Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacodynamics and Pharmacokinetics of Higher-Dose, Double-Bolus Eptifibatide in Percutaneous Coronary Intervention

Background— Pharmacodynamics of eptifibatide, a cyclic heptapeptide antagonist of platelet glycoprotein IIb/IIIa, are substantially altered by anticoagulants that chelate calcium, resulting in overestimation ex vivo of the in vivo effects of this agent. We conducted a dose-ranging study to characterize the pharmacodynamics and pharmacokinetics of eptifibatide under physiological conditions. Methods and Results— Patients (n=39) undergoing elective percutaneous coronary intervention were randomly assigned to an eptifibatide bolus followed by an infusion (180-&mgr;g/kg bolus followed by 2 &mgr;g/kg per minute or 250-&mgr;g/kg bolus followed by 3 &mgr;g/kg per minute) for 18 to 24 hours. In a 2:1 ratio, these patients received either a second bolus of eptifibatide (90 &mgr;g/kg or 125 &mgr;g/kg for the initial 180-&mgr;g/kg or 250-&mgr;g/kg groups, respectively) or placebo 30 minutes after the initial bolus. Bleeding times, ex vivo platelet aggregation, receptor occupancy, and plasma eptifibatide levels at baseline and at 1, 2, 3, 4, 6, and 8 hours were evaluated. Platelet inhibition was dose dependent and >80% in all groups by steady state. The single-bolus regimens had a transient loss of inhibition at 1 hour, consistent with rapid distribution and drug elimination. Pharmacokinetic modeling suggested that optimal dosing of eptifibatide would be obtained with a 180-&mgr;g/kg bolus and a 2-&mgr;g/kg per minute infusion followed by a second 180-&mgr;g/kg bolus 10 minutes later. Conclusions— A novel higher-dose, double-bolus regimen of eptifibatide in coronary intervention attains and maintains >90% inhibition of platelet aggregation in >90% of patients, providing the pharmacodynamic construct for the design of the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial of adjunctive eptifibatide in coronary stent implantation.
New targeted therapies in melanoma.

BACKGROUND The previous 2 years have been an exciting time in melanoma research, due in part to the approval of vemurafenib and ipilimumab for advanced melanoma. Increased knowledge of the molecular biology leading to melanoma has led to the development of several new agents that target specific oncogenes. METHODS The authors review the latest developments in signal transduction inhibitors and in immune modulators for the treatment of melanoma. Investigational agents currently in development are also discussed. RESULTS Vemurafenib and ipilimumab have improved overall survival in patients with metastatic melanoma. Many new agents are in development, including programmed death-1 antibodies and combination signal transduction inhibitors. CONCLUSIONS A recognition of the genetic diversity of melanoma and a better understanding of the immune system have resulted in improvements in overall survival in patients with metastatic melanoma. Refractory cases remain challenging, and combination therapies are being explored in an effort to overcome resistance mechanisms. New molecular targets need to be identified to help the subset of patients who do not harbor BRAF mutations.
Stuck in traffic: how temporal delays affect search behaviour

In this paper we investigate how query response delays and document download delays affect user interactions within a search system. Guided by Information Foraging Theory and Search Economic Theory, five competing hypotheses relating to the behaviours of searchers in the presence of delays are considered and examined in the context of ad-hoc topic retrieval. A between-subjects laboratory study with 48 undergraduate subjects was conducted. Subjects were randomly assigned to one of four conditions that varied the type of delay experienced. When faced with query response delays, subjects did not examine more documents per query as expected. However, when the total amount of time spent per query (a combination of delay and querying time) increased, subjects did examine more documents per query. When faced with document download delays, subjects did not spent more time within documents. Subjects however did spend longer within documents when subjected to both query and document delays. We found a strong and significant correlation between query time (independent of delay) and the interactions of subjects in terms of the number of queries posed, the number of documents examined, and the depth to which subjects went. These findings contrast with previous works on how delays affect search behaviour, and suggest that the theory needs to be refined to make more credible predictions relating to search behaviours.
Coping after recurrent miscarriage: uncertainty and bracing for the worst

Background The aim of this study was to understand how women with single or recurrent miscarriages cope during the waiting periods after miscarriage – waiting for pregnancy or waiting for pregnancy confirmation – and to investigate their perception of a ‘positive reappraisal’ coping intervention designed for these waiting periods. Positive reappraisal is a cognitive strategy to change the meaning of a situation, specifically reinterpreting the situation in a more positive way. Methods A qualitative methodology was used. Data were obtained from two focus groups comprising nine women with one or more miscarriages. Results Two core categories, ‘uncertainty’ and ‘bracing’, were highlighted during the waiting period for confirmation of an ongoing pregnancy. Women who had experienced a single miscarriage appraised this waiting period as benign and used distraction and coping by social support. Women with recurrent miscarriages could not confidently appraise the waiting period as one that would bring hope or joy and used bracing for the worst as their coping strategy to manage this ambivalence. With this strategy, women tried to control their current emotions, and looked into the future to try to minimise their distress if a further miscarriage occurred. Although all women thought that a ‘positive reappraisal’ coping intervention would be practical and applicable during waiting periods, only women with recurrent miscarriages actually wanted to use such an intervention. Conclusions Coping interventions targeting reappraisal of the waiting period stressor situation could help women to cope as they wait for a subsequent pregnancy to be confirmed as ongoing. Coping interventions may need to be tailored, but before any strategy is introduced, further study is needed to identify the most appropriate approach.
Sustainability perspectives: a new methodological approach for quantitative assessment

This paper proposes a new tool to assess sustainability and make the concept of sustainable development operational. It considers its multi-dimensional structure combining the information deriving from a selection of relevant sustainability indicators belonging to economic, social and environmental pillars. The main novelties of this approach are the modelling framework, a recursive-dynamic computable general equilibrium used to calculate the trend of all indicators over time throughout the world, and the aggregation methodology to reconcile them in one aggregate index to measure overall sustainability. The former allows capturing the sector and regional interactions and higher-order effects driven by background assumptions on relevant variables to depict future scenarios. The latter makes it possible to compare sustainability performances, under alternative scenarios, across countries and over time. Main results show that the current sustainability at world level differs from what the traditional measure of well-being, the GDP, depicts, highlighting the trade-offs among different components of sustainability. Moreover, in the next decade a slight decrease in world sustainability may occur, in spite of an expected increase in world domestic product. Finally, dedicated policies increase overall sustainability, showing that social and environmental benefits may be greater than the correlated economic costs.
Prevention of Nonimmunologic Loss of Transplanted Islets in Monkeys

The nonimmunologic loss of islets in the pre‐, peri‐, and early post‐islet transplant periods is profound. To determine the potential role that transplantation of only a marginal mass of functioning beta cells may play in triggering late nonimmunologic graft loss, we studied the effect of treatment with alpha‐1‐antitrypsin (AAT) in the autologous cynomolgus islet transplant model. A marginal mass of autologous islets, that is islets prepared from 70% to 80% of the pancreas, was transplanted at 1600–4100 IEQ/kg into subtotal pancreatectomized, streptozotocin‐treated and insulin‐deficient diabetic hosts. In this marginal mass islet transplant model, islet function is insidiously lost over time and diabetes recurs in all untreated monkeys by 180 days posttransplantation. Short‐term treatment with AAT, an acute phase reactant, in the peri‐transplant period serves to terminate inflammation through effects upon expression of TGFβ, NFκB and AKT and favorably altering expression of cell death and survival pathways, as detected by a system biology approach and histology. These effects enabled functional expansion of the islet mass in transplanted hosts such that graft function improves rather than deteriorating over time.
Fingerprint singular point detection algorithm by Poincaré index

Fingerprint indexing is an efficient technique that greatly improves the performance of Automated Fingerprint Identification Systems. We propose a continuous fingerprint indexing method based on location, direction estimation and correlation of fingerprint singular points. There have been many approaches introduced in the design of feature extraction. Based on orientation field, Firstly, we divide it into blocks to compute the Poincare Index. Then, the blocks which may have singularities are detected in the block images. Experiment show the present algorithm is robust than the traditional method on poor quality images.
Random filter based ultra-wideband channel estimation

Ultra-wideband (UWB) channel estimation based on compressive sensing (CS) is developed. A random filter is exploited in the system to produce the measurement matrix. A new filter which is “all pass” in frequency domain and both real in time and frequency domain is established. Then subsampling and reconstruction algorithm are utilized for channel estimation. The Cramer-Rao bound of the sparse channel estimation is obtained. Numerical results indicate that the estimation algorithm with quite a low sampling rate can get a perfect performance. The results also reveal that the algorithm's Mean Square Error (MSE) approaches the CRB at high Signal-Noise Ratio (SNR).
Estimation of Growth Parameters from Multiple‐Recapture Data

Summary This article develops a method for analysis of growth data with multiple recaptures when the initial ages for all individuals are unknown. The existing approaches either impute the initial ages or model them as random effects. Assumptions about the initial age are not verifiable because all the initial ages are unknown. We present an alternative approach that treats all the lengths including the length at first capture as correlated repeated measures for each individual. Optimal estimating equations are developed using the generalized estimating equations approach that only requires the first two moment assumptions. Explicit expressions for estimation of both mean growth parameters and variance components are given to minimize the computational complexity. Simulation studies indicate that the proposed method works well. Two real data sets are analyzed for illustration, one from whelks (Dicathais aegaota) and the other from southern rock lobster (Jasus edwardsii) in South Australia.
Algorithms for Analysing the Temporal Structure of Discourse

We describe a method for analysing the temporal structure of a discourse which takes into account the effects of tense, aspect, temporal adverbials and rhetorical structure and which minimises unnecessary ambiguity in the temporal structure. It is part of a discourse grammar implemented in Carpenter's ALE formalism. The method for building up the temporal structure of the discourse combines constraints and prefernces: we use constraints to reduce the number of possible structures, exploiting the HPSG type hierarchy and unification for this purpose; and we apply preferences to choose between the remaining options using a temporal centering mechanism. We end by recommending that an underspecified representation of the structure using these techniques be used to avoid generating the temporal/rhetorical structure until higher-level information can be used to disambiguate.
Beyond Classical Inheritance: The Influence of Maternal Genotype upon Child's Brain Morphology and Behavior

Genetic variance has been associated with variations in brain morphology, cognition, behavior, and disease risk. One well studied example of how common genetic variance is associated with brain morphology is the serotonin transporter gene polymorphism within the promoter region (5-HTTLPR). Because serotonin is a key neurotrophic factor during brain development, genetically determined variations in serotonin activity during maturation, in particular during early prenatal development, may underlie the observed association. However, the intrauterine microenvironment is not only determined by the child's, but also the mother's genotype. Therefore, we hypothesized that maternal 5-HTTLPR genotype influences the child's brain development beyond direct inheritance. To test this hypothesis, we investigated 76 children who were all heterozygous for the 5-HTTLPR (sl) and who had mothers who were either homozygous for the long (ll) or the short allele (ss). Using MRI, we assessed brain morphology as a function of maternal genotype. Gray matter density of the somatosensory cortex was found to be greater in children of ss mothers compared with children of ll mothers. Behavioral assessment showed that fine motor task performance was altered in children of ll mothers and the degree of this behavioral effect correlated with somatosensory cortex density across individuals. Our findings provide initial evidence that maternal genotype can affect the child's phenotype beyond effects of classical inheritance. Our observation appears to be explained by intrauterine environmental differences or by differences in maternal behavior.
Estimating News Coverage of Web Search Results

The abundance of content on the web and the lack of quality control require more refined approaches in analyzing online information. In this paper, we propose evaluating the extent to which web search results cover important and recent news related to real-world objects. Our method allows for identifying search results that provide comprehensive overviews of major events related to user queries or that contain most recent information.
Combining targeted drugs to overcome and prevent resistance of solid cancers with some stem-like cell features

Treatment resistance significantly inhibits the efficiency of targeted cancer therapies in drug-sensitive genotypes. In the current work, we studied mechanisms for rapidly occurring, adaptive resistance in targeted therapy-sensitive lung, breast, and melanoma cancer cell lines. The results show that in ALK translocated lung cancer lines H3122 and H2228, cells with cancer stem-like cell features characterized by high expression of cancer stem cell markers and/or in vivo tumorigenesis can mediate adaptive resistance to oncogene ablative therapy. When pharmacological ablation of ALK oncogene was accompanied with PI3K inhibitor or salinomycin therapy, cancer stem-like cell features were reversed which was accompanied with decreased colony formation. Furthermore, co-targeting was able to block the formation of acquired resistance in H3122 line. The results suggest that cells with cancer stem-like cell features can mediate adaptive resistance to targeted therapies. Since these cells follow the stochastic model, concurrent therapy with an oncogene ablating agent and a stem-like cell-targeting drug is needed for maximal therapeutic efficiency.
The large variation in organic carbon consumption in spring in the East China Sea

A tremendous amount of organic carbon respired by plankton communities has been found in summer in the East China Sea (ECS), and this rate has been significantly correlated with fluvial discharge from the Changjiang River. However, respiration data has rarely been collected in other seasons. To evaluate and reveal the potential controlling mechanism of organic carbon consumption in spring in the ECS, two cruises covering almost the entire ECS shelf were conducted in the spring of 2009 and 2010. These results showed that although the fluvial discharge rates were comparable to the high riverine flow in summer, the plankton community respiration (CR) varied widely between the two springs. In 2009, the level of CR was double that of 2010, with mean (± SD) values of 111.7 (±76.3) and 50.7 (±62.9) mg C m −3 d −1 , respectively. The CR was positively correlated with concentrations of particulate organic carbon and/or chlorophyll a (Chl a ) in 2009 (all p 2 ( f CO 2 ) in the surface waters, even with a significant amount of inorganic carbon regenerated via CR. In 2010, even more riverine runoff nutrients were measured in the ECS than in 2009. Surprisingly, the growth of phytoplankton in 2010 was not stimulated by enriched nutrients, and its growth was likely limited by low water temperature and/or low light intensity. Low temperature might also suppress planktonic metabolism, which could explain why the CR was lower in 2010. During this period, lower surface water f CO 2 may have been driven mainly by physical process(es). To conclude, these results indicate that high organic carbon consumption (i.e. CR) in the spring of 2009 could be attributed to high planktonic biomasses, and the lower CR rate during the cold spring of 2010 might be likely limited by low temperature in the ECS. This further suggests that the high inter-annual variability of organic carbon consumption needs to be kept in mind when budgeting the annual carbon balance.
Linear frequency diversity array synthetic aperture radar imaging with enhanced fast back-projection algorithm

Based on the model of linear frequency diversity array synthetic aperture radar (LFDA-SAR) multiple carrier frequency (MCF) signal, the space-variant range offset characteristic of the echo is derived in detail and an enhanced fast back-projection algorithm is proposed. By splitting the original SAR data matrix into sub data blocks, sub image formation and sub image combination recursively, EFBPA effectively rectify the image defocus, geometric distortion problems in traditional back-projection imaging results and greatly reduces the computational complexity of BPA. All results verify the effectiveness of the proposed algorithm.
Feedforward global/inertial sensor fusion algorithm for accurate global positioning of a mobile robot

This paper introduces a coordinate transform method for global/inertial sensor fusion minimizing modification of an existing control program of a mobile robot Most of GPS/INS sensor fusion algorithms use Kalman filters and modify the INS states by feedback loops. Because the structure of the proposed method has a feedforward filter, the proposed method has an advantage in case the user does not want to change an existing control program of mobile robot. The feedback type Kalman filter is designed so that the error between global position from GPS and odometry from INS converges to zero. Therefore the coordinate matching between the odometry and measured global position is not necessary in those approaches. However, in the feedforward structure described in this paper, the errors gradually increase over time. A coordinate transform method has been developed for dealing with the error. This method provides an easy way to make an add-on function without any changes in the existing functions of the control program of a mobile robot
Impact of Human Immunodeficiency Virus Infection on the Etiology and Outcome of Severe Pneumonia in Malawian Children

Background: HIV infection is a major risk factor for death in childhood pneumonia in HIV-endemic regions. Improved case management and preventive strategies require better understanding of the impact of HIV on causes, clinical presentation, and outcome. Methods: A prospective, clinical descriptive study of Malawian infants and children with severe pneumonia included blood culture and nasopharyngeal aspiration for diagnosis of pneumocystis pneumonia (PcP). A select group with consolidation on chest radiograph, and without severe hypoxia or hyperinflation, also had lung aspirate taken for culture and identification of bacterial deoxyribonucleic acid by real-time polymerase chain reaction (PCR). Results: There were 327 study patients with a median age of 11 months (range, 2 months–14 years). HIV prevalence was 51%. There were 58 cases of confirmed bacterial pneumonia, of which the most common bacterial isolates were Streptococcus pneumoniae and Salmonella typhimurium. Of the 54 lung aspirates, only 2 were positive on culture but 27 were positive for bacterial deoxyribonucleic acid by PCR. PcP was confirmed in 16 patients, and was associated with young age, severe hypoxia, HIV infection, and a very poor outcome. The overall case-fatality rate was 10% despite presumptive therapy for PcP and routine broad-spectrum antibiotic treatment appropriate for local antimicrobial susceptibility data. Most of the deaths occurred in infants of 2 to 6 months of age and PcP was associated with 57% of these deaths. Conclusions: PcP is a major barrier in reducing the case-fatality rate of severe pneumonia in infants of HIV-endemic communities. The use of PCR on lung aspirate specimens greatly increased the diagnostic yield.
Prediction of Membrane Proteins : Why , How and When ?

Reliability measures for membrane protein topology prediction algorithms. Topology models for 37 Saccharomyces cerevisiae membrane proteins based on C-terminal reporter fusions and predictions. Experimentally based topology models for E. coli inner membrane proteins. A global topology map of the Saccharomyces cerevisiae membrane proteome. Experimentally constrained topology models for 51,208 bacterial inner membrane proteins. A nine-transmembrane domain topology for presenilin 1.
Variable Length Codes for Degraded Broadcast Channels

This paper investigates the achievable rates using variable length codes when transmitting independent information over a degraded broadcast channel. In this note, we define the transmission rates from the perspective of the receivers and allow the decoders to make their decision at a different instant of time. We give an outer bound to the region of achievable rates, as well as examples of code that achieve this bound in some settings.