Miracle-dz/UniFAR-FTUs huggingface dataset:
Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin-Intolerant Urticaria

Acetyl salicylic acid (ASA) is metabolized by UDP-glucuronosyltransferase 1A6 (UGT1A6), cytochrome P4502C9 (CYP2C9), and N-acetyl transferase 2 (NAT2). Variations in the activities of these enzymes may modulate adverse ASA-related symptoms such as urticaria. We examined whether polymorphisms in the UGT1A6, CYP2C9, and NAT2 genes are related to ASA-intolerant urticaria (AIU). The genotypes of 148 subjects with AIU (AIU group) and 260 normal healthy control subjects (NC group) were analyzed with respect to the following single nucleotide polymorphisms: CYP2C9 -1188T>C and CYP2C9*3A1075C; UGT1A6 T181A A>G and UGT1A6 R184S A>C; and NAT2 9796A>T, NAT2 197G>A, NAT2 286G>A, NAT2 9601A>G, and NAT2 9306A>G. There were significant differences in the allele frequencies for the CYP2C9 polymorphisms between the two groups. The frequency of the minor allele CYP2C9 -1188T>C was significantly higher in the AIU group than in the NC group (P=0.005). The frequency of the variant genotype CC was higher in the AIU group compared with the controls in both the co-dominant (P=0.007) and recessive models (P=0.012). The frequency of haplotype 2 [CA] was also significantly higher in the AIU group in both the co-dominant (P=0.006) and dominant models (P=0.012). There was no significant difference in genotype frequencies for any of the UGT1A6 or NAT2 polymorphisms between the two groups. Clinical parameters did not differ according to genotype. These results suggest that the C allele of CYP2C9 -1188T>C may be associated with AIU.
Enhancing Effective Utilization of Aid in Fragile States

This paper explores the macroeconomic implications of aid flows in countries with weak institutions. It argues that these countries should take into account their overall macroeconomic position, their capacity to absorb aid at the sectoral and subnational levels, and the strength of their fiscal institutions in deciding how much and how fast to spend aid. These considerations may warrant a gradual use of aid, except when aid is provided for humanitarian purposes. There is some basis for frontloading spending for countries emerging from a conflict, otherwise fragile states should seek to smoothen their spending against the background of aid volatility and uncertainty.
The Financial Market Impact of UK Quantitative Easing

After outlining some of the monetary developments associated with Quantitative Easing (QE), we measure the impact of the UK's initial 2009-10 QE Programme on bonds and other assets. First, we use a macro-finance yield curve both to create a counterfactual path for bond yields and to estimate the impact of QE directly. Second, we analyse the impact of individual QE operations on a range of asset prices. We find that QE significantly lowered government bond yields through the portfolio balance channel - by around 50 or so basis points. We also uncover significant effects of individual operations but limited pass through to other assets.
The Adoption of Environmental Practices in Small Hotels. Voluntary or Mandatory? An Empirical Approach

This paper examines small hotels that have some type of environmental certification. A survey of 210 small (less than 50 employees) Catalonian hotels was conducted to investigate whether there are significant differences in the results of the implementation practices between hotels that adopt these certifications due to environmental pressure (from the government, customers, suppliers and other stakeholders) and hotels that voluntarily commit to green policies. Significant differences were identified in the results on the hotels when structural equation modelling (SEM) was undertaken. This investigation suggests that hotels that voluntarily commit to green policies obtain better results than other hotels. The conclusion is that governments must not only regulate, but also promote awareness actions in small and medium-sized (SME) tourism companies to improve the environment. SME tourism companies must understand that both the environment and they themselves will benefit.
The PI 3-kinase isoforms p 110 α and p 110 β have differential roles in PDGF-and insulin-mediated signaling

Phosphoinositide 3′-kinase (PI3-K) activity induced by growth factor activation of several cell surface receptors leads to the production of the membrane lipids phosphatidylinositol3-phosphate (PtdIns(3)P), PtdIns(3,4)P2 and PtdIns(3,4,5)P3. PI3-K is a heterodimer consisting of a regulatory and a catalytic subunit. Recently several isoforms of both the regulatory and catalytic subunits of PI3-K have been identified. The catalytic subunits p110 α, β, and δ have been shown to be associated with p85α, p85β and p55γ adapter proteins which mediate activation by protein tyrosine kinase receptors (Hiles et al., 1992; Hu et al., 1993; Vanhaesebroeck et al., 1997b). The p110γ isoform, in contrast, binds to a p101 adapter protein and is associated with and activated by βγ subunits of G proteins (Stephens et al., 1994; Stoyanov et al., 1995). The p110β subunit has also been found to be activated by the βγ subunits of G proteins (Kurosu et al., 1997). The p110α and p110β isoforms are both widely expressed whereas the p110δ subunit is predominantly expressed in haematopoietic cells. The p85 subunit contains a wide range of domains involved in protein-protein interactions (Cohen et al., 1995). These include an N-terminal Src homology-3 (SH3) domain, two SH2 domains, two proline-rich regions, a region related to the break point cluster region (bcr) gene, and an inter-SH2 domain involved in interaction with p110 and regulation of its kinase activity (Carpenter et al., 1993; Klippel et al., 1994). Binding of platelet-derived growth factor (PDGF) isoforms to their tyrosine kinase receptors causes receptor dimerization leading to autophosphorylation of the receptors on specific tyrosine residues (for review see Heldin et al., 1998). These phosphorylated tyrosine residues then serve as binding sites for many SH2 domain containing proteins (Claesson-Welsh, 1994), such as the p85 subunit of PI3-K which binds to tyrosine residues 740 and 751 in the PDGF β-receptor (Carpenter et al., 1993; Fantl et al., 1992; Kazlauskas et al., 1992). The binding of p85 to these two tyrosine residues, which are localized in YXXM motifs that are known to be optimal for PI3-K binding, probably leads to an activating conformational change in the catalytic p110 subunit and also brings the PI3-K heterodimer in contact with its lipid substrates. PI3-K has been implicated as an important mediator of many PDGF-induced cellular responses, such as prevention of apoptosis (Yao and Cooper, 1995), as well as stimulation of mitogenesis (Roche et al., 1994), actin reorganization and chemotaxis (Hooshmand-Rad et al., 1997; Kundra et al., 1994; Nobes et al., 1995; Wennström et al., 1994a,b). PDGF receptor mutants lacking the tyrosines involved in PI3-K binding are 207 Journal of Cell Science 113, 207-214 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 JCS1044
An Efficient Resource Allocation for TCP Services in IEEE 802.16 Wireless MANs

In IEEE 802.16 Wireless MANs supporting OFDMA- PHY, random access with CDMA-based mechanism is proposed to request bandwidth for uplink data. Collision, which increases the Round Trip Time (RTT), is not avoided due to random access during requesting bandwidth among subscriber stations (SSs). In this paper, we propose an efficient resource allocation for Transmission Control Protocol (TCP) services with resolving RTT increasing problem caused by the wireless access of the best effort service and enhancing network performance in IEEE 802.16 Wireless MANs supporting OFDMA-PHY. The proposed resource allocation estimates the uplink traffic of SS based on the downlink traffic to the SS and allocates the resource to the SS, which transmits uplink traffic with the allocated resource. Our simulation results show that the proposed scheme provides better performance.
Using brain potentials to understand prism adaptation: the error-related negativity and the P300

Prism adaptation (PA) is both a perceptual-motor learning task as well as a promising rehabilitation tool for visuo-spatial neglect (VSN)—a spatial attention disorder often experienced after stroke resulting in slowed and/or inaccurate motor responses to contralesional targets. During PA, individuals are exposed to prism-induced shifts of the visual-field while performing a visuo-guided reaching task. After adaptation, with goggles removed, visuomotor responding is shifted to the opposite direction of that initially induced by the prisms. This visuomotor aftereffect has been used to study visuomotor learning and adaptation and has been applied clinically to reduce VSN severity by improving motor responding to stimuli in contralesional (usually left-sided) space. In order to optimize PA's use for VSN patients, it is important to elucidate the neural and cognitive processes that alter visuomotor function during PA. In the present study, healthy young adults underwent PA while event-related potentials (ERPs) were recorded at the termination of each reach (screen-touch), then binned according to accuracy (hit vs. miss) and phase of exposure block (early, middle, late). Results show that two ERP components were evoked by screen-touch: an error-related negativity (ERN), and a P300. The ERN was consistently evoked on miss trials during adaptation, while the P300 amplitude was largest during the early phase of adaptation for both hit and miss trials. This study provides evidence of two neural signals sensitive to visual feedback during PA that may sub-serve changes in visuomotor responding. Prior ERP research suggests that the ERN reflects an error processing system in medial-frontal cortex, while the P300 is suggested to reflect a system for context updating and learning. Future research is needed to elucidate the role of these ERP components in improving visuomotor responses among individuals with VSN.
Ices in the Edge-on Disk CRBR 2422.8-3423: Spitzer Spectroscopy and Monte Carlo Radiative Transfer Modeling

We present 5.2-37.2 μm spectroscopy of the edge-on circumstellar disk CRBR 2422.8-3423 obtained using the Infrared Spectrograph (IRS) of the Spitzer Space Telescope. The IRS spectrum is combined with ground-based 3-5 μm spectroscopy to obtain a complete inventory of solid-state material present along the line of sight toward the source. Archival JHKs imaging, as well as 350 μm Caltech Submillimeter Observatory mapping, 850 μm SCUBA mapping, and 3 mm Owens Valley Radio Observatory interferometry, is used to obtain a set of spectrophotometric data covering 1.2-3000 μm. The ices observed toward CRBR 2422.8-3423 are compared with archival ISOCAM-CVF 5-16 μm ice spectra of other nearby sources within 2'. We model the object with a two-dimensional axisymmetric (effectively three-dimensional) Monte Carlo radiative transfer code using all the available observations to constrain the source geometry and dust composition. In particular, the location of the observed ices in the disk and envelope material is included in the model. It is found that the model disk, assuming a standard flaring structure, is too warm to contain the very large observed column density of pure CO ice but is possibly responsible for up to 50% of the water, CO2, and minor ice species. In particular, the 6.85 μm band, tentatively ascribed to NH, exhibits a prominent red wing, indicating a significant contribution from warm ice in the disk. The shape of the CO2 bending mode suggests an interaction with up to 20% of the CO ice. It is argued that the pure CO ice is located in the dense core Oph-F in front of the source seen in the submillimeter imaging, with the CO gas in the core highly depleted. Up to 50% of the CO ice embedded in water or CO2 ice (no more than 20% of the total amount of CO) may still be located in the disk, assuming constant abundances of these types of CO ice throughout the system. Discrepancies among the strength of different water ice bands are discussed. Specifically, the observed water ice libration band located at 11-13 μm is significantly weaker than that of the model. The model is used to predict which circumstances are most favorable for direct observations of ices in edge-on circumstellar disks. Ice bands will in general be deepest for inclinations similar to the disk opening angle, i.e., ~70°, except for very tenuous disks. Because of the high optical depths of typical disk midplanes, ice absorption bands will often probe warmer ice located in the upper layers of nearly edge-on disks. The ratios between different ice bands are found to vary by up to an order of magnitude depending on disk inclination because of radiative transfer effects caused by the two-dimensional structure of the disk. Ratios between ice bands of the same species can therefore be used to constrain the location of the ices in a circumstellar disk.
Synaptic Modifications in the Medial Prefrontal Cortex in Susceptibility and Resilience to Stress

When facing stress, most individuals are resilient whereas others are prone to developing mood disorders. The brain mechanisms underlying such divergent behavioral responses remain unclear. Here we used the learned helplessness procedure in mice to examine the role of the medial prefrontal cortex (mPFC), a brain region highly implicated in both clinical and animal models of depression, in adaptive and maladaptive behavioral responses to stress. We found that uncontrollable and inescapable stress induced behavioral state-dependent changes in the excitatory synapses onto a subset of mPFC neurons: those that were activated during behavioral responses as indicated by their expression of the activity reporter c-Fos. Whereas synaptic potentiation was linked to learned helplessness, a depression-like behavior, synaptic weakening, was associated with resilience to stress. Notably, enhancing the activity of mPFC neurons using a chemical–genetic method was sufficient to convert the resilient behavior into helplessness. Our results provide direct evidence that mPFC dysfunction is linked to maladaptive behavioral responses to stress, and suggest that enhanced excitatory synaptic drive onto mPFC neurons may underlie the previously reported hyperactivity of this brain region in depression.
MERTK Interactions with SH2-Domain Proteins in the Retinal Pigment Epithelium

The receptor tyrosine kinase MERTK plays an essential role in the phagocytic uptake of shed photoreceptor membranes by the retinal pigment epithelium (RPE). A fundamental aspect of signal transduction by receptor tyrosine kinases involves autophosphorylation of tyrosine residues that recruit Src-homology 2 (SH2)-domain proteins to the receptor intracellular domain. The goal of the current study was to evaluate the interactions of human MERTK with SH2-domain proteins present in the RPE. The MERTK intracellular domain was expressed as a 6xHis-fusion protein (6xHis-rMERTK571–999), purified and phosphorylated. Ni2+-NTA pull downs were performed using 6xHis-rMERTK571–999 in incubations with recombinant phosphotyrosine-recognition sequences expressed as GST-fusion proteins. In addition, pull downs of native SH2-domain proteins were performed using 6xHis-rMERTK571–999 and protein homogenates from rat RPE/choroid. For both recombinant and native proteins, western analysis detected MERTK interactions with GRB2, PIK3R1 (P85α), VAV3, and SRC. Immunohistochemical analysis localized each protein to mouse RPE. In cultured RPE-J cells incubated with rod outer segments (OS), siRNA knockdown of Grb2 had no effect on OS binding, but significantly reduced OS uptake. Pik3r1 localized to early phagosomes along with Rab5 and Eea1. Phosphorylation and activation of Src was detected downstream of phagocytosis and Mertk activation. These findings suggest that MERTK signaling in the RPE involves a cohort of SH2-domain proteins with the potential to regulate both cytoskeletal rearrangement and membrane movement. Identification of the SH2-domain signaling partners of MERTK is an important step toward further defining the mechanism of RPE phagocytosis that is central to the function and survival of the retina.
Naiad: a timely dataflow system

Naiad is a distributed system for executing data parallel, cyclic dataflow programs. It offers the high throughput of batch processors, the low latency of stream processors, and the ability to perform iterative and incremental computations. Although existing systems offer some of these features, applications that require all three have relied on multiple platforms, at the expense of efficiency, maintainability, and simplicity. Naiad resolves the complexities of combining these features in one framework. A new computational model, timely dataflow, underlies Naiad and captures opportunities for parallelism across a wide class of algorithms. This model enriches dataflow computation with timestamps that represent logical points in the computation and provide the basis for an efficient, lightweight coordination mechanism. We show that many powerful high-level programming models can be built on Naiad's low-level primitives, enabling such diverse tasks as streaming data analysis, iterative machine learning, and interactive graph mining. Naiad outperforms specialized systems in their target application domains, and its unique features enable the development of new high-performance applications.
Three-point correlation function in the quasilinear regime.

Using the second-order Eulerian perturbation theory (SEPT), we study the three-point correlation function in the quasilinear regime for the SCDM, LCDM and MDM models, with the interesting result that these three models have distinc- tive three-point correlation functions. We test this SEPT pre- diction using a large set of high-resolution N-body simulations. The N-body results show that the SEPT prediction for is not accurate even in the quasilinear regime (r < 10h 1 Mpc), in contrast to previous N-body tests on the skewness. However, similar to the perturbation theory, our N-body results still pre- dict a strong dependence of the three-point correlation on the triangleshapewhichisobservableinthedistributionofgalaxies if the galaxies trace the distribution of the underlying mass
Observation and Characterization of the Interaction between a Single Immunoglobulin Binding Domain of Protein L and Two Equivalents of Human κ Light Chains*

Detailed stopped-flow studies in combination with site-directed mutagenesis, isothermal titration calorimetry data and x-ray crystallographic knowledge have revealed that the biphasic pre-equilibrium fluorescence changes reported for a single Ig-binding domain of protein L from Peptostreptococcus magnus binding to κ light chain are due to the binding of the κ light chain at two separate sites on the protein L molecule. Elimination of binding site 2 through the mutation A66W has allowed the Kd for κ light chain binding at site 1 to be measured by stopped-flow fluorescence and isothermal titration calorimetry techniques, giving values of 48.0 ± 8.0 nm and 37.5 ± 7.3 nm respectively. Conversely, a double mutation Y53F/L57H eliminates binding at site 1 and has allowed the Kd for binding at site 2 to be determined. Stopped-flow fluorimetry suggests this to be 3.4 ± 0.8 μm in good agreement with the value of 4.6 ± 0.8 μm determined by isothermal titration calorimetry. The mutation Y53F reduces the affinity of site 1 to approximately that of site 2.
Emotion and professional identities: A comparative study of professionals in Further Education and learning disability support services

This research observes and compares the emotions and professional identities of professionals working in Further Education in the Metropolitan Borough of Kirklees, and for a learning disability charity in the North of England. I wanted to identify the rewards and pressures in order to develop an understanding of how emotional demands inform professional identities. In relation to this, both groups of professionals have obligations with regards providing care for the people they serve, whilst also fulfilling other responsibilities which appear to contrast with this. Education professionals must facilitate achievement, whilst support workers must enable service users to live as independently as possible. Twenty semi-structured, intensive interviews were conducted with participants who were gathered using purposive sampling. It was an exploratory study, broadly following an interpretive grounded theory approach. My findings indicate a positive sense of professional identity is facilitated when the professionals feel they are significant within their professional environment; have a certain amount of control or agency; and hold values which are aligned with the organisation. Professionals were most passionate about their work when they were working with underprivileged or „forgotten‟ members of society, such as low achieving students and people with learning disabilities. Decisions made outside the working environment seemed to negatively affect professionals most. Issues relating to current policy, targets and management pressures were evidenced as concerns for professionals in Further Education. Professionals at the Mencap affiliated organisation involved in the research cited increased paperwork as an issue as it undermined their sense of agency; they felt they were being unnecessarily monitored. The professionals working with people with learning disabilities have great pride in their organisation and worry about the prospect of policy altering the way they work. The findings indicate that greater agency; a less businesslike approach; and the alignment of organisational and personal values proves beneficial to professional identity.
Combined therapy with cinacalcet and low doses of vitamin D sterols in patients with moderate to severe secondary hyperparathyroidism.

BACKGROUND Adequate control of all four KDOQI biochemical targets for chronic kidney disease, bone and mineral disorder (CKD-MBD), which include parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and Ca x P, remains difficult and is accomplished in <6% of patients receiving haemodialysis. The objective of the current study was to determine whether treatment with cinacalcet combined with low doses of vitamin D sterols improves control of both PTH and Ca x P among haemodialysis patients with secondary hyperparathyroidism (sHPT). METHODS This multicentre, open-label study enrolled haemodialysis subjects (N = 444) with moderate to severe sHPT (mean serum biPTH > 160-430 pg/mL) (approximately iPTH 300-800 pg/mL or ng/L). Cinacalcet was titrated sequentially (30-180 mg/day) during an 8-week dose-titration phase to achieve biPTH <or=160 pg/mL (approximately iPTH 300 pg/mL or ng/L) and efficacy was assessed over 8 weeks. At week 2 of the study, subjects receiving vitamin D sterols had doses reduced to the equivalent of 2 mcg of paricalcitol three times a week or 6 mcg/week. Among the efficacy endpoints were the proportion of subjects with mean biPTH <or=160 pg/mL (approximately iPTH 300 pg/mL or ng/L), with mean Ca x P <or=55 mg(2)/dL(2) (4.4 mmol(2)/L(2)) and with both simultaneously during the assessment phase. RESULTS The majority of subjects (n = 375) reached the assessment phase of the study and were included in efficacy analyses; 39 subjects withdrew due to adverse events. Sixty-two percent of subjects achieved the biPTH target, 83% achieved the Ca x P target and 54% reached both targets. Treatment reduced biPTH by 35% (P < 0.0001), calcium by 11% (P < 0.0001), phosphorus by 7% (P < 0.0001) and Ca x P by 17% (P < 0.0001). The proportion of subjects with values for biPTH, for Ca x P and for both biPTH and Ca x P within the target range during the assessment phase did not differ between subjects who received cinacalcet together with vitamin D sterols, and those who received cinacalcet alone. CONCLUSION Among subjects with moderate to severe sHPT undergoing haemodialysis, combined therapy with cinacalcet and low doses of vitamin D sterols improved achievement of the biochemical targets for CKD-MBD recommended by the KDOQI guidelines.