The Role of Constraints in a Segregation Model: The Symmetric Case

In this paper we study the effects of constraints on the dynamics of an adaptive segregation model introduced by Bischi and Merlone (2011). The model is described by a two dimensional piecewise smooth dynamical system in discrete time. It models the dynamics of entry and exit of two populations into a system, whose members have a limited tolerance about the presence of individuals of the other group. The constraints are given by the upper limits for the number of individuals of a population that are allowed to enter the system. They represent possible exogenous controls imposed by an authority in order to regulate the system. Using analytical, geometric and numerical methods, we investigate the border collision bifurcations generated by these constraints assuming that the two groups have similar characteristics and have the same level of tolerance toward the members of the other group. We also discuss the policy implications of the constraints to avoid segregation

HEPPA-II model-measurement intercomparison project: EPP indirect effects during the dynamically perturbed NH winter 2008-2009

Funke, B. et. al..--This work is distributed under the Creative Commons Attribution 3.0 License.We compare simulations from three high-top (with upper lid above 120 km) and five medium-top (with upper lid around 80 km) atmospheric models with observations of odd nitrogen (NOx D NO+NO2), temperature, and carbon monoxide from seven satellite instruments (ACE-FTS on SciSat, GOMOS, MIPAS, and SCIAMACHY on Envisat, MLS on Aura, SABER on TIMED, and SMR on Odin) during the Northern Hemisphere (NH) polar winter 2008/2009. The models included in the comparison are the 3-D chemistry transport model 3dCTM, the ECHAM5/MESSy Atmospheric Chemistry (EMAC) model, FinROSE, the Hamburg Model of the Neutral and Ionized Atmosphere (HAMMO-NIA), the Karlsruhe Simulation Model of the Middle Atmosphere (KASIMA), the modelling tools for SOlar Climate Ozone Links studies (SOCOL and CAO-SOCOL), and the Whole Atmosphere Community Climate Model (WACCM4). The comparison focuses on the energetic particle precipitation (EPP) indirect effect, that is, the polar winter descent of NOx largely produced by EPP in the mesosphere and lower thermosphere. A particular emphasis is given to the impact of the sudden stratospheric warming (SSW) in January 2009 and the subsequent elevated stratopause (ES) event associated with enhanced descent of mesospheric air. The chemistry climate model simulations have been nudged toward reanalysis data in the troposphere and stratosphere while being unconstrained above. An odd nitrogen upper boundary condition obtained from MIPAS observations has further been applied to medium-top models. Most models provide a good representation of the mesospheric tracer descent in general, and the EPP indirect effect in particular, during the unperturbed (pre-SSW) period of the NH winter 2008/2009. The observed NOx descent into the lower mesosphere and stratosphere is generally reproduced within 20 %. Larger discrepancies of a few model simulations could be traced back either to the impact of the models' gravity wave drag scheme on the polar wintertime meridional circulation or to a combination of prescribed NOx mixing ratio at the uppermost model layer and low vertical resolution. In March-April, after the ES event, however, modelled mesospheric and stratospheric NOx distributions deviate significantly from the observations. The too-fast and early downward propagation of the NO x tongue, encountered in most simulations, coincides with a temperature high bias in the lower mesosphere (0.2-0.05 hPa), likely caused by an overestimation of descent velocities. In contrast, upper-mesospheric temperatures (at 0.05-0.001 hPa) are generally underestimated by the high-top models after the onset of the ES event, being indicative for too-slow descent and hence too-low NOx fluxes. As a consequence, the magnitude of the simulated NOx tongue is generally underestimated by these models. Descending NOx amounts simulated with mediumtop models are on average closer to the observations but show a large spread of up to several hundred percent. This is primarily attributed to the different vertical model domains in which the NOx upper boundary condition is applied. In general, the intercomparison demonstrates the ability of state-of- the-art atmospheric models to reproduce the EPP indirect effect in dynamically and geomagnetically quiescent NH winter conditions. The encountered differences between observed and simulated NOx, CO, and temperature distributions during the perturbed phase of the 2009 NH winter, however, emphasize the need for model improvements in the dynamical representation of elevated stratopause events in order to allow for a better description of the EPP indirect effect under these particular conditions.This work has been conducted in the frame of the WCRP/ SPARC SOLARIS-HEPPA activity. The IAA team was supported by the Spanish MCINN under grant ESP2014-54362-P and EC FEDER funds. The MPI-MET team was supported by the Max Planck Gesellschaft (MPG), and computational resources were made available by Deutsches Klimarechenzentrum (DKRZ) through support from Bundesministerium fur Bildung und Forschung (BMBF). The FMI team was supported by the Academy of Finland through the projects 276926 (SECTIC: Sun-Earth Connection Through Ion Chemistry), 258165, and 265005 (CLASP: Climate and Solar Particle Forcing). CAO team was supported by the Russian Science Foundation under grant 15-17-10024. SOCOL team was funded by Swiss National Science Foundation (SNSF) grants 200021-149182 (SILA), 200020-163206 (SIMA), and CRSII2-147659 (FUPSOL-II). S. Bender, M. Sinnhuber, and H. Nieder (all KIT) gratefully acknowledge funding by the Helmholtz Association of German Research Centres (HGF), grant VH-NG-624. NCAR is sponsored by the National Science Foundation (NSF). Computing resources for WACCM simulations were provided by the Climate Simulation Laboratory at NCAR's Computational and Information Systems Laboratory, sponsored by the NSF and other agencies. Work at the Jet Propulsion Laboratory, California Institute of Technology, was carried out under a contract with the National Aeronautics and Space Administration. The Atmospheric Chemistry Experiment (ACE), also known as SciSat, is a Canadian-led mission mainly supported by the Canadian Space Agency. Odin is a Swedish-led satellite project funded jointly by Sweden (SNSB), Canada (CSA), Finland (TEKES), and France (CNES) and is part of European Space Agency's (ESA) third-party mission program. We thank two anonymous reviewers for helpful suggestions that led to improvements in the quality of the present work.Peer reviewe

Mental pain in eating disorders: An exploratory controlled study

Mental pain (MP) is a transdiagnostic feature characterized by depression, suicidal ideation, emotion dysregulation, and associated with worse levels of distress. The study explores the presence and the discriminating role of MP in EDs in detecting patients with higher depressive and ED-related symptoms. Seventy-one ED patients and 90 matched controls completed a Clinical Assessment Scale for MP (CASMP) and the Mental Pain Questionnaire (MPQ). ED patients also completed the Beck Depression Inventory-II (BDI-II), Clinical Interview for Depression (CID-20), and Eating Attitudes Test (EAT-40). ED patients exhibited significantly greater severity and higher number of cases of MP than controls. Moreover, MP resulted the most important cluster predictor followed by BDI-II, CID-20, and EAT-40 in discriminating between patients with different ED and depression severity in a two-step cluster analysis encompassing 87.3% (n = 62) of the total ED sample. Significant positive associations have been found between MP and bulimic symptoms, cognitive and somaticaffective depressive symptoms, suicidal tendencies, and anxiety-related symptoms. In particular, those presenting MP reported significantly higher levels of depressive and anxiety-related symptoms than those without. MP represents a clinical aspect that can help to detect more severe cases of EDs and to better understand the complex interplay between ED and mood symptomatology

Irrational beliefs and their role in specific and non-specific eating disorder symptomatology and cognitive reappraisal in eating disorders

Background: Research on which specific maladaptive cognitions characterize eating disorders (ED) is lacking. This study explores irrational beliefs (IBs) in ED patients and controls and the association between IBs and ED-specific and non-specific ED symptomatology and cognitive reappraisal. Methods: 79 ED outpatients with anorexia nervosa, bulimia nervosa, or other specified feeding or eating disorders and 95 controls completed the Attitudes and Beliefs Scale-2 (ABS-2) for IBs. ED outpatients also completed the Eating Disorder Inventory-3 (EDI-3) for ED-specific (EDI-3-ED Risk) and non-specific (EDI-3-General Psychological Maladjustment) symptomatology; General Health Questionnaire (GHQ) for general psychopathology; Emotion Regulation Questionnaire (ERQ) for cognitive reappraisal. Results: Multivariate analysis of variance with post hoc comparisons showed that ED outpatients exhibit greater ABS-2-Awfulizing, ABS-2-Negative Global Evaluations, and ABS-2-Low Frustration Tolerance than controls. No differences emerged between ED diagnoses. According to stepwise linear regression analyses, body mass index (BMI) and ABS-2-Awfulizing predicted greater EDI-3-ED Risk, while ABS-2-Negative Global Evaluations and GHQ predicted greater EDI-3-General Psychological Maladjustment and lower ERQ-Cognitive Reappraisal. Con-clusion: Awfulizing and negative global evaluation contribute to better explaining ED-specific and non-specific ED symptoms and cognitive reappraisal. Therefore, including them, together with BMI and general psychopathology, when assessing ED patients and planning cognitive–behavioral treatment is warranted

Structural investigation of Rett-inducing MeCP2 mutations

X-ray structure of methyl-CpG binding domain (MBD) of MeCP2, an intrinsically disordered protein (IDP) involved in Rett syndrome, offers a rational basis for defining the spatial distribution for most of the sites where mutations responsible of Rett syndrome, RTT, occur. We have ascribed pathogenicity for mutations of amino acids bearing positively charged side chains, all located at the protein-DNA interface, as positive charge removal cause reduction of the MeCP2-DNA adduct lifetime. Pathogenicity of the frequent proline replacements, outside the DNA contact moiety of MBD, can be attributed to the role of this amino acid for maintaining both unfolded states for unbound MeCP2 and, at the same time, to favor some higher conformational order for stabilizing structural determinants required by protein activity. These hypotheses can be extended to transcription repressor domain, TRD, the other MeCP2-DNA interaction site and, in general, to all the IDP that interact with nucleic acids

Cluster Correlation in Mixed Models

We evaluate the dependence of the cluster correlation length r_c on the mean intercluster separation D_c, for three models with critical matter density, vanishing vacuum energy (Lambda = 0) and COBE normalized: a tilted CDM (tCDM) model (n=0.8) and two blue mixed models with two light massive neutrinos yielding Omega_h = 0.26 and 0.14 (MDM1 and MDM2, respectively). All models approach the observational value of sigma_8 (and, henceforth, the observed cluster abundance) and are consistent with the observed abundance of Damped Lyman_alpha systems. Mixed models have a motivation in recent results of neutrino physics; they also agree with the observed value of the ratio sigma_8/sigma_25, yielding the spectral slope parameter Gamma, and nicely fit LCRS reconstructed spectra. We use parallel AP3M simulations, performed in a wide box (side 360/h Mpc) and with high mass and distance resolution, enabling us to build artificial samples of clusters, whose total number and mass range allow to cover the same D_c interval inspected through APM and Abell cluster clustering data. We find that the tCDM model performs substantially better than n=1 critical density CDM models. Our main finding, however, is that mixed models provide a surprisingly good fit of cluster clustering data.Comment: 22 pages + 10 Postscript figures. Accepted for publication in Ap

Immunotherapeutic approaches for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a cancer with a high mortality rate due to the fact that the diagnosis usually occurs at anadvanced stage. Even in case of curative surgical treatment, recurrence is common. Sorafenib and regorafenib are the only therapeutic agents that have been demonstrated to be effective in advanced HCC, thus novel curative approaches are urgently needed. Recent studies focus on the role of immune system in HCC. In fact, the unique immune response in the liver favors tolerance, which can represent a real challenge for conventional immunotherapy in these patients. Spontaneous immune responses against tumor antigens have been detected, and new immune therapies are under investigation: dendritic cell vaccination, immune-modulator strategy, and immune checkpoint inhibition. In recent years different clinical trials examining the use of immunotherapy to treat HCC have been conducted with initial promising results. This review article will summarize the literature data concerning the potential immunotherapeutic approaches in HCC patient

Utility of neutrophil-to-lymphocyte ratio to identify long-term survivors among HCC patients treated with sorafenib

Sorafenib is the first multikinase inhibitor demonstrating a survival benefit for patients suffering from advanced hepatocellular carcinoma (HCC). However, 1 issue remains open: what is the factor able to predict which patients will be long survivors?In the present study, we harnessed the potential of conditional survival, aiming at estimating the probability that a patient receiving sorafenib survives for more than 3 years.The present multicentric study was conducted on a cohort of 438 HCC patients. The primary end point was conditional overall survival. Kaplan-Meier survival analysis was used to calculate conditional overall survival probabilities at 3 years.The 3-year conditional survival of patients without disease progression highlights that NLR and ECOG are the factors that most accurately predict the probability of long survival. The 3-year conditional survival of patients with disease progression showed a medium effect size for HCV status, alpha-fetoprotein and NLR at all time-points. Macro-vascular portal vein invasion, extra hepatic disease, and BCLC we have a large effect size at 6 months and a medium effect size at 12 and 24 months.Our findings support the use of baseline NLR for the identification of patients with a higher probability of long-survival. NLR should be used as a stratification factor in the forthcoming clinical trials on the drugs for the advanced HCC now in pipeline

Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma

Background: Trastuzumab has recently shown efficacy in the treatment of HER2-positive advanced gastric adenocarcinoma. Although antibody-based therapies target the metastatic disease, HER2 status is usually evaluated in the primary tumour because metastatic sites are rarely biopsied. The aim of this study was to compare HER2 status in primary and paired metastatic sites of gastric adenocarcinoma. Methods: The HER2 status was assessed by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in 72 secondary lesions of gastric adenocarcinoma and in the corresponding primary tumours. Results: Concordance of FISH results, evaluable in 68 primary and matched metastatic sites, was 98.5%. Concordance of IHC results, available in 39 of the 72 paired cases, was 94.9%. Only one case showed discordance between primary tumour and metastasis, being negative by both IHC and FISH in the primary and showing HER2 overexpression and amplification in the corresponding pancreatic lymph node metastasis. Conclusion: The high concordance observed between HER2 results obtained by both IHC and FISH on primary tumours and corresponding metastases suggests that in gastric cancer HER2 status is maintained in most cases unchanged during the metastatic process. Keywords: HER2, gastric cancer, FISH, immunohistochemistr

Cores in warm dark matter haloes: a Catch 22 problem

The free streaming of warm dark matter particles dampens the fluctuation spectrum, flattens the mass function of haloes and imprints a fine grained phase density limit for dark matter structures. The phase space density limit is expected to imprint a constant density core at the halo center on the contrary to what happens for cold dark matter. We explore these effects using high resolution simulations of structure formation in different warm dark matter scenarios. We find that the size of the core we obtain in simulated haloes is in good agreement with theoretical expectations based on Liouville's theorem. However, our simulations show that in order to create a significant core, (r_c~1 kpc), in a dwarf galaxy (M~1e10 Msun), a thermal candidate with a mass as low as 0.1 keV is required. This would fully prevent the formation of the dwarf galaxy in the first place. For candidates satisfying large scale structure constrains (m_wdm larger than 1-2 keV) the expected size of the core is of the order of 10 (20) pc for a dark matter halo with a mass of 1e10 (1e8) Msun. We conclude that "standard" warm dark matter is not viable solution for explaining the presence of cored density profiles in low mass galaxies.Comment: 9 pages, 8 figures, new theory section, fig 8 updated, conclusions unchanged, accepted for publication on MNRA