Miracle-dz/UniFAR-FTUs huggingface dataset:
Organization of oligodendroglial membrane sheets. I: Association of myelin basic protein and 2′,3′‐cyclic nucleotide 3′‐phosphohydrolase with cytoskeleton

Membrane sheets elaborated by cultured murine oligodendroglia provide a unique system for examining associations between myelin proteins and cytoskeletal elements. Interactions can be observed and manipulated more readily than in the multilamellar myelin membrane in vivo. Immunocytochemical staining of 2′,3′‐cyclic nucleotide 3′‐phosphohydrolase (CNPase) shows that it is distributed diffusely in some regions of membrane sheets, but colocalized with tubulin in lacy networks and major veins in other regions. Staining with phalloidin also reveals two distributions of F‐actin: (1) small aggregates within the diffuse CNPase regions and (2) filaments colocalized with tubulin and CNPase in the lacy networks and veins. Application of colchicine at 10 μg/ml for 4 hr disrupts microtubular structures in the lacy network, while those in major veins remain intact. This suggests that microtubules in the lacy network are treadmilling more rapidly than those in the major veins. The distribution of CNPase and F‐actin is not altered under these conditions. In contrast, cytochalasin B disrupts F‐actin, microtubules, and CNPase in the lacy networks, indicating that cross‐linking between these three proteins is disrupted. Both colchicine and cytochalasin B cause fusion of myelin basic protein (MBP) domains in membrane sheets. This appears to be a consequence of disruption of microtubules in the lacy networks, which normally outline the MBP domains. In summary, these results provide evidence for (1) direct association of CNPase with F‐actin and tubulin in cytoskeletal structures and (2) organization of MBP into domains via association with microtubules in the lacy networks.
Novel Technique for Estimating Cerebrovascular Permeability Demonstrates Capsazepine Protection Following Ischemia‐Reperfusion

Objective: There has been some discussion as to whether the pial vasculature behaves in the same way as the blood‐brain barrier as a whole. Recent studies have shown that capsazepine protects these vessels from the effects of ischemia‐reperfusion. We have now used a new method to examine this protection in the whole brain.
Macroprudential policy in a recovering property market: too much too soon?

The aftermath of the 2007/2008 financial crisis has resulted in many central banks and regulatory authorities examining the effectiveness of macroprudential policy in preventing the emergence of future credit bubbles. Specific limits on loan-to-value (LTV) and loan-to-income (LTI) ratios have been introduced in a number of economies as a means of ensuring greater financial stability. The Irish property and credit market were particularly affected in the crisis as the domestic housing market had, since 1995, experienced sustained price and housing supply increases. Much of the activity in the Irish market was fuelled by a credit bubble following the emergence of international wholesale funding post 2003. After a period of pronounced declines, Irish house prices in late 2013 started to increase significantly; in early 2015, in response, the Irish Central Bank imposed new LTV and LTI limits to curb house price inflation. However, the introduction of these measures comes at a time when housing supply and mortgage lending are still at historically low levels. Therefore, in this paper we use a newly developed structural model of the Irish property and credit market to examine the implications of these measures for house prices and key activity variables in the mortgage market.
Computer-aided diagnosis and artificial intelligence in clinical imaging.

Computer-aided diagnosis (CAD) is rapidly entering the radiology mainstream. It has already become a part of the routine clinical work for the detection of breast cancer with mammograms. The computer output is used as a "second opinion" in assisting radiologists' image interpretations. The computer algorithm generally consists of several steps that may include image processing, image feature analysis, and data classification via the use of tools such as artificial neural networks (ANN). In this article, we will explore these and other current processes that have come to be referred to as "artificial intelligence. " One element of CAD, temporal subtraction, has been applied for enhancing interval changes and for suppressing unchanged structures (eg, normal structures) between 2 successive radiologic images. To reduce misregistration artifacts on the temporal subtraction images, a nonlinear image warping technique for matching the previous image to the current one has been developed. Development of the temporal subtraction method originated with chest radiographs, with the method subsequently being applied to chest computed tomography (CT) and nuclear medicine bone scans. The usefulness of the temporal subtraction method for bone scans was demonstrated by an observer study in which reading times and diagnostic accuracy improved significantly. An additional prospective clinical study verified that the temporal subtraction image could be used as a "second opinion" by radiologists with negligible detrimental effects. ANN was first used in 1990 for computerized differential diagnosis of interstitial lung diseases in CAD. Since then, ANN has been widely used in CAD schemes for the detection and diagnosis of various diseases in different imaging modalities, including the differential diagnosis of lung nodules and interstitial lung diseases in chest radiography, CT, and position emission tomography/CT. It is likely that CAD will be integrated into picture archiving and communication systems and will become a standard of care for diagnostic examinations in daily clinical work.
On‐Line Assessment of Metabolic Activities Based on Culture Redox Potential and Dissolved Oxygen Profiles During Aerobic Fermentation

We report here on the utility of on‐line culture redox potential and dissolved oxygen measurements to identify metabolic changes in fermentation by Corynebacterium glutamicum under aerobic conditions. Metabolic changes were identified by observing discrepancies in the profile of culture redox potential and dissolved oxygen. On the basis of these measurements, we can identify the end of the lag phase, threonine exhaustion, and glucose exhaustion during fermentation.
Rational Engineering of a Minimized Immune Inhibitor with Unique Triple-Targeting Properties

Inadequate control of the complement system is the underlying or aggravating factor in many human diseases. Whereas treatment options that specifically target the alternative pathway (AP) of complement activation are considered highly desirable, no such option is available in the clinic. In this study, we present a successful example of protein engineering, guided by structural insight on the complement regulator factor H (FH), yielding a novel complement-targeted therapeutic (mini-FH) with clinical potential. Despite a 70% reduction in size, mini-FH retained and in some respects exceeded the regulatory activity and cell surface–recognition properties of its parent protein FH, including the recently described recognition of sites of oxidative stress. Importantly, the chosen design extended the functional spectrum of the inhibitor, as mini-FH showed increased binding to the surface-bound opsonins iC3b and C3dg when compared with FH. Thus, mini-FH is equipped with a unique and clinically valuable triple-targeting profile toward diseased host cells, through its binding to sites of ongoing complement activation, markers of oxidative damage, and host surface-specific polyanions. When assessed in a clinically relevant AP-mediated disease model of paroxysmal nocturnal hemoglobinuria, mini-FH largely outperformed FH and indicated advantages over clinically evaluated AP inhibitors. Thus, the rational engineering of a streamlined FH construct not only provided insight into the function of a key complement regulator, but also yielded a novel inhibitor that combines a triple-targeting approach with high AP-specific inhibitory activity (IC50 ∼ 40 nM), which may pave the way toward new options for the treatment of complement-mediated diseases.
Transforming Growth Factor β Affects Osteoclast Differentiation via Direct and Indirect Actions

Transforming growth factor β (TGF‐β) is abundant in bone and has complex effects on osteolysis, with both positive and negative effects on osteoclast differentiation, suggesting that it acts via more than one mechanism. Osteoclastogenesis is determined primarily by osteoblast (OB) expression of the tumor necrosis factor (TNF)‐related molecule receptor activator of NF‐κB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG), which are increased and decreased, respectively, by osteolytic factors. A RANKL‐independent osteoclastogenic mechanism mediated by TNF‐α has also been shown. Therefore, we investigated TGF‐β effects on osteoclast formation in culture systems in which osteoclastogenic stimulus is dependent on OBs and culture systems where it was provided by exogenously added RANKL or TNF‐α. Both OPG and TGF‐β inhibited osteoclast formation in hemopoietic cell/OB cocultures, but the kinetics of their action differed. TGF‐β also inhibited osteoclastogenesis in cocultures of cells derived from OPG null (opg−/−) mice. TGF‐β strongly decreased RANKL messenger RNA (mRNA) expression in cultured osteoblasts, and addition of exogenous RANKL to TGFβ‐inhibited cocultures of opg−/− cells partially restored osteoclastogenesis. Combined, these data indicate that the inhibitory actions of TGF‐β were mediated mainly by decreased OB production of RANKL. In contrast, in the absence of OBs, TGF‐β greatly increased osteoclast formation in recombinant RANKL‐ or TNF‐α‐stimulated cultures of hemopoietic cells or RAW 264.7 macrophage‐like cells to levels several‐fold greater than attainable by maximal stimulation by RANKL or TNF‐α. These data suggest that TGF‐β may increase osteoclast formation via action on osteoclast precursors. Therefore, although RANKL (or TNF‐α) is essential for osteoclast formation, factors such as TGF‐β may powerfully modify these osteoclastogenic stimuli. Such actions may be critical to the control of physiological and pathophysiological osteolysis.
Essays in Policy Analysis

My dissertation consists of three essays related to policy analysis. In the first essay we ask, how can developing nations who face revenue mobilization issues and large informal sectors use taxation as a means of nation building? To answer this, we design a dynamic general equilibrium model that accounts for a large informal sector. Contrary to previous studies that model the informal economy, we focus on the importance of the government maintaining its social fiscal contract with its constituents by including the provision of productive public goods in the model. By doing so, we show that increasing taxes can be used to encourage formal sector activity and increase revenue simultaneously. In the second essay, I develop a theoretical outline explaining why treatment effects may lag the treatment event in the context of local labor shocks, and examine the impact properly identifying of treatment date. Using the Clean Air Act Amendments (CAAA) of 1990 as a case study for a negative labor demand shock in the Appalachian coal mining industry, I find lags in treatment effects on the mining industry relative to policy implementation, as well as secondary lags in the multiplier effects on the aggregate economy relative to the labor shock. Building on this, the third essay tests the predictions of the theory in the case of a positive labor demand shock and explores the timing of multiplier effects at the sector level. Using the CAAA as the source of a positive labor demand shock in the Western United States coal industry, I again find lags in the treatment effect on the mining sector, but find variety in the timing of responses of individual sectors. I also discuss the implications these findings have for local policy makers whose communities may experience such shocks, as well as national policy makers concerned with future policy initiatives such as the Clean Power Plan.
Single neuron activity and theta modulation in the posterior parietal cortex in a visuospatial attention task

The posterior parietal cortex (PPC) is implicated in directing and maintaining visual attention to locations in space. We hypothesized that the PPC also engages other cognitive processes in the transformation of behaviorally relevant visual inputs into appropriate actions, for example, monitoring of multiple locations, selection of responses to locations in space, and monitoring the outcome of response selections. We recorded single cells and local field potentials in the rat PPC during performance on a novel visuospatial attention (VSA) task that requires visually monitoring locations in space in order to make appropriate stimulus‐guided locomotor responses. In each trial, rats attended to four locations on the floor of a maze. A randomly chosen location was briefly illuminated. Approach to the correct target location was followed by food reward. We observed that PPC activity correlated with multiple phases of the VSA task, including monitoring for stimulus onset, detection of a target, spatial location of the target, and target choice. A substantial proportion of cells with behavioral correlates were also modulated by outcome of the trial. Our analyses of local field potentials revealed strong oscillatory rhythms in the theta frequency band, and more than a third of PPC neurons were phase locked to theta oscillations. As in other brain regions, theta power correlated with running speed. Peak theta power was higher in superficial layers than deep layers providing evidence against volume conduction from the hippocampus. In addition, theta power was sensitive to the outcome of a choice. Theta power was significantly higher following incorrect choices compared with correct choices, possibly providing a prediction error signal. Our study provides evidence that the rat PPC has multiple roles in the translation of visual information into appropriate behavioral actions. © 2016 Wiley Periodicals, Inc.
Practice and payment preferences of newly practising family physicians in British Columbia.

OBJECTIVE To examine the remuneration model preferences of newly practising family physicians. DESIGN Mixed-methods study comprising a cross-sectional, Web-based survey, as well as qualitative content analysis of answers to open-ended questions. SETTING British Columbia. PARTICIPANTS University of British Columbia family practice residents who graduated between 2000 and 2009. MAIN OUTCOME MEASURES Preferred remuneration models of newly practising physicians. RESULTS The survey response rate was 31% (133 of 430). Of respondents, 71% (93 of 132) preferred non-fee-for-service practice models and 86% (110 of 132) identified the payment model as very or somewhat important in their choice of future practice. Three principal themes were identified from content analysis of respondents' open-ended comments: frustrations with fee-for-service billing, which encompassed issues related to aggravations with "the business side of things" and was seen as impeding "the freedom to focus on medicine"; quality of patient care, which embraced the importance of a payment model that supported "comprehensive patient care" and "quality rather than quantity"; and freedom to choose, which supported the plurality of practice preferences among providers who strived to provide quality care for patients, "whatever model you happen to be working in. " CONCLUSION Newly practising physicians in British Columbia preferred alternatives to fee-for-service payment models, which were perceived as contributing to fewer frustrations with billing systems, improved quality of work life, and better quality of patient care.
Depth-dependent cohesive tensile strength in human donor corneas: implications for refractive surgery.

PURPOSE To determine the cohesive tensile strength throughout the stroma of normal human donor corneas and evaluate the relevance of these findings within the context of current excimer laser surgical techniques. METHODS Twenty normal corneoscleral buttons from 11 donors were obtained from the Georgia Eye Bank. The corneas were cut into 3-mm strips, dissected at varying stromal depths, mechanically separated through the dissection plane using a motorized extensometer, and measured for cohesive tensile strength. Central corneal thickness and dissection depth were measured by routine light microscopy and correlated with cohesive tensile strength measurements. RESULTS A strong negative correlation was noted between stromal depth and cohesive tensile strength (r = -0.93). The anterior corneal stroma directly adjacent to Bowman's layer followed by the underlying anterior 40% of the corneal stroma had the highest cohesive tensile strength. Cohesive tensile strength plateaued from 40% to 90% corneal stromal depth and then declined rapidly from the posterior 10% of the stroma to Descemet's membrane. The anterior 40% of the corneal stroma had significantly higher cohesive tensile strength than the posterior 60% (33.3 g/mm vs 19.6 g/mm, P < .00001). Within the central 40% to 60% depth, a positive correlation was found between increased age and increased tensile strength (r = 0.67), with corneal tensile strength increasing 38% from ages 20 to 78 years. CONCLUSIONS The anterior 40% of the central corneal stroma is the strongest region of the cornea, whereas the posterior 60% of the stroma is at least 50% weaker. The risk for ectasia may therefore be greater with ablations into the posterior stroma. Increasing age is associated with increased corneal cohesive tensile strength.
A tale of two groups: focusing on the differential vulnerability of “climate-induced” and “non-climate-induced” migrants in Dhaka City

Bangladesh is one of the most vulnerable countries in the world under the context of climate change. Each year thousands of migrants arrive in Dhaka City, the capital of the country, mainly forced by events such as floods, cyclone and riverbank erosion. Such group of migrants has been termed as “climate-induced” migrants in this research. The city also received other types of migrants who are not driven by climatic factors; rather their reasons for migration are purely opportunistic. This group has been termed as non-climate-induced migrants. The paper deals with the climate-induced and non-climate-induced migrants in Korail slum of Bangladesh who had arrived in Dhaka after 2006. This research attempted to analyse whether there are any differences in the characteristics, experiences and future aspiration between these two groups in spite of living in the same slum located in the capital of Bangladesh. Questionnaire survey, focus groups and key informant interview were the methods of data collection. Independent sample t-test and Chi-square test have been conducted to analyse data. Results revealed significant differences between the two groups in terms of income and savings, educational level, access to credit, contacts in the city, family structure, pattern of migration and relationship with the place of origin. The study revealed that if not properly planned, migration cannot be a suitable adaptation option.
Mental Health and Substance Use Care Among Young Adults Before and After Affordable Care Act (ACA) Implementation: A Rural and Urban Comparison

PURPOSE Rural young adults experience greater unmet need for mental health (MH) and alcohol or drug (AOD) treatment and lower health insurance coverage than urban residents. It is unknown whether Affordable Care Act (ACA) reforms in 2010 (dependent coverage extended to age 26) or 2014 (Medicaid expansion) closed rural/urban gaps in insurance and treatment. The present study compared changes in rates of health insurance, MH treatment, and AOD treatment for rural and urban young adults over a period of ACA reforms. METHODS Young adult participants (18-25 years) in the National Survey on Drug Use and Health (2008-2014) with past-year psychological distress or AOD abuse were included. Difference-in-differences logistic regression models estimated rural/urban differences in insurance, MH, and AOD treatment pre- versus post-ACA reforms. Analyses adjusted for gender, race, marital status, and health status. RESULTS Among 39,482 young adults with psychological distress or AOD, adjusted insurance rates increased from 72.0% to 81.9% (2008-2014), but a significant rural/urban difference (5.1%) remained in 2014 (P < .05). Among young adults with psychological distress (n = 23,470), MH treatment rates increased following 2010 reforms from 30.2% to 33.0%, but gains did not continue through 2014. Differences in MH treatment over time did not vary by rural/urban status and there were no significant changes in AOD treatment for either group. CONCLUSIONS Although rates of insurance increased for all young adults, a significant rural/urban difference persisted in 2014. Meaningful increases in MH and AOD treatment may require targeted efforts to reduce noninsurance barriers to treatment.
Cutis tricolor parvimaculata: A Distinct Neurocutaneous Syndrome?

An 11-year-old girl had multiple, disseminated, rather small café-au-lait macules and hypochromic spots involving the neck, the trunk and the legs. In part, the two types of macules showed a spatial proximity, suggesting didymosis (twin spotting). The term cutis tricolor has been proposed to describe congenital paired hyperchromic and hypochromic macules on a background of intermediate skin. Because the spots present in this case were much smaller than those described in previous cases of cutis tricolor, we here propose the distinguishing term ‘cutis tricolor parvimaculata’. The underlying gene locus may be a hot spot for postzygotic recombinations, giving rise to multiple twin spots. Moreover, the girl had developed seizures from the age of 10 years, and a large oligodendroglioma involving the left frontal lobe was found. A causal relationship between the cutaneous phenotype and the cerebral tumor is unproven but likely. The skin lesions were reminiscent of a disorder described by Westerhof et al. in 1978 under the term ‘hereditary congenital hypopigmented and hyperpigmented macules’. So far, however, it is not clear whether cutis tricolor parvimaculata is identical with or different from this disorder.
Targeting of Enteropathogenic Escherichia coli EspF to Host Mitochondria Is Essential for Bacterial Pathogenesis

The attachment of enteropathogenic Escherichia coli (EPEC) to host cells and the induction of attaching and effacing (A/E) lesions are prominent pathogenic features. EPEC infection also leads to host cell death and damage to the intestinal mucosa, which is partly dependent upon EspF, one of the effectors. In this study, we demonstrate that EspF is a mitochondrial import protein with a functional mitochondrial targeting signal (MTS), because EspF activity for importing into the mitochondria was abrogated by MTS deletion mutants. Substitution of the 16th leucine with glutamic acid (EspF(L16E)) completely abolished EspF activity. Infection of HeLa cells with wild type but not the espF mutant (ΔespF) decreased mitochondrial membrane potential (ΔΨm), leading to cell death. The ΔΨm decrease and cell death were restored in cells infected with ΔespF/pEspF but not ΔespF/pEspF(L16E), suggesting that the 16th leucine in the MTS is a critical amino acid for EspF function. To demonstrate the impact of EspF in vivo, we exploited Citrobacter rodentium by infecting C3H/HeJ mice with ΔespFCR, ΔespFCR/pEspFCR, or ΔespFCR/pEspF(L16E)CR. These results indicate that EspF activity contributes to bacterial pathogenesis, as judged by murine lethality and intestinal histopathology, and promotion of bacterial colonization of the intestinal mucosa.