Miracle-dz/UniFAR-FTUs huggingface dataset:
A Murine Model of falciparum-Malaria by In Vivo Selection of Competent Strains in Non-Myelodepleted Mice Engrafted with Human Erythrocytes

To counter the global threat caused by Plasmodium falciparum malaria, new drugs and vaccines are urgently needed. However, there are no practical animal models because P. falciparum infects human erythrocytes almost exclusively. Here we describe a reliable falciparum murine model of malaria by generating strains of P. falciparum in vivo that can infect immunodeficient mice engrafted with human erythrocytes. We infected NODscid/β2m−/− mice engrafted with human erythrocytes with P. falciparum obtained from in vitro cultures. After apparent clearance, we obtained isolates of P. falciparum able to grow in peripheral blood of engrafted NODscid/β2m−/− mice. Of the isolates obtained, we expanded in vivo and established the isolate Pf3D70087/N9 as a reference strain for model development. Pf3D70087/N9 caused productive persistent infections in 100% of engrafted mice infected intravenously. The infection caused a relative anemia due to selective elimination of human erythrocytes by a mechanism dependent on parasite density in peripheral blood. Using this model, we implemented and validated a reproducible assay of antimalarial activity useful for drug discovery. Thus, our results demonstrate that P. falciparum contains clones able to grow reproducibly in mice engrafted with human erythrocytes without the use of myeloablative methods.
An open-circuit method for determining lung diffusing capacity during exercise: comparison to rebreathe.

To avoid limitations associated with the use of single-breath and rebreathe methods for assessing the lung diffusing capacity for carbon monoxide (D(L)CO) during exercise, we developed an open-circuit technique. This method does not require rebreathing or alterations in breathing pattern and can be performed with little cognition on the part of the patient. To determine how this technique compared with the traditional rebreathe (D(L)CO,RB) method, we performed both the open-circuit (D(L)CO,OC) and the D(L)CO,RB methods at rest and during exercise (25, 50, and 75% of peak work) in 11 healthy subjects [mean age = 34 yr (SD 11)]. Both D(L)CO,OC and D(L)CO,RB increased linearly with cardiac output and external work. There was a good correlation between D(L)CO,OC and D(L)CO,RB for rest and exercise (mean of individual r2 = 0.88, overall r2 = 0.69, slope = 0.97). D(L)CO,OC and D(L)CO,RB were similar at rest and during exercise [e.g., rest = 27.2 (SD 5.8) vs. 29.3 (SD 5.2), and 75% peak work = 44.0 (SD 7.0) vs. 41.2 ml.min(-1). mmHg(-1) (SD 6.7) for D(L)CO,OC vs. D(L)CO,RB]. The coefficient of variation for repeat measurements of D(L)CO,OC was 7.9% at rest and averaged 3.9% during exercise. These data suggest that the D(L)CO,OC method is a reproducible, well-tolerated alternative for determining D(L)CO, particularly during exercise. The method is linearly associated with cardiac output, suggesting increased alveolar-capillary recruitment, and values were similar to the traditional rebreathe method.
Health Literacy and Task Environment Influence Parents' Burden for Data Entry on Child-Specific Health Information: Randomized Controlled Trial

Background Health care systems increasingly rely on patients’ data entry efforts to organize and assist in care delivery through health information exchange. Objectives We sought to determine (1) the variation in burden imposed on parents by data entry efforts across paper-based and computer-based environments, and (2) the impact, if any, of parents’ health literacy on the task burden. Methods We completed a randomized controlled trial of parent-completed data entry tasks. Parents of children with attention deficit hyperactivity disorder (ADHD) were randomized based on the Test of Functional Health Literacy in Adults (TOFHLA) to either a paper-based or computer-based environment for entry of health information on their children. The primary outcome was the National Aeronautics and Space Administration Task Load Index (TLX) total weighted score. Results We screened 271 parents: 194 (71.6%) were eligible, and 180 of these (92.8%) constituted the study cohort. We analyzed 90 participants from each arm. Parents who completed information tasks on paper reported a higher task burden than those who worked in the computer environment: mean (SD) TLX scores were 22.8 (20.6) for paper and 16.3 (16.1) for computer. Assignment to the paper environment conferred a significant risk of higher task burden (F1,178 = 4.05, P = .046). Adequate literacy was associated with lower task burden (decrease in burden score of 1.15 SD, P = .003). After adjusting for relevant child and parent factors, parents’ TOFHLA score (beta = -.02, P = .02) and task environment (beta = .31, P = .03) remained significantly associated with task burden. Conclusions A tailored computer-based environment provided an improved task experience for data entry compared to the same tasks completed on paper. Health literacy was inversely related to task burden. Trial registration Clinicaltrials.gov NCT00543257; http://www.clinicaltrials. gov/ct2/show/NCT00543257 (Archived by WebCite at http://www.webcitation.org/5vUVH2DYR)
Computer-assisted authoring of interactive narratives

This paper explores new authoring paradigms and computer-assisted authoring tools for free-form interactive narratives. We present a new design formalism, Interactive Behavior Trees (IBT's), which decouples the monitoring of user input, the narrative, and how the user may influence the story outcome. We introduce automation tools for IBT's, to help the author detect and automatically resolve inconsistencies in the authored narrative, or conflicting user interactions that may hinder story progression. We compare IBT's to traditional story graph representations and show that our formalism better scales with the number of story arcs, and the degree and granularity of user input. The authoring time is further reduced with the help of automation, and errors are completely avoided. Our approach enables content creators to easily author complex, branching narratives with multiple story arcs in a modular, extensible fashion while empowering players with the agency to freely interact with the characters in the story and the world they inhabit.
Solving Power Supply Restoration Problems with Planning via Symbolic Model Checking

The past few years have seen a flurry of new approaches for planning under uncertainty, but their applicability to real-world problems is yet to be established since they have been tested only on toy benchmark problems. To fill this gap, the challenge of solving power supply restoration problems with existing planning tools has recently been issued. This requires the ability to deal with incompletely specified initial conditions, fault conditions, unpredictable action effects, and partial observability in real-time. This paper reports a first response to this nontrivial challenge, using the approach of planning via symbolic model-checking as implemented in the MBP planner. We show how the problem can be encoded in MBP's input language, and report very promising experimental results on a number of significant test cases.
Surgical treatment of lymphedema of the penis and scrotum.

PURPOSE Lymphedema of the penis and scrotum, regardless of its etiology, is determined by reduced lymphatic flow with subsequent enlargement of the penis and scrotum. The clinical course of this condition is characterized by extreme discomfort for patients, with limitation of local hygiene, ambulation, sexual intercourse, and voiding in the standing position. The purpose of the present study is to present the experience and results of the treatment of lymphedema of the penis and scrotum by removing affected tissues and correcting the penoscrotal region. MATERIALS AND METHODS Seventeen patients with lymphedema of the penis and scrotum were treated with a modified Charles procedure, which consists of the excision of the affected skin followed by scrotoplasty and midline suture simulating the scrotal raphe. The penis is covered with a split-thickness skin graft by means of a zigzag suture on its ventral surface. RESULTS Regression of symptoms and improvement of previous clinical conditions were verified in the follow-up which ranged from 6 months to 6 years. One patient who had undergone lymphadenectomy with radiation therapy due to penile cancer had recurrent scrotum lymphedema. CONCLUSIONS The modified Charles procedure for the treatment of penoscrotal lymphedema is easily reproducible and allows better local hygiene, easier ambulation, voiding in the standing position, resuming sexual intercourse, and finally, better cosmetic results in the affected area with remarkable improvement in quality of life.
Prognostic Significance of Tumor-Infiltrating Lymphocytes in Oropharyngeal Cancer

The presence of tumor-infiltrating lymphocytes has been shown to significantly improve clinical outcomes in many types of cancer. However, their effects on outcomes in patients with oropharyngeal cancer specifically have yet to be elucidated. We conducted a retrospective study in an effort to shed light on this issue. We reviewed the records of 48 consecutively presenting patients with oropharyngeal cancer, and we performed immunohistochemistry to analyze their archived paraffin-embedded tissue samples for the presence of CD3-positive tumor-infiltrating lymphocytes. We also used real-time polymerase chain reaction testing to look for human papillomavirus type 16 (HPV-16) in the tumors. We found that patients with large numbers of tumor-infiltrating lymphocytes (CD3high) had a significantly lower incidence of metastasis at presentation than did those with low numbers of tumor-infiltrating lymphocytes (CD3low) (40.0 vs. 88.5%; p = 0.001), regardless of HPV status. When HPV status was taken into account, the correlation between a high CD3 count and a lower rate of metastasis was maintained in the HPV-positive patients but not in the HPV-negative patients. We also found that the CD3high patients had higher rates of overall survival and disease-free survival at 3 and 5 years than did the CD3low patients; however, these differences only approached but did not reach statistical significance.
Lateralization threshold of a signal in noise.

Experiments are described in which the accuracy of the perceived lateral position of a signal against a continuous background of masking noise is determined. Both signal and masker consisted of octave bands of thermal noise, with the same center frequency of 500 Hz. The signal‐to‐noise ratio and signal duration served as parameters. The results can be understood on a statistical basis, the random fluctuations of nerve impulses playing an important role. The fluctuations due to “internal” noise are found to have a standard deviation of about 80 μsec. It appeared that, as a result of the increase of the sound‐pressure level, the onset part of the signal contributes more to the lateral position perceived than the ongoing part does. The relation to the precedence effect is discussed. The statistical procedure underlying the accuracy of the lateral position perceived suggests an approach to the binaural masking level difference effect based on a masking pattern in the binaural‐hearing mechanism.
Fraud identification in electricity company customers using decision tree

The objective of this work is to develop a system that pre-select electricity energy company customers who will undergo in-site inspection for frauds or faulty measurement equipments identification. The pre-selection system was built based on the electricity company database. It used attributes such as monthly energy consumption, type of consumers, previous inspection outcome, and others. A decision tree based classification system was used to reach such goal. The identification was designed, trained and tested using MATLAB code. The fraud/faulty equipments identification per number of in-site inspection rate was 40% of the total of pre-selected customers, which was above the expectation.
Modified Brostrom-Evans-Gould Technique for Recurrent Lateral Ankle Ligament Instability

Purpose. To review the outcome of the modified Brostrom-Evans-Gould technique in patients with chronic lateral ankle ligament instability. Methods. Between August 2003 and June 2005, 20 men aged 19 to 35 (mean, 23) years with chronic lateral instability affecting 21 ankles, underwent the modified Brostrom-Evans-Gould technique by a single surgeon. The mean follow-up period was 12 (range, 6–20) months. Patients were assessed preoperatively and postoperatively using the Kaikkonen Ankle Scoring Scale. Results. Preoperatively, all patients had poor scores (<50). Postoperatively, 17 (81%) of the ankles attained excellent scores (85–100) and 4 (19%) attained good scores (70–84). Conclusion. The modified Brostrom-Evans-Gould technique appears effective for chronic lateral ankle ligament instability, particularly in the Asian population with a higher prevalence of generalised joint hyperlaxity.
A clinally varying promoter polymorphism associated with adaptive variation in wing size in Drosophila

Body size often shows adaptive clines in many ectotherms across altitude and latitude, but little is known about the genetic basis of these adaptive clines. Here we identify a polymorphism in the Dca (Drosophila cold acclimation) gene in Drosophila melanogaster that influences wing size, affects wing:thorax allometry and also controls a substantial proportion of the clinal wing‐size variation. A polymorphism in the promoter region of Dca had two common alleles showing strong reciprocal clinal variation in frequency with latitude along the east coast of Australia. The Dca‐237 allele increased towards the tropics where wing size is smaller. A within‐population association study highlighted that an increase in the frequency of this allele decreased wing size but did not influence thorax size. A manipulated increase in the level of expression of Dca achieved through UAS‐GAL4 was associated with a decrease in wing size but had no effect on thorax size. This was consistent with higher Dca expression levels in family lines with higher frequency of the Dca‐237 allele. Genetic variation in the promoter region of the Dca gene appears to influence adaptive size variation in the eastern Australian cline of Drosophila melanogaster and accounts for more than 10% of the genetic variation in size within and between populations.
Nickel exposure induces oxidative damage to mitochondrial DNA in Neuro2a cells: the neuroprotective roles of melatonin

Abstract: Recent studies suggest that oxidative stress and mitochondrial dysfunction play important roles in the neurotoxicity of nickel. Because mitochondrial DNA (mtDNA) is highly vulnerable to oxidative stress and melatonin can efficiently protect mtDNA against oxidative damage in various pathological conditions, the aims of this study were to determine whether mtDNA oxidative damage was involved in the neurotoxicity of nickel and to assay the neuroprotective effects of melatonin in mtDNA. In this study, we exposed mouse neuroblastoma cell lines (Neuro2a) to different concentrations of nickel chloride (NiCl2, 0.125, 0.25, and 0.5 mm) for 24 hr. We found that nickel significantly increased reactive oxygen species (ROS) production and mitochondrial superoxide levels. In addition, nickel exposure increased mitochondrial 8‐hydroxyguanine (8‐OHdG) content and reduced mtDNA content and mtDNA transcript levels. Consistent with this finding, nickel was found to destroy mtDNA nucleoid structure and decrease protein levels of Tfam, a key protein component for nucleoid organization. However, all the oxidative damage to mtDNA induced by nickel was efficiently attenuated by melatonin pretreatment. Our results suggest that oxidative damage to mtDNA may account for the neurotoxicity of nickel. Melatonin has great pharmacological potential in protecting mtDNA against the adverse effects of nickel in the nervous system.
Segregation of VE-cadherin from the LBRC depends on the ectodomain sequence required for homophilic adhesion

ABSTRACT The lateral border recycling compartment (LBRC) is a reticulum of perijunctional tubulovesicular membrane that is continuous with the plasmalemma of endothelial cells and is essential for efficient transendothelial migration (TEM) of leukocytes. The LBRC contains molecules involved in TEM, such as PECAM, PVR and CD99, but not VE-cadherin. Despite its importance, how membrane proteins are included in or excluded from the LBRC is not known. Immunoelectron microscopy and biochemical approaches demonstrate that inclusion into the LBRC is the default pathway for transmembrane molecules present at endothelial cell borders. A chimeric molecule composed of the extracellular domain of VE-cadherin and cytoplasmic tail of PECAM (VE-CAD/PECAM) did not enter the LBRC, suggesting that VE-cadherin was excluded by a mechanism involving its extracellular domain. Deletion of the homophilic interaction domain EC1 or the homophilic interaction motif RVDAE allowed VE-CAD/PECAM and even native VE-cadherin to enter the LBRC. Similarly, treatment with RVDAE peptide to block homophilic VE-cadherin interactions allowed endogenous VE-cadherin to enter the LBRC. This suggests that homophilic interactions of VE-cadherin stabilize it at cell borders and prevent entry into the LBRC.
Destabilizing Domains Mediate Reversible Transgene Expression in the Brain

Regulating transgene expression in vivo by delivering oral drugs has been a long-time goal for the gene therapy field. A novel gene regulating system based on targeted proteasomal degradation has been recently developed. The system is based on a destabilizing domain (DD) of the Escherichia coli dihydrofolate reductase (DHFR) that directs fused proteins to proteasomal destruction. Creating YFP proteins fused to destabilizing domains enabled TMP based induction of YFP expression in the brain, whereas omission of TMP resulted in loss of YFP expression. Moreover, induction of YFP expression was dose dependent and at higher TMP dosages, induced YFP reached levels comparable to expression of unregulated transgene. , Transgene expression could be reversibly regulated using the DD system. Importantly, no adverse effects of TMP treatment or expression of DD-fusion proteins in the brain were observed. To show proof of concept that destabilizing domains derived from DHFR could be used with a biologically active molecule, DD were fused to GDNF, which is a potent neurotrophic factor of dopamine neurons. N-terminal placement of the DD resulted in TMP-regulated release of biologically active GDNF. Our findings suggest that TMP-regulated destabilizing domains can afford transgene regulation in the brain. The fact that GDNF could be regulated is very promising for developing future gene therapies (e.g. for Parkinson's disease) and should be further investigated.
Selective Removal of Hemoglobin from Blood Using Hierarchical Copper Shells Anchored to Magnetic Nanoparticles

Hierarchical copper shells anchored on magnetic nanoparticles were designed and fabricated to selectively deplete hemoglobin from human blood by immobilized metal affinity chromatography. Briefly, CoFe2O4 nanoparticles coated with polyacrylic acid were first synthesized by a one-pot solvothermal method. Hierarchical copper shells were then deposited by immobilizing Cu2+ on nanoparticles and subsequently by reducing between the solid CoFe2O4@COOH and copper solution with NaBH4. The resulting nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectrometry, X-ray photoelectron spectroscopy, and vibrating sample magnetometry. The particles were also tested against purified bovine hemoglobin over a range of pH, contact time, and initial protein concentration. Hemoglobin adsorption followed pseudo-second-order kinetics and reached equilibrium in 90 min. Isothermal data also fit the Langmuir model well, with calculated maximum adsorption capacity 666 mg g−1. Due to the high density of Cu2+ on the shell, the nanoparticles efficiently and selectively deplete hemoglobin from human blood. Taken together, the results demonstrate that the particles with hierarchical copper shells effectively remove abundant, histidine-rich proteins, such as hemoglobin from human blood, and thereby minimize interference in diagnostic and other assays.
COMPTEL detection of the high-energy γ-ray source 2 CG 135 + 01

We present an analysis of COMPTEL observations made between November 1991 and May 1994 of 2CG 135+01, a bright γ-ray source located near the Galactic plane. At energies above 1 MeV, an excess consistent with the position of 2CG 135+01 is detected in the sum of the observations, at flux levels which are a factor of 10 − 100 below those published in the past. The detection significance of this excess, when the possible presence of underlying Galactic diffuse emission is neglected, is 6. 6σ for 3 degrees of freedom. The differential photon spectrum in the 1–30 MeV energy range can be described by a power law with a spectral index of 1.95 −0.3. Due to the uncertainties involved in modelling the Galacticdisk diffuse emission underneath the source, the absolute flux levels must be considered uncertain by a factor of two. They are consistent with the extrapolation of the time-averaged spectrum of 2CG 135+01 measured with EGRET, thereby strengthening the identification. No significant temporal correlation between the γ-ray emission and the monitored radio emission of the possible counterpart radio source GT 0236+610 (showing a 26.5 day modulation) is found.
Solutions to the Module Orientation and Rotation Problems by Neural Computation Networks

In this paper we study two strategies for modifying a given placement of modules in order to improve the quality of the routing results in the next stage of design. We assume that the modules have already been placed. The first strategy seeks to minimize the total wire length by flipping each module about its vertical and/or horizontal axes of symmetry. The second strategy seeks to minimize the total wire length by rotating each module by a multiple of 90 degrees. We introduce a new algorithm based on the Hopfield-Tank neuralnet model to solve these problems. Our algorithm performs better than the best algorithms known for these problems. Both problems are shown to be NP-Complete.
Spectrum occupancy in the 2.36–2.4 GHZ band: Measurements and analysis

In this paper, we analyze spectrum occupancy of the 2.36–2.4 GHz band. Interest in this band has risen recently, as secondary allocation of this radio spectrum is being considered for body sensor network operation to offer wireless healthcare services. We present spectrum measurements conducted in the Eindhoven area, in the Netherlands, where the 2.36–2.4 GHz band is currently used for land mobile and amateur radio services. Our objective is to show the spectrum usage in this band, provide statistics for the received power of active transmissions and obtain their occupation time.
Which random processes describe the tree of life? A large-scale study of phylogenetic tree imbalance.

The explosion of phylogenetic studies not only provides a clear snapshot of biodiversity, but also makes it possible to infer how the diversity has arisen (see for example, Purvis and Hector, 2000; Harvey et al., 1996; Nee et al., 1996; Mace et al., 2003). To this aim, variation in speciation and extinction rates have been investigated through their signatures in the shapes of phylogenetic trees (Mooers and Heard, 1997). This issue is of great importance, as fitting stochastic models to tree data would help to understand underlying macroevolutionary processes. Although the prevailing view is that it does not represent phylogenies so well, the most popular model of phylogenetic trees is a branching process introduced by Yule, in which lineages split at random (Yule, 1924). Here we report the study of one major database of published