Miracle-dz/UniFAR-FTUs huggingface dataset:
β-Catenin Is Required for Specification of Proximal/Distal Cell Fate during Lung Morphogenesis*

The lungs are divided, both structurally and functionally, into two distinct components, the proximal airways, which conduct air, and the peripheral airways, which mediate gas exchange. The mechanisms that control the specification of these two structures during lung development are currently unknown. Here we show that β-catenin signaling is required for the formation of the distal, but not the proximal, airways. When the gene for β-catenin was conditionally excised in epithelial cells of the developing mouse lung prior to embryonic day 14.5, the proximal lung tubules grew and differentiated appropriately. The mice, however, died at birth because of respiratory failure. Analysis of the lungs by in situ hybridization and immunohistochemistry, using molecular markers of the epithelial and mesenchymal components of both proximal and peripheral airways, showed that the lungs were composed primarily of proximal airways. These observations establish, for the first time, both the sites and timing of specification of the proximal and peripheral airways in the developing lung, and that β-catenin is one of the essential components of this specification.
miR-129-2 mediates down-regulation of progesterone receptor in response to progesterone in breast cancer cells

ABSTRACT Objective: Hormonal therapy is an important component of first line of treatment for breast cancer. Response to hormonal therapy is influenced by the progesterone receptor (PR)-status of breast cancer patients. However as an early effect, exposure to progesterone decreases expression of PR in breast cancer cells. An understanding of the mechanism underlying down-regulation of PR could help improve response to hormonal therapy. Methods: We performed small RNA sequencing of breast cancer cells for identification of microRNAs targeting PR in response to progesterone treatment. Biochemical approaches were used to validate the findings in breast cancer cells. Results: Analysis of small RNA sequencing of four breast cancer cell lines treated with progesterone revealed an up-regulation of miR-129-2 independent of the PR status of the cells. We show that miR-129-2 targets 3′UTR of PR to down-regulate its expression. Furthermore, inhibition of miR-129-2 expression rescues the down-regulation of PR in breast cancer cells. Also, the expression levels of miR-129-2 was observed to be elevated in patients with low expression of PR in the TCGA cohort (n = 359). Conclusion: miR-129-2 mediates down-regulation of PR in breast cancer cells in response to progesterone, while anti-miR-129-2 could potentiate PR expression levels among patients with inadequate PR levels. Thus, modulation of activity of miR-129-2 could stabilize PR expression and potentially improve response to hormonal therapy under adjuvant or neo-adjuvant settings.
SOX2 Expression in Gastrointestinal Cancers of Iranian Patients

Purpose Gastrointestinal (GI) malignancies are among the 5 most common cancers in Iran, and their high associated mortality rates are attributable to late diagnosis and poor treatment options. SOX2, a transcription factor necessary for maintenance and induction of pluripotency and self-renewal, has been identified as a lineage-survival oncogene in several cancers. In the present study, we examined SOX2 expression in esophageal squamous cell carcinoma (ESCC), gastric adenocarcinoma and colon squamous cell carcinoma (SCC), as well as normal GI tissues, in Iranian patients. Methods To elucidate the role of SOX2 in GI carcinogenesis, formalin-fixed tissues were analyzed using immunohistochemistry (IHC), while frozen ESCC samples were studied by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results IHC studies indicated presence of SOX2+ cells in a subset of cancerous and normal tissues of stomach and colon, while no significant difference was observed between groups, and no correlation was found between SOX2 expression and tumors grades. Nevertheless, studying ESCC samples with IHC and qRT-PCR revealed overexpression of SOX2 in comparison with normal adjacent tissues. Conclusions The present results are in line with other studies and indicate SOX2 up-regulation in ESCC; however, due to our small sample size and contradictory reports, more research is needed to determine the importance of SOX2 in GI cancers.
Tyrosine Kinase Inhibitors in Pediatric Malignancies

Tyrosine kinase inhibitors have been used to treat adult cancers for over a decade. Since the discovery of imatinib mesylate (STI–571, Gleevec; Novartis), tyrosine kinase inhibitors have ushered in a new age of targeted therapy. Although the United States Food and Drug Administration has approved several kinase inhibitors for use in adult cancers, currently only imatinib mesylate is approved for use in children with cancer. This review highlights the mechanisms of tyrosine kinase inhibition, the potential role of tyrosine kinase pathways in the treatment of pediatric cancers, and the current status of pediatric clinical investigation of a spectrum of tyrosine kinase inhibitors for the treatment of childhood cancer.
New restaurants and their intra-industry effects: Evidence from Portugal

This paper investigates the intra-industry effects resulting from the birth of a new restaurant at Portugal. Using event-study methods, this paper finds that, in the year the new competitors open for business, industry rivals experience an average abnormal loss of -17.6% in their return-on-assets, which is due to a significant decrease in their profit margin, and asset turnover ratio. Regression analysis further shows that high industry concentration, low labor productivity, and low asset profitability magnify the rivals’ underperformance, which is particularly acute when the restaurants are located at Lisboa and Porto, the two most heavily populated Portuguese cities. Overall, this paper contributes to the literature studying the economics of the eating-places industry, and has important implications for both practice, and public policy.
Characterizing polymorphisms and allelic diversity of von Willebrand factor gene in the 1000 Genomes

The von Willebrand factor (VWF) gene is highly polymorphic, with variants correlated with VWF antigen levels, adhesion activity, clearance and factor VIII binding. VWF mutations are detected in patients with von Willebrand disease (VWD), whereas polymorphic variants could be associated with thrombosis. However, information on the ethnic diversity of VWF variants and their association with diseases is limited.
Circadian waves of cytosolic calcium concentration and long‐range network connections in rat suprachiasmatic nucleus

The suprachiasmatic nucleus (SCN) is the master clock in mammals governing the daily physiological and behavioral rhythms. It is composed of thousands of clock cells with their own intrinsic periods varying over a wide range (20–28 h). Despite this heterogeneity, an intact SCN maintains a coherent 24 h periodic rhythm through some cell‐to‐cell coupling mechanisms. This study examined how the clock cells are connected to each other and how their phases are organized in space by monitoring the cytosolic free calcium ion concentration ([Ca2+]c) of clock cells using the calcium‐binding fluorescent protein, cameleon. Extensive analysis of 18 different organotypic slice cultures of the SCN showed that the SCN calcium dynamics is coordinated by phase‐synchronizing networks of long‐range neurites as well as by diffusively propagating phase waves. The networks appear quite extensive and far‐reaching, and the clock cells connected by them exhibit heterogeneous responses in their amplitudes and periods of oscillation to tetrodotoxin treatments. Taken together, our study suggests that the network of long‐range cellular connectivity has an important role for the SCN in achieving its phase and period coherence.
Enabling effective and inclusive learning opportunities with software-based remote access laboratories

Practical or laboratory-based learning activities are an important part of engineering and surveying education. Offering such activities to distance education students is both difficult and expensive. Remote Access Laboratory (RAL) systems are gaining popularity to provide students with access to on-campus rigs or hardware. Such RAL systems are equally versatile in providing on-campus software access to distance students. In the discipline of Surveying and Spatial Science, the RAL system is being used as an avenue for providing Geographic Information System (GIS) software access to distance students. In this study, the effectiveness of RAL based software activities in supporting student learning is investigated as part of a larger study involving its general use. This project investigates the research question whether RAL-based software activities can address the same learning outcomes as face-to-face practical classes. Data collected from students' discussion forum and via interviews with teaching staff members were analysed. This project provides a clear case in which the use of RAL technology has provided inclusive educational opportunities more efficiently. The key outcomes that students can achieve similar learning outcomes undertaking the activities remotely, system access and usability are critical, the learning activity needs to be supported by comprehensive learning materials and the staff effort to develop such an activity is considerable. These general results are also applicable to experiments that involve physical hardware.
Voluntary disclosure of intangibles and analysts’ earnings forecasts and recommendations

Purpose - The purpose of this paper is to investigate the relationship between voluntary disclosure of intangibles and financial analysts’ earnings forecasts properties. Design/methodology/approach - Disclosures about intangible assets were hand-collected through content analysis of annual reports of a sample of US non-financial firms, while analysts’ earnings forecasts properties were collected from Bloomberg Professional database. The authors relied on correlation and multivariate regression analyses to test the research hypotheses. Findings - The results show that increased intangible disclosures affect analysts’ earnings forecasts accuracy, dispersion, and favourable consensus recommendations. However, this effect varies according to the nature of intangible assets. Practical implications - The results may be of interest to different market participants such as corporate managers, financial analysts, and standards setting bodies that recently published guidelines on voluntary disclosure of intangibles. Originality/value - This study develops a new comprehensive index to measure the content of narrative disclosures about a large number of intangibles, such as human, structural, and relational assets. The findings contribute to the current debate on the value-relevance of narrative disclosures on intangibles to investors and financial analysts.
High level of cryptic species diversity revealed by sympatric lineages of Southeast Asian forest frogs

Amphibians tend to exhibit conservative morphological evolution, and the application of molecular and bioacoustic tools in systematic studies have been effective at revealing morphologically ‘cryptic’ species within taxa that were previously considered to be a single species. We report molecular genetic findings on two forest-dwelling ranid frogs from localities across Southeast Asia, and show that sympatric evolutionary lineages of morphologically cryptic frogs are a common pattern. These findings imply that species diversity of Southeast Asian frogs remains significantly underestimated, and taken in concert with other molecular investigations, suggest there may not be any geographically widespread, forest-dwelling frog species in the region. Accurate assessments of diversity and distributions are needed to mitigate extinctions of evolutionary lineages in these threatened vertebrates.
Analysis of the morphogenesis and cell proliferation in the retina of a pleuronectiform fish, the turbot psetta maxima (Pleuronectiformes: Teleostei)

The morphogenesis and cell proliferation in the retina of turbot (Psetta maxima, Pleuronectiformes: Teleostei) from embryo through metamorphosis have been examined by using proliferating cell nuclear antigen (PCNA)‐immunohistochemistry and general histological procedures. In the embryonic retina, cell proliferation and spatial cell reorganization form the anlage of the pigment epithelium and neural retina. Neurogenesis begins around hatching in the temporal retina, dorsal to the optic nerve exit, and then a wave of cell differentiation spreads to the nasal retina to yield a laminated retina by the end of the prolarval turbot stage. Germinal zones in the differentiated retina persist as a rim at the retinal margin, as well as surrounding the optic fissure in premetamorphic and metamorphic turbot larvae. In these zones, progenitor cells with different morphologies show a similar spatial arrangement, which suggests that they have a similar retinogenic potential. During metamorphosis, asymmetric proliferative activity in turbot germinal zones is associated with a marked expansion of the retinal tissue. Scattered stem cells in the laminated retina, related to the lineage of rod photoreceptors, were also observed both in large premetamorphic larvae and metamorphic turbots. The proliferative activity of these cells increases considerably during metamorphosis, when rod photoreceptors become morphologically differentiated. Microsc. Res. Tech. 76:588–597, 2013. © 2013 Wiley Periodicals, Inc.
Association between 5-hydroxytryptamine transporter gene-linked polymorphic region and smoking behavior in Chinese males.

BACKGROUND Tobacco use is the major risk factor for numerous health problems. However, only 5% of smokers can successfully quit without therapy owing to the highly addictive properties of nicotine. The serotoninergic system may be involved in smoking behavior because nicotine increases brain serotonin secretion, nicotine withdrawal decreases serotonin levels, and a selective serotonin reuptake inhibitor antagonizes the response to nicotine withdrawal. Serotonin transporter (5-HTT) is the most important protein, as it adjusts the serotonin concentration in the synaptic cleft. There is a polymorphism in the upstream regulatory region of the 5-HTT gene, named 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR). Compared with the L allele, the S allele of the polymorphism is associated with decreased transcription efficiency of the 5-HTT gene. In this study, we investigated the relationship between this gene polymorphism and smoking behavior in Chinese males. METHODS Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find 5-HTTLPR gene polymorphisms in 144 smokers and 135 age-matched healthy non-smokers. A questionnaire was completed in all recruited subjects. RESULTS The proportion of L/L (15.3% vs 5.2%) and S/L (50.0% vs 33.3%) genotypes was significantly higher in the smokers than that in the non-smokers (chi(2) = 21.9; P < 0.01). The odds ratio (OR) adjusted by age, education, effects of family members and friends who smoke, and alcohol intake was 2.9 (95% CI 1.78 +/- 4.80). In smokers, the number of cigarettes/day (L/L vs S/L vs S/S: 28 +/- 12 vs 20 +/- 8 vs 16 +/- 6, chi(2) = 18.5, P < 0.01), smoking index (L/L vs S/L vs S/S: 561 +/- 446 vs 393 +/- 341 vs 237 +/- 201, chi(2) = 12.5, P < 0.01) and score on the Fagerström test for nicotine dependence (FTND) (L/L vs S/L vs S/S: 7.8 +/- 1.6 vs 6.2 +/- 2.5 vs 3.5 +/- 2.1, chi(2) = 48.3, P < 0.01) were significantly higher in smokers with an L/L or S/L genotype than that in the smokers with the S/S genotype. There were no significant differences in the proportion of starting smoking before 20 years old (P = 0.219) and those who succeeded in quitting smoking for more than 1 month (P = 0.456) between individuals with different 5-HTTLPR genotypes in smokers. CONCLUSIONS 5-HTTLPR polymorphism may be associated with susceptibility to cigarette smoking in Chinese males. The proportion of the L/L and S/L genotype in smokers was higher than that in non-smokers. In smokers, the level of nicotine dependence and resultant cigarettes consumption may be much higher in individuals with an L/L or S/L genotype than those with the S/S genotype.
Acute cardiorespiratory responses of hypertensive rats to swimming and treadmill exercise.

The acute cardiorespiratory responses of spontaneously hypertensive rats (SHR) to swimming and running exercise was investigated because SHR populations are hyperresponsive to external stimuli, of the paucity of existing data, and of the uncertainty on the role of exercise stimuli for training adaptations to occur. Male rats were assigned to one of five groups (n = 5-6/group) and designated as controls (C), inexperienced or naive free swimmers (NFS), experienced free swimmers (FS), experienced weighted swimmers (WS) (attached weights equal to 2% of their body weight) or experienced runners (R) who ran at an intensity of 75% of their VO2max. After 75 min in the water, all groups were acidotic and hypercapnic with the WS experiencing the greatest changes. Heart rate (HR) was increased in all swimmers during the initial 10 min, but declined thereafter, and after 75 min, the HR of WS (348 +/- 1 beats/min) was significantly lower than the C group (416 +/- 22 beats/min). At the same time interval, mean arterial blood pressure (MAP) was decreased in all swimming groups to values lower than the C animals. In addition, an exaggerated diving reflex was frequently noted when the rats were submerged. When the magnitudes of the changes were evaluated in the swimming animals they were directly associated with their submergence times, i.e., during 65-75 min of the swim, NFS, FS, and WS were submerged for 43, 46, and 66% of their total swim time, respectively. In sharp contrast to the swimmers, the runners exhibited increases in HR and MAP with their blood gas measurements being indicative of hyperventilation. We concluded that swimming as an exercise mode for hypertensive rats is best served to study the combined effects of excitement, prolonged submergence, and the consequences of the diving reflex.
Circulating ApoE level is independently associated with urinary albumin excretion in type 2 diabetic patients.

OBJECTIVE Evidence from many studies suggests that dyslipidemia has a pathogenetic role in the development and progression of diabetic nephropathy. The objective of this study was to evaluate the relationships between serum lipid parameters and urinary albumin excretion in type 2 diabetic patients from Shanghai, China. METHODS A total of 1094 type 2 diabetic patients were recruited. The urinary albumin to creatinine ratio (ACR), serum total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), apolipoprotein A I (ApoA I), apolipoprotein B (ApoB), apolipoprotein E (ApoE) and lipoprotein (a) [Lp(a)] were measured and low density lipoprotein cholesterol (LDL-C) was calculated according to the Friedewald formula. An ACR of ≥30 µg/mg was defined as albuminuria, and <30 µg/mg as normoalbuminuria. RESULTS The levels of ApoE and triglyceride were significantly higher in albuminuric group compared with normoalbuminuric group (p<0.001 and p=0.003, respectively). Differences of ACR among the groups based on the tertile of ApoE and the tertile of triglyceride were significant (both p<0.001). In a multiple linear regression model, ApoE was independently associated with ACR (β=0.003, 95%CI 0.002-0.005, p<0.001). CONCLUSION Serum ApoE level was independently associated with urinary albumin excretion in type 2 diabetic patients from Shanghai, China.
A study to gain insights into effectiveness of fiscal policy between countries with high and low public debt, pre- and post- 2007 great recession

The Great Recession in 2008 has provided the researcher with an opportunity to study the effectiveness of fiscal policy in high debt and low debt countries in the pre-recession and post-recession period. The research was centred around the effect of national debt level on the effectiveness of fiscal stimuli which has become increasingly crucial in the current economic condition as increasing number of countries has fallen into the high debt category. In order to investigate the impact of fiscal stimuli in different national debt level countries, the researcher has utilised hierarchical multiple linear regression model. In this study, the researcher has performed preliminary statistical analysis of fiscal stimulus, investigation of the behaviour of the marginal propensity to consume (MPC) and investment slope coefficient before performing the hierarchical multiple linear regression analysis. Result for hierarchical multiple linear regression analysis on high and low debt countries suggested that the effect of fiscal stimulus in low debt countries were larger than the effect of fiscal stimulus in high debt countries. This research is important because better understanding of the impact of national debt on fiscal policy could add to the current literature bodies on the researched topic. From a policy perspective, these findings could provide additional support to national economic policymakers to design substantially enhanced, effective and efficient fiscal stimulus packages.
Do inhaled carbon nanoparticles translocate directly into the circulation in humans?

RATIONALE Increased exposure to particulate air pollution (PM(10)) is a risk factor for death and hospitalization with cardiovascular disease. It has been suggested that the nanoparticulate component of PM(10) is capable of translocating into the circulation with the potential for direct effects on the vasculature. OBJECTIVE The study's aim was to determine the extent to which inhaled technetium-99m ((99m)Tc)-labeled carbon nanoparticles (Technegas) were able to access the systemic circulation. METHODS AND MAIN RESULTS Ten healthy volunteers inhaled Technegas and blood samples were taken sequentially over the following 6 h. Technegas particles were 4-20 nm in diameter and aggregated to a median particle diameter of approximately 100 nm. Radioactivity was immediately detected in blood, with levels increasing over 60 min. Thin-layer chromatography of whole blood identified a species that moved with the solvent front, corresponding to unbound (99m)Tc-pertechnetate, which was excreted in urine. There was no evidence of particle-bound (99m)Tc at the origin. gamma Camera images demonstrated high levels of Technegas retention (95.6 +/- 1.7% at 6 h) in the lungs, with no accumulation of radioactivity detected over the liver or spleen. CONCLUSIONS The majority of (99m)Tc-labeled carbon nanoparticles remain within the lung up to 6 h after inhalation. In contrast to previous published studies, thin-layer chromatography did not support the hypothesis that inhaled Technegas carbon nanoparticles pass directly from the lungs into the systemic circulation.
Data Snooping in Equity Premium Prediction

Abstract We analyze the performance of a comprehensive set of equity premium forecasting strategies. All strategies were found to outperform the mean in previous academic publications. However, using a multiple testing framework to account for data snooping, our findings support Welch and Goyal (2008) in that almost all equity premium forecasts fail to beat the mean out-of-sample. Only few forecasting strategies that are based on Ferreira and Santa-Clara’s (2011) sum-of-the-parts approach generate robust and statistically significant economic gains relative to the historical mean even after controlling for data snooping and accounting for transaction costs.