Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of the Dorsolateral Prefrontal Cortex: Evidence from the Effects of Contextual Constraint in a Sentence Completion Task

Although the prefrontal cortices, in particular the dorsolateral prefrontal cortex (DLPFC), have been examined in numerous imaging and neuropsychological studies, it has proved difficult to assign a specific function to this brain region. The aim of this study was therefore to delineate the function of the DLPFC first by using positron emission tomography with a word generation task and second by comparing these findings with a series of different circumstances in which the DLPFC is activated in association with response selection. Six healthy volunteers were presented with a sentence completion task based on the Hayling test. In each of two conditions, (A) response initiation and (B) response suppression, volunteers saw a sentence with the final word omitted. In condition A they had to provide a word that fitted at the end of the sentence and in condition B they had to provide a word that did not fit. The corpus of sentences used varied systematically in their level of contextual constraint, ranging from low to high. With all levels of constraint combined, significant greater activation was observed in the left DLPFC (BA46/9) under the suppression condition and in the medial orbitofrontal cortex (BA11) under the initiation condition. Under the high-constraint condition with both tasks combined, significant right middle temporal activity (BA21) was observed, whereas under low constraint, the left DLPFC was significantly activated. An interaction of task and constraint revealed that the left DLPFC was significantly more active in the suppression task at all levels of constraint, but only under the low-constraint conditions in the initiation task. The reaction time analyses mirrored the pattern of activity observed, with slower reaction times under conditions of suppression and under conditions of initiation with low constraint. By comparing these findings with other studies of response selection, we argue that the most likely single cognitive function of the DLPFC is to specify a set of responses suitable for a given task and to bias these for selection (sculpting the response space). This function resembles the biasing of competition between stimuli in the model of Desimone and Duncan and is analogous to the component of the Supervisory Attentional System that modulates the contention scheduling system.
In situ expression patterns of melanoma inhibitory activity 2 in healthy and diseased livers

Abstract: Recently we identified a novel gene of the MIA gene family, melanoma inhibitory activity 2 (MIA2) and found that MIA2 mRNA is selectively expressed in hepatocytes. Here, we analyzed the in situ expression of MIA2 protein and mRNA in healthy and diseased livers to get first insights into the function of MIA2.
Characterization of the Expression, Intracellular Localization, and Replication Complex Association of the Putative Mouse Hepatitis Virus RNA-Dependent RNA Polymerase

ABSTRACT Mouse hepatitis virus (MHV) RNA synthesis is mediated by a viral RNA-dependent RNA polymerase (RdRp) on membrane-bound replication complexes in the host cell cytoplasm. However, it is not known how the putative MHV RdRp (Pol) is targeted to and retained on cellular membranes. In this report, we show that a 100-kDa protein was stably detected by an anti-Pol antiserum as a mature product throughout the virus life cycle. Gradient fractionation and biochemical extraction experiments demonstrated that Pol was not an integral membrane protein but was tightly associated with membranes and coimmunoprecipitated with the replicase proteins 3CLpro, p22, and p12. By immunofluorescence confocal microscopy, Pol colocalized with viral proteins at replication complexes, distinct from sites of virion assembly, over the entire course of infection. To determine if Pol associated with cellular membranes in the absence of other viral factors, the pol domain of gene 1 was cloned and expressed in cells as a fusion with green fluorescent protein, termed Gpol. In Gpol-expressing cells that were infected with MHV, but not in mock-infected cells, Gpol relocalized from a diffuse distribution in the cytoplasm to punctate foci that colocalized with markers for replication complexes. Expression of Gpol deletion mutants established that the conserved enzymatic domains of Pol were dispensable for replication complex association, but a 38-amino-acid domain in the RdRp unique region of Pol was required. This study demonstrates that viral or virus-induced factors are necessary for Pol to associate with membranes of replication complexes, and it identifies a defined region of Pol that may mediate its interactions with those factors.
Correlation between Inflammatory Markers of Atherosclerosis and Carotid Intima-Media Thickness in Obstructive Sleep Apnea

Obstructive Sleep Apnea (OSA) is a sleep-related breathing disorder associated with the development of cardiovascular diseases and atherosclerosis. Systemic inflammation plays an important role in the development of cardiovascular complications in OSA patients. The aim of the study was to evaluate the relationship between carotid intima-media thickness (cIMT) and inflammatory markers plasma levels in OSA patients. We enrolled 80 OSA patients and 40 controls matched for age and body mass index (BMI). The presence and severity of sleep apnea was determined by in-laboratory portable monitoring (PM). Demographic data, blood pressure, heart rate, and cIMT were measured. High-sensitive C-Reactive Protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and pentraxin (PTX)-3 serum concentrations were detected. cIMT was higher in OSA patients than controls (0.89 ± 0.13 mm vs. 0.65 ± 0.1 mm, p < 0.01). Moderate-severe OSA patients (0.95 ± 0.09 mm) had significantly increased cIMT than mild OSA (0.76 ± 0.1 mm; p < 0.01) and control (0.65 ± 0.1 mm; p < 0.01). hsCRP, IL-6, TNF-α, and PTX-3 in patients with OSA (1.67 ± 0.66 mg/L, 2.86 ± 1.39 pg/mL, 20.09 ± 5.39 pg/mL, 2.1 ± 0.59 ng/mL, respectively) were significantly higher than in controls (1.08 ± 0.53 mg/L, p < 0.01; 1.5 ± 0.67 pg/mL, p < 0.01; 12.53 ± 3.48 pg/mL, p < 0.01; 1.45 ± 0.41 ng/mL, p < 0.01, respectively). Carotid IMT was significantly correlated to CRP (r = 0.44; p < 0.01), IL-6 (r = 0.42; p < 0.01), TNF-α (r = 0.53; p < 0.01), and PTX-3 (r = 0.49; p < 0.01). OSA patients showed increased cIMT, CRP, IL-6, TNF-α, and PTX-3 levels. Inflammatory markers levels are correlated to cIMT in OSA patients.
Fibromyalgia and Nondipper Circadian Blood Pressure Variability

Background and ObjectivesAberrant circadian rhythm with persistent nocturnal sympathetic hyperactivity has pointed out malfunctioning autonomic nervous system in fibromyalgia (FM) patients. This is a common pathogenesis shared also by patients with nondipping blood pressure (BP) pattern. Therefore, we aimed to investigate the frequency of nondipping BP pattern in normotensive women with newly diagnosed FM compared with healthy women. MethodsSixty-seven normotensive women with new diagnosis of FM and 38 age-matched healthy volunteer women were recruited into the study. All subjects underwent 24-hour ambulatory BP monitoring on a usual working day. Individuals were defined as “dippers” if their nocturnal BP values decreased by more than 10% compared with daytime values; defined as “nondippers” in case of a decline less than 10%. Serum creatinine, fasting blood glucose, cholesterol levels, albumin, and thyroid-stimulating hormone levels were assessed. ResultsAmbulatory measurements showed significantly higher diastolic BP values in patients with FM for both average of 24-hour recordings. Patients with FM had significantly lower systolic (9.1 ± 3.9 vs 11.5 ± 4.9, P = 0.010) and diastolic dipping ratios (12.3 ± 6.1 vs 16.1 ± 6.4, P = 0.004). The number of nondippers in the FM group was significantly higher than that of controls for both systolic (66% vs 34%, P = 0.002) and diastolic BP measurements (42% vs 21%, P=0.031). Patients with FM were 3.68 times more likely to be systolic nondipper and 2.69 times more likely to be diastolic nondipper. ConclusionsWe have demonstrated a significant relationship between FM and nondipping BP pattern, and we suggest that nondipping profile, which has been closely associated with cardiovascular morbidity, may appear as an additional risk factor in patients with FM.
Premarital Sex Initiation and the Time Interval to First Marriage Among Indonesians

This study examines the determinants of premarital sex and its effect on the ages at which Indonesians first marry. Survival analysis has been applied to the 2012 Indonesia Demographic and Health Survey (IDHS), in which 11% of Indonesians reported they had had premarital sex. Our study shows the prevalence of premarital sex is higher when based on reports from married females and males aged 15–24 instead of reports from unmarried Indonesians. Males, less-educated people, and rural residents are also more likely to have premarital sex, while females, more-educated people and rural residents marry sooner after first having sex. Generally, however, Indonesians who have had premarital sex marry later than their counterparts. The long time span between Indonesians initiating premarital sex and marrying needs to be considered in policy that provides unmarried adolescents with rights to comprehensive sexual reproductive health (SRH) services.
Transforming the Nigerian Agricultural Sector into an Agribusiness Model – the Role of Government, Business, and Society

Abstract This paper proposes that the transformation of the agric sector into an agribusiness model will contribute to repositioning Nigerian economy from its backwater position in the world’s economy. This proposition was investigated with the help of a review of literature and analysis of secondary time series data from the period of 2005–2014, which represented the contributions of the agricultural, manufacturing, oil and gas, and service sectors in Nigeria. One hypothesis was formulated and investigated with the t-test, correlation, and regression tests. The test results were positive and statistically significant at.05 alpha level, and they showed that agriculture has the potential to consistently have a significant effect in contributing to the growth of the Nigerian GDP both in the short and long run. These results justify the clarion call within the government and business sectors to diversify the economy and return to agriculture as the country’s bedrock for economic stability, especially as global economy becomes more volatile, uncertain, turbulent, and ambiguous. To this end, six strategies and twelve policy recommendations are suggested towards the implementation of a Structural Adjustment for Agribusiness Promotion (SAFAP) in Nigeria, and this is to be implemented as an action plan for pursuing a nationwide agricultural revolution. The paper concludes that, in view of its Vision 20:2020 to be among the top twenty economies in the world, Nigeria can become positioned to be a major player in global economy by diversifying from an oil-dependent economy into agribusiness and agric trade.
Myocardial protection by brief ischemia in noncardiac tissue.

BACKGROUND Brief coronary artery occlusions (CAOs) protect both the artery's own perfusion territory ("myocardial preconditioning") and adjacent "virgin" myocardium. Whether ischemia in remote organs protects myocardium is unknown. We examined whether brief occlusion of the anterior mesenteric artery (MAO) or left renal artery (RAO) protects against myocardial infarction. METHODS AND RESULTS Area at risk (AR) and infarcted area (IA) were determined in anesthetized rats after 180 minutes of reperfusion following a 60-minute CAO. At normothermia (body temperature, 36.5 degrees C to 37.5 degrees C), IA/AR was 68 +/- 2% (mean +/- SEM, n = 11) in control rats and 50 +/- 3% (n = 9, P < .001) in rats preconditioned by 15-minute CAO 10 minutes before 60-minute CAO. A 15-minute MAO was equally protective (IA/AR = 50 +/- 3%, n = 10, P < .001), whereas 15-minute RAO failed to limit IA/AR (72 +/- 5%, n = 8). Hypothermia (body temperature, 30 degrees C to 31 degrees C) did not affect IA/AR (67 +/- 3%, n = 11) in control animals but enhanced protection by 15-minute CAO (IA/AR = 22 +/- 3%, n = 8), whereas protection by 15-minute MAO (IA/AR = 44 +/- 5%, n = 11, P < .001) was minimally enhanced. Hypothermia unmasked protection by 15-minute RAO (IA/AR = 46 +/- 6%, n = 9, P < .01). Hexamethonium (20 mg/kg IV) did not alter protection by 15-minute CAO, but it abolished protection by 15-minute MAO. When MAO was sustained throughout the study, cardioprotection was absent. CONCLUSIONS Brief ischemia in "remote" organs protects myocardium against infarction as effectively as myocardial preconditioning. The mechanism of protection by MAO differs from that of CAO, because ganglion blockade abolished protection by MAO but not by CAO. The neurogenic pathway is activated during reperfusion after 15-minute MAO, because sustained MAO failed to produce cardioprotection.
Molecular cytogenetic characterization of the 11q13 amplicon in head and neck squamous cell carcinoma

Amplification of 11q13 DNA sequences and overexpression of CCND1 are common findings in head and neck squamous cell carcinoma (HNSCC), identified in about 30% of the cases. However, little is known about initiation of the amplification and the organization of the amplicon. In order to study the structure of the amplicon in more detail and to learn more about the mechanisms involved in its initiation, prometaphase, metaphase, and anaphase fluorescence in situ hybridization (FISH) with 40 BAC clones spanning a 16-Mb region in chromosome bands 11q12.2 to 11q13.5 was performed in nine HNSCC cell lines with homogeneously staining regions. FISH analysis showed that the size of the amplicon varied among the nine cell lines, the smallest being 2.12 Mb and the largest 8.97 Mb. The smallest overlapping region of amplification was approximately 1.61 Mb, covering the region from BAC 729E14 to BAC 102B19. This region contained several genes previously shown to be amplified and overexpressed in HNSCC, including CCDN1, CTTN, SHANK2, and ORAOV1. The cell lines were also used to study the internal structure of the amplicon. Various patterns of amplified DNA sequences within the amplicon were found among the nine cell lines. Even within the same cell line, different amplicon structures could be found in different cell populations, indicating that the mechanisms involved in the development of the amplicons in HNSCC were more complex than previously assumed. The frequent finding of inverted repeats within the amplicons, however, suggests that breakage-fusion-bridge cycles are important in the initiation, but the fact that such repeats constituted only small parts of the amplicons indicate that they are further rearranged during tumor progression.
Evaluation of land-use and transport network effects on cyclists' route choices in the Copenhagen Region in value-of-distance space

ABSTRACT Growing interest in sustainable transportation systems has driven decision-makers toward policies and investments aimed at promoting cycling, but little to no effort has been made toward incorporating bicycle transport in transport planning models. This study contributes toward this direction by estimating a bicycle route choice model in value-of-distance space from a large sample of 3384 cycling trips that were traced with GPS devices in the Copenhagen Region. The novelty of this study lies in (i) observing cyclists' behavior in a cycling-oriented country, (ii) exploiting rich data about the cycling environment, (iii) estimating the model in value-of-distance rather than preference space, and (iv) not focusing only on preferences for traditional variables (e.g., distance, turns, hilliness, intersections, motorized road characteristics), but also on perceptions and preferences for bicycle facilities (e.g., bicycle lanes, bicycle paths, bicycle traces) and land-use designations (e.g., residential, industrial, sports, scenic areas). The findings from the model show that: (i) cyclists exhibit heterogeneous preferences for avoiding right and left turns, cycling the wrong way, using roundabouts and bridges, and cycling alongside residential and scenic areas; (ii) cyclists dislike cycling on unpaved and hilly surfaces and alongside larger roads; (iii) cyclists have clear perceptions about different types of bicycle facilities, with a preference for bicycle lanes and segregated paths; (iv) cyclists have clear perceptions about land-use designations, with a preference for cycling alongside sports and scenic areas; (v) time-of-day and air temperature contribute to the perceptions of cyclists and their preferences for bicycle facilities and land-use designations.
The impact of glaucoma on the quality of life of patients in Norway. I. Results from a self-administered questionnaire.

PURPOSE To evaluate the feelings and experiences of patients living with glaucoma. METHODS A questionnaire was delivered to patients willing to take part, at a regular visit to their ophthalmologist, for filling in anonymously at home. A total of 589 questionnaires were returned. RESULTS More than 80% reported negative emotions on learning that they had glaucoma, one-third were afraid of going blind. Half the patients had no visual problem at all, 14% complained of poor or very poor vision. This proportion increased with age. One-fourth of the patients on topical medication experienced adverse effects of moderate or high degree. About half the patients being treated with laser or surgery felt their situation had improved afterwards. Nine-tenths of the individuals were satisfied with the information and care given, although their knowledge about glaucoma was rather incomplete. One-fifth missed information, mainly on causes, treatment and prognosis of the disease. The younger patients were more anxious and inquiring, reported more side effects and were less satisfied than the older patients. The women were in general more dissatisfied than the men. CONCLUSION Giving a patient a diagnosis of glaucoma influences his quality of life negatively. Only half of our patients experienced any visual difficulties, whereas one-fourth reported adverse reactions due to the therapy. Most of the patients were very satisfied with the information and care given. Ophthalmologists in private practice are quite central in the management and care of the glaucoma patients in a medical setting like ours.
Differential Activation of Human Monocyte-Derived and Plasmacytoid Dendritic Cells by West Nile Virus Generated in Different Host Cells

ABSTRACT Dendritic cells (DCs) play a central role in innate immunity and antiviral responses. In this study, we investigated the production of alpha interferon (IFN-α) and inducible chemokines by human monocyte-derived dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) infected with West Nile virus (WNV), an emergent pathogen whose infection can lead to severe cases of encephalitis in the elderly, children, and immunocompromised individuals. Our experiments demonstrated that WNV grown in mammalian cells (WNVVero) was a potent inducer of IFN-α secretion in pDCs and, to a lesser degree, in mDCs. The ability of WNVVero to induce IFN-α in pDCs did not require viral replication and was prevented by the treatment of cells with bafilomycin A1 and chloroquine, suggesting that it was dependent on endosomal Toll-like receptor recognition. On the other hand, IFN-α production in mDCs required viral replication and was associated with the nuclear translocation of IRF3 and viral antigen expression. Strikingly, pDCs failed to produce IFN-α when stimulated with WNV grown in mosquito cells (WNVC7/10), while mDCs responded similarly to WNVVero or WNVC7/10. Moreover, the IFN-dependent chemokine IP-10 was produced in substantial amounts by pDCs in response to WNVVero but not WNVC7/10, while interleukin-8 was produced in greater amounts by mDCs infected with WNVC7/10 than in those infected with WNVVero. These findings suggest that cell-specific mechanisms of WNV recognition leading to the production of type I IFN and inflammatory chemokines by DCs may contribute to both the innate immune response and disease pathogenesis in human infections.
Empirical studies on the cross-section of corporate bond and stock markets

This dissertation contains five empirical studies on the efficiency of corporate bond and stock markets. In Chapter 2, the pricing of interest rate risk in the stock market is analyzed. Over the long run, 1927 to 2015, the price of bearing interest rate risk is positive as expected, but there is substantial time variation in this premium. Chapter 3 investigates the cross-sectional relation between firm-level stock and corporate bond expected returns. In contrast to theory, a strong negative relation between bond-implied stock returns and realized stock returns is found in the data. In Chapter 4 the role of cross-sectional volatility dispersion in the momentum effect for both stock and corporate bond markets is analyzed. The inclusion of volatility in the construction of the momentum portfolio vastly improves the risk-return profile. Chapter 5 studies the spilling over of past stock returns to future corporate bond returns. There is strong evidence for this momentum spillover effect, especially if systematic returns are removed from the stock momentum signal. Chapter 6 concludes by estimating premiums for the size, low-risk, value and momentum factors in investment grade and high yield corporate bond markets. These factors, well-known in stock markets, also have positive and significant premiums in the corporate bond market.
Ca2+ Triggers a Novel Clathrin‐Independent but Actin‐Dependent Fast Endocytosis in Pancreatic Beta Cells

The existence of clathrin‐independent recycling of secretory vesicles has been controversial. By combining patch‐clamp capacitance recording, optical methods and specific molecular interventions, we dissect two types of mechanistically different endocytosis in pancreatic β cells, both of which require GTP and dynamin. The fast one is a novel clathrin‐independent but actin‐dependent endocytosis that is triggered by high cytoplasmic Ca2+ concentration ([Ca2+]i). Large fluorescent dextran (10 nm in diameter) was able to be internalized by this pathway, indicating that it was not likely to be ‘kiss and run’. The slow endocytosis is a clathrin‐dependent process in which actin plays a complementary role. For the first time, we show that the rate constants for both types of endocytosis exhibit supralinear dependence on increase in [Ca2+]i. Compared with the slow endocytosis, higher [Ca2+]i level was required to fully accelerate the fast one, indicative of distinct Ca2+ sensors for different endocytosis. In the end, we show that physiologically relevant stimulation induces clathrin‐independent endocytosis in intact β cells, implying that it may contribute to the normal recycling of secretory vesicles in vivo.