Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding principles of miRNA target recognition and function through integrated biological and bioinformatics approaches

In recent times, microRNA (miRNA) have emerged as primary regulators of fundamental biological processes including cellular differentiation, proliferation, apoptosis, as well as synaptic plasticity. However, miRNAs bind their targets with only partial complementarity, making it very challenging to determine exactly how a miRNA is functioning in specific biological environments. This review discusses key principles of miRNA target recognition and function which have emerged through the progressive advancement of biological and bioinformatics approaches. Ultimately, the integration of gene expression and biochemical methods with sequence‐ and systems‐based bioinformatics approaches will reveal profound insights regarding the importance of target contextual features in determining miRNA target recognition and regulatory outcome, as well as the importance of RNA interaction networks in enabling miRNA to regulate different target genes and functions in specific biological contexts. There is therefore a demand for the elegant design of future experiments such that principles of context‐specific miRNA target recognition and regulatory outcome can be accurately modeled in normal developmental and disease states.
A Unique Feature of Toll/IL-1 Receptor Domain-Containing Adaptor Protein Is Partially Responsible for Lipopolysaccharide Insensitivity in Zebrafish with a Highly Conserved Function of Myd88

MyD88 and Toll/IL-1R domain-containing adaptor protein (TIRAP) are required for the TLR4 response to LPS stimulation in mammals, but the functions of the two adaptors and their involvement in zebrafish insensitivity to LPS remains unknown. We present a functional analysis of zebrafish Myd88 and Tirap and suggest that Myd88 is more important than Tirap for the activation of Tlr-mediated NF-κB, which may be a novel mechanism of Myd88-dependent TLR signaling in teleosts. Zebrafish Tirap lacks the phosphatidylinositol 4,5-bisphosphate binding motif required for human TIRAP location and has leucine at position 233 rather than the conserved proline of human TIRAP, as well as 105 additional aa at the N terminus. Overexpression of zebrafish Tirap in HEK293T cells did not activate NF-κB and IFN-β, but slightly activated NF-κB in carp leukocyte cells. Zebrafish Myd88 alone strongly induced the activation of NF-κB and IFN-β both in HEK293T and carp leukocyte cells. The function of Myd88 was dependent on its cellular location and the proline in the Toll/IL-1R domain. Although zebrafish Tirap was distributed throughout the cell rather than localized to the cytoplasmic membrane, its impaired ability to activate downstream Tlr molecules was unlikely to be related to its location because chimera TIRAP with a human TIRAP N terminus and membrane-binding domain also did not activate NF-κB. However, the mutation of leucine to proline increased the ability of Tirap to activate NF-κB. We suggest that the zebrafish Tirap needs a longer N terminus to perform its function and could be partially responsible for the resistance to LPS in zebrafish.
One Europe, One Product, Two Prices - The Price Disparity in the EU

This article examines the price dispersion in the European Union in the last fifteen years (1990-2005). The analysis of price convergence is examined on aggregate and disaggregate levels. The macro approach is based on Comparative Price Level index calculated as the ratio between PPPs and exchange rate. The disaggregate analysis utilizes actual prices of 148 individual products sold in the 15 capital cities of the EU. The calculations comprise of sigma and beta convergence adopted from the real growth literature. The different results of the speed of convergence are obtained according to the different econometric methods. Moreover the gravity model is tested to measure the contribution of different factors in explaining the observed convergence pattern.
Automatic Coronary Calcium Scoring in Low-Dose Chest Computed Tomography

The calcium burden as estimated from non-ECG-synchronized computed tomography (CT) exams acquired in screening of heavy smokers has been shown to be a strong predictor of cardiovascular events. We present a method for automatic coronary calcium scoring with low-dose, non-contrast-enhanced, non-ECG-synchronized chest CT. First, a probabilistic coronary calcium map was created using multi-atlas segmentation. This map assigned an a priori probability for the presence of coronary calcifications at every location in a scan. Subsequently, a statistical pattern recognition system was designed to identify coronary calcifications by texture, size, and spatial features; the spatial features were computed using the coronary calcium map. The detected calcifications were quantified in terms of volume and Agatston score. The best results were obtained by merging the results of three different supervised classification systems, namely direct classification with a nearest neighbor classifier, and two-stage classification with nearest neighbor and support vector machine classifiers. We used a total of 231 test scans containing 45 674mm of coronary calcifications. The presented method detected on average 157/198mm (sensitivity 79.2%) of coronary calcium volume with on average 4 mm false positive volume. Calcium scoring can be performed automatically in low-dose, noncontrast enhanced, non-ECG-synchronized chest CT in screening of heavy smokers to identify subjects who might benefit from preventive treatment.
Break Point Estimation and Spurious Rejections With Endogenous Unit Root Tests

This paper examines the accuracy of break point estimation using the endogenous break unit root tests of Zivot and Andrews (1992) and Perron (1997). We find that these tests tend to identify the break point incorrectly at one-period behind (T[subscript B] - 1) the true break point (T[subscript B]), where bias in estimating the persistence parameter and spurious rejections are the greatest. In addition, this outcome occurs under the null and alternative hypotheses, and more so as the magnitude of the break increases. Consequences of utilizing these endogenous break tests are similar to (incorrectly) omitting the break term B[subscript t] in Perron's (1989) exogenous test. Copyright 2001 by Blackwell Publishing Ltd
Firing patterns of gastrocnemius motor units in the decerebrate cat

1. The patterns of medial gastrocnemius (MG) motor unit firing in response to MG muscle stretch have been studied in decerebrate cats, using intracellular recording techniques. In most of the units, the motoneurone axonal conduction velocity and cell input resistance were measured, and the maximum amplitude and wave form of the group Ia composite EPSP evoked by MG nerve stimulation were determined. The mechanical properties of the muscle unit portion of each motor unit were also studied.
The Putative Pore-Forming Domain of Bax Regulates Mitochondrial Localization and Interaction with Bcl-XL

ABSTRACT Bax is a proapoptotic member of the Bcl-2 family of proteins which localizes to and uses mitochondria as its major site of action. Bax normally resides in the cytoplasm and translocates to mitochondria in response to apoptotic stimuli, and it promotes apoptosis in two ways: (i) by disrupting mitochondrial membrane barrier function by formation of ion-permeable pores in mitochondrial membranes and (ii) by binding to antiapoptotic Bcl-2 family proteins via its BH3 domain and inhibiting their functions. A hairpin pair of amphipathic α-helices (α5-α6) in Bax has been predicted to participate in membrane insertion and pore formation by Bax. We mutagenized several charged residues in the α5-α6 domain of Bax, changing them to alanine. These substitution mutants of Bax constitutively localized to mitochondria and displayed a gain-of-function phenotype when expressed in mammalian cells. Furthermore, substitution of 8 out of 10 charged residues in the α5-α6 domain of Bax resulted in a loss of cytotoxicity in yeast but a gain-of-function phenotype in mammalian cells. The enhanced function of this Bax mutant was correlated with increased binding to Bcl-XL, through a BH3-independent mechanism. These observations reveal new functions for the α5-α6 hairpin loop of Bax: (i) regulation of mitochondrial targeting and (ii) modulation of binding to antiapoptotic Bcl-2 proteins.
Levels of Serum Ceruloplasmin Associate With Pediatric Nonalcoholic Fatty Liver Disease

Objectives: Nonalcoholic fatty liver disease (NAFLD) in adolescents and children is rapidly becoming one of the most common causes of chronic liver disease worldwide. NAFLD varies from simple fatty liver to nonalcoholic steatohepatitis (NASH) with possible fibrosis. Several studies suggest that oxidative stress plays a central role in several metabolic abnormalities and cellular damage that characterize NAFLD. We investigated whether transition metals and their related proteins were related to NAFLD symptoms and their underlying processes. Methods: We measured copper, iron, ceruloplasmin (Cp) concentration and activity, transferrin (Tf), ferroxidase activity, and ferritin, and we calculated Tf saturation and Cp to Tf ratio (Cp/Tf) as an index of the activity of the antioxidant Cp-Tf system in 100 children with biopsy-proven NAFLD. Pediatric patients were grouped by nonalcoholic fatty liver disease score (NAS) ≥ 5 (30 subjects) and NAS < 5 (70). Results: Cp distinguished children with NAS ≥ 5 from those with NAS < 5 with an accuracy of 82%. Specifically, a receiver operator characteristics curve showed that a cutoff of 28.6 mg/dL separated NAS ≥ 5 from NAS < 5 with a specificity of 92% and a sensitivity of 76%. The Cp/Tf ratio, as well as copper concentration and Cp activity, decreased in the NAS ≥ 5 group, pointing out an imbalance in metal regulation. Either copper or Cp concentrations were lower in subjects having ballooning. Conclusions: Serum antioxidant capacity owing to Cp failure is strongly associated with NAFLD-related damage. Further studies are, however, required to clarify the role of Cp in NAFLD pathogenesis and to evaluate its potential application as diagnostic marker.
Elevated serum and bronchoalveolar lavage fluid levels of interleukin 8 and granulocyte colony‐stimulating factor associated with the acute chest syndrome in patients with sickle cell disease

The role of cytokines in the development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) was studied. Serum interleukin 8 (IL‐8) levels were elevated in 14 episodes and undetectable in six out of 20 episodes of ACS in 19 patients with SCD. In contrast, IL‐8 levels were undetectable in the sera of 29 control patients with SCD studied during routine clinic visits or hospitalization for vaso‐occlusive crises. The differences in mean IL‐8 levels and the proportion of patients with detectable levels between the two groups were highly significant (P < 0·0001 and 0·04 respectively). The mean IL‐8 level in bronchial fluid samples from children with ACS was also significantly higher than that in sickle cell patients undergoing elective surgery (5500 ± 1400 pg/ml vs. 1900 ± 470 pg/ml, P = 0·03). Granulocyte colony‐stimulating factor (G‐CSF) (2000 ± 1700 pg/ml) was present in five out of six samples of bronchial fluid, but not serum, from children with ACS. All but one of the patients with ACS studied were negative for the Duffy red cell antigen, which is a receptor that binds and inactivates IL‐8 and other chemokines. These findings suggest that IL‐8 and G‐CSF may play a role in the development of the ACS and the complications associated with it.
A linear microstrip antenna array having low sidelobe level

A microstrip antenna linear array having 5 elements, fed by Dolph-Chebyshev amplitude weights and equal phases is proposed. A suitable microstrip divider is placed below the plane of the elements and its output ports are connected by vertical wires to the microstrip elements. It is shown that in order to reduce the strong mutual coupling between the divider and the microstrip elements one needs to set the microstrip elements above the ground plane, where the divider strips are below the common ground plane. The antenna was simulated and measured, having approximate bandwidth of 18% and sidelobe level of about 17 dB. Good agreement between simulation and measurement was achieved.
Multimedia telehomecare system using standard TV set

Nowadays, there are a very large number of patients that need specific health support at home. The deployment of broadband communication networks is making feasible the provision of home care services with a proper quality of service. This paper presents a telehomecare multimedia platform that runs over integrated services digital network and internet protocol using videoconferencing standards H.320 and H.323, and a standard TV set for patient interaction. This platform allows online remote monitoring: ECG, heart sound, blood pressure. Usability, affordability, and interoperability were considered for the design and development of its hardware and software components. A first evaluation of technical and usability aspects were carried forward with 52 patients of a private clinic and 10 students in the University. Results show a high rate (mean = 4.33, standard deviation-SD = 1.63 in a five-points Likert scale) in the global perception of users on the quality of images, voice, and feeling of virtual presence.
On Identification of Backward Blocks

Consequent on the recommendations of the second Administrative Reforms Commission, the Backward Region Grant Fund (BRGF) programme awaits some major restructuring in the 12th plan. Blocks are expected to replace the districts as primary units for redressing regional backwardness. This necessarily warrants objective identification of backward blocks based on composite criteria for targeted subvention. Relying on the joint distribution of a set of backwardness indicators, this paper offers an identification scheme that fulfills a few desirable welfare properties. The proposed scheme yields efficient and equitable results, also insightful policy implications.
Affiliative social relationships but not dominance rank affects endo-parasite product excretion in a cooperatively breeding bird species

In group living animals behavioural interactions with conspecifics strongly modulate an individual’s physiological stress response. A secure social embedding, with stable social relationships is expected to dampen an individual’s stress response which is in turn will affect the immune system and health. Ultimately, positive health effects of stable social bonds may contribute to maintain group living. We investigated whether, in cooperatively breeding carrion crows (Corvus corone), the quality of social relationships have measurable effects on patterns of gastrointestinal parasite product excretion. We repeatably collected behavioural data on dyadic social interactions and individual droppings to quantify parasite products, from 34 individuals in a captive population of carrion crows in northern Spain. Individuals with strong social bonds and living with more related individuals in a group, excreted less samples containing coccidian oocysts. Sex, group size, number of social bonds and dominance rank had no significant effect on number of samples containing coccidian oocysts. Also, the likelihood to excrete samples containing nematode eggs was not affected by any of the factors we considered. Our data presents evidence for affiliative social relationships to be linked to coccidian oocyst excretion, indicating that the social environment has strong fitness implications. This suggests that next to humans and other primate species, social relationships may be important in driving the evolution of complex sociality in a larger variety of taxa, including birds.
Role of the Histone Acetyl Transferase Tip60 in the p53 Pathway*

The histone acetyl transferase Tip60 (HTATIP) shares many properties with the tumor suppressor p53 (TP53). Both proteins are involved in the cellular response to DNA damage, are subjected to proteasomal digestion following Mdm2-mediated ubiquitination, and accumulate after UV irradiation. We found here that knock-down of Tip60 affects the p53-dependent response following actinomycin D treatment, most likely because it inhibits p21 (CDKN1A) accumulation. Moreover, Tip60 is required for p53 to activate the endogenous p21 promoter, suggesting that it functions as a p53 co-activator. However, we also found that knock-down of Tip60 increases the turnover rate of p53 under normal growth conditions. Tip60 interferes with Mdm2-mediated degradation of p53, probably because it affects its subcellular localization. Taken together, our results suggest that Tip60 plays a double role in the p53 pathway: under normal growth conditions, Tip60 contributes to maintain a basal pool of p53 by interfering with its degradation; following DNA damage, Tip60 functions as p53 co-activator. That these two distinct roles are linked during the p53-dependent response is an attractive hypothesis.
Inequality and the State: Comparing U.S. And German Preferences

Survey data from the United States, West Germany and East Germany are analyzed to compare individual attitudes towards political redistribution in each country. In West Germany the "homo oeconomicus effect", the "social rivalry effect" and the "public values effect" simultaneously retain an independent explanatory power of individual attitudes. In the United States the third effect disappears. In East Germany both the second and the third effect disappear.
A Maxwell Garnett Model for Dielectric Mixtures Containing Conducting Particles at Optical Frequencies

Mathematical modeling of composites made of a dielectric base and randomly oriented metal inclusions is considered. Different sources of frequency-dependent metal conductivity at optical frequen- cies are taken into account. These include the skin-effect, dimensional (length-size) resonance of metal particles, and the Drude model. Also, the mean free path of electrons in metals can be smaller than the char- acteristic sizes of nanoparticles, and this leads to the decrease in con- ductivity of the metal inclusions. These effects are incorporated in the Maxwell Garnett mixing formulation, and give degrees of freedom for forming desirable optical frequency characteristics of composite media containing conducting particles.
An HMM-based recognition framework for endovascular manipulations

Robotic surgical systems are becoming increasingly popular for the treatment of cardiovascular diseases. However, most of them have been designed without considering techniques and skills of natural surgical manipulations, which are key factors to clinical success of percutaneous coronary intervention. This paper proposes an HMM-based framework to recognize six typical endovascular manipulations for surgical skill analysis. A simulative surgical platform is built for endovascular manipulations assessed by five subjects (1 expert and 4 novices). The performances of the proposed framework are evaluated by three experimental schemes with the optimal model parameters. The results show that endovascular manipulations are recognized with high accuracy and reliable performance. Furthermore, the acceptable results can also be applied to the design of next generation vascular interventional robots.
Doing More with Less? Employee Reactions to Psychological Contract Breach Via Target Similarity or Spillover During Public Sector Organizational Change

Many countries are facing the twin pressures of austerity and recession following the 2007–2008 global financial crisis. This paper uses the UK public sector and a major national announcement of budget cuts signalling extensive organizational cutbacks as its setting. We examine (a) whether organizational changes following the national announcement affect public sector employees' psychological contract breach, (b) whether employee reactions to psychological contract breach are consistent with the target similarity model and vary across foci, namely the organization, co-workers and public service users, and (c) whether some of these relationships are moderated by job insecurity or public sector commitment. We collected longitudinal survey data before and after the announcement of budget cuts, using a sample of 340 employees from a range of public organizations and locations. Results largely confirm the hypotheses. Increases in organizational change predicted psychological contract breach, which in turn predicted decreases in contributions towards the organization; however, contributions towards co-workers and public service users were unaffected, which can be explained with a target similarity, rather than a spillover, model. Furthermore, the relationship between breach and employee behaviours directed toward the public was moderated by job insecurity and public sector commitment.
TKTL1 Is Activated by Promoter Hypomethylation and Contributes to Head and Neck Squamous Cell Carcinoma Carcinogenesis through Increased Aerobic Glycolysis and HIF1α Stabilization

Purpose: This study aims to investigate the role of the aberrant expression of Transkelolase-like 1 (TKTL1) in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and to characterize TKTL1 contribution to HNSCC tumorigenesis through aerobic glycolysis and HIF1α stabilization. Experimental Design: TKTL1 promoter hypomethylation and mRNA/protein aberrant expression were studied in human HNSCC tumor samples and normal mucosas. Oncogenic functions of TKTL1 were examined in HNSCC cell line panels and tumor xenograft models with TKTL1 expression construct. The metabolite levels of fructose-6-phosphate, glyceraldehydes-3-phosphate, pyruvate, lactate, and the levels of HIF1α protein and its downsteam glycolytic targets were compared between the TKTL1-expressing and vehicle-expressing HNSCC cells. Meanwhile, the effects of HIF1α/glycolytic inhibitors were evaluated on the TKTL1 transfectants. Results: TKTL1 exhibits high frequency of promoter hypomethylation in HNSCC tumors compared with the normal mucosas, correlating with its overexpression in HNSCC. Overexpression of TKTL1 in HNSCC cells promoted cellular proliferation and enhanced tumor growth in vitro and in vivo. Overexpression of TKTL1 increased the production of fructose-6-phosphate and glyceraldehyde-3-phosphate, in turn elevating the production of pyruvate and lactate, resulting in the normoxic stabilization of the malignancy-promoting transcription factor HIF1α and the upregulation of downstream glycolytic enzymes. Notably, the reduction of TKTL1 expression decreased HIF1α accumulation and inhibition with HIF1α and/or the glycolysis inhibitor could abrogate the growth effects mediated by TKTL1 overexpression. Conclusion: TKTL1 is a novel candidate oncogene that is epigenetically activated by aberrant hypomethlation and contributes to a malignant phenotype through altered glycolytic metabolism and HIF1α accumulation. Clin Cancer Res; 16(3); 857–66
Customer Markets, Credit Market Imperfections and Real Price Rigidity

According to standard theory, an increase in demand should raise prices of goods, given factor prices. Empirically, however, prices appear to be unaffected by short-run variations in demand. This paper suggests an explanation of this observation. If customers react slowly to price changes and credit markets are imperfect, prices may be unchanged or even fall when demand increases. The reason is that when demand is high, profits are high, and firms can compete more intensely for customers without increasing their borrowing. Copyright 1991 by The London School of Economics and Political Science.