Standardization of the antibody-dependent respiratory burst assay with human neutrophils and Plasmodium falciparum malaria.

The assessment of naturally-acquired and vaccine-induced immunity to blood-stage Plasmodium falciparum malaria is of long-standing interest. However, the field has suffered from a paucity of in vitro assays that reproducibly measure the anti-parasitic activity induced by antibodies in conjunction with immune cells. Here we optimize the antibody-dependent respiratory burst (ADRB) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutrophils in response to P. falciparum blood-stage parasites. We focus particularly on assay parameters affecting serum preparation and concentration, and importantly assess reproducibility. Our standardized protocol involves testing each serum sample in singlicate with three independent neutrophil donors, and indexing responses against a standard positive control of pooled hyper-immune Kenyan sera. The protocol can be used to quickly screen large cohorts of samples from individuals enrolled in immuno-epidemiological studies or clinical vaccine trials, and requires only 6 μL of serum per sample. Using a cohort of 86 samples, we show that malaria-exposed individuals induce higher ADRB activity than malaria-naïve individuals. The development of the ADRB assay complements the use of cell-independent assays in blood-stage malaria, such as the assay of growth inhibitory activity, and provides an important standardized cell-based assay in the field

Implications For The Origin Of GRB 051103 From LIGO Observations

We present the results of a LIGO search for gravitational waves (GWs) associated with GRB 051103, a short-duration hard-spectrum gamma-ray burst (GRB) whose electromagnetically determined sky position is coincident with the spiral galaxy M81, which is 3.6 Mpc from Earth. Possible progenitors for short-hard GRBs include compact object mergers and soft gamma repeater (SGR) giant flares. A merger progenitor would produce a characteristic GW signal that should be detectable at the distance of M81, while GW emission from an SGR is not expected to be detectable at that distance. We found no evidence of a GW signal associated with GRB 051103. Assuming weakly beamed gamma-ray emission with a jet semi-angle of 30 deg we exclude a binary neutron star merger in M81 as the progenitor with a confidence of 98%. Neutron star-black hole mergers are excluded with > 99% confidence. If the event occurred in M81 our findings support the the hypothesis that GRB 051103 was due to an SGR giant flare, making it the most distant extragalactic magnetar observed to date.Comment: 8 pages, 3 figures. For a repository of data used in the publication, go to: https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=15166 . Also see the announcement for this paper on ligo.org at: http://www.ligo.org/science/Publication-GRB051103/index.ph

Sensitivity to Gravitational Waves from Compact Binary Coalescences Achieved during LIGO's Fifth and Virgo's First Science Run

We summarize the sensitivity achieved by the LIGO and Virgo gravitational wave detectors for compact binary coalescence (CBC) searches during LIGO's fifth science run and Virgo's first science run. We present noise spectral density curves for each of the four detectors that operated during these science runs which are representative of the typical performance achieved by the detectors for CBC searches. These spectra are intended for release to the public as a summary of detector performance for CBC searches during these science runs.Comment: 12 pages, 5 figure

Search for Gravitational Wave Bursts from Six Magnetars

Soft gamma repeaters (SGRs) and anomalous X-ray pulsars (AXPs) are thought to be magnetars: neutron stars powered by extreme magnetic fields. These rare objects are characterized by repeated and sometimes spectacular gamma-ray bursts. The burst mechanism might involve crustal fractures and excitation of non-radial modes which would emit gravitational waves (GWs). We present the results of a search for GW bursts from six galactic magnetars that is sensitive to neutron star f-modes, thought to be the most efficient GW emitting oscillatory modes in compact stars. One of them, SGR 0501+4516, is likely similar to 1 kpc from Earth, an order of magnitude closer than magnetars targeted in previous GW searches. A second, AXP 1E 1547.0-5408, gave a burst with an estimated isotropic energy >10(44) erg which is comparable to the giant flares. We find no evidence of GWs associated with a sample of 1279 electromagnetic triggers from six magnetars occurring between 2006 November and 2009 June, in GW data from the LIGO, Virgo, and GEO600 detectors. Our lowest model-dependent GW emission energy upper limits for band-and time-limited white noise bursts in the detector sensitive band, and for f-mode ringdowns (at 1090 Hz), are 3.0 x 10(44)d(1)(2) erg and 1.4 x 10(47)d(1)(2) erg, respectively, where d(1) = d(0501)/1 kpc and d(0501) is the distance to SGR 0501+4516. These limits on GW emission from f-modes are an order of magnitude lower than any previous, and approach the range of electromagnetic energies seen in SGR giant flares for the first time.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyItalian Istituto Nazionale di Fisica NucleareFrench Centre National de la Recherche ScientifiqueAustralian Research CouncilCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Educacion y CienciaConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsFoundation for Fundamental Research on Matter supported by the Netherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFoundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space Administration NNH07ZDA001-GLASTCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationRussian Space AgencyRFBR 09-02-00166aIPN JPL Y503559 (Odyssey), NASA NNG06GH00G, NASA NNX07AM42G, NASA NNX08AC89G (INTEGRAL), NASA NNG06GI896, NASA NNX07AJ65G, NASA NNX08AN23G (Swift), NASA NNX07AR71G (MESSENGER), NASA NNX06AI36G, NASA NNX08AB84G, NASA NNX08AZ85G (Suzaku), NASA NNX09AU03G (Fermi)Astronom

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Private information arrival, trading activity, and price formation: Evidence from nonpublic merger negotiations

Abstract: We provide evidence on how stock prices and trading activity respond to the arrival of private information about firm value using the dates of material nonpublic merger negotiations to proxy for private information arrival. Target firm returns are 0.41% higher over two days following each nonpublic negotiation event. Trading volume, order imbalance, and trade size also spike in this window. Larger price reactions following negotiation events preempt deal announcement returns. The price response following negotiation events is explained by proxies for the expected profits and price impact of informed trading, prior press speculation, institutional ownership, and contemporaneous trading activity signals. We thank Linda Bamber, Diane Del Guercio, Ro Gutierrez, Kathy Kahle, Ron Kaniel, Eric Kelley, Chris Lamoureux, Jochen Lawrenz, Lubo Litov, Wayne Mikkelson, Bill Schwert, Rick Sias, Jerry Warner, and workshop participants at MIT, and the Universities of Arizona, Georgia, Innsbruck, Oregon, Rochester, and Utah for helpful comments. We are also grateful to Denis Sosyura (discussant) and participants at the 2012 University of Washington Summer Finance Conference. We recognize the excellent research assistance provided by Tyler Brough, Michael Dambra, Douglas Fairhurst, Jordan Neyland, and Matthew Serfling. * Rochester, NY 14627; phone: 585.273.4818; email: [email protected] ** Tucson, AZ 85721; phone: 520.621.8761; email: [email protected] 1 Understanding the degree to which investors rapidly acquire and trade on new private information about firm value and how their trades affect price formation is central to the design of securities regulation and inferences about the efficiency of financial markets. The evidence in a number of recent studies shows that informed investors obtain private information in a variety of ways, such as through connections to insiders, and that they use this information to make profitable trades. For instance, To infer private information-based trades, the aforementioned studies often begin with a firm's disclosure of earnings or the announcement of a merger agreement and examine trading behavior and price movements over a brief window before the disclosure. But, ascertaining whether connected investors trade on private information is challenging in part due to the difficulty of tying stock returns and trading decisions to the underlying arrival of private information. Because securities regulation does not generally compel managers to disclose material nonpublic information immediately, traders can acquire and exploit private information weeks or months before the firm is required to disclose it. In this paper we study underlying events that produce and distribute private information about the value of a firm. Specifically, we use the dates of merger negotiations that occur privately, but are disclosed weeks or months after the deal is announced, to more precisely identify when private information is actually generated. These data allow us to examine whether informed investors promptly trade on private information that arrives during the course of merger 2 negotiations and if their trading has an economically important effect on target firms' stock prices. 1 For a sample of 545 completed acquisitions announced between 1995 and 2006, we use Securities and Exchange Commission (SEC)-mandated background disclosures to identify the dates and types of various material "events" that occur during negotiations between the target and potential acquirers before an acquisition deal is announced. These nonpublic negotiation events include, for example, the initiation of merger talks, a bidder making a private offer for the target, the retention of a financial advisor, or a meeting of the target's board to evaluate a proposed deal. On average, over the three months prior to the merging parties' disclosure of a preliminary merger agreement (hereafter, referred to as the deal announcement), there are about seven unique trading days during which at least one material negotiation event occurs. After controlling for the impact of press speculation about a potential acquisition deal (which affects 18% of the deals in our sample) we find that for each nonpublic negotiation event, target firm excess abnormal returns average 0.18% the same day and 0.23% the day after the event, resulting in a two-day estimated excess return of 0.41%. These returns are incremental to the average positive abnormal returns during the negotiation period and thus provide a lower-bound estimate of the price impact of trading on private information about merger negotiations. To more fully understand the source of these returns, we examine whether non-price measures of informed trading are also related to the arrival of private information during merger negotiations. We document significant spikes in abnormal trading volume, buyer-initiated transactions measured by order imbalance, and medium-size trades over the two-day window following a nonpublic negotiation event. Moreover, we also find that increases in contemporaneous 1 Informed trading before a merger announcement includes both illegal insider trading on material nonpublic information and legitimate trading based on superior information acquisition and processing. Moreover, the term "insider" in insider trading as used in this paper refers to any individual that knowingly trades on material nonpublic information. This could include, but is not limited to, corporate insiders as defined under Section 16 requirements for reporting trades (e.g., officers, directors, and some blockholders). See Agrawal and Jaffe (1995) and Agrawal and Nasser (2012) for evidence on trading by corporate insiders prior to merger announcements. 3 volume, buy-sell order imbalance, and medium-size trades predict stock returns following negotiation events. For example, a ten percentage point increase in abnormal trading volume is associated with a 12 basis point larger stock price reaction to each negotiation event. These effects are incremental to the typical effect of trading activity on stock returns and suggest that the arrival of private information about merger negotiations has substantive implications for understanding the trading decisions of informed investors and the informational efficiency of stock prices. Next, we investigate whether firm and deal-specific factors explain how quickly target stock prices respond to the arrival of private information. We show that stock returns following negotiation events are increasing in both the expected profits from trading on private information, as measured by the offer premium, and the likelihood of deal completion, captured by a tender offer or target termination fee clause. We further document that the magnitude of the stock price response is increasing in the adverse selection costs of trading in the target firm's shares, proxied by PIN (probability of informed trading) and low analyst coverage. In other words, stock returns are more sensitive to negotiation events for firms whose stock price is generally more sensitive to informed trades. We also find that higher institutional ownership is associated with a decrease in the sensitivity of stock returns to negotiation events. This evidence suggests that institutions may be less willing than individuals to trade on private information from negotiation events or that if they do trade on this information, they do not do so immediately after a negotiation event. We also examine whether media speculation about a deal is related to the sensitivity of target firm stock returns to nonpublic negotiation events. Controlling for the market's reaction to a rumor, we show that for the 18% of the deals in our sample with at least one published rumor prior to the deal announcement, the target firm's stock returns respond significantly more to negotiation events. Further, we document that this effect is most pronounced for nonpublic negotiation events that occur after the rumor is published. These findings are consistent with the conventional wisdom that 4 the litigation risk from trading on private information is decreasing in the amount of existing public information about a potential deal and with the notion that because press speculation increases target firms' stock return volatility, news rumors make it easier for informed investors to trade without detection from other traders. We investigate the factors that determine the timing and occurrence of press speculation. Indicating that private information from merger negotiations is in some instances quickly leaked to the media, we show that although press rumors tend to follow observable abnormal stock returns and trading volume, they are incrementally more likely to take place over the two days following a nonpublic negotiation event. Further, implying that informed investors are potentially responsible for at least some of this leakage, we find that a deal is more likely to be rumored when the set of investors with private information about deal negotiations is larger, proxied for with measures for the number of deal insiders (Acharya and Johnson One interpretation of this finding is that, at times, informed investors intentionally leak some of their private information to the press so they can more easily trade on the remainder of their information. To further assess the economic importance of informed trading following the arrival of private information, we examine the extent to which the price impact of this trading affects the target's acquisition price and the market's reaction to the announcement of a merger agreement. Schwert's (1996) evidence suggests that for every 1 increase in the target's stock price prior to the deal announcement, the target negotiates more than a 1 increase in the final acquisition price from the acquirer. However, acquirers and targets know the dates they negotiated, and thus, acquirers should be able to discount stock price movements occurring just after negotiation events. Our results suggest that a $1 increase in stock price attributable to informed trading following nonpublic negotiation events leads to a$0.81 increase in the final transaction price, a significant 29% discount from the $1.14 increase in the final transaction price for each$1 of non-event price increase. In 5 other words, deal negotiators place a lower weight on stock returns linked to nonpublic negotiation event days than stock returns on other days. We also find that a one percent increase in the target's stock price attributable to informed trading following nonpublic negotiation events reduces the market's reaction to the deal announcement by 26 basis points. However, a similar one percent increase in stock price during the period prior to the deal announcement that is not attributable to negotiation events reduces the market's reaction by only 13 basis points. These findings imply that private information-based trading following merger negotiations is economically important in preempting the information in the deal announcement. Our study contributes to the literature that considers how public and private information impacts trading decisions and price formation. We use a novel but intuitive approach to provide insights on private information-based trading and its impact on price formation by focusing on the dates when private information is created. Our evidence indicates that well-informed traders rapidly exploit their information advantage. Their trades are reflected in volume, order flow, and trade size, and have an economically important effect on a firm's stock price. Further, we identify several factors that determine the magnitude of the stock price reaction to the arrival of private information during merger negotiations. The stock price reaction depends on contemporaneous volume and order flow, expected profits from trading on private information, the expected price impact of informed trading, institutional ownership, and whether a private negotiation event is preceded by press speculation. Implying that informed trading following merger negotiations preempts information in the deal announcement, we also show that stock returns linked to days with private information events are associated with significantly smaller deal announcement returns. This study also contributes to the emerging literature on how traders' characteristics and connections to insiders impact the timing and profitability of their trades and the efficiency of stock 6 prices. Our focus on days when information is produced and distributed provides an avenue for future research to examine how the trades of specific investors correlate with the arrival of private information. Given that we document trading activity and stock returns respond quickly to the arrival of new private information about firm value, our evidence also speaks to the SEC's focus on hedge funds, brokerages, deal advisers, and exchange traders and their access to and use of confidential inside information. The remainder of the paper is organized as follows. Section 1 reviews prior work on private information-based trading and discusses the potential for such trading activity subsequent to merger negotiations. Section 2 presents our empirical results. Section 3 concludes. Informed Trading and the Timing of Nonpublic Merger Negotiations Asymmetric information is a pervasive trait of capital markets. The intent of disclosure regulation is to ensure that material information is disclosed to investors, but there are few mandatory obligations for real-time disclosure of new information. As a result, stock prices can diverge from their full information value. Public disclosure of material nonpublic information may be delayed for weeks or even months, thereby providing incentives for traders to uncover private information. Traders with more precise information about a firm's value are more likely to trade on their information. In the absence of public disclosure of new information, the speed at which price converges to its full information value depends on informed trading. Profit-maximizing informed traders have incentives to camouflage their trades by spreading them out over time As the number of privately-informed investors grows, competition between them can create incentives to trade more aggressively, leading to more efficient prices (Holden and Subrahmanyam 7 (1992)). In contrast, 2 We focus on the timing of nonpublic merger negotiations to identify informed trading activity and its effect on price formation. 3 An informed investor's trading incentives depend on how negotiations progress, the expected offer price relative to the current price (the premium), and the likelihood of a successful deal. The distribution of that private information during negotiations also matters. The initial contact between the merging parties is often between CEOs and a few close advisors and directors. As discussions progress, the target's (and often the acquirer's) entire board is informed, financial and legal advisors are retained, investment bankers are contacted to assist with financing, and lower-level managers and auditors are brought in to support the due diligence process and integration planning. While the negotiating managers, directors, advisors, and financing 2 Prior studies that attempt to link trading on private information prior to acquisitions with target stock price formation look at the magnitude of stock price runups in acquisition targets 5 4 Expert networks are one of the interesting targets of recent insider trading investigations. Expert networks retain current and past managers and other industry specialists as consultants to investors such as mutual funds and hedge funds. While expert network firms have policies that bar their consultants from passing along confidential information, it appears that many consultants have done so. A recent complaint filed by the SEC alleges that ten consultants and one investment advisor working for the expert network firm Primary Global Research (PGR) passed along material nonpublic information to hedge funds and other PGR clients in exchange for cash compensation. The SEC alleges that the clients of PGR earned about $30 million in illicit profits as a result (SEC vs. Longria et a

Competition and substitution between public transport modes

The management and understanding of modal split between public transport (PT) modes is of interest for numerous reasons. It may, for example, be desirable to stimulate passengers to switch from crowded buses and over to higher capacity rail. This requires a good understanding of drivers of transit modal substitution. The evidence put forward in this paper is based on more than 150 empirically estimated cross elasticities between PT modes from over 20 sources collected from Australia, Europe and USA. These sources include scientifically published evidence as well as grey literature. This evidence is coded into a database from which our paper presents and analyses the available cross-PT-modal demand relations. We focus on evidence for how fares, travel time and service intervals on PT ‘mode A’ affect the demand for PT ‘mode B’. Despite generally low levels of substitution between PT modes, passengers are particularly sensitive to in-vehicle, access/egress and waiting time in choosing PT mode and less so for fare variations. In general, rail demand is less sensitive to changes in bus than bus demand is to changes in rail. We also find that peak-hour demand more markedly switches between PT modes than off-peak demand does

Sensitivity of the Advanced LIGO detectors at the beginning of gravitational wave astronomy

The Laser Interferometer Gravitational Wave Observatory (LIGO) consists of two widely separated 4 km laser interferometers designed to detect gravitational waves from distant astrophysical sources in the frequency range from 10 Hz to 10 kHz. The first observation run of the Advanced LIGO detectors started in September 2015 and ended in January 2016. A strain sensitivity of better than 10−23/Hz−−−√ was achieved around 100 Hz. Understanding both the fundamental and the technical noise sources was critical for increasing the astrophysical strain sensitivity. The average distance at which coalescing binary black hole systems with individual masses of 30  M⊙ could be detected above a signal-to-noise ratio (SNR) of 8 was 1.3 Gpc, and the range for binary neutron star inspirals was about 75 Mpc. With respect to the initial detectors, the observable volume of the Universe increased by a factor 69 and 43, respectively. These improvements helped Advanced LIGO to detect the gravitational wave signal from the binary black hole coalescence, known as GW150914

Search for post-merger gravitational waves from the remnant of the binary neutron star merger GW170817

In Advanced LIGO, detection and astrophysical source parameter estimation of the binary black hole merger GW150914 requires a calibrated estimate of the gravitational-wave strain sensed by the detectors. Producing an estimate from each detector's differential arm length control loop readout signals requires applying time domain filters, which are designed from a frequency domain model of the detector's gravitational-wave response. The gravitational-wave response model is determined by the detector's opto-mechanical response and the properties of its feedback control system. The measurements used to validate the model and characterize its uncertainty are derived primarily from a dedicated photon radiation pressure actuator, with cross-checks provided by optical and radio frequency references. We describe how the gravitational-wave readout signal is calibrated into equivalent gravitational-wave-induced strain and how the statistical uncertainties and systematic errors are assessed. Detector data collected over 38 calendar days, from September 12 to October 20, 2015, contain the event GW150914 and approximately 16 of coincident data used to estimate the event false alarm probability. The calibration uncertainty is less than 10% in magnitude and 10 degrees in phase across the relevant frequency band 20 Hz to 1 kHz

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands