Hawkes process as a model of social interactions: a view on video dynamics

We study by computer simulation the "Hawkes process" that was proposed in a recent paper by Crane and Sornette (Proc. Nat. Acad. Sci. USA 105, 15649 (2008)) as a plausible model for the dynamics of YouTube video viewing numbers. We test the claims made there that robust identification is possible for classes of dynamic response following activity bursts. Our simulated timeseries for the Hawkes process indeed fall into the different categories predicted by Crane and Sornette. However the Hawkes process gives a much narrower spread of decay exponents than the YouTube data, suggesting limits to the universality of the Hawkes-based analysis.Comment: Added errors to parameter estimates and further description. IOP style, 13 pages, 5 figure

Approximate Methods for State-Space Models

State-space models provide an important body of techniques for analyzing time-series, but their use requires estimating unobserved states. The optimal estimate of the state is its conditional expectation given the observation histories, and computing this expectation is hard when there are nonlinearities. Existing filtering methods, including sequential Monte Carlo, tend to be either inaccurate or slow. In this paper, we study a nonlinear filter for nonlinear/non-Gaussian state-space models, which uses Laplace's method, an asymptotic series expansion, to approximate the state's conditional mean and variance, together with a Gaussian conditional distribution. This {\em Laplace-Gaussian filter} (LGF) gives fast, recursive, deterministic state estimates, with an error which is set by the stochastic characteristics of the model and is, we show, stable over time. We illustrate the estimation ability of the LGF by applying it to the problem of neural decoding and compare it to sequential Monte Carlo both in simulations and with real data. We find that the LGF can deliver superior results in a small fraction of the computing time.Comment: 31 pages, 4 figures. Different pagination from journal version due to incompatible style files but same content; the supplemental file for the journal appears here as appendices B--E

Power-law distributions in empirical data

Power-law distributions occur in many situations of scientific interest and have significant consequences for our understanding of natural and man-made phenomena. Unfortunately, the detection and characterization of power laws is complicated by the large fluctuations that occur in the tail of the distribution -- the part of the distribution representing large but rare events -- and by the difficulty of identifying the range over which power-law behavior holds. Commonly used methods for analyzing power-law data, such as least-squares fitting, can produce substantially inaccurate estimates of parameters for power-law distributions, and even in cases where such methods return accurate answers they are still unsatisfactory because they give no indication of whether the data obey a power law at all. Here we present a principled statistical framework for discerning and quantifying power-law behavior in empirical data. Our approach combines maximum-likelihood fitting methods with goodness-of-fit tests based on the Kolmogorov-Smirnov statistic and likelihood ratios. We evaluate the effectiveness of the approach with tests on synthetic data and give critical comparisons to previous approaches. We also apply the proposed methods to twenty-four real-world data sets from a range of different disciplines, each of which has been conjectured to follow a power-law distribution. In some cases we find these conjectures to be consistent with the data while in others the power law is ruled out.Comment: 43 pages, 11 figures, 7 tables, 4 appendices; code available at http://www.santafe.edu/~aaronc/powerlaws

Differentiation and Protective Capacity of Virus-Specific CD8

Noroviruses can establish chronic infections with active viral shedding in healthy humans but whether persistence is associated with adaptive immune dysfunction is unknown. We used genetically engineered strains of mouse norovirus (MNV) to investigate CD8+ T cell differentiation during chronic infection. We found that chronic infection drove MNV-specific tissue-resident memory (Trm) CD8+ T cells to a differentiation state resembling inflationary effector responses against latent cytomegalovirus with only limited evidence of exhaustion. These MNV-specific Trm cells remained highly functional yet appeared ignorant of ongoing viral replication. Pre-existing MNV-specific Trm cells provided partial protection against chronic infection but largely ceased to detect virus within 72 hours of challenge, demonstrating rapid sequestration of viral replication away from T cells. Our studies revealed a strategy of immune evasion by MNV via the induction of a CD8+ T cell program normally reserved for latent pathogens and persistence in an immune-privileged enteric niche. Chronic infections often cause T cell dysfunction, but how noroviruses (NV) evade immunity is unknown. Tomov et al. show that gut-resident T cells against NV remain functional but ignorant of chronic viral replication, suggesting that NV persists in an immune-privileged enteric niche. © 2017 Elsevier Inc

Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44.

Sulfatase modifying factor 1 (SUMF1) encodes for the formylglicine generating enzyme, which activates sulfatases by modifying a key cysteine residue within their catalytic domains. SUMF1 is mutated in patients affected by multiple sulfatase deficiency, a rare recessive disorder in which all sulfatase activities are impaired. Despite the absence of canonical retention/retrieval signals, SUMF1 is largely retained in the endoplasmic reticulum (ER), where it exerts its enzymatic activity on nascent sulfatases. Part of SUMF1 is secreted and paracrinally taken up by distant cells. Here we show that SUMF1 interacts with protein disulfide isomerase (PDI) and ERp44, two thioredoxin family members residing in the early secretory pathway, and with ERGIC-53, a lectin that shuttles between the ER and the Golgi. Functional assays reveal that these interactions are crucial for controlling SUMF1 traffic and function. PDI couples SUMF1 retention and activation in the ER. ERGIC-53 and ERp44 act downstream, favoring SUMF1 export from and retrieval to the ER, respectively. Silencing ERGIC-53 causes proteasomal degradation of SUMF1, while down-regulating ERp44 promotes its secretion. When over-expressed, each of three interactors favors intracellular accumulation. Our results reveal a multistep control of SUMF1 trafficking, with sequential interactions dynamically determining ER localization, activity and secretion

Targeting the mRNA-binding protein HuR impairs malignant characteristics of pancreatic ductal adenocarcinoma cells.

Post-transcriptional regulation is a powerful mediator of gene expression, and can rapidly alter the expression of numerous transcripts involved in tumorigenesis. We have previously shown that the mRNA-binding protein HuR (ELAVL1) is elevated in human pancreatic ductal adenocarcinoma (PDA) specimens compared to normal pancreatic tissues, and its cytoplasmic localization is associated with increased tumor stage. To gain a better insight into HuR\u27s role in PDA biology and to assess it as a candidate therapeutic target, we altered HuR expression in PDA cell lines and characterized the resulting phenotype in preclinical models. HuR silencing by short hairpin and small interfering RNAs significantly decreased cell proliferation and anchorage-independent growth, as well as impaired migration and invasion. In comparison, HuR overexpression increased migration and invasion, but had no significant effects on cell proliferation and anchorage-independent growth. Importantly, two distinct targeted approaches to HuR silencing showed marked impairment in tumor growth in mouse xenografts. NanoString nCounter® analyses demonstrated that HuR regulates core biological processes, highlighting that HuR inhibition likely thwarts PDA viability through post-transcriptional regulation of diverse signaling pathways (e.g. cell cycle, apoptosis, DNA repair). Taken together, our study suggests that targeted inhibition of HuR may be a novel, promising approach to the treatment of PDA

How Does Financial Market Evaluate Business Models? Evidence From European Banks

This paper investigates the way in which the financial market defines and evaluates different business models/business mix, using a sample of listed European banking groups, with a total asset value greater than 50 billion US$, for the period 2006-2015. The main results suggest that non-interest components foster market valuation and that financial market seems to associate a better risk-return trade-off to non-banking fees compared to the banking ones. This evidence enables us to identify 3 clusters of European banking groups based on the main components of income. These findings have strategic implications both for bank managers, regulators and supervisors due to the impact of the crisis on banking business, bank profitability and riskiness and the new challenges they entail

The non-conventional use of 99mTc-Tetrofosmine for dynamic hepatobiliary scintigraphy

BACKGROUND: Classic dynamic hepatobiliary scintigraphy (DHBS) is commonly performed with 99mTc-Iminodiacetic Acid (IDA) derivatives and represents a non-invasive diagnosis method for biliary dyskinesia, fistulas, surgical anastomosis, etc (1). This study assesses the possibility of performing DHBS with 99mTc-Tetrofosmine (TF), a radiopharmaceutical (RF) dedicated to myocardial perfusion scintigraphy (MPS), but being excreted through the liver. The possibility to use 99mTc-TF for DHBS may be important in situations when the standardized RF for this procedure (IDA derivatives) is not available. MATERIAL AND METHODS: We performed DHBS for 30 patients referred for investigation by internal medicine and surgery departments. The patients had been fasting for12 hours. The dynamic investigation started simultaneously with the intravenous (IV) administration of 37–110 MBq (1–3 mCi) 99mTc-TF. Dynamic images were recorded for 30–45 minutes, one image per minute, followed by static scintigraphy at 1 h, 1.5 h, 2 h, and 3 h after IV injection. RESULTS: The quality of scintigraphic images of the liver and biliary tree obtained at DHBS with 99mTc-TF ensured the correct diagnosis of biliary dyskinesia, stasis, stenosis, and fistulas. CONCLUSIONS: DHBS using 99mTc-TF is justified by the image quality and by the good cost/benefits ratio. Because the IDA derivatives are not always available, this finding may be important for medical practice. 99mTc-TF evacuated through the bile duct allows DHBS interpretation, while the necessary dose is approximately 8 to 20 times smaller than that used for myocardial perfusion scintigraphy. Nuclear Med Rev 2011; 14, 2: 79–8