Miracle-dz/UniFAR-FTUs huggingface dataset:
The Severity of Plasmodium falciparum Infection Is Associated with Transcript Levels of var Genes Encoding Endothelial Protein C Receptor-Binding P. falciparum Erythrocyte Membrane Protein 1

ABSTRACT By attaching infected erythrocytes to the vascular lining, Plasmodium falciparum parasites leave blood circulation and avoid splenic clearance. This sequestration is central to pathogenesis. Severe malaria is associated with parasites expressing an antigenically distinct P. falciparum erythrocyte membrane protein 1 (PfEMP1) subset mediating binding to endothelial receptors. Previous studies indicate that PfEMP1 adhesins with so-called CIDRα1 domains capable of binding endothelial protein C receptor (EPCR) constitute the PfEMP1 subset associated with severe pediatric malaria. To analyze the relative importance of different subtypes of CIDRα1 domains, we compared Pfemp1 transcript levels in children with severe malaria (including 9 fatal and 114 surviving cases), children hospitalized with uncomplicated malaria (n = 42), children with mild malaria not requiring hospitalization (n = 10), and children with parasitemia and no ongoing fever (n = 12). High levels of transcripts encoding EPCR-binding PfEMP1 were found in patients with symptomatic infections, and the abundance of these transcripts increased with disease severity. The compositions of CIDRα1 subtype transcripts varied markedly between patients, and none of the subtypes were dominant. Transcript-level analyses targeting other domain types indicated that subtypes of DBLβ or DBLζ domains might mediate binding phenomena that, in conjunction with EPCR binding, could contribute to pathogenesis. These observations strengthen the rationale for targeting the PfEMP1-EPCR interaction by vaccines and adjunctive therapies. Interventions should target EPCR binding of all CIDRα1 subtypes.
The Road to Chaos by Time-Asymmetric Hebbian Learning in Recurrent Neural Networks

This letter aims at studying the impact of iterative Hebbian learning algorithms on the recurrent neural network's underlying dynamics. First, an iterative supervised learning algorithm is discussed. An essential improvement of this algorithm consists of indexing the attractor information items by means of external stimuli rather than by using only initial conditions, as Hopfield originally proposed. Modifying the stimuli mainly results in a change of the entire internal dynamics, leading to an enlargement of the set of attractors and potential memory bags. The impact of the learning on the network's dynamics is the following: the more information to be stored as limit cycle attractors of the neural network, the more chaos prevails as the background dynamical regime of the network. In fact, the background chaos spreads widely and adopts a very unstructured shape similar to white noise. Next, we introduce a new form of supervised learning that is more plausible from a biological point of view: the network has to learn to react to an external stimulus by cycling through a sequence that is no longer specified a priori. Based on its spontaneous dynamics, the network decides on its own the dynamical patterns to be associated with the stimuli. Compared with classical supervised learning, huge enhancements in storing capacity and computational cost have been observed. Moreover, this new form of supervised learning, by being more respectful of the network intrinsic dynamics, maintains much more structure in the obtained chaos. It is still possible to observe the traces of the learned attractors in the chaotic regime. This complex but still very informative regime is referred to as frustrated chaos.
Gross overestimation of total allowable error based on biological variation.

To the Editor: Westgard was the first to introduce the concept of total error (TE)1 in 1974. Analytical imprecision and bias [i.e., systematic error (SE)] were combined into a single measure of the uncertainty of a test result: TE = Bias + 1 . 65 × Imprecision The factor 1.65 implies that 95% of the results (1-sided) will fall within the TE limit, given a gaussian distribution. When the bias and imprecision are known, the uncertainty of the result can be calculated. When the maximum allowable total error (TEa) is known (e.g., on the basis of clinical needs or biological variation), the maximum allowable bias and imprecision can be calculated. The expression used in general for calculating TEa is: TEa = Allowable Bias + 1 . 65 × Allowable Imprecision, where the allowable bias = 0.25 × (CVw2 + CVb2)1/2, the allowable imprecision = 0.5 × CVw, CVb is the interindividual imprecision, and CVw is the intraindividual imprecision. Values for CVb, CVw, and TEa are easily available (1), but where does this expression for TEa come from? The allowable imprecision …
Phase estimation for thermal Gaussian states

We give the optimal bounds on the phase-estimation precision for mixed Gaussian states in the single-copy and many-copy regimes. Specifically, we focus on displaced thermal and squeezed thermal states. We find that while for displaced thermal states an increase in temperature reduces the estimation fidelity, for squeezed thermal states a larger temperature can enhance the estimation fidelity. The many-copy optimal bounds are compared with the minimum variance achieved by three important single-shot measurement strategies. We show that the single-copy canonical phase measurement does not always attain the optimal bounds in the many-copy scenario. Adaptive homodyning schemes do attain the bounds for displaced thermal states, but for squeezed states they yield fidelities that are insensitive to temperature variations and are, therefore, suboptimal. Finally, we find that heterodyne measurements perform very poorly for pure states but can attain the optimal bounds for sufficiently mixed states. We apply our results to investigate the influence of losses in an optical metrology experiment. In the presence of losses squeezed states cease to provide the Heisenberg limited precision, and their performance is close to that of coherent states with the same mean photon number.
The Impact of Star Power on NBA Gate Revenues

Investigations into the level of competitive balance within the four major North American professional team sports leagues suggest that the National Basketball Association (NBA) exhibits the lowest level of competitive balance. Given the role competitive balance plays in maintaining consumer demand, the authors examine the role the star attractions of the NBA play in promoting fan interest. The evidence presented suggests the choice of functional form alters the significance of the relationships uncovered. Specifically, the significance of star power is only uncovered in a multiplicative model rather than in the commonly employed linear form. Additional empirical results are reported in the text.
Slowing the growth of health care costs--lessons from regional variation.

Most observers see rising health care costs as an inexorable force. Dr. Elliott Fisher, Dr. Julie Bynum, and Jonathan Skinner write that by learning from regions that have attained sustainable growth rates and building on successful models of delivery-system and payment-system reform, we might manage to “bend the cost curve. ”
Lethal congenital arthrogryposis presents with increased nuchal translucency at 10–14 weeks of gestation

This study examines the ultrasonographic features of congenital lethal arthrogryposis. In 27 cases of arthrogryposis diagnosed in the second and third trimesters there was severe bilateral talipes, fixed flexion deformities of the wrists and elbows and either fixed flexion or extension of the knees. In seven (26%) of the cases there was nuchal edema. In two fetuses with arthrogryposis that were examined at 13 weeks of gestation the nuchal translucency thickness was above the 99th centile of the normal range for crown‐rump length. In three other women with previously affected pregnancies, ultrasound examination at 10–14 weeks demonstrated normal fetal nuchal translucency thickness and none of these fetuses were subsequently found to have arthrogryposis. These findings suggest that lethal arthrogryposis, which is usually diagnosed by the demonstration of multiple joint contractures during the second or third trimester of pregnancy, may present as increased nuchal translucency thickness at 10–14 weeks of gestation. Copyright © 1997 International Society of Ultrasound in Obstetrics and Gynecology
Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx

In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A24 Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carriers were further compared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers. Among these, genes associated with cellular proliferation and the immune response–such as chemokines, cytokines and genes regulating T and B cells–were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E2 production and the induction of regulatory T cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells.
Plant abiotic stress: insights from the genomics era

Agricultural crop plants make up a large proportion of the world's economy and in many countries constitute the main sustenance for humans. Therefore maximizing crop yield is of extreme importance and interest. There are many factors that can limit the yield of a crop; however the main causes of crop failure are abiotic stresses such as salinity, drought, extremes in temperature, intense light, and oxidative stress caused by reactive oxygen species. Plants have evolved mechanisms and pathways allowing them to cope with the environment by modifying their physiological and cellular states. For example, plants living in colder regions undergo a phenomenon known as cold acclimation, resulting in cell membrane composition and protein concentration changes to reduce intracellular ice crystal formation and dehydration due to freezing (Thomashow, 1998). Abiotic stresses alter gene networks and signaling cascades in an effort to restore cellular homeostasis. It has been demonstrated (Reddy, 2007, Palusa et al., 2007) that abiotic stress conditions alter the alternative splicing of a number of genes. Alternative pre-mRNA splicing in higher eukaryotes is a highly regulated mechanism, often allowing for many proteins (isoforms) to be derived from a single gene, thereby increasing overall proteome diversity. These alternative transcripts often result in functionally and structurally distinct proteins (Biamonti, 2009) with their own functions in development, cellular localization, and responses to the environment (Tanabe et al., 2006). Recently genome and transcriptome-wide surveys (Rensink et al., 2005, Kreps et al., 2002, Egawa et al., 2006, Filichkin et al., 2010) have offered glimpses into transcript abundance profiles under abiotic stresses, demonstrating dramatic shifts in alternative splicing patterns, as well as upregulation of key transcription factors controlling stress-induced signaling cascades. This research offers the potential for discovery of candidate genes that, through genetic engineering, may confer increased tolerance to abiotic stresses, several examples of which will be discussed in this chapter. Recent research has demonstrated the possibility of pre-disposing plants to stress tolerance by overexpressing a gene known to be upregulated in response to a certain stress (for example: Haake et al., 2002, Forment et al., 2002, Kim et al., 2010) often acting upstream or in conjunction with a longer signaling cascade, such as the mitogen-activated protein (MAP) kinase cascade (Xiong et al. 2003), salt overly sensitive (SOS) pathway (Liu and Zhu, 1998; Ishitani et al., 2000, Qiu et al., 2004), or C-repeat-binding factor/dehydration-responsive element (CBF/DREB) pathway (Thomashow, 2010).
Plasma pro-adrenomedullin but not plasma pro-endothelin predicts survival in exacerbations of COPD.

BACKGROUND Plasma endothelin and adrenomedullin are increased in patients with pulmonary arterial hypertension, hypoxia, and pulmonary infections, conditions that predict survival in patients with COPD. We investigated whether plasma pro-endothelin-1 (proET-1) and/or pro-adrenomedullin (proADM) on admission to the hospital for acute exacerbation predict survival in patients with COPD. METHODS We examined 167 patients who had been admitted to the hospital for acute exacerbation, and we followed them up for 2 years. We measured plasma C-terminal (CT) proET-1 and mid-regional (MR) proADM on hospital admission, after 14 to 18 days, and after 6 months. In addition to plasma CT proET-1 and MR proADM, we assessed with Cox regression univariate and multivariate analyses the predictive value of clinical, functional, and laboratory parameters on 2-year survival. We analyzed the time to death by Kaplan-Meier curves. RESULTS Compared to recovery and stable state, CT-proET-1 and MR-proADM were significantly increased on hospital admission (p < 0.001 and p = 0.002, respectively). MR-proADM, but not CT-proET-1, was associated with increased in-hospital mortality (p = 0.049) and independently predicted 2-year survival (p = 0.017). ProADM plasma levels > 0.84 nmol/L on hospital admission increased the mortality risk within 2 years from 13 to 32% (p = 0.004). By contrast, age (p = 0.779), Charlson comorbidity score (p = 0.971), body mass index (p = 0.802), FEV(1) percent predicted (p = 0.741), PAo(2) (p = 0.744), PAco(2) (p = 0.284), leukocyte counts (p = 0.333), C-reactive protein (p = 0.772), procalcitonin (p = 0.069), pulmonary arterial hypertension (p = 0.971), and CT-proET-1 (p = 0.223) were not independently associated with 2-year survival. CONCLUSIONS This study shows that plasma proADM but not plasma proET-1 on admission to the hospital for acute exacerbation independently predicts survival, thus suggesting that this biomarker could be used to predict prognosis in patients with COPD.
Managing the challenge of PTLD in liver and bowel transplant recipients

Post‐transplant lymphoproliferative disorder (PTLD) remains a common complication of liver and bowel transplantion. The ubiquity of Epstein‐Barr virus (EBV) combined with engraftment of organs rich with lymphatic tissue and the requirement of highly immunosuppressive regimens are factors that account for the high frequency and poor prognosis of PTLD in this population. Early detection of the virus followed by pre‐emptive reduction of immunosuppression are essential components in the management of PTLD, but can increase the risk of graft loss. More recently, the anti‐CD20 monoclonal antibody (rituximab) has been shown to improve survival in various transplant populations with PTLD, while other therapeutic options, such as chemotherapy, surgery or radiotherapy, have minimal clinical impact. EBV‐directed cytotoxic T cells have shown promise in the management of PTLD but clinical use is currently limited by lack of technical facilities worldwide.
Acetylcholinesterase-polyaniline biosensor investigation of organophosphate pesticides in selected organic solvents

The behavior of an amperometric organic-phase biosensor consisting of a gold electrode modified first with a mercaptobenzothiazole self-assembled monolayer, followed by electropolymerization of polyaniline in which acetylcholinesterase as enzyme was immobilized, has been developed and evaluated for organophosphorous pesticide detection. The voltammetric results have shown that the formal potential shifts anodically as the Au/MBT/PANI/AChE/PVAc thick-film biosensor responded to acetylthiocholine substrate addition under anaerobic conditions in selected organic solvent media containing 2% v/v 0.05 M phosphate buffer, 0.1 M KCl (pH 7.2) solution. Detection limits in the order of 0.147 ppb for diazinon and 0.172 ppb for fenthion in acetone-saline phosphate buffer solution, and 0.180 ppb for diazinon and 0.194 ppb for fenthion in ethanol-saline phosphate buffer solution has been achieved.
The Neurogenically Maintained Component in Hypertension

The blood pressure may be subdivided into neurogenically maintained (NM) and not neurogenically maintained (NNM) components. The hexamethonium floor gives an indication of the magnitude of the NNM component, and the blood pressure fall with hexamethonium of the NM component. Rises in the NM component of up to 100 mm Hg systolic, 50 mm Hg diastolic may occur to combat hypotensive agencies, and falls in the NM component as large as 75 mm Hg systolic, 35 mm Hg diastolic to combat hypertensive agencies. There is an important NM component of the blood pressure of a subject in the horizontal posture which is usually much larger in hypertension than in normotension. The NM component is concerned in the production of hypertensive disease, and effective treatment by sympatholytic agents depends on reduction of the magnitude of this component. The basal blood pressure in man has an important NM component. Rats with spontaneous genetic hypertension and rats with experimental renal hypertension have both NM and NNM blood pressure components, the NM component being proportionately larger in the genetic hypertensive rats. Immunosympathectomy decreases the rise of blood pressure with age and prevents the development of hypertension in rats from our genetic hypertensive colony.
Dielectric losses in multi-layer Josephson junction qubits

We have measured the excited state lifetimes in Josephson junction phase and transmon qubits, all of which were fabricated with the same scalable multi-layer process. We have compared the lifetimes of phase qubits before and after removal of the isolating dielectric, SiNx, and find a fourfold improvement of the relaxation time after the removal. Together with the results from the transmon qubit and measurements on coplanar waveguide resonators, these measurements indicate that the lifetimes are limited by losses from the dielectric constituents of the qubits. We have extracted the individual loss contributions from the dielectrics in the tunnel junction barrier, AlOx, the isolating dielectric, SiNx, and the substrate, Si/SiO2, by weighting the total loss with the parts of the electric field over the different dielectric materials. Our results agree well with and complement the findings from other studies, demonstrating that superconducting qubits can be used as a reliable tool for high-frequency characterization of dielectric materials. We conclude with a discussion of how changes in design and material choice could improve qubit lifetimes by up to a factor of 4.
The Influence of Subjects ’ Personality Traits on Predicting Comfortable Human-Robot Approach Distances

This study began with the hypothesis that the approach distances people prefer when interacting with a robot are similar to those that strangers prefer when interacting with each other. Our experiments involving humans interacting with a mobile robot confirm this hypothesis: the results show that a majority (60%) of the human subjects tested take up initial approach distances that are compatible with normal human-human social interaction distances. However, surprisingly, a large minority of subjects in the experiments (40%) took up positions which were significantly closer, suggesting that they were not treating the robot as a ‘social entity’. We then tested the hypothesis that this large minority of subjects’ had common personality factors that predicted their likely approach distance preferences. The subjects’ personalities were assessed using several traits from the threefactor Eysenck personality model. Further analysis of the data identified four new factors, different from Eysenck’s model, tentatively labeled “Proactiveness”, “Social Reluctance”, “Timidity” and “Nervousness”. When testing for correlations between approach distances and personality data, “Proactiveness” correlates with social distance, i.e. subjects that score higher on this factor come less close to the robot.
Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses

Background. Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. Methods. To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012–2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS). Results. Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9–36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade. Conclusions. C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.