Impact of Secondary Acceleration in Gamma-Ray Bursts

We discuss the acceleration of secondary muons, pions, and kaons in gamma-ray bursts within the internal shock scenario, and their impact on the neutrino fluxes. We introduce a two-zone model consisting of an acceleration zone (the shocks) and a radiation zone (the plasma downstream the shocks). The acceleration in the shocks, which is an unavoidable consequence of the efficient proton acceleration, requires efficient transport from the radiation back to the acceleration zone. On the other hand, stochastic acceleration in the radiation zone can enhance the secondary spectra of muons and kaons significantly if there is a sufficiently large turbulent region. Overall, it is plausible that neutrino spectra can be enhanced by up to a factor of two at the peak by stochastic acceleration, that an additional spectral peaks appears from shock acceleration of the secondary muons and pions, and that the neutrino production from kaon decays is enhanced. Depending on the GRB parameters, the general conclusions concerning the limits to the internal shock scenario obtained by recent IceCube and ANTARES analyses may be affected by up to a factor of two by secondary acceleration. Most of the changes occur at energies above 10^7 GeV, so the effects for next-generation radio-detection experiments will be more pronounced. In the future, however, if GRBs are detected as high-energy neutrino sources, the detection of one or several pronounced peaks around 10^6 GeV or higher energies could help to derive the basic properties of the magnetic field strength in the GRB.Comment: 10 pages, 5 figures, 1 tabl

Adenine Nucleotide Translocase 1 Expression is Coupled to the HSP27-Mediated TLR4 Signaling in Cardiomyocytes

The cardiac-specific overexpression of the adenine nucleotide translocase 1 (ANT1) has cardioprotective effects in various experimental heart disease models. Here, we analyzed the link between ANT1 expression and heat shock protein 27 (HSP27)-mediated toll-like receptor 4 (TLR4) signaling, which represents a novel communication pathway between mitochondria and the extracellular environment. The interaction between ANT1 and HSP27 was identified by co-immunoprecipitation from neonatal rat cardiomyocytes. ANT1 transgenic (ANT1-TG) cardiomyocytes demonstrated elevated HSP27 expression levels. Increased levels of HSP27 were released from the ANT1-TG cardiomyocytes under both normoxic and hypoxic conditions. Extracellular HSP27 stimulated TLR4 signaling via protein kinase B (AKT). The HSP27-mediated activation of the TLR4 pathway was more pronounced in ANT1-TG cardiomyocytes than in wild-type (WT) cardiomyocytes. HSP27-specific antibodies inhibited TLR4 activation and the expression of HSP27. Inhibition of the HSP27-mediated TLR4 signaling pathway with the TLR4 inhibitor oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) reduced the mitochondrial membrane potential (∆ψm) and increased caspase 3/7 activity, which are both markers for cell stress. Conversely, treating cardiomyocytes with recombinant HSP27 protein stimulated TLR4 signaling, induced HSP27 and ANT1 expression, and stabilized the mitochondrial membrane potential. The activation of HSP27 signaling was verified in ischemic ANT1-TG heart tissue, where it correlated with ANT1 expression and the tightness of the inner mitochondrial membrane. Our study shows a new mechanism by which ANT1 is part of the cardioprotective HSP27-mediated TLR4 signaling

Expressed Emotion, Mental Health, and Functioning in Families of Children with and without Asthma

Introduction: Expressed emotion (EE), the affective attitudes and behaviors of one toward another, can affect caregivers’ behaviors toward their child. Research examining associations between EE and child/family outcomes is mixed; these associations may be affected by other influences such as the presence of a chronic disease or parent mental health. In this study of families living in an urban area, we examined associations between EE and child outcomes (anxiety/depressive symptoms) and family functioning, with parent anxiety as a covariate. We evaluated child asthma status as a moderator in these associations as the presence of a chronic illness may strengthen the association between EE and child/family outcomes. Methods: 96 children (mean±SD age=8.83±2.03 years, 48.9% female, 92.6% African American; 47 with asthma) and their parents (81.3% annual household income\u3c$25,000) completed an observational study including interviews and questionnaires. Measures included the Multidimensional Anxiety Scale for Children (MASC), Children’s Depressive Symptoms Inventory (CDI), Self-Report Family Inventory (SFI), Generalized Anxiety Disorder scale (GAD-7), and Five-Minute Speech Sample (FMSS) coded for EE. To examine study aims, regression analyses were conducted using PROCESS macro version 3.1. Asthma status (yes/no) was examined as a moderator. Results: EE was associated with child anxiety symptoms, child depressive symptoms, and family functioning, controlling for parent anxiety symptoms (F(1,70) =6.74, p=.011; F(1,69) =7.803, p=.007; F(1,68) =8.637, p=.004). Asthma status did not moderate any of the associations. Conclusions: Results suggested that high levels of caregiver EE were associated with child mental health symptoms and family functioning, but asthma status did not moderate associations. It is possible that regardless of additional family demands related to asthma, EE is associated with child mental health and family functioning. Further examination into other systemic stressors that may moderate these associations is warranted, as well as the impact that minimizing parent anxiety might have on overall EE.https://scholarscompass.vcu.edu/gradposters/1075/thumbnail.jp

Blood Vessel Density in Basal Cell Carcinomas and Benign Trichogenic Tumors as a Marker for Differential Diagnosis in Dermatopathology

In order to get insight into the density of blood vessels in the stroma of benign and malignant trichogenic neoplasms, immunohistological quantification of CD 31 positive vessels was performed in 112 tumors, comprised of 50 BCCs of nodular (35) or morphoeic (15) growth patterns, 17 Pinkus' tumors, as well as 17 trichoepitheliomas of which 6 were desmoplastic, 8 trichofolliculomas, and 20 trichoblastomas. Methods. Vessel density was counted within the tumors, in the tumor-surrounding stroma, and, as a control, in the normal skin of the operation specimen. The results were compared using statistical methods. Results. Whereas, irrespective of the patients' age and location of tumors, the vessel density in normal skin showed no significant differences (8.8 ± 2.7), the counts in the peritumoral stroma revealed significant differences between the different tumors investigated. The highest counts were obtained in BCC (24.7 ± 6.7) and the lowest in benign trichogenic neoplasms (around 14) Pinkus' tumors revealed intermediate counts (19.7 ± 6.6). The vessel densities within the tumors were generally low, and no correlation to the dignity was found. Conclusion. Determination of blood vessel density in the peritumoral stroma may be an additional parameter for differential diagnosis of trichogenic tumors of uncertain dignity

From intracellular signaling cascades to behavior: towards a better understanding of oxytocin's molecular effects

The neuropeptide oxytocin (OT) plays a prominent role in the regulation of a variety of behavioral processes like maternal behavior, anxiety-, and stress-related behaviors as well as social behaviors. Due to the well-known link to psychiatric disorders associated with anxiety, fear, and socio-emotional dysfunctions, OT is considered a viable treatment option for these diseases (Neumann and Slattery, 2016). Despite the profound knowledge from various rodent (Blume et al., 2008; Jurek et al., 2015; Jurek et al., 2012) and human studies (MacDonald and Feifel, 2014; Meyer-Lindenberg et al., 2011) on the beneficial effects of acute or short-term OT applications, the impact of extended treatment duration on the behavioral outcomes and OT receptor (OTR) signaling cascades remains rather sparsely investigated (Neumann and Slattery, 2016). Thus, the thesis presented here aimed to unravel the molecular mechanisms and the behavioral effects that are caused by chronic OT. Intracerebroventricular infusions of a high dose of OT (10 ng/h) via osmotic minipumps for 14 days led to increased anxiety-related behavior in male rats, whereas a lower dose (1 ng/h) had no effect. Additionally, a strong sexual dimorphism was observable. Female rats showed increased anxiety levels induced by the low dose of chronic OT and a trend in the higher dose, suggesting a higher sensitivity of females to OT. On a molecular level, I identified a sex-specific signaling cascade mediating the observed chronic OT-induced anxiogenic phenotype. Chronic OT stimulated mitogen-activated protein kinase (MAPK) signaling via phosphorylation of the kinases mitogen-activated protein kinase kinase (MEK1/2) and the extracellular signal-regulated kinase 1/2 (ERK1/2), and recruited further downstream the transcription factor myocyte enhancer factor 2 (MEF2). In more detail, dephosphorylation of the isoform MEF2A at the amino acid residue serine 408, a transcriptional inhibitory phosphorylation site, appeared to be the main player in chronic OT-induced anxiogenesis in male rats. Subsequent analysis of several stress-, anxiety-, and neuroplasticity-related MEF2-target genes revealed an involvement of the corticotropin releasing factor receptor 2 α (CRFR2α). In comparison to the CRFR1, CRFR2 has overall anxiolytic properties, brain region- and stress-dependent anxiogenic effects have been previously observed, though (Dedic et al., 2018; Deussing and Chen, 2018)and references therein). I confirmed the anxiolytic properties of CRFR2 activity in the paraventricular nucleus (PVN) of the hypothalamus of male rats in an agonist/antagonist experiment under mild stress conditions. The close link between stress and the OT system (Winter and Jurek, 2019)and references therein) was confirmed in my study, as the anxiogenic effect of chronic OT depended on a mild stressor 24 h prior to behavioral testing. The Crfr2 mRNA undergoes several alternative splicing events, resulting in two different isoforms in rodents (CRFR2α, CRFR2β) and an additional one in humans (CRFR2γ). I found changes in the expression of the brain-specific CRFR2α in male rats after chronic OT treatment. Not only was the expression of CRFR2α altered, but also an additional alternative splicing event of Crfr2α mRNA towards a shorter soluble isoform, sCRFR2α (Chen et al., 2005; Evans and Seasholtz, 2009) could be linked to chronic OT infusions. I detected a shift from membrane-associated mCRFR2α expression towards cytoplasmic distribution and extracellular release of the soluble sCRFR2α caused by chronic OT. Manipulation of either mCRFR2α or sCRFR2α expression conferred anxiogenic properties to the splice variant sCRFR2α. Knockdown studies in vitro linked both the expression and alternative splicing of the CRFR2α to MEF2A activity. However, in females no activation of MEF2 and downstream of CRFR2α, and alternative splicing could be detected. Signaling via alternative MAPK targets is conceivable and deserves further investigation. Furthermore, with OT-induced changes in neuronal morphology shown in previous studies (Lestanova et al., 2016a; Meyer et al., 2018) as well as in this thesis, OT caused significant neurite retraction, and the behavioral consequences due to chronic administration of OT, treatment duration and dosage have to be considered carefully in a clinical context. The establishment of a new OTR knockout cell line by means of CRISPR-Cas9 enables further comparative signaling as well as morphological analysis. Here, the impairment of MAPK signaling and neurite retraction could be linked to the loss of the OTR. Overall, the presented data elucidate the differential behavioral as well as molecular consequences of acute versus chronic OT applications in rodents. It provides a general strategy for the analysis of neuropeptide effects both in vitro and in vivo and challenges the beneficial effects of OT and its status as a potential treatment option for psychiatric disorders. Treatment dosage, duration as well as the gender of the patients have to be taken into account. However, the newly discovered connection between anxiety and the soluble splice variant sCRFR2α might lead to new anamnesis and treatment approaches for anxiety disorders

A cohort study of the recovery of health and wellbeing following colorectal cancer (CREW study): protocol paper

Background: the number of people surviving colorectal cancer has doubled in recent years. While much of the literature suggests that most people return to near pre-diagnosis status following surgery for colorectal cancer, this literature has largely focused on physical side effects. Longitudinal studies in colorectal cancer have either been small scale or taken a narrow focus on recovery after surgery. There is a need for a comprehensive, long-term study exploring all aspects of health and wellbeing in colorectal cancer patients. The aim of this study is to establish the natural history of health and wellbeing in people who have been treated for colorectal cancer. People have different dispositions, supports and resources, likely resulting in individual differences in restoration of health and wellbeing. The protocol described in this paper is of a study which will identify who is most at risk of problems, assess how quickly people return to a state of subjective health and wellbeing, and will measure factors which influence the course of recovery. Methods: this is a prospective, longitudinal cohort study following 1000 people with colorectal cancer over a period of two years, recruiting from 30 NHS cancer treatment centres across the UK. Questionnaires will be administered prior to surgery, and 3, 9, 15 and 24 months after surgery, with the potential to return to this cohort to explore on-going issues related to recovery after cancer. Discussion: outcomes will help inform health care providers about what helps or hinders rapid and effective recovery from cancer, and identify areas for intervention development to aid this process. Once established the cohort can be followed up for longer periods and be approached to participate in related projects as appropriate and subject to funding<br/

Disaster Tales as Communication Tool for Increasing Risk Resilience

Agencies in charge of flood management use disaster reports (DRs) as the preferred source of information on past flooding events. A systematic survey of DRs prepared by Italian agencies suggests that DRs could be widely enhanced in view of targeting more effective communication to citizens, reinforcing the communication pillar in civil protection planning and management, and improving the resilience of the population to extreme events. Without loss of the rigor and details required for all the usual technical uses of DRs, we suggest recompiling them in the form of “disaster tales” (DTs), as tools that offer wider knowledge of the events to improve people’s preparedness and self-protection behavior. Recent major flooding events have demonstrated the communication potential that videos and pictures taken by citizens have for risk perception and disaster preparedness. By watching and listening to what has happened the communication recipient can better understand the feelings of the people experiencing an emergency. The structure of the improved reports, we suggest, will finally integrate data, graphs, and maps with interactive tools and be able to present handier multimedia views of the events. Application to three case studies of flooding in Italy illustrates how to concretely implement the suggested disaster reports to create more readily accessible disaster tales

Measuring the Cognitive Complexity in the Comprehension of Modular Process Models

Modularization in process models is a method to cope with the inherent complexity in such models (e.g., model size reduction). Modularization is capable to increase the quality, the ease of reuse, and the scalability of process models. Prior conducted research studied the effects of modular process models to enhance their comprehension. However, the effects of modularization on cognitive factors during process model comprehension are less understood so far. Therefore, this paper presents the results of two exploratory studies (i.e., a survey research study with N = 95 participants; a follow-up eye tracking study with N = 19 participants), in which three types of modularization (i.e., horizontal, vertical, orthogonal) were applied to process models expressed in terms of the Business Process Model and Notation (BPMN) 2.0. Further, the effects of modularization on the cognitive load, the level of acceptability, and the performance in process model comprehension were investigated. In general, the results revealed that participants were confronted with challenges during the comprehension of modularized process models. Further, performance in the comprehension of modularized process models showed only a few significant differences, however, the results obtained regarding the cognitive load revealed that the complexity and concept of modularization in process models were misjudged initially. The insights unraveled that the attitude towards the application and the behavioral intention to apply modularization in process model is still not clear. In this context, horizontal modularization appeared to be the best comprehensible modularization approach leading to a more fine-grained comprehension of respective process models. The findings indicate that alterations in modular process models (e.g., change in the representation) are important to foster and enable their comprehension. Finally, based on our results, implications for research and practice as well as directions for future work are discussed in this paper