Miracle-dz/UniFAR-FTUs huggingface dataset:
A Pilot Randomised Trial of Induced Blood-Stage Plasmodium falciparum Infections in Healthy Volunteers for Testing Efficacy of New Antimalarial Drugs

Background Critical to the development of new drugs for treatment of malaria is the capacity to safely evaluate their activity in human subjects. The approach that has been most commonly used is testing in subjects with natural malaria infection, a methodology that may expose symptomatic subjects to the risk of ineffective treatment. Here we describe the development and pilot testing of a system to undertake experimental infection using blood stage Plasmodium falciparum parasites (BSP). The objectives of the study were to assess the feasibility and safety of induced BSP infection as a method for assessment of efficacy of new drug candidates for the treatment of P. falciparum infection. Methods and Findings A prospective, unblinded, Phase IIa trial was undertaken in 19 healthy, malaria-naïve, male adult volunteers who were infected with BSP and followed with careful clinical and laboratory observation, including a sensitive, quantitative malaria PCR assay. Volunteers were randomly allocated to treatment with either of two licensed antimalarial drug combinations, artemether–lumefantrine (A/L) or atovaquone-proguanil (A/P). In the first cohort (n = 6) where volunteers received ∼360 BSP, none reached the target parasitemia of 1,000 before the day designated for antimalarial treatment (day 6). In the second and third cohorts, 13 volunteers received 1,800 BSP, with all reaching the target parasitemia before receiving treatment (A/L, n = 6; A/P, n = 7) The study demonstrated safety in the 19 volunteers tested, and a significant difference in the clearance kinetics of parasitemia between the drugs in the 13 evaluable subjects, with mean parasite reduction ratios of 759 for A/L and 17 for A/P (95% CI 120–4786 and 7–40 respectively; p<0.01). Conclusions This system offers a flexible and safe approach to testing the in vivo activity of novel antimalarials. Trial Registration: ClinicalTrials.gov NCT01055002
A Distant Supervision Method for Product Aspect Extraction from Customer Reviews

In this paper, we describe a distant supervision approach for the task of detecting product aspect mentions in customer reviews (e.g., in hotel reviews, we want to associate the aspect ``sleep quality" to a sentence such as "We both slept like rocks."). Detecting such aspects represents an important subtask of aspect-oriented review mining systems, which aim at automatically generating structured summaries of customer opinions. The main advantage of the proposed method is that it allows for the high accuracy of a supervised approach and at the same time avoids the costs of manually labeling a training set. We show how to exploit the inherent structure of customer reviews to automatically gather large amounts of labeled data. Our experimental results show that the method achieves a performance as good as a traditional, fully supervised approach.
Interest of using genetically manipulated mice as models of depression to evaluate antidepressant drugs activity: a review

Among the multiple possibilities to study human depressive disorders, animal models remain important preclinical tools. They allow the understanding of the mechanisms of action of antidepressant drugs. Primarily developed in rat, animal models of depression have been adapted to the mouse, an easy‐to‐use mammal with better genetic possibilities than rats. As an example, genetic manipulation of the serotoninergic 5‐hydroxytryptamine‐HT; (5‐HT) system provided important opportunities to investigate the role of this monoamine in mood disorders. The contribution of either constitutive knockout (KO), tissue specific, or inducible KO mice and animal models in the current knowledge of the pathophysiology and treatment of depression is unanimously recognized. The phenotype of genetically manipulated animals is strongly influenced by both the genetic background of the animal as well as environmental factors. For these reasons, it is necessary to underline that KO mice have been generated on various genetic backgrounds, which strongly influence the behavioral and neurochemical responses to the tests. The present review will thus focus on KO mice lacking G protein‐coupled monoaminergic receptors (e.g; 5‐HT1B, 5‐HT1A, and 5‐HT4 receptors) and the 5‐HT serotonin transporter, which is the main target of antidepressant drugs (or strategies). The importance of KO mice for neurotrophic factors, particularly for brain‐derived neurotrophic factor and its main receptor displaying a tyrosine kinase activity, will also be addressed to illustrate the fact that in preclinical studies, combination of genetic manipulations with pharmacological ones should allow further progress in the field of neuropsychopharmacology.
Enhancement of AODV routing protocol in MASNETs

The rapid development of wireless communication technologies and portable mobile devices such as laptops, PDAs, smart phones and wireless sensors brings the best out of mobile computing particularly mobile ad-hoc and sensor networks. Nowadays, most of researchers working on Wireless Sensor Networks (WSNs) focus on Mobile Ad-hoc and Sensor Networks (MASNETs) due to their wide range of potential applications ranging from underwater monitoring to search and rescue mobile robotics applications. In this research work, through extensive simulation, we have evaluated the capability of Ad-hoc On Demand Distance Vector (AODV) routing protocol on how far it can react to different mobility duration of mobile nodes in MASNETs. The performance of AODV is investigated in terms of the average percentage of packet loss and energy consumption. The initial performance study demonstrates that the performance of AODV is signicantly decreased in mobile environment due to the frequent topology change in MASNETs. Therefore, in order to enhance the performance of AODV in MASNETs, the new routing algorithm based on the estimated distance is proposed to replace the hop count for the selection of next node during the packet transmission. The estimated distance is computed based on the Received Signal Strength Indicator (RSSI) values that are collected during the communication between the sensor nodes. The performance of the proposed solution is also further evaluated and compared with the existing AODV routing protocol in term of their energy consumption and percentage of packet loss. Our study demonstrates that the proposed solution outperform the existing AODV in MASNETs.
Review of Limitations on Namespace Distribution for Cloud Filesystems

There are many challenges today for storing, processing and transferring intensive amounts of data in a distributed, large scale environment like cloud computing systems, where Apache Hadoop is a recent, well-known platform to provide such services. Such platforms use HDSF File System organized on two key components: the Hadoop Distributed File System (HDSF) for file storage and MapReduce, a distributed processing system for intensive cloud data applications. The main features of this structure are scalability, increased fault tolerance, efficiency and high-performance for the whole system. Hadoop supports today scientific applications, like high energy physics, astronomy genetics or even meteorology. Many organizations, including Yahoo! and Facebook have successfully implemented Hadoop as their internal distributed platform. Because HDSF architecture relies on a master/slave model, where a single name-node server is responsible for managing the namespace and all metadata operations in the file system. As a result this poses a limit on its growth and ability to scale due to the amount of RAM available on the single namespace server. A bottleneck resource is another problem that derives from this internal organization. By analyzing the limitations of HDSF architecture and resource distribution challenges, this paper reviews many solutions for addressing such limitations. This is done by discussing and comparing two file systems: Ceph Distributed File System and the Scalable Distributed File System. We will discuss and evaluate their main features, strengths and weaknesses with regards to increased scalability and performance. Also we will analyse and compare from a qualitative approach the algorithms implemented in these schemes such as CRUSH, RADOS algorithm for Ceph and RA, RM algorithms
Locomotion skills for simulated quadrupeds

We develop an integrated set of gaits and skills for a physics-based simulation of a quadruped. The motion repertoire for our simulated dog includes walk, trot, pace, canter, transverse gallop, rotary gallop, leaps capable of jumping on-and-off platforms and over obstacles, sitting, lying down, standing up, and getting up from a fall. The controllers use a representation based on gait graphs, a dual leg frame model, a flexible spine model, and the extensive use of internal virtual forces applied via the Jacobian transpose. Optimizations are applied to these control abstractions in order to achieve robust gaits and leaps with desired motion styles. The resulting gaits are evaluated for robustness with respect to push disturbances and the traversal of variable terrain. The simulated motions are also compared to motion data captured from a filmed dog.
ABTS: A transformation-based consistency control algorithm for wide-area collaborative applications

Operational transformation (OT) is an established optimistic consistency control method in collaborative applications. Most existing OT algorithms are developed under a well-accepted framework with a condition that cannot be formally proved. In addition, they generally support two character-based primitive operations, insert and delete, in a linear data structure. This paper proposes a novel OT algorithm that addresses the above two challenges as follows: First, it is based on a recent theoretical framework with formal conditions such that its correctness can be proved. Secondly, it supports two string-based primitive operations and handles overlapping and splitting of operations. As a result, this algorithm can be applied in a wide range of practical collaborative applications.
On the limits of cache-obliviousness

In this paper, we present lower bounds for permuting and sorting in the cache-oblivious model. We prove that (1) I/O optimal cache-oblivious comparison based sorting is not possible without a tall cache assumption, and (2) there does not exist an I/O optimal cache-oblivious algorithm for permuting, not even in the presence of a tall cache assumption.Our results for sorting show the existence of an inherent trade-off in the cache-oblivious model between the strength of the tall cache assumption and the overhead for the case M » B, and show that Funnelsort and recursive binary mergesort are optimal algorithms in the sense that they attain this trade-off.
Imaging Cellular Inorganic Phosphate in Caenorhabditis elegans Using a Genetically Encoded FRET-Based Biosensor

Inorganic phosphate (Pi) has central roles in metabolism, cell signaling and energy conversion. The distribution of Pi to each cell and cellular compartment of an animal must be tightly coordinated with its dietary supply and with the varied metabolic demands of individual cells. An analytical method for monitoring Pi dynamics with spatial and temporal resolution is therefore needed to gain a comprehensive understanding of mechanisms governing the transport and recycling of this essential nutrient. Here we demonstrate the utility of a genetically encoded FRET-based Pi sensor to assess cellular Pi levels in the nematode Caenorhabditis elegans. The sensor was expressed in different cells and tissues of the animal, including head neurons, tail neurons, pharyngeal muscle, and the intestine. Cytosolic Pi concentrations were monitored using ratiometric imaging. Injection of phosphate buffer into intestinal cells confirmed that the sensor was responsive to changes in Pi concentration in vivo. Live Pi imaging revealed cell-specific and developmental stage-specific differences in cytosolic Pi concentrations. In addition, cellular Pi levels were perturbed by food deprivation and by exposure to the respiratory inhibitor cyanide. These results suggest that Pi concentration is a sensitive indicator of metabolic status. Moreover, we propose that live Pi imaging in C. elegans is a powerful approach to discern mechanisms that govern Pi distribution in individual cells and throughout an animal.
Quinolone Resistance in Oligella Urethralis- Associated Urinary Tract Infection

The importance of oxidase-positive, nonfermentative, Gram-negative bacilli in a variety of pathological processes is becoming increasingly important. Oligella urethralis is an organism which is normally isolated as a commensal from the genitourinary tract. We have described one case of urinary tract infection caused by this organism. This isolated organism is found to be resistant to quinolones, while relatively sensitive to a wide variety of antibiotics. These findings clearly indicate that this organism may be an opportunistic pathogen and that extensive application of quinolones may provide a selective pressure for the emergence of resistance. We believe that this is the firs report of isolation and quinolone resistance in Oligella in Iran.
Measurements of organic gases during aerosol formation events in the boreal forest atmosphere during QUEST

Abstract. Biogenic VOCs are important in the growth and possibly also in the early stages of formation of atmospheric aerosol particles. In this work, we present 10 min-time resolution measurements of organic trace gases at Hyytiala, Finland during March 2002. The measurements were part of the project QUEST (Quantification of Aerosol Nucleation in the European Boundary Layer) and took place during a two-week period when nucleation events occurred with various intensities nearly every day. Using a ground-based Chemical Ionization Mass Spectrometer (CIMS) instrument, the following trace gases were detected: acetone, TMA, DMA, mass 68amu (candidate=isoprene), monoterpenes, methyl vinyl ketone (MVK) and methacrolein (MaCR) and monoterpene oxidation products (MTOP). For all of them except for the amines, we present daily variations during different classes of nucleation events, and non-event days. BVOC oxidation products (MVK, MaCR and MTOP) show a higher ratio to the CS on event days compared to non-event days, indicating that their abundance relative to the surface of aerosol available is higher on nucleation days. Moreover, BVOC oxidation products are found to show significant correlations with the condensational sink (CS) on nucleation event days, which indicates that they are representative of less volatile organic compounds that contribute to the growth of the nucleated particles and generally secondary organic aerosol formation. Behaviors of BVOC on event and non event days are compared to the behavior of CO.
Comparative Studies on the Characteristics of ZnO Thin Films Deposited by Single-Step and Two-Step Method Using RF Sputtering

ZnO thin films are deposited by single step and a two-step method on Si (100) substrates by using RF sputtering. The comparisons are based on structural, surface morphology and topography of ZnO thin films. XRD pattern of the ZnO film derived by two-step method exhibited single crystalline wurtzite structure. AFM results revealed the crystallite size and roughness of the ZnO thin film.
Neonatal-Mouse Infectivity of Intact Cryptosporidium parvum Oocysts Isolated after Optimized In Vitro Excystation

ABSTRACT We reexamined the finding of Neumann et al. (10) that intact Cryptosporidium parvum oocysts obtained after in vitro excystation were infectious for neonatal CD-1 mice. We used both established excystation protocols and our own protocol that maximized excystation (2). Although intact oocysts isolated after any of three protocols were infectious for neonatal CD-1 mice, the infectivity of intact oocysts isolated with our optimized excystation protocol was significantly lower than the infectivity of intact oocysts isolated after established protocols or from fresh oocysts. Excystation should not be considered a valid measure of C. parvum viability, given that it is biologically implausible for oocysts to be nonviable and yet infectious.
Optimal Formations for Cooperative Localization of Mobile Robots

This paper studies the effects of the geometry of a mobile robot formation on the accuracy of the robots’ localization. The general case of heterogeneous (in terms of sensor accuracy) robot teams performing Cooperative Localization is considered. An analysis of the time evolution of the covariance matrix of the position estimates allows us to express the steady-state positioning uncertainty of the robots as an analytic function of the relative positions of the robots in the formation. This metric encapsulates the effect of formation geometry on the information content of the exteroceptive measurements, as well as the effect of the influx of uncertainty due to the errors in the robots’ odometry. Thus, by minimizing the trace of the steady state covariance matrix with respect to the positions of the robots, the optimal robot configuration can be determined. Numerical experiments are presented, which indicate that it is possible to derive a practical rule for determining optimal formations, without the need to resort to extensive simulations, or experimentation.
CT perfusion analysis by nonlinear regression for predicting hemorrhagic transformation in ischemic stroke.

PURPOSE Intravenous thrombolysis can improve clinical outcome in acute ischemic stroke patients but increases the risk of hemorrhagic transformation (HT). Blood-brain barrier damage, which can be quantified by the vascular permeability for contrast agents, is a potential predictor for HT. This study aimed to assess whether this prediction can be improved by measuring vascular permeability using a novel fast nonlinear regression (NLR) method instead of Patlak analysis. METHODS From a prospective ischemic stroke multicenter cohort study, 20 patients with HT on follow-up imaging and 40 patients without HT were selected. The permeability transfer constant K(trans) was measured in three ways; using standard Patlak analysis, Patlak analysis with a fixed offset, and the NLR method. In addition, the permeability-surface (PS) area product and the conventional perfusion parameters (blood volume, flow, and mean transit time) were measured using the NLR method. Relative values were calculated in two ways, i.e., by dividing the average in the infarct core by the average in the contralateral hemisphere, and by dividing the average in the ipsilateral hemisphere by the average in the contralateral hemisphere. Mann-Whitney U tests and receiver operating characteristic (ROC) analyses were performed to assess the discriminative power of each of the relative parameters. RESULTS Both the infarct-core and whole-hemisphere averaged relative K(trans) (rK(trans)) values, measured with the NLR method, were significantly higher in the patients who developed HT as compared with those who did not. The rK(trans) measured with standard Patlak analysis was not significantly different. The relative PS (rPS), measured with NLR, had the highest discriminative power (P = 0.002). ROC analysis of rPS showed an area under the curve (AUC) of 0.75 (95% confidence interval: 0.62-0.89) and a sensitivity of 0.75 at a specificity of 0.75. The AUCs of the Patlak rK(trans), the Patlak rK(trans) with fixed offset, and the NLR rK(trans) were 0.58, 0.66, and 0.67, respectively. CONCLUSIONS CT perfusion analysis may aid in predicting HT, but standard Patlak analysis did not provide estimates for rK(trans) that were significantly higher in the HT group. The rPS, measured in the infarct core with NLR, had superior discriminative power compared with K(trans) measured with either Patlak analysis with a fixed offset or NLR, and conventional perfusion parameters.
Hydrogel contact lens ageing.

PURPOSE To determine if hydrogel lens water content decreases over wearing periods of up to four weeks; that is, demonstrate an 'ageing' effect. METHODS Six subjects (4 males, 2 females; age range: 34.8 +/- 11.0 years) wore each of the following lenses for one month: Acuvue, Frequency 38, Gentle Touch and Proclear. Pre-insertion and post-removal lens water content was measured daily by the subjects using an Atago CL-1 Soft Contact Lens Refractometer for a 28 day period. Post-insertion and pre-removal comfort was recorded over the same period. RESULTS A significant lens ageing effect was noted whereby the pre-insertion lens water content decreased significantly over the 28 day cycle for all lenses (P < 0.05). The pattern for daily dehydration remained consistent for the 28 day period for the Acuvue lens and the Gentle Touch lens but decreased for the Frequency 38 lens and the Proclear lens. Comfort decreased significantly by the end of the day for three of the four lens types investigated. CONCLUSIONS It is apparent that the extent of lens dehydration changes over time, and that this pattern of change is different for different lens types. The associated loss of oxygen performance with dehydration is demonstrated. These data will assist practitioners in understanding the clinical effects of soft lens dehydration over time.
Minimal Set of Essential Resource Disjoint Pairs for Exploring Feasible 3D Schedules

In many synthesis approaches, scheduling is completed before resource binding. Binding centric approaches and simultaneous scheduling/binding approaches such as 3D scheduling are alternative approaches to the high level synthesis. In those approaches, binding is often performed before completion of scheduling. The objective of this paper is to identify and characterize a "feasible" resource binding which guarantees schedulability. The paper introduces the concept of "essential resource disjointness" which is an unavoidable resource disjointness for a valid schedule. It also introduces the concept of "minimal set" of essential resource disjoint pairs (MinERD), and show that MinERD can be characterized by a single processor schedule. By only taking care of MinERD, a schedulable resource binding is always guaranteed
Correlation of cancer stem cell markers and immune cell markers in resected non-small cell lung cancer

Background: Recent studies confirmed that immunotherapy showed prominent efficacy in non-small cell lung cancer (NSCLC). Cancer stem cells/cancer initiating cells are resistant to anticancer treatment. The purpose of the study was to analyze the correlation of cancer stem cells/cancer initiating cells and tumor-infiltrating immune cells in NSCLC. Methods: CD133, octamer 4 (OCT-4), CD8, CD56, human leukocyte antigen (HLA) class I and programmed death ligand-1 (PD-L1) were assessed in 172 resected NSCLC samples. The staining was analyzed and scored by the pathologist who was blinded to the clinical pathological data of the patients. Results: High CD8+ T cell infiltration was correlated significantly with squamous cell carcinoma histology (p=0.008). High PD-L1 expression (≥10%) was associated with high tumor status (p=0.043). Pearson's correlation test showed that CD56+ cells were negatively correlated with CD133 expression (r=-0.361, p<0.001) and weakly correlated with negative OCT-4 expression (r=-0.180, p=0.018). There was a strong positive correlation between CD8 and HLA class I (r=0.573, p<0.001). In the survival analysis, high CD8+ T cell infiltration is an independent predictor of improved disease-free survival and overall survival. Patients with low CD133 expression and high CD56 expression had a longer overall survival than those with high CD133 expression and/or low CD56 expression (p=0.013). Conclusion: There is a negative correlation between CD56+ cells and cancer stem cell markers. This correlation may confirm the possibility that natural killer cells can target CD133+ cancer stem cells/cancer initiating cells in non-small cell lung cancer.