Miracle-dz/UniFAR-FTUs huggingface dataset:
Brain glucose utilization in mice with a targeted mutation in the thyroid hormone α or β receptor gene

Brain glucose utilization is markedly depressed in adult rats made cretinous after birth. To ascertain which subtype of thyroid hormone (TH) receptors, TRα1 or TRβ, is involved in the regulation of glucose utilization during brain development, we used the 2-[14C]deoxyglucose method in mice with a mutation in either their TRα or TRβ gene. A C insertion produced a frameshift mutation in their carboxyl terminus. These mutants lacked TH binding and transactivation activities and exhibited potent dominant negative activity. Glucose utilization in the homozygous TRβPV mutant mice and their wild-type siblings was almost identical in 19 brain regions, whereas it was markedly reduced in all brain regions of the heterozygous TRα1PV mice. These suggest that the α1 receptor mediates the TH effects in brain. Inasmuch as local cerebral glucose utilization is closely related to local synaptic activity, we also examined which thyroid hormone receptor is involved in the expression of synaptotagmin-related gene 1 (Srg1), a TH-positively regulated gene involved in the formation and function of synapses [Thompson, C. C. (1996) J. Neurosci. 16, 7832–7840]. Northern analysis showed that Srg1 expression was markedly reduced in the cerebellum of TRαPV/+ mice but not TRβPV/PV mice. These results show that the same receptor, TRα1, is involved in the regulation by TH of both glucose utilization and Srg1 expression.
Comparison of speciated arsenic levels in the liver and brain of mice between arsenate and arsenite exposure at the early life

The aim of this study was to compare the risk from exposure to arsenate (iAsV) or arsenite (iAsIII) at the early life. Mother mice were exposed to equimolar dose of iAsV and iAsIII via drinking water during gestation and lactation. Their offspring continually drank the same water after weaning. Levels of speciated arsenic in both liver and brain were analyzed by hydride generation of volatile arsines and atomic absorption spectrophotometry (HG‐AAS). In the liver, inorganic arsenic (iAs) levels significantly increased from postnatal day (PND) 15, and those on PND 35 were significantly higher than on PND 15 and 21 in iAsIII exposed mice, but iAs levels did not significantly differ until PND 35 in iAsV exposed mice; Furthermore, all speciated arsenic levels on PND 35 and dimethylarsinic acid (DMA) levels on PND 1 were significantly higher in iAsIII exposed mice than those in iAsV exposed mice. In the brain, iAs levels increased significantly on PND 21, but those declined sharply on PND 35 in either iAsIII or iAsV exposed mice, however the mean difference between the two exposure groups was not significant; whereas DMA levels in iAsIII exposed mice were significantly higher than those in iAsV exposed mice on both PND 1 and 35. In conclusion, findings from this study suggested that iAsIII was preferentially accumulated into liver, and expected to result in more efficient methylation capacity than iAsV; either iAsV or iAsIII might be accumulated in the brain readily, when immature blood brain barrier can not limit it into brain. Hence, exposure to either iAsV or iAsIII at the early life may increase the risk of iAs exposure in the brain. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 797–803, 2014.
Impact of the introduction of rituximab in first‐line follicular lymphoma: a retrospective study of 247 unselected patients referred to a single institution with a long‐term follow‐up

Rituximab was approved in France in 2004, following randomized trials that demonstrated efficacy in newly diagnosed high tumour burden follicular lymphoma (FL). This retrospective study compared the management and outcome of FL in unselected patients treated in a single institution before and after rituximab approval. Two hundred and forty‐seven adult patients were referred with first‐line FL between 1996 and 2010 and are included in this study. The 103 pre‐rituximab patients comprising cohort 1 were diagnosed between January 1996 and December 2003; cohort 2 includes the 144 patients diagnosed after the approval of rituximab between January 2004 and December 2010. Baseline clinical and biological data, type of therapy, treatment response, progression‐free survival (PFS) and overall survival (OS) rates were compared. There were no statistically significant differences between the two cohorts with respect to baseline clinical and disease characteristics, including FL International Prognostic Index score. The major difference between the two cohorts is the use of rituximab in first line. Seventy‐one per cent of patients in cohort 2 received rituximab (19% alone, 52% with chemotherapy) versus 10% in cohort 1 (2% alone, 8% with chemotherapy; p < 0.0001). The objective response rate (ORR) was significantly higher for cohort 2 (ORR 84% compared with 72% for cohort 1; p = 0.03). The PFS and OS rates were also significantly better: 3‐year PFS 72% [95% confidence interval (CI) 64–80%] versus 55% (95% CI 45–64%), p = 0.0039 and 3‐year OS 98% (95% CI 94–99%) versus 83% (95% CI 74–90%), p = 0.0007. Effect of period of study is significant when using multivariate analysis on PFS and OS and lactate dehydrogenase level (PFS and OS) and age (OS). These data from everyday practice confirm the benefit for patients with FL treated in the last decade through availability of rituximab in first line used alone or in association with various chemotherapy regimens. Copyright © 2014 John Wiley & Sons, Ltd.
Does Financial Openness Lead to Deeper Domestic Financial Markets ?

Advanced and emerging market economies have rapidly integrated into international capital markets and this growing globalization of financial markets has led to some important changes in the patterns of saving and investment across the world. The main goal of this paper is to test whether the cross-border asset trade has led to improvements in the intermediation of these savings -- that is, foster development of domestic financial markets. The authors have collected annual information on financial market development, financial openness, and other control variables for a sample of 145 countries for the period 1974-2007. Controlling for the likely endogeneity of financial openness, the analysis finds that rising financial openness expands private credit, bank assets, and stock market and private bond market development, and generates efficiency gains in the banking system. However, the impact of financial openness on domestic financial development may depend on the level of institutional quality, the extent of investor protection, and the degree of trade openness. In general, rising financial openness will enlarge the size and activity of financial intermediaries, improve efficiency in the banking system, and contribute to deepen private bond markets in countries with moderate to high levels of institutional quality and investor protection as well as in countries with high trade openness.
Segmentation, alignment and statistical analysis of biosignals with application to disease classification

We present a novel methodology for a comprehensive statistical analysis of approximately periodic biosignal data. There are two main challenges in such analysis: (1) the automatic extraction (segmentation) of cycles from long, cyclostationary biosignals and (2) the subsequent statistical analysis, which in many cases involves the separation of temporal and amplitude variabilities. The proposed framework provides a principled approach for statistical analysis of such signals, which in turn allows for an efficient cycle segmentation algorithm. This is achieved using a convenient representation of functions called the square-root velocity function (SRVF). The segmented cycles, represented by SRVFs, are temporally aligned using the notion of the Karcher mean, which in turn allows for more efficient statistical summaries of signals. We show the strengths of this method through various disease classification experiments. In the case of myocardial infarction detection and localization, we show that our method compares favorably to methods described in the current literature.
MNE’s Regional Location Choice - A Comparative Perspective on East Germany, the Czech Republic and Poland

The focus of this article is the empirical identification of factors influencing Foreign Direct Investment (FDI) in transition economies on a regional level (NUTS 2). The analysis is designed as benchmark between three neighboring post-communist regions, i.e. East Germany, the Czech Republic and Poland. Their different transition paths have not only resulted in economic differences. We can also observe today that the importance of pull factors for FDI varies significantly across the regions. This analysis shows that in comparison with Poland and the Czech Republic, East Germany's major benefit is its purchasing power, its geographical proximity to West European markets, and its modern infrastructure. Furthermore, the analysis suggests that intra-industry linkages such as specialization and agglomeration economies are relevant factors for the location decision of foreign investors. This result can help to explain the regional divergence of FDI streams in transition economies.
Efficient Lytic Infection of Human Arterial Endothelial Cells by Human Cytomegalovirus Strains

ABSTRACT Endothelial cells (EC) are common targets of permissive infection by human cytomegalovirus (HCMV) in vivo during acute disease. However, studies of HCMV-EC interactions in vitro have generated discordant results. While lytic infection of cultured venous EC has been well established, Fish et al. (K. N. Fish, C. Soderberg Naucler, L. K. Mills, S. Stenglein, and J. A. Nelson, J. Virol. 72:5661–5668) have reported noncytopathic persistence of the virus in cultured aortic EC. We propose that interstrain differences in viral host cell tropism rather than the vascular bed of origin of infected EC might account for these discrepancies. In the present investigation we compared the responses of EC derived from human adult iliac artery, placental microvasculature, and umbilical vein to infection with various HCMV strains. Regardless of the vascular bed of origin, infection with EC-propagated HCMV strains induced 100% efficient cytopathic change progressing to complete lysis of inoculated monolayers. While fibroblast-propagated strains persisted at low titer in infected arterial EC cultures, they were also cytolytic for individual infected cells. The finding of cytopathic lytic infection of arterial EC by HCMV implicates a mechanism of vascular injury in the pathogenesis of HCMV infection.
Epidemiologic evidence for supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism

This study examines whether maternal vitamin D deficiency is a risk factor for infantile autism disease (IAD). We used epidemiologic data seasonal variation of birth rates and prevalence of IAD for cohorts born before 1985. For seven studies reporting spring-to-summer excess birth rates for IAD, the season progressed from broad near 30° N latitude, spring/summer in midlatitudes, to winter at the highest latitude. Also, using data from 10 studies, we found a strong effective latitudinal (related to wintertime solar ultraviolet B radiation) increase in IAD prevalence. These findings are consistent with maternal vitamin D deficiency’s being a risk factor for IAD, possibly by affecting fetal brain development as well as possibly by affecting maternal immune system status during pregnancy,. Further investigation of this hypothesis is warranted.
Polyclonal MHC Ib-Restricted CD8+ T Cells Undergo Homeostatic Expansion in the Absence of Conventional MHC-Restricted T Cells1

Naive T cells have the capacity to expand in a lymphopenic environment in a process called homeostatic expansion, where they gain a memory-like phenotype. Homeostatic expansion is dependent on competition for a number of factors, including growth factors and interactions with their selecting self-MHC molecules. In contrast to conventional T cells, it is unclear whether class Ib-restricted CD8+ T cells have a capacity to undergo homeostatic expansion. In this study, we demonstrate that polyclonal MHC Ib-restricted CD8+ T cells can undergo homeostatic expansion and that their peripheral expansion is suppressed by conventional MHC-restricted T cells. The acute depletion of CD4+ T cells in MHC class Ia-deficient Kb−/−Db−/− mice led to the substantial expansion of class Ib-restricted CD8+ T cells. Adoptive transfer of class Ib-restricted CD8+ T cells to congenic lymphopenic recipients revealed their ability to undergo homeostatic expansion in a MHC Ib-dependent manner. To further study the homeostatic expansion of MHC Ib-restricted T cells in the absence of all conventional MHC-restricted T cells, we generated mice that express only MHC Ib molecules by crossing H-2Kb−/−Db−/− with CIITA−/− mice. CD8+ T cells in these mice exhibit all of the hallmarks of naive T cells actively undergoing homeostatic expansion with constitutive memory-like surface and functional phenotype. These findings provide direct evidence that MHC Ib-restricted CD8+ T cells have the capacity to undergo homeostatic expansion. Their peripheral expansion is suppressed under normal conditions by a numerical excess of conventional MHC class Ia- and class II-restricted T cells.
Umbilical bleeding: a presenting feature for congenital afibrinogenemia

Congenital afibrinogenemia is a very rare inherited coagulation disorder characterized by absence of plasma fibrinogen (factor I). There are only about 250 cases reported in the world literature. We describe a case of congenital afibrinogenemia which presented as an umbilical cord bleeding.
Knowing More Than We Can Tell

There is no question that biases exist in self-perceptions of personality. To what extent do people have insight into their positive and negative self-biases? In two samples (total N = 130), people with positive biases (i.e., self-perceptions that are more positive than a reputation-based criterion measure) accurately described themselves as positively biased, and people with negative biases accurately described themselves as negatively biased. Furthermore, people were able to distinguish which traits they were more or less biased about. These findings suggest that people may know more about themselves than they initially admit. Implications for the use of self-reports and the study of self-knowledge are discussed.
Expression of Connexin 43 in Rat Mandibular Bone and Periodontal Ligament (PDL) Cells during Experimental Tooth Movement

Bone remodeling in response to force requires the coordinated action of osteoblasts, osteoclasts, osteocytes, and periodontal ligament cells. Coordination among these cells may be mediated, in part, by cell-to-cell communication via gap junctions. This study tests the hypothesis that the regulation of expression of connexin 43, a gap junction protein, is part of the transduction mechanism between force as applied to bone during orthodontic tooth movement and bone remodeling. To test this hypothesis, we examined connexin 43 expression in a rat model system of experimental tooth movement. To establish the model, we extracted maxillary first molars to initiate supra-eruption of opposing mandibular molars. The rats were killed at 0, 6, 12, 24, and 48 hrs post-extraction. The mandibles were removed, demineralized, and embedded in paraffin. To localize connexin 43 protein and mRNA, we used a specific antibody for immunohistochemistry and a specific cDNA probe for in situ hybridization. Western and Northern blot analyses were used to assess the specificity of the connexin 43 antibody and cDNA probe, respectively. We found connexin 43 protein expressed by osteoclasts (++++) and periodontal ligament cells (+++) in compression zones, and by osteoblasts (++++) and osteocytes (++++) in tension zones of the periodontal ligament. In addition, connexin 43 mRNA was found in some bone and periodontal ligament cells. Connexin 43 protein was found, by densitometric analysis, to be higher in the periodontal ligament after exposure to force compared with controls (P < 0.001). The number of osteocytes expressing connexin 43 48 hrs after molar extraction was also significantly greater in bone subjected to tension when compared with controls (P < 0.001). The results of this study support the hypothesis that connexin 43 plays a role in the coordination of events during experimentally induced alveolar bone remodeling.
Auditors' responsibility for fraud detection: New wine in old bottles?

204 Auditors’ Responsibility for Fraud Detection: New Wine in Old Bottles? Lawrence Chui Byron Pike* Fraud is costly. According to the Association of Certified Fraud Examinations (ACFE), an estimated $3.5 trillion worldwide were lost due to fraudulent financial statements, asset misappropriation, and corruption in 2011 (ACFE, 2012). In the U.S. alone, the ACFE projected an annual revenue loss of $994 billion due to fraud. These staggering losses represent approximately 7% of the U.S. Gross Domestic Product (ACFE, 2008; ACFE, 2009). Based on the U.S. fiscal year 2011 budget, losses resulting from fraud exceeded the net costs of the department of defense, homeland security, transportation, and education combined for fiscal year 2008. Fraud is not only costly, but it also damages the reputation and the credibility of the audit profession. The loss of public trust seems justified when audited financial statements turn out to be unreliable and must be restated due to fraud. As a result, the investing public is elevating its expectations for auditors to detect fraud (Eillot and Jacobson, 1987; Hooks, 1991; Nicolaisen, D. T., 2005; Silverstone and Davia, 2005; Hogan et al., 2008). Accounting researchers, practitioners, and standard setters alike expressed concern for auditors’ apparent failures in detecting fraud during an audit. Joseph T. Wells, founder of the ACFE, criticized auditors for their lack of training and readiness in fraud detection. He contends that “[a]s a group, CPAs are neither stupid nor crooked. But the majority are still ignorant about fraud.for the last 80 years, untrained accounting graduates have been drafted to wage war against sophisticated liars and thieves” (Wells, 2005b). Jamal (2008) agrees with Wells’
The effects of elevated temperature and dissolved ρCO 2 on a marine foundation species

Abstract Understanding how climate change and other environmental stressors will affect species is a fundamental concern of modern ecology. Indeed, numerous studies have documented how climate stressors affect species distributions and population persistence. However, relatively few studies have investigated how multiple climate stressors might affect species. In this study, we investigate the impacts of how two climate change factors affect an important foundation species. Specifically, we tested how ocean acidification from dissolution of CO 2 and increased sea surface temperatures affect multiple characteristics of juvenile eastern oysters (Crassostrea virginica). We found strong impacts of each stressor, but no interaction between the two. Simulated warming to mimic heat stressed summers reduced oyster growth, survival, and filtration rates. Additionally, we found that CO 2‐induced acidification reduced strength of oyster shells, which could potentially facilitate crab predation. As past studies have detected few impacts of these stressors on adult oysters, these results indicate that early life stages of calcareous marine organisms may be more susceptible to effects of ocean acidification and global warming. Overall, these data show that predicted changes in temperature and CO 2 can differentially influence direct effects on individual species, which could have important implications for the nature of their trophic interactions.
Local stability analysis and eigenvalue sensitivity of reacting bluff-body wakes

This paper presents an experimental and theoretical investigation of high-Reynolds-number low-density reacting wakes near a hydrodynamic Hopf bifurcation. This configuration is applicable to the wake flows that are commonly used to stabilize flames in high-velocity flows. First, an experimental study is conducted to measure the limit-cycle oscillation of this reacting bluff-body wake. The experiment is repeated while independently varying the bluff-body lip velocity and the density ratio across the flame. In all cases, the wake exhibits a sinuous oscillation. Linear stability analysis is performed on the measured time-averaged velocity and density fields. In the first stage of this analysis, a local spatiotemporal stability analysis is performed on the measured time-averaged velocity and density fields. The stability analysis results are compared to the experimental measurement and demonstrate that the local stability analysis correctly captures the influence of the lip-velocity and density-ratio parameters on the sinuous mode. In the second stage of the analysis, the linear direct and adjoint global modes are estimated by combining the local results. The sensitivity of the eigenvalue to changes in intrinsic feedback mechanisms is found by combining the direct and adjoint global modes. This is referred to as the eigenvalue sensitivity throughout the paper for reasons of brevity. The predicted global mode frequency is consistently within 10 % of the measured value, and the linear global mode shape closely resembles the measured nonlinear oscillations. The adjoint global mode reveals that the oscillation is strongly sensitive to open-loop forcing in the shear layers. The eigenvalue sensitivity identifies a wavemaker in the recirculation zone of the wake. A parametric study shows that these regions change little when the density ratio and lip velocity change. In the third stage of the analysis, the stability analysis is repeated for the varicose hydrodynamic mode. Although not physically observed in this unforced flow, the varicose mode can lock into longitudinal acoustic waves and cause thermoacoustic oscillations to occur. The paper shows that the local stability analysis successfully predicts the global hydrodynamic stability characteristics of this flow and shows that experimental data can be post-processed with this method in order to identify the wavemaker regions and the regions that are most sensitive to external forcing, for example from acoustic waves.
Regional variation in the incidence of dialysis-requiring AKI in the United States.

BACKGROUND AND OBJECTIVES Little is known about geographic differences in the incidence of AKI. The objective of this study was to determine if regional variation exists in the population incidence of dialysis-requiring AKI in the United States. DESIGN, SETTING, PARTICIPANTS, & METHODS Data from the Nationwide Inpatient Sample, a US nationally representative sample of hospitalizations, were used to determine the incidence rates of dialysis-requiring AKI between 2007 and 2009 among the four US Census-designated regions. Cases were identified using validated discharge codes. Poisson regression models were used to estimate overall regional rates, accounting for the data's sampling scheme. RESULTS In 2007-2009, the population incidence rates of dialysis-requiring AKI differed across the four Census-designated regions (P=0.04). Incidence was highest in the Midwest (523 cases/million person-yr, 95% confidence interval=483 to 568) and lowest in the Northeast (457 cases/million person-yr, 95% confidence interval=426 to 492). The pattern of regional variation in the incidence of dialysis-requiring AKI was not the same as the pattern of regional variation in the incidence of renal replacement therapy-requiring ESRD (obtained from the US Renal Data System). In-hospital mortality associated with dialysis-requiring AKI differed across the four regions, with the highest case fatality in the Northeast (25.9%) and the lowest case fatality in the Midwest (19.4%). CONCLUSIONS Significant regional variation exists in the population incidence of dialysis-requiring AKI in the United States, and additional investigation is warranted to uncover potential causes behind these geographic differences.