112,085 research outputs found
Spero-Hannah/Teton-Dam-Failure-Example: Teton Dam Example Problem
No full textRelease v.1.0.1
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INVOLVEMENT OF OXIDATIVE BALANCE IN THE ETIOLOGY, PATHOPHYSIOLOGY AND TREATMENT OF STRESS-RELATED PSYCHIATRIC DISORDERS
No full textPsychiatric disorders are severe and heterogeneous pathologies affecting an individual’s cognition, emotional regulation and behaviour. In 2019, 1 over 8 people was living with a mental illness, with major depressive disorder (MDD) identified as the leading global cause of disability, and with the spread of COVID-19 there has been a strong increase in the prevalence of MDD, anxiety disorder (AD) and eating disorders (ED). Moreover, the pharmacological treatment of psychopathologies is still largely ineffective and presents several critical aspects, such as the latency of therapeutic effects and the number of non-responder patients. On these bases, it is crucial to study psychiatric disorders to identify new molecular systems involved in their pathophysiology, with the aim to develop novel pharmacological strategies. In this context, to help the diagnosis and treatment of such pathologies, and based on the fact that some features are shared among the different pathologies, the Research Domain Criteria (RDoC) initiative has been launched by the National Institute of Mental Health. Indeed, the aetiology of many different psychiatric disorders relies on the same basis: the interaction between susceptibility genes and environmental stimuli, with the most important one being stress. Of course, it must be considered that not all the subjects exposed to stress will develop a psychopathology, and that not all types of stressors have detrimental effects on the organism. Indeed, acute stressors can be considered a fuel for the brain and body, helping to achieve expected results, however, if the stressors persist for longer periods, are too intense, or the molecular underpinnings of the body response have been primed to a maladaptive response by genetic or environmental backgrounds, the outcome of stress could be pathological. Moreover, although particularly defining for MDD, another common feature among different psychiatric diseases is the symptom of anhedonia, the inability to experience pleasure in situations considered satisfying. These common aspects are exploited by researchers and clinicians to study and understand them. Thus, my PhD project aims to study, at preclinical level, the molecular effects produced by different types of stress. In order to do so, I exploited different types and combination of stressors, such as the Chronic Mild Stress (CMS) model of depression, combined with acute physical (restraint stress) and inflammatory (lipopolysaccharide or LPS) challenges, and the Activity-Based Anorexia (ABA) model of anorexia nervosa, focusing on the involvement of oxidative balance, investigated mainly at mRNA and protein levels in such aspects. The choice of this molecular system relies on the fact that the brain requires a lot of energy -that is a generator of oxidative stress- to support neuronal activity, and on the fact that oxidative stress could act as a bridge between neuroinflammation and the dysregulation in synaptic processes (i.e. neurotransmitter and receptors expression and/or function, signalling pathways), both important players in the neurobiology of psychiatric disorders. Considering the choice of the CMS paradigm, it is important to underline that this model is able to produce two different subpopulations of stressed animals: the vulnerable one, that develops the anhedonic -depressive-like- phenotype and the resilient one that, despite stress exposure, does not, and this has a great translational value and allowed us to study, at molecular level, also the population that is not susceptible to stress exposure.
The results of my PhD project revealed that oxidative balance is crucial for the proper stress response. Indeed, stress exposure was able to cause oxidative stress in different areas of the CNS of vulnerable animals, but not of resilient ones. This derangement is accompanied by a malfunctioning of the antioxidant pathway of Nrf2, modulation that is once again specific for vulnerable animals, as opposed to resilient ones that showed an increased activation of the antioxidant system. Moreover, the derangement produced by CMS, are exacerbated after a further acute inflammatory challenge, in response to which stress-vulnerable animals showed even higher levels of oxidative stress. In addition, I also demonstrated a role for the antioxidant machinery in the acute stress-response (through the gene expression analysis of different antioxidant enzymes), and its destabilization in chronically stressed animals. We also found that the pharmacological treatments examined (chronic administrations of antipsychotics blonanserin and lurasidone) were able –at least in part and in an anatomical –specific manner- to prevent the negative effects of chronic stress and to re-establish the proper acute response in stressed animals. Finally, the analyses conducted in the ABA model of anorexia nervosa revealed that also in this case the oxidative balance is affected by the stressful experimental paradigm. Considering the very few information available about this model and about anorexia nervosa patients, we expanded our research also to neuroinflammation, with whom it has a very well-known crosstalk, and to neuroplasticity, an important process that is often impaired in psychiatric conditions. We observed that in this early phase of the pathology there is still an adaptive/compensatory response of the animals and a strong effect of the single components of the paradigm, therefore, future studies are necessary to deeply understand the involvement of the molecular systems considered.
The results obtained in this thesis indicates a clear involvement of oxidative balance and other systems related to it in the pathophysiology of psychiatric disorders. Indeed, the anhedonic behavior is characterized by an unbalanced equilibrium between pro- and antioxidant factors, that participates in the impaired ability of those animals to respond to subsequent challenges. The pharmacological treatment is able, at least in part, to re-establish the correct oxidative balance, that might therefore represent an important target to take into consideration to improve the pharmacotherapy of psychiatric disorders, however, more studies are necessary to prove the behavioral and molecular effects of compounds able to act directly on the antioxidant machinery
Comparison between a dynamic assessment procedure and the WMLS-R in distinguishing language abilities among Hispanic children in first grade
No full textHistorically, educators have had significant difficulty assessing the needs of culturally and linguistically diverse (CLD) learners, especially when determining special education classification. Hispanic students seem especially vulnerable to schools’ traditionally inadequate means of assessing language ability in CLD students. Dynamic assessment is one approach that has been identified as promising in the development of more culturally competent evaluation procedures. The purpose of this dissertation was to compare a traditional language assessment to a dynamic assessment procedure in regard to their utility for identifying students at-risk for Speech or Language Impairment (SLI). Twenty-five Hispanic, bilingual first graders from an urban school district were administered a standardized measure of language (Woodcock-Munoz Language Survey-Revised) as a traditional indicator of language ability. Students scoring one standard deviation below the mean were labeled at risk for SLI classification, while those scoring at the mean or higher were deemed typically developing. All children then underwent a dynamic assessment of language ability involving a pretest, two 30-minute mediated learning experiences, and a posttest. Following dynamic assessment, both groups made significant improvements in story complexity and completeness, and did so to a comparable degree. Furthermore, 100% of students classified at risk for SLI by the standardized measure were deemed typically developing according to dynamic assessment. Consistent with previous dynamic assessment studies, the results indicate that reliance on a traditional, standardized measure of language to assess Hispanic students for SLI may underestimate their language abilities and, thus, increase the risk for special education classification. Further, dynamic assessment appears to be a valuable tool for discerning language differences from true language disorders in Hispanic children. Both dynamic assessment and standardized measures of language may assess different aspects of language ability, which together may comprise a more reliable assessment strategy for identifying SLI in Hispanic children. Implications for the use of dynamic assessment in SLI evaluation and intervention are discussed in light of concerns about misclassification of CLD students. Additionally, implications for the role of school psychologists related to dynamic assessment are addressed.Psy. D.Includes bibliographical referencesby Jill Marie Sper
author-bios-SRD-19-0063.R1 – Supplemental material for The Network Structure of Police Misconduct
No full textSupplemental material, author-bios-SRD-19-0063.R1 for The Network Structure of Police Misconduct by George Wood, Daria Roithmayr and Andrew V. Papachristos in Socius</p
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Altered responsiveness of the antioxidant system in chronically stressed animals: modulation by chronic lurasidone treatment
No full textRationale: Although the occurrence of stressful events is very common during life, their impact may be different depending on the experience severity and duration. Specifically, acute challenges may trigger adaptive responses and even improve the individual’s performance. However, such a physiological positive coping can only take place if the underlying molecular mechanisms are properly functioning. Indeed, if these systems are compromised by genetic factors or previous adverse conditions, the response set in motion by an acute challenge may be maladaptive and even cause the insurgence or the relapse of stress-related psychiatric disorders. Objectives: On these bases, we evaluated in the rat brain the role of the antioxidant component of the redox machinery on the acute stress responsiveness and its modulation by potential detrimental or beneficial events. Methods: The expression of several antioxidant enzymes was assessed in different brain areas of adult male rats exposed to acute stress 3 weeks after a chronic immobilization paradigm with or without a concomitant treatment with the antipsychotic lurasidone. Results: The acute challenge was able to trigger a marked antioxidant response that, despite the washout period, was impaired by the previous adverse experience and restored by lurasidone in an anatomical-specific manner. Conclusions: We found that a working antioxidant machinery takes part in acute stress response and may be differentially affected by other experiences. Given the essential role of stress responsiveness in almost every life process, the identification of the underlying mechanisms and their potential pharmacological modulation add further translational value to our data
The induction of the activity-based anorexia is associated to the modulation of neuroinflammatory and oxidative balance mediators in the rat prefrontal cortex
No full textAnorexia nervosa (AN) is a life-threatening and complex psychiatric disorder characterized by altered body perception and the adoption of disturbed eating behavior and excessively exercising to reach the desired thinness. Reiteration of these habits leads to severe consequences for general and mental health, and the presence of psychiatric comorbidities makes this disorder one of those with the highest mortality rate. Although the exact molecular mechanisms underlying AN development have not been fully elucidated, clinical and preclinical data suggest the involvement of the immune system as well as of mediators of the redox balance, systems with an established role also in other psychiatric disorders. On these bases, aim of our study was to assess cerebral levels of specific mediators of neuroinflammation and redox balance by using the activity-based anorexia (ABA) model.
After a period of acclimation and adaptation, adolescent Sprague-Dawley female rats were divided in four experimental groups to be exposed for 6 days to (1) a combination of food restriction and wheel activity (ABA group), (2) voluntary running wheel activity (EXE group), (3) food restriction (RESTR group), (4) normal maintenance procedure (CTRL group). During the whole experiments, running wheel activity and animal body-weight were constantly monitored. The animals were then euthanized, the prefrontal cortex rapidly dissected and frozen in dry ice for the subsequent molecular analyses. Specifically, by using real time RT-PCR, we measured the gene expression of cardinal markers of neuroinflammation including pro-inflammatory and anti-inflammatory cytokines as well as markers of microglia activation. Moreover, we assessed the mRNA levels of specific mediators of the antioxidant component of the redox machinery.
We observed an overall reduction of neuroinflammation in the ABA group, as indicated by a significant decrease of the pro-inflammatory cytokines TNF-α and IL-1β, the inflammasome NLRP3, and the marker of microglia activation CD11b. Conversely, we found a significant increase of the mRNA levels for IL-6, whose dual role as pro- and anti-inflammatory cytokine is well-established. These effects were paralleled by the upregulation of the antioxidant enzymes GPX1, SRXN1 and MT1α.
Our data clearly indicate that the induction of activity-based anorexia in adolescent female rats is associated with alteration of both mediators of inflammation and oxidative balance in the prefrontal cortex. In particular we found that animals in the ABA group were characterized by lower neuroinflammation and increased antioxidant response. Since our experimental paradigm mimics the early stage of this complex pathology, we may hypothesize that the observed changes are the result of an adaptive response to the ABA induction Accordingly, further studies aimed to evaluate long-term effects will be crucial to better understand the molecular impact of ABA in the brain
Využití sociálních médií v B2B prodeji
No full textTato diplomová práce se zabývá tím, jak mohou B2B obchodníci využívat sociální média v prodeji. Na základě systematické rešerše literatury, autor zjistil, že akademici, zkoumající danou problematiku, navrhují další výzkum, a to: v kterých konkrétních krocích se dají využít sociální média v prodeji (Salo, 2017). Autor se na základě toho rozhodl zjistit, jaké sociální sítě, různé technologie a pluginy se dají využít v B2B prodeji - tzv. social sellingu. Social selling se v této práci týká primárně procesu akvizice a okrajově péčí o stávající zákazníky. Autor si vybral kvalitativní průzkum pomocí 10 hloubkových polo-strukturovaných rozhovorů, aby odhalil jak, která sociální média to jsou, tak i motivaci prodejců, proč tato média používat/nepoužívat. Aby autor dodržel správnost vyhodnocení výsledků, data byla analyzována pomocí Tématické analýzy, která v této studii vykrystalizovala 2 hlavní strategické přístupy v social sellingu. Tyto přístupy (tzv. Push a Pull strategie) obsahují praktické příklady a konkrétní aktivity, které mohou prodejci využívat v každodenní praxi. Tyto výsledky jsou prezentovány s důrazem na praktičnost a jednoduchost implementace. Tvoří proto hlavní přínos autorovo výzkumu. V poslední části autor zmiňuje výzvy a manažerská doporučení, které mohou obchodníci využít v každodenním pracovním životě.This diploma thesis focuses on social media usage in B2B sales. Based on the systematic literature review conducted by the author, he has found out that recent researchers (Salo, 2017) suggest further research in the area of how and in which sales phase should various social networking sites, technologies and plugins used. To further fill this research gap, author decided to identify these social media and their usage among B2B salespeople in the so-called social selling process. The social selling process in this thesis applies mainly to acquiring new prospects and tangentially to taking care of existing clients (follow-up step). Author has chosen a qualitative research method via conducting 10 in-depth semi-structured interviews to reveal these instruments as well as motivation of a sales person on why to use social media in the selling process. The collected data was analyzed using Thematic analysis to ensure the right procedure and to identify main themes which crystalized into 2 main strategic approaches in social selling. These approaches (Push and Pull) include practical examples of concrete activities which sales people can use in their daily jobs and are presented with focus on practicality and ease of implementation. These also form the main contribution of author`s research. In the last part, author mentions challenges in social selling and recommended managerial implications for salesforce
TeX v jednoduchém unixovém prostředí
No full textsummary:Při ladění TeXového dokumentu potřebujeme mnohokrát opakovaně pouštět TeX, podívat se, jak dopadl výsledek v prohlížeči DVI nebo PDF souboru, mrknout na výpis TeXu na terminálu, podívat se případně do logu a celou činnost opakovat. V tomto článku je ukázáno, jak tuto práci dělá autor článku. Proces "editor-TeX-kuk" je zde podporován jednoduchými unixovými nástroji: bashovým skriptem texloop, který si autor pro tyto účely vytvořil, dále terminálem Xterm a jednoduchým editorem, který umí navázat na klávesovou zkratku spuštění příkazu v systému. Čtenář se zde může inspirovat a přizpůsobit tyto nástroje svým vlastním potřebám. V článku je popsána funkce skriptu texloop, dále je neformálně rozveden dlouholetý vývoj autorova vztahu k textovým editorům a konečně je zde uvedena konfigurace terminálu Xterm, aby vyhovoval českému prostředí jak v kódování ISO-8859-2, tak v kódování UTF-8. Pro kódování UTF-8 si v závěru článku vygenerujeme TeXový formát csplain.summary:By debugging a TeX document it is necessary many times repeatedly to run TeX, to look for the result in DVI or PDF file, to gander the TeX output on the terminal, or eventually to have a look in the log-file, and all that action to repeat. In the paper it is show, how this work is made by author. The process '‘'editor-TeX-look' is supported by simple Unix tools: bash script texloop, created by author for these purposes, Xterm terminal and a simple editor, which is able to link to the shortcut key the activation of a system command. The reader could be inspired with the solution and to adapt these tools to his/her own needs. In the paper the function of the texloop script is described, and further the longstanding evolution of the author's relation to text editors is informal elaborated and finally a configuration of Xterm terminal, suitable for the czech environment with both ISO-8859-2 and UTF-8 encoding is introduced. For UTF-8 encoding the TeX format csplain is generated at the end of the paper
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