cold, on-axis, refractive optics. BICEP2 also adopted a new detector design in which beam-defining slot antenna arrays couple to transition-edge sensor (TES) bolometers, all fabricated on a common substrate. The antenna-coupled TES detectors supported scalable fabrication and multiplexed readout that allowed BICEP2 to achieve a high detector count of 500 bolometers at 150 GHz, giving unprecedented sensitivity to B-modes at degree angular scales. After optimization of detector and readout parameters, BICEP2 achieved an instrument noise-equivalent temperature of 15.8 $\mu$K sqrt(s). The full data set reached Stokes Q and U map depths of 87.2 nK in square-degree pixels (5.2 $\mu$K arcmin) over an effective area of 384 square degrees within a 1000 square degree field. These are the deepest CMB polarization maps at degree angular scales to date. The power spectrum analysis presented in a companion paper has resulted in a significant detection of B-mode polarization at degree scales.Comment: 30 pages, 24 figure

BICEP2 / Keck Array V: Measurements of B-mode Polarization at Degree Angular Scales and 150 GHz by the Keck Array

The Keck Array is a system of cosmic microwave background (CMB) polarimeters, each similar to the BICEP2 experiment. In this paper we report results from the 2012 and 2013 observing seasons, during which the Keck Array consisted of five receivers all operating in the same (150 GHz) frequency band and observing field as BICEP2. We again find an excess of B-mode power over the lensed-$\Lambda$CDM expectation of $> 5 \sigma$ in the range $30 < \ell < 150$ and confirm that this is not due to systematics using jackknife tests and simulations based on detailed calibration measurements. In map difference and spectral difference tests these new data are shown to be consistent with BICEP2. Finally, we combine the maps from the two experiments to produce final Q and U maps which have a depth of 57 nK deg (3.4 $\mu$K arcmin) over an effective area of 400 deg$^2$ for an equivalent survey weight of 250,000 $\mu$K$^{-2}$. The final BB band powers have noise uncertainty a factor of 2.3 times better than the previous results, and a significance of detection of excess power of $> 6\sigma$.Comment: 13 pages, 9 figure

Internal delensing of cosmic microwave background polarization B-Modes with the POLARBEAR experiment

International audienceUsing only cosmic microwave background polarization data from the polarbear experiment, we measure B-mode polarization delensing on subdegree scales at more than 5σ significance. We achieve a 14% B-mode power variance reduction, the highest to date for internal delensing, and improve this result to 22% by applying for the first time an iterative maximum a posteriori delensing method. Our analysis demonstrates the capability of internal delensing as a means of improving constraints on inflationary models, paving the way for the optimal analysis of next-generation primordial B-mode experiments

BICEP2 / Keck Array VIII: Measurement of gravitational lensing from large-scale B-mode polarization

We present measurements of polarization lensing using the 150 GHz maps which include all data taken by the BICEP2 & Keck Array CMB polarization experiments up to and including the 2014 observing season (BK14). Despite their modest angular resolution ($\sim 0.5^\circ$), the excellent sensitivity ($\sim 3\mu$K-arcmin) of these maps makes it possible to directly reconstruct the lensing potential using only information at larger angular scales ($\ell\leq 700$). From the auto-spectrum of the reconstructed potential we measure an amplitude of the spectrum to be $A^{\phi\phi}_{\rm L}=1.15\pm 0.36$ (Planck $\Lambda$CDM prediction corresponds to $A^{\phi\phi}_{\rm L}=1$), and reject the no-lensing hypothesis at 5.8$\sigma$, which is the highest significance achieved to date using an EB lensing estimator. Taking the cross-spectrum of the reconstructed potential with the Planck 2015 lensing map yields $A^{\phi\phi}_{\rm L}=1.13\pm 0.20$. These direct measurements of $A^{\phi\phi}_{\rm L}$ are consistent with the $\Lambda$CDM cosmology, and with that derived from the previously reported BK14 B-mode auto-spectrum ($A^{\rm BB}_{\rm L}=1.20\pm 0.17$). We perform a series of null tests and consistency checks to show that these results are robust against systematics and are insensitive to analysis choices. These results unambiguously demonstrate that the B-modes previously reported by BICEP / Keck at intermediate angular scales ($150\lesssim\ell\lesssim 350$) are dominated by gravitational lensing. The good agreement between the lensing amplitudes obtained from the lensing reconstruction and B-mode spectrum starts to place constraints on any alternative cosmological sources of B-modes at these angular scales.Comment: 12 pages, 8 figure

Antenna-coupled TES bolometers used in BICEP2, Keck array, and SPIDER

We have developed antenna-coupled transition-edge sensor (TES) bolometers for a wide range of cosmic microwave background (CMB) polarimetry experiments, including BICEP2, Keck Array, and the balloon borne SPIDER. These detectors have reached maturity and this paper reports on their design principles, overall performance, and key challenges associated with design and production. Our detector arrays repeatedly produce spectral bands with 20%-30% bandwidth at 95, 150, or 220~GHz. The integrated antenna arrays synthesize symmetric co-aligned beams with controlled side-lobe levels. Cross-polarized response on boresight is typically ~0.5%, consistent with cross-talk in our multiplexed readout system. End-to-end optical efficiencies in our cameras are routinely 35% or higher, with per detector sensitivities of NET~300 uKrts. Thanks to the scalability of this design, we have deployed 2560 detectors as 1280 matched pairs in Keck Array with a combined instantaneous sensitivity of ~9 uKrts, as measured directly from CMB maps in the 2013 season. Similar arrays have recently flown in the SPIDER instrument, and development of this technology is ongoing.Comment: 16 pgs, 20 fig