Miracle-dz/UniFAR-FTUs huggingface dataset:
Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice*

Background: The prion protein (PrPC) functions as a scaffold for cell surface signaling systems, and plays a role in neurodegenerative diseases that include clinical depression among their symptoms. Results: PrPC-null mice showed depressive-like behavior concomitant with functional changes in monoaminergic systems. Conclusion: PrPC regulates functions of monoaminergic synapses. Significance: PrPC may be involved in major depression and related neuropsychiatric disorders. We sought to examine interactions of the prion protein (PrPC) with monoaminergic systems due to: the role of PrPC in both Prion and Alzheimer diseases, which include clinical depression among their symptoms, the implication of monoamines in depression, and the hypothesis that PrPC serves as a scaffold for signaling systems. To that effect we compared both behavior and monoaminergic markers in wild type (WT) and PrPC-null (PrP−/−) mice. PrP−/− mice performed poorly when compared with WT in forced swimming, tail suspension, and novelty suppressed feeding tests, typical of depressive-like behavior, but not in the control open field nor rotarod motor tests; cyclic AMP responses to stimulation of D1 receptors by dopamine was selectively impaired in PrP−/− mice, and responses to serotonin, but not to norepinephrine, also differed between genotypes. Contents of dopamine, tyrosine hydroxylase, and the 5-HT5A serotonin receptor were increased in the cerebral cortex of PrP−/−, as compared with WT mice. Microscopic colocalization, as well as binding in overlay assays were found of PrPC with both the 5HT5A and D1, but not D4 receptors. The data are consistent with the scaffolding of monoaminergic signaling modules by PrPC, and may help understand the pathogenesis of clinical depression and neurodegenerative disorders.
Social Work Ethics and Organizational Culture: A Gap in Social Work Education and Social Work Field Education

Social work education and the signature pedagogy of social work, field education, allow students to learn social work ethics. Within the agency setting of field placement, social work students experience organizational culture and organizational climate. The purpose of this banded dissertation is to understand the relationship between ethics learned within the classroom and field education, specific to organizational culture and organizational climate. Ecological and general systems theory provides the conceptual framework to understand the relationship. Social work ethics and organizational culture are experienced in field education. Product One, a conceptual paper, asserts the need for understanding organizational culture and its relevance to field education. Understanding ethics and organizational culture is imperative to students’ learning and preparation for field education. Incorporation of organizational culture in social work ethics education will enhance social work education and ethical practice. A qualitative systematic review research study for Product Two, asked the question how might field education effectively bring students’ attention and understanding to the intersection of social work ethics and organizational culture? Study results indicate the relevance of incorporating organizational culture, organizational climate and social work ethics in teaching social work field education. A workshop presentation was given at the National Association of Social Workers Ohio Chapter Conference for Product Three. This presentation presented the concept of social work ethics and organizational culture with field education, based upon Product One of the banded dissertation. Organizational culture and organizational climate are important factors that influence and impact social work ethics and practice. There is a need for these concepts to be incorporated into ETHICS AND ORGANIZATIONAL CULTURE iii social work ethics education and the pedagogy of field education. Without such education, social work students are not adequately prepared for field education or acculturation to the profession and ethical practice of social work. ETHICS AND ORGANIZATIONAL CULTURE iv Dedication/Acknowledgements Dedicated to the glory of God, in thankfulness for being my rock, strength and guide to complete this journey, fulfilling a God given dream for a DSW; to my daughters, Emily and Natalie, for your love, support and belief in me, you are my inspiration; and thankfulness for the love from heaven of my parents and love of my life, Larry. Thank you to the faculty and staff, my roommates, cohort 2 I have learned from each of you and gained my voice. Thank you to my ‘village’-my family, friends, church and Emmaus family-who have walked this journey with me with love and encouragement to take the next step; special thanks to Jane Hoyt-Oliver, PhD, Rebecca Evanoff and Rebecca Fort for your mentorship, support and guidance. ETHICS AND ORGANIZATIONAL CULTURE v
Surgeon Reliability in Rating Physical Deformity in Adolescent Idiopathic Scoliosis

Study Design. Cross sectional survey. Objectives. To compare pediatric spine surgeons' relative rankings of the importance of surgical considerations, and their reliability of ratings of the physical deformity of patients with adolescent idiopathic scoliosis (AIS). Summary of Background Data. Adolescents' appearance is a factor in surgical decision-making. Although the reliability of the Cobb angle has been extensively studied, less attention has been directed toward the reliability of surgeons' assessment of physical appearance. Methods. Five surgeons ranked the relative importance of 13 surgical considerations. While viewing clinical photographs of 40 patients, surgeons rated the following: shoulder blades, shoulders, waist asymmetry, and the “overall appearance” of the back. Results. “Severity of deformity” was consistently ranked the most important surgical consideration. Surgeons, however, varied widely in their reliability of their ratings of physical appearance: shoulder blades (&kgr; = 0.34), shoulders (&kgr; = 0.22), waist (&kgr; = 0.24), and overall appearance (&kgr; = 0.40). Conclusion. Because patients' physical appearance is an important element of surgical decision-making, differences among surgeons could be contributing to inconsistent recommendations.
Intellectual Property Rights and Diaspora Knowledge Networks: Can Patent Protection Generate Brain Gain from Skilled Migration?

This paper studies the mechanism through which intellectual property rights (IPR) protection can influence the impact of skilled migration on innovation activities in developing countries. We argue that knowledge acquired by emigrants abroad can flow back to their country of origin through diaspora networks. IPR protection in the sending country facilitates this channel by increasing returns to skills and encouraging workers to move into the innovation sector. An expansion of the innovation sector allows diaspora knowledge to be absorbed by a larger range of workers. Strong IPR enforcement therefore makes it more likely for brain drain to be transformed into brain gain.
Treatment of asymptomatic rectal Chlamydia trachomatis: is single-dose azithromycin effective?

Rectal infection with Chlamydia trachomatis affects approximately 7% of men having sex with men (MSM), attending departments of Genito-Urinary (GU) Medicine [Manavi et al. Int J STD AIDS 2004;15:162–4], and the British Association for Sexual Health and HIV (BASHH) guidelines for the treatment of uncomplicated genital C. trachomatis infection include 1 g of single-dose oral azithromycin as a recommended regimen [BASHH 2006]. A retrospective analysis was performed on case-notes from all patients diagnosed with rectal C. trachomatis infection in the department of GU Medicine, Edinburgh for the one-year period from 1 June 2005. Of 101 new episodes of rectal chlamydial infection, only 9% were associated with anorectal symptoms. Excluding these, 85% of asymptomatic patients were treated with a single dose of azithromycin 1 g orally, with a calculated treatment failure rate of 13% (nine of 68). This suggests that single-dose azithromycin may be a less than effective treatment in asymptomatic rectal C. trachomatis infection. The potential treatment failure rate with this regimen emphasizes the need for a test of cure at the appropriate interval following treatment to ensure clearance of infection.
Exploring the binding diversity of intrinsically disordered proteins involved in one‐to‐many binding

Molecular recognition features (MoRFs) are intrinsically disordered protein regions that bind to partners via disorder‐to‐order transitions. In one‐to‐many binding, a single MoRF binds to two or more different partners individually. MoRF‐based one‐to‐many protein–protein interaction (PPI) examples were collected from the Protein Data Bank, yielding 23 MoRFs bound to 2–9 partners, with all pairs of same‐MoRF partners having less than 25% sequence identity. Of these, 8 MoRFs were bound to 2–9 partners having completely different folds, whereas 15 MoRFs were bound to 2–5 partners having the same folds but with low sequence identities. For both types of partner variation, backbone and side chain torsion angle rotations were used to bring about the conformational changes needed to enable close fits between a single MoRF and distinct partners. Alternative splicing events (ASEs) and posttranslational modifications (PTMs) were also found to contribute to distinct partner binding. Because ASEs and PTMs both commonly occur in disordered regions, and because both ASEs and PTMs are often tissue‐specific, these data suggest that MoRFs, ASEs, and PTMs may collaborate to alter PPI networks in different cell types. These data enlarge the set of carefully studied MoRFs that use inherent flexibility and that also use ASE‐based and/or PTM‐based surface modifications to enable the same disordered segment to selectively associate with two or more partners. The small number of residues involved in MoRFs and in their modifications by ASEs or PTMs may simplify the evolvability of signaling network diversity.
Reconciling 3-D Mixed-Mode Simulations and Measured Single-Event Transients in SiGe HBTs

Comprehensive 3-D mixed-mode simulations, including accurate modeling of parasitic elements present in the experimental setup, resulted in close agreement between simulated and experimentally-measured heavy-ion-induced transients in first-generation SiGe HBTs. We have identified the key factors affecting previous simulations and observed experimental differences. The approach employed is also applicable to other submicron, high-speed technologies. Furthermore, we present a plausible answer to the previously unexplained issue of higher collector currents in single-transistor SiGe HBT single-event transients under positive collector bias. The new observations and conclusions facilitate improved understanding and potential mitigation options.
Blood pressure responses to dynamic exercise with lower-body positive pressure.

Cardiovascular responses were obtained during cycling with graded levels of lower-body positive pressure (LBPP) applied to the exercising limbs. Seven men performed four incremental work rate (25 W.min-1) exercise (IWREx) tests to their limit of tolerance while exposed to 0, 15, 30, or 45 Torr LBPP. They also performed four, 6-min constant work rate exercise (CWREx) bouts at two work rates with LBPP's of 0 and 45 Torr. Cardiovascular data were obtained at rest and at 40%, 55%, 75%, and 90% of VO2peak, as well as at minute 5 of CWREx. LBPP did not alter VO2, HR, SV, or cardiac output (Qc) responses at rest or during exercise. However, both 30 and 45 Torr LBPP produced increases in MAP at rest and during exercise (P < 0.05). During CWREx, elevations in blood pressure were mediated via increases in TPR (P < 0.05). Only 45 Torr LBPP elicited a significantly greater blood pressure increase during exercise than rest, suggesting muscle blood flow restriction at this level of LBPP was sufficient to activate a muscle metabo-reflex. These findings suggest that the muscle metabo-reflex is not tonically active during dynamic exercise under normal conditions, but may instead require a critical reduction in muscle blood flow before it is activated.
Essays on pay-as-you-go pension schemes, demographics, fiscal policy, credit rationing and house prices

The four essays collected in this PhD thesis concern pay-as-you-go pension schemes, demographics, fiscal policy, credit constraints and house prices. The first essay shows how a pay-as-you-go pension scheme affects an individual’s optimal investment portfolio over the lifecycle. The second essay investigates policy options to keep the pay-as-you-go pension scheme in the Netherlands (AOW scheme) sustainable in the face of increasing longevity, declining fertility rates and changes in labour participation. The third essay demonstrates how tax-benefit policies impact aggregate consumption in a world of heterogeneous consumers, profit maximizing banks and imperfect information about future income shocks. The fourth essay studies the joint effect of changes in credit constraints, user cost and demographic factors on regional house prices in the Netherlands in conjunction with changes in the housing stock.
High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment trial.

OBJECTIVE To identify factors associated with a high and low risk of developing multiple sclerosis after an initial episode of optic neuritis. METHODS Three hundred eighty-eight patients who experienced acute optic neuritis between July 1, 1988, and June 30, 1991, were followed up prospectively for the development of multiple sclerosis. Consenting patients were reassessed after 10 to 13 years. RESULTS The 10-year risk of multiple sclerosis was 38% (95% confidence interval, 33%-43%). Patients (160) who had 1 or more typical lesions on the baseline magnetic resonance imaging (MRI) scan of the brain had a 56% risk; those with no lesions (191) had a 22% risk (P<.001, log rank test). Among the patients who had no lesions on MRI, male gender and optic disc swelling were associated with a lower risk of multiple sclerosis, as was the presence of the following atypical features for optic neuritis: no light perception vision; absence of pain; and ophthalmoscopic findings of severe optic disc edema, peripapillary hemorrhages, or retinal exudates. CONCLUSIONS The 10-year risk of multiple sclerosis following an initial episode of acute optic neuritis is significantly higher if there is a single brain MRI lesion; higher numbers of lesions do not appreciably increase that risk. However, even when brain lesions are seen on MRI, more than 40% of the patients will not develop clinical multiple sclerosis after 10 years. In the absence of MRI lesions, certain demographic and clinical features seem to predict a very low likelihood of developing multiple sclerosis. This natural history information is a critical input for estimating a patient's 10-year multiple sclerosis risk and for weighing the benefit of initiating prophylactic treatment at the time of optic neuritis or other initial demyelinating events in the central nervous system.
Integration and Interruption in the Masking of Form by Form

Pairs of geometric forms of equal area were presented, one form after another, with interstimulus intervals t ranging from 0 to 250 ms. The subject's task in experiment 1 was to recognise both stimuli. Identification of the form presented first (backward masking) across all values of t was of a nonmonotonic nature, with greatest impairment at values of t from 30 to 60 ms. Identification of the second form presented (forward masking) increased monotonically with increasing t. Different forms were recognised with different effectiveness across all values of t where masking took place. The results are interpreted on the basis of a multiple-stage processing model which assumes interaction between stimuli at different levels at different values of t. In experiment 2 the subject's task was to detect the presence or absence of a predesignated form. This condition yielded monotonic functions for both backward and forward masking. An explanation in terms of attention-dependent masking is given.
How to enhance SMEs customer involvement using social media: The role of Social CRM

Despite increasing attention to the influence of customer involvement and social media in developing innovation in small- and medium-sized enterprises (SMEs), few studies have specifically investigated how to improve the effectiveness of social media–based customer involvement. Drawing on the knowledge-based view, social network and capability theories, we address this question by arguing that Social Customer Relation Management (CRM) enhances the effect of social media–based customer involvement upon innovation. Two key capabilities further enhance the moderating effect of Social CRM: social media network and customer information processing capabilities. The results from a longitudinal dataset of 317 SMEs indicate that SME customer involvement, enabled by Social CRM, social media network and customer information processing capabilities increases innovation. These findings have important implications for researchers and managers interested in enhancing the efficacy of SME customer involvement using social media.
Heavy-metal pollution and potential ecological risk assessment of sediments from Baihua Lake, Guizhou, P.R. China

Baihua Lake, a man-made reservoir, is one of the five drinking water sources for Guiyang City in China's southwestern province of Guizhou. In the present research, the distribution and accumulation characteristics of heavy metals (Pb, Cd, As, Cu and Zn) for the sediment of this lake were analyzed by examination of 10 recently collected samples. A method based on toxic-response factor was applied to assess the potential ecological risk of these heavy metals to the water body. For comparison, the two sets of reference data representing the pre-industrial and the local baseline pollution levels were employed to derive the accumulating coefficients for the heavy metals under study. The calculated potential ecological risk indices show that the lake was polluted by heavy metals and both cadmium and arsenic loadings were critical factors responsible for the ecological hazards posed to Baihua Lake by the five elements.
Time and concentration dependency in the potentially affected fraction of species: The case of hydrogen peroxide treatment of ballast water

Transport of large volumes of ballast water contributes greatly to invasions of species. Hydrogen peroxide (H2O2) can be used as a disinfectant to prevent the spread of exotic species via ballast water. Instead of using environmental risk assessment techniques for protecting a certain fraction of the species from being affected, the present study aimed to apply these techniques to define treatment regimes of H2O2 and effectively eliminate as many species as possible. Based on time‐dependent dose–response curves for five marine species (Corophium volutator, Artemia salina, Brachionus plicatilis, Dunaliella teriolecta, and Skeletonema costatum), time‐dependent species‐sensitivity distributions (SSDs) were derived for different effect sizes. The present study showed that H2O2 can be used effectively to treat ballast water but that relatively high concentrations and long treatment durations are required to eliminate the vast majority of species in ballast water. The described toxicant effectiveness approach using SSDs also has other potential fields of application, including short‐term application of biocides.
Complement Activation in Cystic Fibrosis Respiratory Fluids: in Vivo and in Vitro Generation of C5a and Chemotactic Activity

ABSTRACT. Experiments performed in vitro have demonstrated that leukocyte neutral proteases produce an important mediator of inflammation, C5a, by proteolysis of the C5 component of the complement system. Cystic fibrosis (CF) lung fluids were characterized by high levels of neutrophils (39% of total cells versus 2% in normals) and contained significantly elevated amounts of elastolytic activity (mean 17.7 ng/µg total protein) compared to the lung fluids obtained from normal volunteers (0.2 ng elastolytic activity/µg protein, p = 0.001). The objective of these studies was to determine if complement activation and complement-derived chemotactic activity are present in CF lung fluids. C3c peptide representing activation of C3 could not be identified in the bronchial-alveolar lung lavage fluids of normal subjects but was readily identified by means of crossed immunoelectrophoresis in CF lung fluids (n = 9, mean 49% of C3); the mean level of C3 was decreased in CF lung specimens. Chemotactic activity was significantly elevated in lung fluids of the CF patients when compared to normal lung fluids. Using gel-filtration chromatography and a sensitive radioimmunoassay the chemotaxin present in CF specimens was identified as the anaphylatoxin C5a. C5a levels in the bronchial-alveolar lavage fluids of CF patients was inversely related to volume in liters expired in 1 s of a forced expiratory maneuver expressed as a percent of vital capacity determined from a forced expiratory maneuver (r = -0.72). Because there was a direct relationship between the total elastolytic activity present in CF airways and the concentration of C5a (r = 0.97, p = 0.03), it was postulated that airway proteases with elastolytic activity also cleave C5, nonimmunologically producing C5a. Detailed inhibition assays revealed that much of the total elastolytic activity had the inhibition profile of a serine proteinase. The levels of the serine proteinases were closely correlated with the numbers of neutrophilic leukocytes present per ml of lavage fluid (r = 0.7, p = 0.05). However, inhibitors of leukocyte serine proteases did not prevent the generation of additional chemotactic activity and the proteolysis of radiolabeled C5 substrate was not prevented by inhibitors of neutrophil elastase. Although the purified metalloelastase of Pseudomonas aeruginosa was active on cell-bound and free C5 yielding C5a, inhibition of this bacterial protease in CF lung fluids only partially blocked cleavage of the α- and β-chains of C5. Simultaneous inhibition of the serine and metalloprotease activities of CF lung fluids effectively blocked the in vitro generation of C5a leukocyte chemotactic activity. We conclude that CF lung fluids contain markedly increased levels of elastolytic activity which are closely linked to the extent of CF lung disease and which are capable of proteolytically generating C5a. Both a serine proteinase and a metalloenzyme in these lung fluids contribute to the nonimmunologic generation of C5a.