bluuebunny/crossref_metadata_2025_split huggingface dataset:
Airgun blasts used in marine seismic surveys have limited effects on mortality, and no sublethal effects on behaviour or gene expression, in the copepod Calanus finmarchicus
Authors: Fields David M , Handegard Nils Olav , Dalen John , Eichner Christiane , Malde Ketil , Karlsen Ørjan , Skiftesvik Anne Berit , Durif Caroline M F , Browman Howard I 
Published: June 2019

Abstract
Seismic surveys use airguns that emit low frequency high magnitude sound to detect subsea resources and to map seabed geology. The effect of seismic blasts on Calanus spp., a key food source for commercially important fish, was assessed in field experiments. Immediate mortality of copepods was significantly different from controls at distances of 5 m or less from the airguns. Mortality 1 week after the airgun blast was significantly higher—by 9% relative to controls—in the copepods placed 10 m from the airgun blast but was not significantly different from the controls at a distance of 20 m from the airgun blast. The increase in mortality—relative to controls—did not exceed 30% at any distance from the airgun blast. Only two genes changed in response to the airgun blast; however, their function is unknown. There were no sublethal effects of the seismic blasts on the escape performance or the sensory threshold needed to initiate an escape response at any of the distances from the airgun blast that were tested. Results from these experiments suggest that seismic blasts have limited effects on the mortality or escape response of Calanus sp. within 10 m of the blast and no measurable impact at greater distances.
A central limit theorem for Lp transportation cost on the real line with application to fairness assessment in machine learning
Authors: del Barrio Eustasio , Gordaliza Paula , Loubes Jean-Michel 
Published: June 2019

Abstract
We provide a central limit theorem for the Monge–Kantorovich distance between two empirical distributions with sizes $n$ and $m$, $\mathcal{W}_p(P_n,Q_m), \ p\geqslant 1,$ for observations on the real line. In the case $p&gt;1$ our assumptions are sharp in terms of moments and smoothness. We prove results dealing with the choice of centring constants. We provide a consistent estimate of the asymptotic variance, which enables to build two sample tests and confidence intervals to certify the similarity between two distributions. These are then used to assess a new criterion of data set fairness in classification.
A Riemann–Hilbert Problem Approach to Infinite Gap Hill's Operators and the Korteweg–de Vries Equation
Authors: T-R McLaughlin Kenneth , Nabelek Patrik V 
Published: June 2019

Abstract
We formulate the inverse spectral theory of infinite gap Hill’s operators with bounded periodic potentials as a Riemann–Hilbert problem on a typically infinite collection of spectral bands and gaps. We establish a uniqueness theorem for this Riemann–Hilbert problem, which provides a new route to establishing unique determination of periodic potentials from spectral data. As the potentials evolve according to the Korteweg–de Vries Equation (KdV) equation, we use integrability to derive an associated Riemann–Hilbert problem with explicit time dependence. Basic principles from the theory of Riemann–Hilbert problems yield a new characterization of spectra for periodic potentials in terms of the existence of a solution to a scalar Riemann–Hilbert problem, and we derive a similar condition on the spectrum for the temporal periodicity for an evolution under the KdV equation.
Primary Resources, Secondary Labor: Natural Resources and Immigration Policy
Authors: Shin Adrian J 
Published: June 2019

AbstractThis article argues that substantial natural resource wealth leads to more restrictive low-skill immigration policy in advanced democracies. High-value natural resource production often crowds out labor-intensive firms that produce tradable goods. When these proimmigration business interests disappear due to deindustrialization, also known as the Dutch Disease, the proimmigration coalition weakens in domestic politics. Without strong business pressure for increased immigration, policy-makers close their doors to immigrants to accommodate anti-immigrant interests. Using a newly expanded dataset on immigration policy across twenty-four wealthy democracies, I find that oil-rich democracies are more likely to restrict low-skill immigration, especially when their economies are exposed to foreign competition in international trade. The results supplement the voter-based theories of immigration policy and contribute to an emerging literature on the political economy of natural resources and international migration.
Task Specialization in U.S. Cities from 1880 to 2000
Authors: Michaels Guy , Rauch Ferdinand , Redding Stephen J 
Published: June 2019

Abstract
We develop a new methodology for quantifying the tasks undertaken within occupations using over 3,000 verbs from more than 12,000 occupational descriptions in the Dictionary of Occupational Titles (DOTs). Using micro data from the United States from 1880 to 2000, we find an increase in the employment share of interactive occupations within sectors over time that is larger in metro areas than nonmetro areas. We interpret these findings using a model in which reductions in transport and communication costs induce urban areas to specialize according to their comparative advantage in interactive tasks. We present suggestive evidence relating increases in employment in interactive occupations to improvements in transport and communication technologies. Our findings highlight a change in the nature of agglomeration over time toward an increased emphasis on human interaction.
Modal logic with non-deterministic semantics: Part I—Propositional case
Authors: Coniglio Marcelo E , Luis Fariñas Del Cerro , Newton Marques Peron 
Published: June 2019

AbstractDugundji proved in 1940 that most parts of standard modal systems cannot be characterized by a single finite deterministic matrix. In the eighties, Ivlev proposed a semantics of four-valued non-deterministic matrices (which he called quasi-matrices), in order to characterize a hierarchy of weak modal logics without the necessitation rule. In a previous paper, we extended some systems of Ivlev’s hierarchy, also proposing weaker six-valued systems in which the (T) axiom was replaced by the deontic (D) axiom. In this paper, we propose even weaker systems, by eliminating both axioms, which are characterized by eight-valued non-deterministic matrices. In addition, we prove completeness for those new systems. It is natural to ask if a characterization by finite ordinary (deterministic) logical matrices would be possible for all those Ivlev-like systems. We will show that finite deterministic matrices do not characterize any of them.
Art and real estate: German Federal Supreme Court balances moral rights and property rights
Authors: Gärtner Anette , Plagge Michael 
Published: June 2019

Abstract
German Federal Supreme Court (‘BGH’), Decisions of 21 February 2019, I ZR 87/17, BeckRS 2019, 5360–HHole (for Mannheim); I ZR 99/17, BeckRS 2019, 5358–PHaradise; I ZR 15/18, BeckRS 2019, 5361 – Brunneninstallation
Antibiotic Resistance Evolution Is Contingent on the Quorum-Sensing Response in Pseudomonas aeruginosa
Authors: Hernando-Amado Sara , Sanz-García Fernando , Martínez José Luis 
Published: June 2019

Abstract
Different works have explored independently the evolution toward antibiotic resistance and the role of eco-adaptive mutations in the adaptation to a new habitat (as the infected host) of bacterial pathogens. However, knowledge about the connection between both processes is still limited. We address this issue by comparing the evolutionary trajectories toward antibiotic resistance of a Pseudomonas aeruginosa lasR defective mutant and its parental wild-type strain, when growing in presence of two ribosome-targeting antibiotics. Quorum-sensing lasR defective mutants are selected in P. aeruginosa populations causing chronic infections. Further, we observed they are also selected in vitro as a first adaptation for growing in culture medium. By using experimental evolution and whole-genome sequencing, we found that the evolutionary trajectories of P. aeruginosa in presence of these antibiotics are different in lasR defective and in wild-type backgrounds, both at the phenotypic and the genotypic levels. Recreation of a set of mutants in both genomic backgrounds (either wild type or lasR defective) allowed us to determine the existence of negative epistatic interactions between lasR and antibiotic resistance determinants. These epistatic interactions could lead to mutual contingency in the evolution of antibiotic resistance when P. aeruginosa colonizes a new habitat in presence of antibiotics. If lasR mutants are selected first, this would constraint antibiotic resistance evolution. Conversely, when resistance mutations (at least those studied in the present work) are selected, lasR mutants may not be selected in presence of antibiotics. These results underlie the importance of contingency and epistatic interactions in modulating antibiotic resistance evolution.
Kinetic theory of discontinuous rheological phase transition for a dilute inertial suspension
Authors: Hayakawa Hisao , Takada Satoshi 
Published: June 2019

Abstract
A kinetic theory for a dilute inertial suspension under a simple shear is developed. With the aid of the corresponding Boltzmann equation, it is found that the flow curves (the relations between the stress and the strain rate) exhibit the crossovers from the Newtonian to the Bagnoldian for a granular suspension and from the Newtonian to a fluid having a viscosity proportional to the square of the shear rate for a suspension consisting of elastic particles, respectively. The existence of the negative slope in the flow curve directly leads to a discontinuous shear thickening (DST). This DST corresponds to the discontinuous transition of the kinetic temperature between a quenched state and an ignited state. The results of the event-driven Langevin simulation of hard spheres perfectly agree with the theoretical results without any fitting parameter. The introduction of an attractive interaction between particles is also another source of the DST in dilute suspensions. Namely, there are two discontinuous jumps in the flow curve if the suspension particles have the attractive interaction.
Zeroes of polynomials on definable hypersurfaces: pathologies exist, but they are rare
Authors: Basu Saugata , Lerario Antonio , Natarajan Abhiram 
Published: June 2019

Abstract
Given a sequence $\{Z_d\}_{d\in \mathbb{N}}$ of smooth and compact hypersurfaces in ${\mathbb{R}}^{n-1}$, we prove that (up to extracting subsequences) there exists a regular definable hypersurface $\Gamma \subset {\mathbb{R}}\textrm{P}^n$ such that each manifold $Z_d$ is diffeomorphic to a component of the zero set on $\Gamma$ of some polynomial of degree $d$. (This is in sharp contrast with the case when $\Gamma$ is semialgebraic, where for example the homological complexity of the zero set of a polynomial $p$ on $\Gamma$ is bounded by a polynomial in $\deg (p)$.) More precisely, given the above sequence of hypersurfaces, we construct a regular, compact, semianalytic hypersurface $\Gamma \subset {\mathbb{R}}\textrm{P}^{n}$ containing a subset $D$ homeomorphic to a disk, and a family of polynomials $\{p_m\}_{m\in \mathbb{N}}$ of degree $\deg (p_m)=d_m$ such that $(D, Z(p_m)\cap D)\sim ({\mathbb{R}}^{n-1}, Z_{d_m}),$ i.e. the zero set of $p_m$ in $D$ is isotopic to $Z_{d_m}$ in ${\mathbb{R}}^{n-1}$. This says that, up to extracting subsequences, the intersection of $\Gamma$ with a hypersurface of degree $d$ can be as complicated as we want. We call these ‘pathological examples’. In particular, we show that for every $0 \leq k \leq n-2$ and every sequence of natural numbers $a=\{a_d\}_{d\in \mathbb{N}}$ there is a regular, compact semianalytic hypersurface $\Gamma \subset {\mathbb{R}}\textrm{P}^n$, a subsequence $\{a_{d_m}\}_{m\in \mathbb{N}}$ and homogeneous polynomials $\{p_{m}\}_{m\in \mathbb{N}}$ of degree $\deg (p_m)=d_m$ such that (0.1)$$\begin{equation}b_k(\Gamma\cap Z(p_m))\geq a_{d_m}.\end{equation}$$ (Here $b_k$ denotes the $k$th Betti number.) This generalizes a result of Gwoździewicz et al. [13]. On the other hand, for a given definable $\Gamma$ we show that the Fubini–Study measure, in the Gaussian probability space of polynomials of degree $d$, of the set $\Sigma _{d_m,a, \Gamma }$ of polynomials verifying (0.1) is positive, but there exists a constant $c_\Gamma$ such that $$\begin{equation*}0&lt;{\mathbb{P}}(\Sigma_{d_m, a, \Gamma})\leq \frac{c_{\Gamma} d_m^{\frac{n-1}{2}}}{a_{d_m}}.\end{equation*}$$ This shows that the set of ‘pathological examples’ has ‘small’ measure (the faster $a$ grows, the smaller the measure and pathologies are therefore rare). In fact we show that given $\Gamma$, for most polynomials a Bézout-type bound holds for the intersection $\Gamma \cap Z(p)$: for every $0\leq k\leq n-2$ and $t&gt;0$: $$\begin{equation*}{\mathbb{P}}\left(\{b_k(\Gamma\cap Z(p))\geq t d^{n-1} \}\right)\leq \frac{c_\Gamma}{td^{\frac{n-1}{2}}}.\end{equation*}$$
PF403 NEGATIVE MR4.0 CHRONIC MYELOID LEUKEMIA AND ITS IMPLICATIONS FOR TREATMENT‐FREE REMISSION
Authors: Cerveira N. , Diamond J. , Matos S. , Amorim M.L. , Coucelo M. , Bizarro S. , Simões A.T. , Pierdomenico F. , Lopes M. , Ribeiro L. , Carmo‐Fonseca M. , Guimarães J.E. , Almeida A. , Teixeira M.R. 
Published: June 2019

Background:In the last few years, several clinical discontinuation trials have demonstrated that 40–60% of chronic phase CML patients (CP‐CML) who have achieved a stable deep molecular response, can stop therapy without relapsing. However, there is no consensus as to whether or not the depth of the molecular response is a prognostic factor for treatment‐free remission (TFR), which is reflected in the discrepancy between the various guidelines and opinions of experts in the field regarding the optimal molecular response required, MR4.0 or MR4.5, for a TFR attempt.Aims:In this work, we hypothesize that a discrepancy in the classification of the level of molecular response between laboratories involved in clinical trials could introduce a bias in the evaluation of the prognostic impact of treatment‐free remission (TFR).Methods:In an attempt to clarify this issue, we stratified by molecular response a cohort of 1087 CML patients and compared our results with those of 200 patients enrolled in the EURO‐SKI trial.Results:We found that none of the patients classified as MR4.0 had detectable disease (0/169) (Figure 1A). In addition, the frequency of undetectable disease negative cases increased to 29% (61/211) and 65% (149/230) in the MR4.5 and MR5.0 groups, respectively (Figure 1A). By contrast, the frequency of MR4.0 with undetectable disease in the EURO‐SKI trial was 72% (49/68), decreasing to 56% (48/85) and 58% (25/43) in the MR4.5 and MR5.0 groups, respectively (Figure 1B).Summary/Conclusion:Our results suggest that (1) There may be a bias in patient stratification by molecular response in the EURO‐SKI trial, making it impractical to attempt any association between molecular response depth and TFR success, (2) we should reassess the current classification of MR4.0 to include only patients with detectable disease and (3) the minimum quality criteria for scoring molecular response when disease is undetectable should be raised, with samples with <32000 ABL1 or <77000 GUSB transcripts be considered as unevaluable for classification of DMR.image
PF631 HEALTH‐RELATED QUALITY OF LIFE WITH POMALIDOMIDE + LOW‐DOSE DEXAMETHASONE + DARATUMUMAB IN PATIENTS WITH RELAPSED REFRACTORY MULTIPLE MYELOMA AFTER LENALIDOMIDE TREATMENT
Authors: Reece D. , Bahlis N.J. , Samaras C. , Sebag M. , Berdeja J. , Ganguly S. , Matous J. , Song K. , Seet C.S. , Talamo G. , Acosta‐Rivera M. , Bar M. , Quick D. , Anz B. , Fonseca G. , Agarwal A. , Chung W. , Zafar F. , Siegel D.S. 
Published: June 2019

Background:Treatment of relapsed refractory multiple myeloma (RRMM) is complex and requires evaluation of disease and patient factors to maximize efficacy and minimize toxicity. As survival has improved with therapeutic advances, maintaining quality of life has become an important aspect of multiple myeloma treatment. Results from cohort B of the ongoing phase 2 MM‐014 trial (NCT01946477) have demonstrated that pomalidomide (POM) + low‐dose dexamethasone (LoDEX) + daratumumab (DARA) is safe and effective in patients with RRMM after first‐ or second‐line lenalidomide (LEN)‐based treatment.Aims:To evaluate the impact of POM+ LoDEX + DARA on health‐related quality of life (HRQoL) in patients with RRMM who received this regimen after first‐ or second‐line LEN.Methods:Patients with RRMM and 1 to 2 prior lines of treatment, LEN‐based treatment as their most recent regimen, and progressive disease during or after their last treatment line were eligible for inclusion in cohort B. In 28‐day cycles, patients received POM 4 mg/day on days 1–21 + LoDEX 40 mg/day (20 mg/day if aged > 75 years) on days 1, 8, 15, and 22, and DARA 16 mg/kg IV on DEX dosing days of cycles 1 and 2, then on days 1 and 15 of cycles 3–6, and then on day 1 of cycle 7 and beyond. Thromboprophylaxis was mandatory. The primary endpoint was overall response rate. HRQoL, an exploratory endpoint for cohort B, was assessed via EQ‐5D.Results:As of 15 October 2018, 108 patients were evaluable for HRQoL. Baseline characteristics were similar to those of the ITT population (N = 112). EQ‐5D completion rates for each cycle (1–6) were ≥ 88%. Through 6 treatment cycles, mean change from baseline in the EQ‐5D index and VAS health score was stable. At cycle 6, minimum clinically important improvement in the EQ‐5D index (≥ 0.1) and VAS health score (≥ 6) was achieved by 28.8% and 39.0% of patients, respectively. EQ‐5D index values were stable; however, a trend toward improvement was observed in usual activities, pain/discomfort, and anxiety/depression (Figure).Summary/Conclusion:In patients with RRMM who received POM + LoDEX + DARA after first‐ or ‐second‐line LEN based treatment, HRQoL was maintained or trended toward improvement, despite the combination of 3 drugs with distinct toxicity profiles. In context with the previously reported safety and efficacy data from cohort B of MM‐014, the results of this HRQoL analysis further support the earlier use of POM‐based treatment in RRMM immediately following treatment with LEN.image
PF725 REAL WORLD ASSESSMENT OF PRACTICE EFFICIENCY WITH THE INTRODUCTION OF SUBCUTANEOUS RITUXIMAB
Authors: Qiu A. , Shapouri S. , Drill E. , Schade J. , Ravelo A. , Ni A. , Tu‐My T. , Dawson K. , Matasar M. 
Published: June 2019

Background:Rituximab (R), available as an intravenous (IV; R‐IV) infusion or subcutaneous (SC; R‐SC) injection, is used in the treatment of follicular lymphoma (FL), diffuse large B‐cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL).Aims:This study evaluated real‐world practice efficiency changes associated with the adoption of R‐SC by studying differences in chair time by route of administration.Methods:We conducted a retrospective analysis of practice care delivery measures before and after adoption of R‐SC at Memorial Sloan Kettering Cancer Center (MSKCC). Data for patients (pts) with FL, DLBCL, or CLL receiving R‐based therapy from September 2016 to September 2018 were extracted from the electronic medical record. A linear mixed effect multivariate model with random intercept was used to analyze the association between treatment type (R‐IV vs R‐SC) and chair time (defined as the difference in pt room‐in and room‐out times) in the year prior to and following R‐SC adoption at MSKCC. Model covariates included treatment time and location, therapy type (monotherapy vs combination), and pt demographics. Given the prolonged infusion time, patients’ first dose of R‐IV was excluded from the analysis.Results:Data were collected during 6744 visits (3018 visits prior to R‐SC adoption and 3726 after) for 1503 pts receiving R. Pts receiving R‐IV combination therapy had a mean chair time of 203 minutes (min); overall, R‐SC injection reduced chair time by a mean of 92 min (p < 0.001 vs R‐IV). Monotherapy, regardless of route, reduced chair time by a mean of 30 min (p < 0.001) compared with combination therapy, and mean chair time was further reduced by 39 min (p < 0.001) for R‐SC pts receiving monotherapy. Reductions in chair time increased over time following initial adoption of R‐SC (p = 0.042), and were greater at the lymphoma‐specific site than multispecialty oncology infusion centers (p < 0.001).Summary/Conclusion:Adoption of R‐SC results in substantial time savings for both the pt and health system as measured by reduced chair time and improved pt throughput. Given increasing constraints on infusion chair space, increased utilization of R‐SC may improve practice efficiency and pt access to care.
PS927 PHOSPHOCHROMATOME ANALYSIS UNCOVERS UNEXPECTED ROLES OF CDK6 IN REGULATING TRANSCRIPTION
Authors: Nebenfuehr S. , Bellutti F. , Kollmann K. , Farlik M. , Müller A.C. , Sexl V. 
Published: June 2019

Background:Cyclin‐dependent kinase 6 (CDK6) together with its close homologue CDK4 enables the progression of cells through the early G1 phase of the cell cycle. CDK4/6‐cyclin D complexes phosphorylate members of the retinoblastoma (Rb) protein family, allowing for the release of E2F transcription factors that induce genes required for cell cycle progression and DNA replication. Alterations of the CDK4/6‐Rb pathway are frequently observed in human malignancies. Recent studies focusing on acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) have uncovered a novel role for CDK6 in regulating transcription. Our group has identified CDK6 as part of chromatin‐bound complexes which drive transcription of disease–relevant genes including the cell cycle inhibitor p16INK4a, the angiogenesis‐promoting factor VEGF‐A (vascular endothelial factor A) and the proto‐oncogene FLT3 (Fms like tyrosine kinase 3).Aims:The aim of this study is to identify novel binding partners of CDK6 on chromatin and to investigate their target gene sets. A better understanding of CDK6 functionality in tumor formation and promotion may help in the design and selection of adequate treatment options.Methods:For further investigation of CDK6́s role in transcription, we transduced murine Cdk6
+/+ and Cdk6
−/− primary bone marrow with the oncogene Bcr/Abl
p185. To systematically gain insights on how CDK6 takes influence on chromatin‐binding and activity of transcription factors we performed RNA‐seq paralleled by mass spectrometry‐based phosphoproteomics of chromatin‐bound proteins (Phospho‐Chromatome).Results:RNA‐seq analysis of Cdk6
+/+ and Cdk6
−/− BCR‐ABL transformed cells identified more than 1700 genes that are differentially expressed. Phospho‐Chromatome studies performed in parallel revealed significant changes in the phosphorylation status of the transcription factors ZBTB7A, EBF1 and YY1. In vitro kinase assays verified a direct phosphorylation of ZBTB7A and EBF1 by active CDK6/CyclinD3 complexes.Summary/Conclusion:We show that CDK6 is broadly associated with chromatin where it fulfils different tasks: beside its well‐known role in the E2F‐release it enhances the phosphorylation of various transcription factors and chromatin‐regulating enzymes. This results in pronounced changes in associated gene expression. Therefor our data indicate that the function of CDK6 is not limited to cell cycle progression but regulates a plethora of tumor‐relevant transcriptional programs. Future therapies may consider this unexpected role and even exploit it to improve personalized and cancer‐specific treatment protocols.