The International Pulsar Timing Array: First Data Release

The highly stable spin of neutron stars can be exploited for a variety of (astro)physical investigations. In particular, arrays of pulsars with rotational periods of the order of milliseconds can be used to detect correlated signals such as those caused by gravitational waves. Three such \u27pulsar timing arrays\u27 (PTAs) have been set up around the world over the past decades and collectively form the \u27International\u27 PTA (IPTA). In this paper, we describe the first joint analysis of the data from the three regional PTAs, i.e. of the first IPTA data set. We describe the available PTA data, the approach presently followed for its combination and suggest improvements for future PTA research. Particular attention is paid to subtle details (such as underestimation of measurement uncertainty and long-period noise) that have often been ignored but which become important in this unprecedentedly large and inhomogeneous data set. We identify and describe in detail several factors that complicate IPTA research and provide recommendations for future pulsar timing efforts. The first IPTA data release presented here (and available on-line) is used to demonstrate the IPTA\u27s potential of improving upon gravitational-wave limit

No Change in Perceptual or Chronotropic Outcome When Altering Preferred Step Frequency for a Short Duration

IIntroduction: Millions of individuals incorporate jogging into their physical activity routines as a leisurely pursuit and as a way to achieve positive health outcomes. People appear to choose jogging speed and the associated step frequency on pure, natural preference. Understandably, kinesthetics are important, but another important underlying factor is metabolic cost. The purpose of this work was to investigate if preferred step frequency (at a preferred jogging pace) also minimizes perceived effort (Borg Rating of Perceived Exertion, 6-20; RPE) and chronotropic stress (heart rate; HR) during a ten-minute activity bout when compared with step frequencies altered by 5%. Methods: Recreationally-trained male subjects underwent two testing visits. The first visit was used to establish RPE and HR responses during a 10-minute jogging activity at preferred speed and step frequency. On a subsequent visit, between two and four days later, with preferred speed maintained, subjects were guided by metronome to strike at either 95% or 105% of their preferred step frequency. The 10-minute runs were randomized, crossed-over, and separated by 20 minutes. RPE and HR were analyzed by repeated measures ANOVA. Results: Fourteen subjects (age: 21.1 ± 0.95; body mass index: 23.2 ± 2.5) enrolled. Preferred jogging speed (speed. 6.4 ± 1.0 miles per hour; 10.2 ± 1.6 kilometers per hour) and step frequency (steps. 161.2 ± 10.3 steps/minute) were determined at the first visit, along with RPE (11.3 ± 1.7) and HR (166.4 ± 12.7). At the second visit, preferred speed was maintained while the frequency of foot-strike was altered. Neither differences in RPE (p = 0.252; 11.3 ± 1.7, 11.6 ± 1.9, 11.8 ± 1.5) nor HR (p = 0.547; 166.4 ± 12.7, 164.7 ± 14.9, 165.2 ± 15.3) were different when comparing the preferred, 95%, and 105% step frequency trials, respectively. Although anecdotal, some subjects verbalized displeasure with the change in pace and most all appeared to markedly alter the initial foot strike phase of the gait to meet the directed foot strike tempo. Discussion: Our data must be interpreted cautiously. While altering step frequency by 5% for a short duration does not appear to alter an individual’s RPE or HR appreciably, the result during longer duration activity may not be the same. In addition, the implications for biomechanical loading and metabolic cost were not presently investigated

Localization of ABCG5 and ABCG8 proteins in human liver, gall bladder and intestine

BACKGROUND: The molecular mechanisms that regulate the entry of dietary sterols into the body and their removal via hepatobiliary secretion are now beginning to be defined. These processes are specifically disrupted in the rare autosomal recessive disease, Sitosterolemia (MIM 210250). Mutations in either, but not both, of two genes ABCG5 or ABCG8, comprising the STSL locus, are now known to cause this disease and their protein products are proposed to function as heterodimers. Under normal circumstances cholesterol, but not non-cholesterol sterols, is preferentially absorbed from the diet. Additionally, any small amounts of non-cholesterol sterols that are absorbed are rapidly taken up by the liver and preferentially excreted into bile. Based upon the defects in sitosterolemia, ABCG5 and ABCG8 serve specifically to exclude non-cholesterol sterol entry at the intestinal level and are involved in sterol excretion at the hepatobiliary level. METHODS: Here we report the biochemical and immuno-localization of ABCG5 and ABCG8 in human liver, gallbladder and intestine using cell fractionation and immunohistochemical analyses. RESULTS: We raised peptide antibodies against ABCG5 and ABCG8 proteins. Using human liver samples, cell fractionation studies showed both proteins are found in membrane fractions, but they did not co-localize with caveolin-rafts, ER, Golgi or mitochondrial markers. Although their distribution in the sub-fractions was similar, they were not completely contiguous. Immunohistochemical analyses showed that while both proteins were readily detectable in the liver, ABCG5 was found predominately lining canalicular membranes, whereas ABCG8 was found in association with bile duct epithelia. At the cellular level, ABCG5 appeared to be apically expressed, whereas ABCG8 had a more diffuse expression pattern. Both ABCG5 and ABCG8 appeared to localize apically as shown by co-localization with MRP2. The distribution patterns of ABCG5 and ABCG8 in the gallbladder were very similar to each other. In the small intestine both ABCG5 and ABCG8 appear to line the brush border. However, at the level of the enterocyte, the cellular distribution patterns of ABCG5 and ABCG8 differed, such that ABCG5 was more diffuse, but ABCG8 was principally apical. Using standard deglycosylation methods, ABCG5 and ABCG8 do not appear to be glycosylated, suggesting a difference between human and mouse proteins. CONCLUSION: We report the distribution patterns of ABCG5 and ABCG8 in human tissues. Cell fractionation studies showed that both proteins co-fractionated in general, but could also be found independent of each other. As predicted, they are expressed apically in both intestine and liver, although their intracellular expression patterns are not completely congruent. These studies support the concept of heterodimerization of ABCG5 and ABCG8, but also support the notion that these proteins may have an independent function

The chemerin knockout rat reveals chemerin dependence in female, but not male, experimental hypertension

Measures of the adipokine chemerin are elevated in multiple cardiovascular diseases, including hypertension, but little mechanistic work has been done to implicate chemerin as being causative in such diseases. The chemerin knockout (KO) rat was created to test the hypothesis that removal of chemerin would reduce pressure in the normal and hypertensive state. Western analyses confirmed loss of chemerin in the plasma and tissues of the KO vs. wild‐type (WT) rats. Chemerin concentration in plasma and tissues was lower in WT females than in WT males, as determined by Western analysis. Conscious male and female KO rats had modest differences in baseline measures vs. the WT that included systolic, diastolic, mean arterial and pulse pressures, and heart rate, all measured telemetrically. The mineralocorticoid deoxycorticosterone acetate (DOCA) and salt water, combined with uninephrectomy as a hypertensive stimulus, elevated mean and systolic blood pressures of the male KO higher than the male WT. By contrast, all pressures in the female KO were lower than their WT throughout DOCA‐salt treatment. These results revealed an unexpected sex difference in chemerin expression and the ability of chemerin to modify blood pressure in response to a hypertensive challenge.—Watts, S. W., Darios, E. S., Mullick, A. E., Garver, H., Saunders, T. L., Hughes, E. D., Filipiak, W. E., Zeidler, M. G., McMullen, N., Sinal, C. J., Kumar, R. K., Ferland, D. J., Fink, G. D. The chemerin knockout rat reveals chemerin dependence in female, but not male, experimental hypertension. FASEB J. 32, 6596–6614 (2018). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154357/1/fsb2fj201800479.pd

The NANOGrav 11-Year Data Set: Limits on Gravitational Waves from Individual Supermassive Black Hole Binaries

Observations indicate that nearly all galaxies contain supermassive black holes (SMBHs) at their centers. When galaxies merge, their component black holes form SMBH binaries (SMBHBs), which emit low-frequency gravitational waves (GWs) that can be detected by pulsar timing arrays (PTAs). We have searched the recently-released North American Nanohertz Observatory for Gravitational Waves (NANOGrav) 11-year data set for GWs from individual SMBHBs in circular orbits. As we did not find strong evidence for GWs in our data, we placed 95\% upper limits on the strength of GWs from such sources as a function of GW frequency and sky location. We placed a sky-averaged upper limit on the GW strain of $h_0 < 7.3(3) \times 10^{-15}$ at $f_\mathrm{gw}= 8$ nHz. We also developed a technique to determine the significance of a particular signal in each pulsar using ``dropout' parameters as a way of identifying spurious signals in measurements from individual pulsars. We used our upper limits on the GW strain to place lower limits on the distances to individual SMBHBs. At the most-sensitive sky location, we ruled out SMBHBs emitting GWs with $f_\mathrm{gw}= 8$ nHz within 120 Mpc for $\mathcal{M} = 10^9 \, M_\odot$, and within 5.5 Gpc for $\mathcal{M} = 10^{10} \, M_\odot$. We also determined that there are no SMBHBs with $\mathcal{M} > 1.6 \times 10^9 \, M_\odot$ emitting GWs in the Virgo Cluster. Finally, we estimated the number of potentially detectable sources given our current strain upper limits based on galaxies in Two Micron All-Sky Survey (2MASS) and merger rates from the Illustris cosmological simulation project. Only 34 out of 75,000 realizations of the local Universe contained a detectable source, from which we concluded it was unsurprising that we did not detect any individual sources given our current sensitivity to GWs.Comment: 10 pages, 11 figures. Accepted by Astrophysical Journal. Please send any comments/questions to S. J. Vigeland ([email protected]

Chiang Kai-shek’s “secret deal” at Xian and the start of the Sino-Japanese War

Using newly available archives, particularly the diary and the presidential papers of Chiang Kai-shek, this article challenges the conventional interpretations of the Xian Incident (1936), in particular the widely held belief that the kidnapping of China’s leader Chiang by two rebellious generals forced him to form a united front with the Communist Party to confront Japanese aggression, and of the outbreak of the Sino-Japanese War 7 months later. It puts forth the interpretation that full-scale war between China and Japan was started not by Japan but by Chiang after a Japanese provocation, and the united front was only formed after Chiang ordered his best army units to attack Japanese forces in Shanghai in August 1937 turning it into the largest land battle after the First World War. It must be noted, however, that Japan acted provocatively and aggressively in a local incident outside Beijing a month earlier. Chiang decided on war not because he reached an agreement with the Chinese Communists to form a united front whilst a captive in Xian but because in Xian he received a signal from Josef Stalin that the Soviet Union would support him in a war with Japan. Chiang read Stalin right and the Soviet Union became the largest supplier of weapons to China in the first 4 years of China’s 8-year war with Japan. The hitherto unknown or “secret deal” Chiang made in Xian was an implicit one with Stalin, not with the Chinese Communist Party or its man on the spot Zhou Enlai

Accounting Problems Under the Excess Profits Tax

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p

Ovulation, In Vivo Emotion Regulation Problems, and Sexual Risk Recognition Deficits

Objective: To examine associations between menstrual cycle phase, negative mood, sexual risk recog-nition deficits (assessed via an analogue risk vignette), and in vivo emotion dysregulation. Partici-pants: Participants were 714 college women recruited between February 2007 and December 2009. Methods: Participants were randomly assigned to a negative or neutral mood induction and in-structed to identify sexual risk during an audiotaped sexual coercion vignette. Participants reported menstrual cycle information, in vivo emotional nonacceptance, and attention during the vignette. Results: In the negative mood condition, ovulation was associated with longer risk recognition laten-cies relative to the luteal and follicular phases of the menstrual cycle. Increased in vivo emotional nonacceptance and decreased attention to the vignette mediated associations between ovulation and risk recognition deficits in the negative mood condition. Conclusions: Sexual assault risk reduction programs could provide psychoeducation regarding negative mood during ovulation and empha-size emotional acceptance and attention to external stimuli when distressed

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Hard and Blind: On Wittgenstein's Genealogical View of Logical Necessity

My main aim is to sketch a certain reading (‘genealogical') of later Wittgenstein's views on logical necessity. Along the way, I engage with the inferentialism currently debated in the literature on the epistemology of deductive logic.publishedVersio