Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional analysis of RET with Hirschsprung mutations affecting its kinase domain.

BACKGROUND AND AIMS Many missense mutations in the RET proto-oncogene were found in familial and sporadic cases of Hirschsprung disease (HSCR). The aim of this study was to make clear the mechanisms of RET dysfunction by HSCR mutations identified in its kinase domain. METHODS Ten kinase domain HSCR mutations were introduced into wild-type RET and constitutively activated RET with a multiple endocrine neoplasia 2A mutation, and the resulting mutant complementary DNAs were transfected into SK-N-MC primitive neuroectodermal tumor cells or NIH 3T3 fibroblast cells. The levels of activation of mutant RET and representative signaling molecules were investigated in the transfectants. RESULTS E762Q, S767R, R972G, and M980T mutations partially impaired the RET kinase activity and the representative signaling pathways. In particular, these mutations severely impaired the phospholipase C-gamma signaling pathway in SK-N-MC cells. S765P, R873Q, F893L, R897Q, and E921K mutations resulted in a complete loss of the RET kinase activity. The P973L mutation markedly decreased the expression of the RET protein with normal kinase activity. CONCLUSIONS Hirschsprung disease can result from these distant functional classes of kinase domain mutation of RET.
The German Economy Today: Exports, Foreign Investment, and East-Central Europe

Many causes lay behind Germany’s success as an exporter. The varieties of capitalism literature, for example, looks to the deeper structural roots of the German economy, highlighting its Mittelstand of small and specialized firms, its vocational schooling system, its banking system, and the influence its labor unions wield through co-determination. 4 More recently, scholars have pointed to the Hartz IV reforms of the early 2000s. These liberalized Germany’s labor market, allowed small firms to hire and fire workers more easily, and reduced welfare benefits. A recent if provocative study estimates that roughly half of Germany’s recent success in outperforming the rest of Europe in exports stems from the Hartz IV reforms, the other half coming from the
Bile Acids Induce Pancreatic Acinar Cell Injury and Pancreatitis by Activating Calcineurin*

Background: Bile acid exposure causes pancreatic acinar cell injury through a sustained rise in cytosolic Ca2+. Results: Pharmacologic and genetic inhibition of the Ca2+-activated phosphatase calcineurin dramatically reduces acinar cell injury and in vivo pancreatitis resulting from bile acid exposure. Conclusion: Acinar cell calcineurin mediates acinar cell injury and pancreatitis resulting from bile acid exposure. Significance: Calcineurin inhibitors may provide an adjunctive therapy for biliary pancreatitis. Biliary pancreatitis is the leading cause of acute pancreatitis in both children and adults. A proposed mechanism is the reflux of bile into the pancreatic duct. Bile acid exposure causes pancreatic acinar cell injury through a sustained rise in cytosolic Ca2+. Thus, it would be clinically relevant to know the targets of this aberrant Ca2+ signal. We hypothesized that the Ca2+-activated phosphatase calcineurin is such a Ca2+ target. To examine calcineurin activation, we infected primary acinar cells from mice with an adenovirus expressing the promoter for a downstream calcineurin effector, nuclear factor of activated T-cells (NFAT). The bile acid taurolithocholic acid-3-sulfate (TLCS) was primarily used to examine bile acid responses. TLCS caused calcineurin activation only at concentrations that cause acinar cell injury. The activation of calcineurin by TLCS was abolished by chelating intracellular Ca2+. Pretreatment with 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (acetoxymethyl ester) (BAPTA-AM) or the three specific calcineurin inhibitors FK506, cyclosporine A, or calcineurin inhibitory peptide prevented bile acid-induced acinar cell injury as measured by lactate dehydrogenase leakage and propidium iodide uptake. The calcineurin inhibitors reduced the intra-acinar activation of chymotrypsinogen within 30 min of TLCS administration, and they also prevented NF-κB activation. In vivo, mice that received FK506 or were deficient in the calcineurin isoform Aβ (CnAβ) subunit had reduced pancreatitis severity after infusion of TLCS or taurocholic acid into the pancreatic duct. In summary, we demonstrate that acinar cell calcineurin is activated in response to Ca2+ generated by bile acid exposure, bile acid-induced pancreatic injury is dependent on calcineurin activation, and calcineurin inhibitors may provide an adjunctive therapy for biliary pancreatitis.
Genetic association of TNF-α-308 G/A and -863 C/A polymorphisms with late onset Alzheimer's disease in Azeri Turk population of Iran

BACKGROUND: Recent findings suggest that production of pro-inflammatory cytokines, such as Tumour Necrosis Factor-alpha (TNF-α), is increased in the brain tissue of patients suffering late-onset Alzheimer's disease (LOAD) and play an important role in the pathogenesis of this disease. Several epidemiological studies also suggest that patients taking anti-inflammatory drugs have a decreased risk of developing AD. TNF-α is an important pro inflammatory cytokine that is unregulated in Alzheimer's patients. Functional polymorphisms in tumor necrosis factor alpha (TNF-α) can affect immune response, inflammation, tissue injury and possibly the susceptibility to Alzheimer disease (AD). METHODS: We used the polymorphic DNA markers (-308G/A) and (-863C/A) to study the association of TNF-α gene mutations with Late-onset Alzheimer's disease (LOAD) and the relation between clinical features and genotypes in affected individuals. A total of 160 patient samples and 163 healthy controls from west northern Iran (Eastern Azerbaijan) were genotyped for the two polymorphisms by the PCR-RFLP method and genotype frequencies were statistically determined. RESULTS: Our data showed significant difference in TNF-α-308 G/A genotype and pro inflammatory cytokine allele frequencies between the Alzheimer disease patients and healthy subjects. Contrary to that, no significant difference was observed in TNF-α-863 C/A genotype and allele frequencies between these two groups. CONCLUSIONS: TNF-α-308 G/A gene polymorphism could affect cerebral inflammatory response and the risk of late-onset Alzheimer disease but -863 C/A polymorphism does not influence the risk of this disease and this possible association between TNF-α -308G/A and -863C/A gene polymorphisms have to be further elucidated in larger case control studies.
Are seeds suitable for flow cytometric estimation of plant genome size?

Nuclear DNA content in plants is commonly estimated using flow cytometry (FCM). Plant material suitable for FCM measurement should contain the majority of its cells arrested in the G0/G1 phase of the cell cycle. Usually young, rapidly growing leaves are used for analysis. However, in some cases seeds would be more convenient because they can be easily transported and analyzed without the delays and additional costs required to raise seedlings. Using seeds would be particularly suitable for species that contain leaf cytosol compounds affecting fluorochrome accessibility to the DNA. Therefore, the usefulness of seeds or their specific tissues for FCM genome size estimation was investigated, and the results are presented here.
Local Business, Local Peace: the Peacebuilding Potential of the Domestic Private Sector

The Afghan conflict lasted 24 years and, despite its complexity, evolved through several distinct phases. It began as a popular insurrection against a revolutionary regime (1978-79), but evolved into a jihad against occupation by the Soviet Union (1980-89). After 1989 it mutated into a civil war between the communist regime and its enemies (1989-92) but, after the collapse of Soviet communism, it continued as a civil war between the factions. From 1992 onwards, central government effectively collapsed, but while factional fighting was rare in the south, southeast and east from 1992-94, lack of policing and the existence of roaming bands of gunmen led to large-scale abuses against the civilian population, including rape, summary killings and repeated looting. Partly as a result of the loss of external support brought about by the end of communism, military commanders increasingly faced the problem of how to fund their armies in the face of the civilian population’s declining propensity to contribute to the war effort. 1 Warlordism became a prominent feature of the Afghan conflict from this point, though its origins can be traced back to the early years of the war. 2 Though not the only factor sustaining conflict, revenue collection became a dominant preoccupation for factional leaders, increasing predation on the civilian population, and stimulating their involvement with international criminal networks. In reaction to these conditions, an extreme movement such as the Taliban, with its promise to restore order, found it fairly easy to win acceptance. From 1994, the conflict increasingly pitted Afghanistan’s various factions and warlords against the Taliban, which captured Kabul, the capital, in 1996. This phase of the conflict came to an end in 2001, due to the direct intervention of the United States on the side of the anti-Taliban coalition, known as the United Front.
Learner autonomy, teacher autonomy and the European Language Portolio

Defining learner autonomy • Learners take their first step towards autonomy when they recognize that they are responsible for their own learning (Holec 1979, Little 1991) • They exercise that responsibility through their involvement in all aspects of the learning process – planning, implementing, evaluating (ibid.) • Their autonomy grows as a result of their neverending effort to understand the WHY, the WHAT and the HOW of their learning (Dam 1995) • Learner autonomy entails a variety of self-regulatory behaviours that develop – through practice – as a fully integrated part of the knowledge and skills that are the goal of learning • Thus in formal language learning the development of autonomy requires that learners use the target language at once as medium of classroom communication, channel of learning, and tool for reflection.
A Hybrid Collaborative Filtering Model with Deep Structure for Recommender Systems

Collaborative filtering (CF) is a widely used approach in recommender systems to solve many real-world problems. Traditional CF-based methods employ the user-item matrix which encodes the individual preferences of users for items for learning to make recommendation. In real applications, the rating matrix is usually very sparse, causing CF-based methods to degrade significantly in recommendation performance. In this case, some improved CF methods utilize the increasing amount of side information to address the data sparsity problem as well as the cold start problem. However, the learned latent factors may not be effective due to the sparse nature of the user-item matrix and the side information. To address this problem, we utilize advances of learning effective representations in deep learning, and propose a hybrid model which jointly performs deep users and items’ latent factors learning from side information and collaborative filtering from the rating matrix. Extensive experimental results on three real-world datasets show that our hybrid model outperforms other methods in effectively utilizing side information and achieves performance improvement.
Forecast Uncertainty—Ex Ante and Ex Post: U.S. Inflation and Output Growth

Survey respondents who make point predictions and histogram forecasts of macro-variables reveal both how uncertain they believe the future to be, ex ante, as well as their ex post performance. Macroeconomic forecasters tend to be overconfident at horizons of a year or more, but overestimate (i.e., are underconfident regarding) the uncertainty surrounding their predictions at short horizons. Ex ante uncertainty remains at a high level compared to the ex post measure as the forecast horizon shortens. There is little evidence of a link between individuals’ ex post forecast accuracy and their ex ante subjective assessments.
Cost-effectiveness analysis of neonatal screening of critical congenital heart defects in China

Background: Pulse oximetry screening is a highly accurate tool for the early detection of critical congenital heart disease (CCHD) in newborn infants. As the technique is simple, noninvasive, and inexpensive, it has potentially significant benefits for developing countries. The aim of this study is to provide information for future clinical and health policy decisions by assessing the cost-effectiveness of CCHD screening in China. Methods and Findings: We developed a cohort model to evaluate the cost-effectiveness of screening all Chinese newborns annually using 3 possible screening options compared to no intervention: pulse oximetry alone, clinical assessment alone, and pulse oximetry as an adjunct to clinical assessment. We calculated the incremental cost per averted disability-adjusted life years (DALYs) in 2015 international dollars to measure cost-effectiveness. One-way sensitivity analysis and multivariate probabilistic sensitivity analysis were performed to test the robustness of the model. Of the three screening options, we found that clinical assessment is the most cost-effective strategy compared to no intervention with an incremental cost-effectiveness ratio (ICER) of Int$5,728/DALY, while pulse oximetry plus clinical assessment with the highest ICER yielded the best health outcomes. Sensitivity analysis showed that when the treatment rate increased up to 57.5%, pulse oximetry plus clinical assessment showed the best expected values among the three screening options. Conclusion: In China, for neonatal screening for CCHD at the national level, clinical assessment was a very cost-effective preliminary choice and pulse oximetry plus clinical assessment was worth considering for the long term. Improvement in accessibility to treatment is crucial to expand the potential health benefits of screening.
Admissible Rate Bases, Fair Rates of Return and the Structure of Regulation

A CENTRAL QUESTION in the theory of regulation is what constitutes a "fair" return on a utility's assets. The current legal answer is that provided by the Supreme Court in its Hope Natural Gas decision. A "fair" return should be "commensurate with returns on investment in other enterprises having corresponding risk" (the comparable return standard) and sufficient to "attract capital"l (the capital attraction standard). Unfortunately, in practice these guidelines are ambiguous and, as a result, are not uniformly applied. In one sense, they are definitional. There is an emerging consensus that a "fair" percentage rate of return should equal a utility's market determined "cost of capital. "2 However, the Hope Decision did not specify how the value of a utility's assets, to which the "fair" percentage return could be applied, was to be calculated. This paper
Ethyl acetate extract and its major constituent, isorhamnetin 3‐O‐rutinoside, from Nitraria retusa leaves, promote apoptosis of human myelogenous erythroleukaemia cells

Objective: Fractionation of ethyl acetate extract (EA) obtained from Nitraria retusa leaves was assessed using different methods of chromatography, and isorhamnetin3‐O‐rutinoside (I3‐O‐R) was isolated from this extract. Its structure was determined using data obtained from 1H and 13C NMR spectra, as well as by various correlation experiments (COSY, HMQC and HMBC). Both EA extract and I3‐O‐R were investigated for their ability to induce apoptosis in human chronic myelogenous erythroleukaemia cells (K562).
Endoscopic Ultrasound-Guided Drainage of Pancreatic Pseudocysts or Pancreatic Abscesses Using a Therapeutic Echo Endoscope

STUDY AIMS The purpose of this study is to evaluate a new drainage technique for pancreatic pseudocysts or pancreatic abscesses entirely guided by endoscopic ultrasound (EUS) and using an interventional echo endoscope with a linear curved array transducer. PATIENTS AND METHODS Between July 1996 and September 1999, EUS-guided drainage of a pancreatic pseudocyst or pancreatic abscess was carried out in 35 patients (26 men, 9 women; mean age 56.7, range 29-69). The mean size of the 35 pancreatic cysts was 7.8 cm (4-12 cm). Pancreatic pseudocysts were located in the head of the pancreas in two cases, in the body in six cases and in the tail in seven cases. On the other hand, the pancreatic abscesses were located in the tail of the pancreas in 17 cases and in the gastric wall in three cases. The EUS instrument used was the FG 38X endoscope manufactured by Pentax-Hitachi. RESULTS No major complication occurred except in one case of a pneumoperitoneum, which was managed medically. Placement of the 7-F nasocystic drain was successful in 18/20 cases of pancreatic abscess. Surgery was performed in the two other patients. Concerning the pancreatic pseudocysts, placement of an 8.5-French stent was successful in 10 patients and of a nasopancreatic drain in five patients. In one case, only a puncture-aspiration was performed. One recurrence among the 15 pancreatic pseudocysts and two relapses of the 18 pancreatic abscesses have been observed, over a mean follow-up of 27 months (6-48 months). EUS-guided drainage was successful in 31/35 patients (88.5%); only four patients with pancreatic abscesses underwent surgery. No bleeding occurred during the time of this study. CONCLUSION Internal drainage of pancreatic pseudocysts and abscesses exclusively performed with an echo endoscope is a safe and efficient method which should be evaluated further in larger studies.
Iterative cage-based registration for dynamic shape capture

Recent advances in low-cost dynamic scanning turn the cross-parametrization of non-rigid animatable surface into a vision-oriented ill-posed problem. In contrast with [Li et al. 2012], we propose a novel detail-preserving registration approach with resolution-independent control. Furthermore, our skin-detached surface registration avoids patch-based segmentation or affine fitting to maintain the local plasticity, as required in [Budd and Hilton 2010]. In particular, we leverage the problem of highly non-rigid spacetime registration by employing an elasto-plastic coarse cage. Thus, we perform scalable handle-aware harmonic shape registration, relying on the high-level of shape abstraction offered by the space-based paradigm. To the best of our knowledge, our technique is the first to investigate handle-aware elastic overlapping-rigidities for registering life-like dynamic shapes in full-body clothing.
In search of e-service value: technology-exploitation vs. certainty-seeking online behaviours

The primary aim of this article is to ascertain whether the e-service value formation process changes as a function of consumers' technology readiness (TR). Through a field survey about ‘e-tail’ service value, this study finds that monetary cost is equally important for both high- and low-TR consumers. The positive effects of service-enhancing value components on overall e-service value perception are stronger in the high-TR group than in the low-TR group, whereas the positive effects of risk-reducing value components are greater in the low-TR group than in the high-TR group. High-TR consumers tend to maximise shopping value for themselves through planned online searching and purchasing. Overall, high-TR consumers are able to improve their shopping value through both ex ante and post hoc vehicles. In addition, high-TR consumers exhibit technology-exploitation online behaviours, whereas low-TR consumers exhibit certainty-seeking online behaviours. The article discusses study implications and suggestions for future research from the perspectives of diffusion of innovations, online transaction costs, and relationship marketing.
Magnetic resonance imaging of normal lumbar intervertebral foraminal height.

OBJECTIVE To study the pattern and changes of lumbar intervertebral foraminal heights in an asymptomatic Jordanian sample relative to age, sex, level, and correlate values with midpoint vertebral and disc heights. METHODS One hundred and fifty-three patients (87 male and 66 female) were selected during the study period. The study was carried out at the Jordan University Hospital, Amman, Jordan from June 1999 to June 2000. Parasagittal magnetic resonance images were used to measure intervertebral foraminal heights at all lumbar levels. Values were statistically analyzed and the significance of differences in the means of foraminal heights at different levels in every age group and among age groups was determined. Foraminal height indices and correlation coefficients with midpoint vertebral and disc heights were calculated. RESULTS The study revealed that the mean foraminal height measured is 20.9 mm 1.7 with a range of 17.1-24 mm. Foraminal heights increased significantly in a craniocaudal pattern reaching a maximum at lumber (L)2/3 in females and at L3/4 in males followed by continuous significant decrease reaching their minimum at L5/sacral (S) 1. In relation to age, foraminal heights decreased significantly in females reaching their minimum in the 7th decade. In males, foraminal heights at L3/4 until L5/S1 increased significantly reaching their maximum in the 5th decade followed by significant decrease reaching their minimum in the 7th decade. Foraminal height indices remained relatively constant. A fair degree of correlation of foraminal heights with intervertebral disc heights and vertebral body heights was evident. CONCLUSION Foraminal heights show different level and age-dependent characteristic pattern of change between asymptomatic males and females. Changes of foraminal heights seem to directly reflect changes of vertebral body heights. These changes are considered normal age-dependent changes, and are discussed under consideration of adaptation to physical activity and changing hormonal levels.
The Role of Human Capital in Lowering the Barriers to Engaging in Innovation: Evidence from the Spanish Innovation Survey

This paper focuses on the role of human capital in reducing the barriers to firms' engagement in innovation activities. The paper distinguishes between firms facing barriers that stop them from engaging in any innovation activity, and firms that face impediments in the course of their innovation activity. We investigate whether human capital has a particularly strong impact in relation to lowering barriers among the former group of firms, since a strong skill base is likely to compensate for lack of experience in innovation-related activities or the complementary assets needed for innovation. We draw on four waves of the Spanish Innovation Survey and examine the impact of human capital on three types of obstacles to innovation: cost, knowledge and market barriers. We find that human capital has a significant impact on reducing the barriers to innovation represented by knowledge shortages and market uncertainties.