Constraints on cosmic strings using data from the first Advanced LIGO observing run

Cosmic strings are topological defects which can be formed in grand unified theory scale phase transitions in the early universe. They are also predicted to form in the context of string theory. The main mechanism for a network of Nambu-Goto cosmic strings to lose energy is through the production of loops and the subsequent emission of gravitational waves, thus offering an experimental signature for the existence of cosmic strings. Here we report on the analysis conducted to specifically search for gravitational-wave bursts from cosmic string loops in the data of Advanced LIGO 2015-2016 observing run (O1). No evidence of such signals was found in the data, and as a result we set upper limits on the cosmic string parameters for three recent loop distribution models. In this paper, we initially derive constraints on the string tension Gμ and the intercommutation probability, using not only the burst analysis performed on the O1 data set but also results from the previously published LIGO stochastic O1 analysis, pulsar timing arrays, cosmic microwave background and big-bang nucleosynthesis experiments. We show that these data sets are complementary in that they probe gravitational waves produced by cosmic string loops during very different epochs. Finally, we show that the data sets exclude large parts of the parameter space of the three loop distribution models we consider

THE RATE OF BINARY BLACK HOLE MERGERS INFERRED FROM ADVANCED LIGO OBSERVATIONS SURROUNDING GW150914

A transient gravitational-wave signal, GW150914, was identi fi ed in the twin Advanced LIGO detectors on 2015 September 2015 at 09:50:45 UTC. To asse ss the implications of this discovery, the detectors remained in operation with unchanged con fi gurations over a period of 39 days around the time of t he signal. At the detection statistic threshold corresponding to that observed for GW150914, our search of the 16 days of simultaneous two-detector observational data is estimated to have a false-alarm rate ( FAR ) of < ́ -- 4.9 10 yr 61 , yielding a p -value for GW150914 of < ́ - 210 7 . Parameter estimation follo w-up on this trigger identi fi es its source as a binary black hole ( BBH ) merger with component masses ( )( ) = - + - + mm M ,36,29 12 4 5 4 4 at redshift = - + z 0.09 0.04 0.03 ( median and 90% credible range ) . Here, we report on the constraints these observations place on the rate of BBH coalescences. Considering only GW150914, assuming that all BBHs in the universe have the same masses and spins as this event, imposing a search FAR threshold of 1 per 100 years, and assuming that the BBH merger rate is constant in the comoving frame, we infer a 90% credible range of merger rates between – -- 2 53 Gpc yr 31 ( comoving frame ) . Incorporating all search triggers that pass a much lower threshold while accounting for the uncerta inty in the astrophysical origin of each trigger, we estimate a higher rate, ranging from – -- 13 600 Gpc yr 31 depending on assumptions about the BBH mass distribution. All together, our various rate estimat es fall in the conservative range – -- 2 600 Gpc yr 31

Activation of the p53 tumor suppressor protein

The p53 tumor suppressor gene plays an important role in preventing cancer development, by arresting or killing potential tumor cells. Mutations within the p53 gene, leading to the loss of p53 activity, are found in about half of all human cancers, while many of the tumors that retain wild type p53 carry mutations in the pathways that allow full activation of p53. In either case, the result is a defect in the ability to induce a p53 response in cells undergoing oncogenic stress. Significant advances have been made recently in our understanding of the molecular pathways through which p53 activity is regulated, bringing with them fresh possibilities for the design of cancer therapies based on reactivation of the p53 respons

The role of p53 in glucose metabolism

The p53 protein functions to prevent tumour development by inhibiting the outgrowth of stressed or damaged cells. In addition to well established functions to block cell proliferation, recent studies have revealed a role for p53 in the regulation of pathways involved in glucose metabolism. The metabolic functions of p53 resist the shift to glycolysis that is characteristically seen in cancers, and also help cells adapt to and survive limited periods of metabolic stress. Such activities of p53 would not only help to prevent cancer development, but might also contribute to non-tumour related roles for p53, such as in the regulation of longevity. These new functions of p53 are providing interesting possibilities for the development of novel therapie

Tumor suppression by p53: fall of the triumvirate?

p53 is a key tumor suppressor protein that has numerous functions. Its primary mode of action has generally been ascribed to the induction of cell-cycle arrest, apoptosis, or senescence upon stress. Li et al. challenge this dogma with evidence that all three of these programs are dispensable for p53's tumor suppressive role

Mutant p53 in cancer: New functions and therapeutic opportunities

Many different types of cancer show a high incidence of TP53 mutations, leading to the expression of mutant p53 proteins. There is growing evidence that these mutant p53s have both lost wild-type p53 tumor suppressor activity and gained functions that help to contribute to malignant progression. Understanding the functions of mutant p53 will help in the development of new therapeutic approaches that may be useful in a broad range of cancer types

An indirect role for ASPP1 in limiting p53-dependent p21 expression and cellular senescence

In addition to acting as a transcriptional cofactor for p53, ASPP1 has been shown to function in the cytoplasm to regulate the nuclear localization and activity of YAP/TAZ. We show here that the ability of ASPP1 to activate YAP results in the decreased expression of LATS2, which lowers the ability of p53 to induce p21, cell-cycle arrest and senescence. ASPP1 expression peaks in S-phase, and down-regulation of ASPP1 leads to a reduction in DNA synthesis and enhanced senescence in response to drugs that impede DNA replication. These activities of cytoplasmic ASPP1 in opposing p53-mediated p21 expression are in contrast to the role of nuclear ASPP1 in cooperating with p53 to induce the expression of apoptotic target genes, and may help to dampen p53 activity in normal cells

The role of ubiquitin modification in the regulation of p53

The p53 tumor suppressor protein is involved in regulating a wide variety of stress responses, from senescence and apoptosis to more recently discovered roles in allowing adaptation to metabolic and oxidative stress. After 34 years of research, significant progress has been made in unraveling the complexity of the p53 network, and it is clear that the regulation of p53 protein stability is critical in the control of p53 activity. This article focuses on our current understanding of how the level and activity of p53 is controlled by this seemingly simple mechanism. This article is part of a Special Issue entitled: Ubiquitin–Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf

P53 mutations in cancer

In the past fifteen years, it has become apparent that tumour-associated p53 mutations can provoke activities that are different to those resulting from simply loss of wild-type tumour-suppressing p53 function. Many of these mutant p53 proteins acquire oncogenic properties that enable them to promote invasion, metastasis, proliferation and cell survival. Here we highlight some of the emerging molecular mechanisms through which mutant p53 proteins can exert these oncogenic functions

Control of glycolysis through regulation of PFK1: old friends and recent additions

Regulation of glucose metabolism is a crucial aspect of cell physiology in normal and disease conditions. Many regulatory events are involved in determining the metabolic fate of glucose and the pathways into which it is directed. The first reaction that commits glucose to the glycolytic pathway is catalyzed by the enzyme phosphofructokinase-1 (PFK-1) and is tightly regulated. One of the most potent activators of PFK-1 is fructose 2,6 bisphosphate (F2,6BP) and its cellular levels are correlated with glycolytic flux. F2,6BP is synthesized and degraded by a family of bifunctional enzymes—the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB). The interplay among F2,6BP levels, the enzymes that generate and degrade it, and PFK-1 activity has important consequences for several different aspects of cell metabolism as well as for systemic metabolic conditions. TIGAR, a recently identified F2,6 bisphosphatase (F2,6BPase), could also contribute to this complexity and participate in shaping the metabolic profile of the cell