Miracle-dz/UniFAR-FTUs huggingface dataset:
Graphical calibration curves and the integrated calibration index (ICI) for survival models

In the context of survival analysis, calibration refers to the agreement between predicted probabilities and observed event rates or frequencies of the outcome within a given duration of time. We aimed to describe and evaluate methods for graphically assessing the calibration of survival models. We focus on hazard regression models and restricted cubic splines in conjunction with a Cox proportional hazards model. We also describe modifications of the Integrated Calibration Index, of E50 and of E90. In this context, this is the average (respectively, median or 90th percentile) absolute difference between predicted survival probabilities and smoothed survival frequencies. We conducted a series of Monte Carlo simulations to evaluate the performance of these calibration measures when the underlying model has been correctly specified and under different types of model mis‐specification. We illustrate the utility of calibration curves and the three calibration metrics by using them to compare the calibration of a Cox proportional hazards regression model with that of a random survival forest for predicting mortality in patients hospitalized with heart failure. Under a correctly specified regression model, differences between the two methods for constructing calibration curves were minimal, although the performance of the method based on restricted cubic splines tended to be slightly better. In contrast, under a mis‐specified model, the smoothed calibration curved constructed using hazard regression tended to be closer to the true calibration curve. The use of calibration curves and of these numeric calibration metrics permits for a comprehensive comparison of the calibration of competing survival models.
TP53 Status, Patient Sex, and the Immune Response as Determinants of Lung Cancer Patient Survival

Lung cancer poses the greatest cancer-related death risk and males have poorer outcomes than females, for unknown reasons. Patient sex is not a biological variable considered in lung cancer standard of care. Correlating patient genetics with outcomes is predicted to open avenues for improved management. Using a bioinformatics approach across non-small cell lung cancer (NSCLC) subtypes, we identified where patient sex, mutation of the major tumor suppressor gene, Tumour protein P53 (TP53), and immune signatures stratified outcomes in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), among datasets of The Cancer Genome Atlas (TCGA). We exposed sex and TP53 gene mutations as prognostic for LUAD survival. Longest survival in LUAD occurred among females with wild-type (wt) TP53 genes, high levels of immune infiltration and enrichment for pathway signatures of Interferon Gamma (INF-γ), Tumour Necrosis Factor (TNF) and macrophages-monocytes. In contrast, poor survival in men with LUAD and wt TP53 genes corresponded with enrichment of Transforming Growth Factor Beta 1 (TGFB1, hereafter TGF-β) and wound healing signatures. In LUAD with wt TP53 genes, elevated gene expression of immune checkpoint CD274 (hereafter: PD-L1) and also protein 53 (p53) negative-regulators of the Mouse Double Minute (MDM)-family predict novel avenues for combined immunotherapies. LUSC is dominated by male smokers with TP53 gene mutations, while a minor population of TCGA LC patients with wt TP53 genes unexpectedly had the poorest survival, suggestive of a separate etiology. We conclude that advanced approaches to LUAD and LUSC therapy lie in the consideration of patient sex, TP53 gene mutation status and immune signatures.
R&D INVESTMENTS: EVIDENCE FROM ITALIAN SMES

Self-financing has often been seen as an important source for research-and-development (R&D) funding. However, an in-depth comparison between the determinants of self-financing in the case of traditional investments versus those in R&D has not been provided yet. We use a comprehensive data set of Italian manufacturing firms to investigate this issue. We analyse the role of a wide number of financial variables in driving the rate of self-financing of firms, in both traditional and R&D investments, and we focus on public subsidies and firm size as critical factors explaining heterogeneity. First, we perform logit and logistic regressions separately for traditional and R&D self-financing, finding that they are positively correlated, and that the availability of public subsidies reduces self-financing. Subsequent poolability tests show that public subsidies and firm size are crucial discriminating factors for self-financing behaviour. Our main finding is that, in the absence of public subsidies, no internal or external market variable is able to explain the firms’
Solid substitution: theory versus experiment

Gassmann fluid substitution is widely used in geophysical practice. In the last few years, the topic of fluid/solid substitution has emerged, where the substances filling the pore space can be solids, fluids, or visco-elastic materials, such as heavy oils. Solid substitution cannot be accomplished with the Gassmann theory because the finite rigidity of the pore fill (either solid or viscoelastic) prevents pressure communication throughout the pore space, which is a key assumption of the Gassmann theory. In this paper we explore applicability of solid substitution techniques by using a sandstone saturated with a solid substance, octodecane. This substance is a hydrocarbon with a melting point of 28°C, making it convenient to use in the lab in both solid and fluid form. Our approach is to measure a dry sandstone sample under different confining pressure, then saturate it with liquid Octodecane at 35°C and measure again. After that, we cool it to 20-25°C and carry out the measurement once more. The dry properties can be used to obtain parameters necessary for fluid and solid substitution. The results show that moduli of the dry sandstone exhibit significant pressure dependency, which is reduced for the solid filled rock. Also the prediction of the Gassmann theory and Ciz and Shapiro theory underestimate the velocities. This suggests that stiffening occurs due to substantial reduction of compliance of grain contacts by the solid infill. This effect is accounted for by the solid squirt theory. The results give direct evidence of the solid squirt effect and can be used to verify and calibrate theoretical solutions for rocks saturated with solid or viscoelastic substances.
De novo design of protein peptides to block association of the SARS-CoV-2 spike protein with human ACE2

The outbreak of COVID-19 has now become a global pandemic that has severely impacted lives and economic stability. There is, however, no effective antiviral drug that can be used to treat COVID-19 to date. Built on the fact that SARS-CoV-2 initiates its entry into human cells by the receptor binding domain (RBD) of its spike protein binding to the angiotensin-converting enzyme 2 (hACE2), we extended a recently developed approach, EvoDesign, to design multiple peptide sequences that can competitively bind to the SARS-CoV-2 RBD to inhibit the virus from entering human cells. The protocol starts with the construction of a hybrid peptidic scaffold by linking two fragments grafted from the interface of the hACE2 protein (a.a. 22-44 and 351-357) with a linker glycine, which is followed by the redesign and refinement simulations of the peptide sequence to optimize its binding affinity to the interface of the SARS-CoV-2 RBD. The binding experiment analyses showed that the designed peptides exhibited a significantly stronger binding potency to hACE2 than the wild-type hACE2 receptor (with -53.35 vs. -46.46 EvoEF2 energy unit scores for the top designed and wild-type peptides, respectively). This study demonstrates a new avenue to utilize computationally designed peptide motifs to treat the COVID-19 disease by blocking the critical spike-RBD and hACE2 interactions.
Numerical Methods for the Calculation of Material Parameter Values for Three-layered Aortic Valve Leaflets

Aortic valve leaflets are comprised of three layers, each of which has a different composition and consequently, different mechanical properties. Each layer exhibits non-linear stress-strain behaviour and is modelled using a hyperelastic material model. Our objective is to determine the mechanical properties of each layer from experimental force-indentation depth data, ensuring that the material model parameters in each layer are unique and have converged to their correct values. To achieve this objective, material model parameters are calculated using inverse finite element simulations and non-linear optimization methods. To ensure that these parameters converge to their correct values, mathematical models of the indentation problem are used to obtain approximate values of these parameters to be used as initial conditions in the finite element simulations. This paper describes our progress with the development of these mathematical models and numerical simulations, as well as our ongoing work to achieve our defined objective.
Analysis of 2019 novel coronavirus infection and clinical characteristics of outpatients: An epidemiological study from a fever clinic in Wuhan, China

Since the outbreak of 2019 novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]) pneumonia, thousands of patients with fever or cough were flocked into fever clinic of designated hospitals in Wuhan, China. To date, no data have ever been reported to reflect the prevalence of coronavirus disease 2019 (COVID‐19) among these outpatients. Moreover, it is almost unknown to discriminate COVID‐19 and nucleic acid negative patients based on clinical features in the fever clinics.
Analysis of the Impact of Intangible Resources at Macroeconomic Level. The Case of Romania

Abstract The results of literature analysis confirm the strategic value of intangible resources in creating wealth and conferring competitive advantages to nations. However, there are few academic papers related to intangible resources at country level. At national level, economic growth is increasingly based on knowledge and other intangible resources than on physical ones. To test this hypothesis in Romania, this article analyses how intangible resources influence economic growth, and correlation indices between different types of intangible resources and gross domestic product value are calculated. The analysis shows that there are very strong positive correlations between GDP and most of the intangible resource variables. Despite the importance of intangible resources at national level and the fact that they are an important factor in determining economic growth in the current knowledge-based economy, Romania's position in the international context regarding intangible assets is very weak, with many weak points in research and innovation performance compared to other EU Member States. Therefore, there is a need in our country to re-evaluate the areas where all efforts need to be focused to stimulate innovation performance, to properly manage national intangible resources, a crucial process for improving the quality of life
Lithium Use during Pregnancy and the Risk of Miscarriage

Recent studies have provided new data on the teratogenicity of lithium. Less is known about the risk of miscarriage after lithium use during pregnancy. The aim of this study was to investigate the association between lithium use during pregnancy and miscarriage. Participants were women with bipolar I disorder and one or more pregnancies, of which information on medication use and pregnancy outcome was available (n = 443). The unadjusted odds ratios for miscarriage after lithium use during pregnancy was calculated. Multilevel logistic regression was used to calculate the odds ratio, adjusted for the age at conception and the clustering of pregnancies per woman. Miscarriages occurred in 20.8% of the lithium-exposed pregnancies (16/77), compared with 10.9% of the unexposed pregnancies (40/366) (OR = 2.14; 95% CI: 1.13–4.06). The adjusted odds ratio of miscarriage after lithium use during pregnancy was 2.94 (95% CI: 1.39–6.22). Lithium use during pregnancy may increase the risk of miscarriage.
The Need for Robust Epidemiological Evidence During a Pandemic

EDITORIAL COMMENTARY • cid 2020:XX (XX XXXX) • 1 Received 31 May 2020; editorial decision 4 June 2020; accepted 11 June 2020; published online June 16, 2020. Correspondence: S. G. Sullivan, WHO Collaborating Centre for Reference and Research on Influenza, Royal Melbourne Hospital, and Doherty Department, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia (sheena. sullivan@influenzacentre.org; sheena.sullivan@mh. org.au). Clinical Infectious Diseases 2020;XX(XX):1–2 © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. DOI: 10.1093/cid/ciaa770 The Need for Robust Epidemiological Evidence During a Pandemic
TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties

Helicobacter pylori infection, the main risk factor for gastric cancer (GC), leads to an epithelial–mesenchymal transition (EMT) of gastric epithelium contributing to gastric cancer stem cell (CSC) emergence. The Hippo pathway effectors yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) control cancer initiation and progression in many cancers including GC. Here, we investigated the role of TAZ in the early steps of H. pylori-mediated gastric carcinogenesis. TAZ implication in EMT, invasion, and CSC-related tumorigenic properties were evaluated in three gastric epithelial cell lines infected by H. pylori. We showed that H. pylori infection increased TAZ nuclear expression and transcriptional enhancer TEA domain (TEAD) transcription factors transcriptional activity. Nuclear TAZ and zinc finger E-box-binding homeobox 1 (ZEB1) were co-overexpressed in cells harboring a mesenchymal phenotype in vitro, and in areas of regenerative hyperplasia in gastric mucosa of H. pylori-infected patients and experimentally infected mice, as well as at the invasive front of gastric carcinoma. TAZ silencing reduced ZEB1 expression and EMT phenotype, and strongly inhibited invasion and tumorsphere formation induced by H. pylori. In conclusion, TAZ activation in response to H. pylori infection contributes to H. pylori-induced EMT, invasion, and CSC-like tumorigenic properties. TAZ overexpression in H. pylori-induced pre-neoplastic lesions and in GC could therefore constitute a biomarker of early transformation in gastric carcinogenesis.
The Tristetraprolin Family of RNA-Binding Proteins in Cancer: Progress and Future Prospects

Post-transcriptional regulation of gene expression plays a key role in cellular proliferation, differentiation, migration, and apoptosis. Increasing evidence suggests dysregulated post-transcriptional gene expression as an important mechanism in the pathogenesis of cancer. The tristetraprolin family of RNA-binding proteins (RBPs), which include Zinc Finger Protein 36 (ZFP36; commonly referred to as tristetraprolin (TTP)), Zinc Finger Protein 36 like 1 (ZFP36L1), and Zinc Finger Protein 36 like 2 (ZFP36L2), play key roles in the post-transcriptional regulation of gene expression. Mechanistically, these proteins function by binding to the AU-rich elements within the 3′-untranslated regions of their target mRNAs and, in turn, increasing mRNA turnover. The TTP family RBPs are emerging as key regulators of multiple biological processes relevant to cancer and are aberrantly expressed in numerous human cancers. The TTP family RBPs have tumor-suppressive properties and are also associated with cancer prognosis, metastasis, and resistance to chemotherapy. Herein, we summarize the various hallmark molecular traits of cancers that are reported to be regulated by the TTP family RBPs. We emphasize the role of the TTP family RBPs in the regulation of trait-associated mRNA targets in relevant cancer types/cell lines. Finally, we highlight the potential of the TTP family RBPs as prognostic indicators and discuss the possibility of targeting these TTP family RBPs for therapeutic benefits.
Highly efficient heterogeneous modal superposition method for the full-wave analysis of arbitrarily shaped H-plane structures fed through rectangular waveguides

A new fully modal characterisation procedure is proposed to reduce the number of unknowns needed to characterise the ports of an arbitrary H-plane device in rectangular waveguide, so that no equivalent currents will be involved in the characterisation of the ports. Moreover, since no currents are needed to characterise the ports, the weights of the scattered modes can be unknowns of the resulting system of equations. This is an important fact, since, to find the wanted modal weights, a subsequent projection step is not necessary anymore. The new method is then advantageous when compared to other hybrid alternatives in the literature, not only because the ports are solved using fewer unknowns, which is the main advantage of the proposal, but also because the scattering parameters can be computed directly, once the system of equations is posed.
Attention to Counter-Attitudinal Messages in a State Election Campaign

Research following the "selective exposure" model has focused on avoidance of political messages with which a person might disagree. But positive attention to such "counter-attitudinal" messages is worthy of study, in part because normative theories of democracy value exposure to information that might disturb citizens' political predispositions. Surveys of youth (N = 417) and parents (N = 430) examine attention to newspaper, television, and Web messages about candidates. While there is somewhat more attention to messages about and for a person's favored political candidate or party, forms of political involvement (knowledge, curiosity, and discussion) that predict this "attitude-consistent" attention also predict counter-attitudinal attention at least as strongly. Parents' education and students' exposure to civics lessons also predict both kinds of attention. These results suggest that attention to counterattitudinal political messages is worthy of further study as an important goal of political socialization and a criterion of citizen performance in democracy.
Learning Theory and Heterogeneous Play in a Signaling-Game Experiment

We study the effect of how types are assigned to participants in a signaling-game experiment. The sender has two actions, In and Out, and two types. In one treatment, types are i.i. d. in every period, and senders gather experience with both types. In the other, types are assigned once-and-for-all, and feedback is type specific. The theory of learning in games predicts that the non-Nash but self-confirming equilibrium where some fraction of types play Out can persist in the fixed-type treatment but not when types are i.i. d. Our results confirm that more senders do play Out in the fixed-type treatment. (JEL C92, D82, D83)
Hodge-Laplace eigenvalues of convex bodies

We give upper and lower bounds of the first eigenvalue of the Hodge Laplacian acting on smooth p-forms on a convex Euclidean domain for the absolute and relative boundary conditions. In particular, for the absolute conditions we show that it behaves like the squared inverse of the p-th longest principal axis of the ellipsoid of maximal volume included in the domain (the John ellipsoid). Using John's theorem, we then give a spectral geometric interpretation of the bounds and relate the eigenvalues with the largest volume of a p-dimensional section of the domain.
Looking for the stars: Estimating the natural rate of interest

Natural rate of interest or r-star and the natural rate of output growth are important policy benchmarks widely used by central banks to determine the stance of an economy. It is well recognized that r-star, linearly related to the natural rate of output growth within the New Keynesian framework, is subject to low-frequency fl uctuations. To track its evolution over time, we propose an unobserved components model with similar cycles based on the work of Holston et al. (2017). Our model takes an estimate of the time-varying natural rate of output growth as input via a first-stage model based on a first-difference version of Okun's law with time-varying parameters. In the second-stage, the full model is estimated using Kalman filter. We also show that the similar cycles imply a Taylor rule and a hybrid New Keynesian Phillips curve. For US, EA and UK, our estimates suggest that the decline of natural rate of output growth started from the 1960s, while r-star for US and EA started to fall from 1985. R-star of UK started low during 1960s, but rose and stayed relatively high in the 80s until a big drop took place during the GFC.
The flat-spectrum radio quasar 3C 345 from the high to the low emission state

We report simultaneous observations at different energy bands in radio, optical, UV, X-rays and γ rays of the flat-spectrum radio-quasar 3C 345. We built the light curve of the source at different frequencies from 2008, the beginning of the Fermi all-sky survey, to 2016, using new data and public archives. In particular we obtained several optical spectra, to study the behavior of emission lines and the continuum in different activity states and to derive the black hole mass. 3C 345 showed two flaring episodes in 2009, which occurred simultaneously in γ ray, optical/UV and X-rays, and were later followed in radio. The source shows an inverse Compton dominated spectral energy distribution, which moved from higher to lower frequencies from the high to the low state. The reverberation of emission lines during one outburst event allowed us to constrain the location of production of γ rays very close to the broad-line region, and possibly in the jet-base. We report the observation of an increased accretion after the outburst, possibly induced by the decrease of magnetic field intensity with respect to the low state.
How Does Collective Reputation Affect Hiring ? Selection and Sorting in an Online Labour Market ∗

Using data from an online labour market where the country of residence is the salient group characteristic, we document a mechanism through which collective reputation perpetuates group inequality. Using an IV strategy, we identify reputational externalities between an employer’s first hire and the propensity to contract more workers from the same country. Employers, contingent on their first worker’s performance, continue to almost exclusively hire from the same country. This coincides with a positive sorting response: Observing their predecessor’s success, workers from the same country disproportionately apply and are of higher quality. Employers, facing better applicants, in turn provide higher ratings. JEL codes: J7, J16, M51 ∗I am indebted to Oriana Bandiera and Robin Burgess for their supervision and continued guidance. I thank Esteban Aucejo, Michael Boehm, Jon DeQuidt, Thiemo Fetzer, Maitreesh Ghatak, Rocco Macchiavello, Dennis Novy, Heather Sarsons, Pedro Souza, Chris Stanton and Sandra Sequeira for their valuable comments. All errors remain my own. This paper supersedes a previous version under the title “The Value of Reputation: Evidence from Outsourcing”. †London School of Economics, Department of Economics and STICERD, Houghton Street, London WC2A 2AE, United Kingdom (e-mail: g.xu2@lse.ac.uk)