Miracle-dz/UniFAR-FTUs huggingface dataset:
Autologous stem cell transplantation for elderly patients with acute myeloid leukaemia conditioned with continuous infusion idarubicin and busulphan

Different studies have suggested the potential utility of autologous stem cell transplantation (ASCT) in acute myeloid leukaemia (AML) of the elderly with encouraging results in selected patients. However, while the introduction of peripheral blood stem cells (PBSC) has consistently reduced morbidity and mortality of the procedure, relapse still represents the major cause of ASCT failure. One possibility to ameliorate therapeutic results could rely on the adoption of conditioning regimens specifically designed for AML. We report therapeutic results from a series of 40 AML patients older than 60 years (median age 67 years) autografted in first complete remission (CR), after conditioning with continuous infusion (c.i.) high dose idarubicin and busulphan. Fourty patients (median age: 67 years) received 2 days c.i. idarubicin at 20 mg/m2/day, followed by 3 days oral or intravenous busulphan (4 mg/kg/day) as conditioning. No case of transplant‐related mortality occurred. Cardiac toxicity was absent, while 31 patients (77%) had grade 3–4 mucositis. After a median follow‐up of 25 months, median disease free and overall survival (OS) for the whole patient population were 13 and 22 months, respectively. Three patients died while in CR from causes unrelated to AML. Better results were achieved in patients with intermediate karyotype as opposed to those with adverse cytogenetics. Our data confirm the feasibility of a conditioning regimen based on high‐dose idarubicin plus busulphan in older selected AML patients and suggest clinical improvement in patients with normal cytogenetics. Copyright © 2009 John Wiley & Sons, Ltd.
Pastor Paulo vs. Doctor Carlos: Professional Titles as Voting Heuristics in Brazil

In low-information elections, voters are likely to rely on heuristics when choosing candidates. Based on survey experiments conducted prior to Brazil's 2012 municipal elections, I examine the effect of candidates’ professional titles, such as “doctor” and “pastor,” on voting behavior. Using the “pastor” title in one's electoral name tends to decrease vote intention, although evangelical Christians respond positively while members of other religious groups are repelled. The broader atmosphere of political competition between Brazilian evangelicals and Catholics helps explain the presence of both out-group and in-group cueing effects. The “doctor” title has a positive effect on vote intention that appears to be mediated by the positive stereotypes, such as intelligence and competence, associated with members of this profession.
ESC working group position paper on myocardial infarction with non-obstructive coronary arteries.

The management of acute myocardial infarction (AMI)1 has evolved over the past century and particularly in the past 50 years. Important milestones include the development of the electrocardiogram, coronary care units, coronary angiography, reperfusion therapies, and troponin assays. These innovations are the foundation of contemporary AMI management strategies that include a diagnosis centred on elevated troponin values associated with corroborative clinical evidence,1 early use of coronary angiography, and reperfusion therapies.2–4 Pivotal in the evolution of these contemporary strategies were the early AMI coronary angiography studies undertaken by DeWood et al. These pioneering studies demonstrated that, in patients presenting with ST elevation myocardial infarction (STEMI), almost 90% had an occluded coronary artery provided that angiography was undertaken within 4 h of chest pain onset.5 In contrast, in AMI patients who did not present with ST elevation (non-ST elevation myocardial infarction or NSTEMI), only 26% had an occluded coronary artery when angiography was performed within 24 h of symptom onset.6 In both of these landmark studies,5,6 >90% of the acute MI patients had angiographic evidence of obstructive coronary artery disease (CAD), underscoring the importance of the atherosclerotic process in the pathogenesis of AMI. Although DeWood's studies underscore the importance of obstructive CAD in AMI, it is fascinating that ∼10% had no significant CAD on coronary angiography. This is confirmed in several large AMI registries7–9 where 1–13% of AMI's occurred in the absence of obstructive CAD thereby eliciting an important set of questions—what is the mechanism of the myocardial damage in these patients? Do these patients differ from those with obstructive CAD? Should they be …
Immunostimulatory DNA as an Adjuvant in Vaccination against Leishmania major

ABSTRACT Oligodeoxynucleotides (ODN) which contain immunostimulatory CG motifs (CpG ODN) can promote T helper 1 (Th1) responses, an adjuvant activity that is desirable for vaccination against leishmaniasis. To test this, susceptible BALB/c mice were vaccinated with soluble leishmanial antigen (SLA) with or without CpG ODN as adjuvant and then challenged with Leishmania major metacyclic promastigotes. CpG ODN alone gave partial protection when injected up to 5 weeks prior to infection, and longer if the ODN was bound to alum. To demonstrate an antigen-specific adjuvant effect, a minimum of 6 weeks between vaccination and infection was required. Subcutaneous administration of SLA alone, SLA plus alum, or SLA plus non-CpG ODN resulted in exacerbated disease compared to unvaccinated mice. Mice receiving SLA plus CpG ODN showed a highly significant (P < 5 × 10−5) reduction in swelling compared to SLA-vaccinated mice and enhanced survival compared to unvaccinated mice. The modulation of the response to SLA by CpG ODN was maintained even when mice were infected 6 months after vaccination. CpG ODN was not an effective adjuvant for antibody production in response to SLA unless given together with alum, when it promoted production of immunoglobulin G2a, a Th1-associated isotype. Our results suggest that with an appropriate antigen, CpG ODN would provide a stable, cost-effective adjuvant for use in vaccination against leishmaniasis.
Combination of Advanced Inversion Techniques for an Accurate Target Localization via GPR for Demining Applications

We used advanced ground-penetrating radar (GPR) inversion techniques for detecting landmines in laboratory conditions. The radar data were acquired with a calibrated vector network analyzer combined with an off-ground monostatic horn antenna, thereby setting up a stepped-frequency continuous-wave radar. Major antenna effects and interactions with the soil and targets were filtered out using frequency-dependent complex antenna transfer functions. The proposed strategy first exploits inversion approaches that are able to give an accurate characterization of the antenna-soil interaction and a reliable estimate of the soil permittivity. The outcomes of this first phase are at the basis of the application of a microwave tomographic approach based on the Born approximation to achieve the imaging of the subsurface. The algorithms were applied for imaging three landmines of different sizes and buried at different depths in sand. Although the radar system was off the ground, the results showed that it was possible to reconstruct all mines, including a shallow plastic mine as small as 5.6 cm in diameter. This last mine was invisible in the raw radar data, and the use of common GPR imaging techniques did not lead to satisfactory results. The proposed integrated method shows great promise for shallow subsurface imaging in a demining context, particularly because it automatically provides accurate information on the shallow soil dielectric permittivity.
Intratumoral Delivery of Low Doses of Anti-CD40 mAb Combined With Monophosphoryl Lipid A Induces Local and Systemic Antitumor Effects in Immunocompetent and T Cell-Deficient Mice

In this study, an agonistic anti-CD40 monoclonal antibody was combined with monophosphoryl lipid A (MPL), a nontoxic derivative of lipopolysaccharide and agonist of toll-like receptor-4, to assess the immunomodulatory and antitumor synergy between the 2 agents in mice. Anti-CD40 was capable of priming macrophages to subsequent ex vivo activation by MPL in immunocompetent and T-cell–depleted mice. Intraperitoneal injections of anti-CD40+MPL induced additive to synergistic suppression of poorly immunogenic B16-F10 melanoma growing subcutaneously in syngeneic mice. When anti-CD40+MPL were injected directly into the subcutaneous tumor, the combination treatment was more effective, even with a 25-fold reduction in dose. Low-dose intratumoral treatment also slowed the growth of a secondary tumor growing simultaneously at a distant, untreated site. Antitumor effects were also induced in severe combined immunodeficiency mice and in T-cell–depleted C57BL/6 mice. Taken together, our results show that the antitumor effects of anti-CD40 are enhanced by subsequent treatment with MPL, even in T-cell–deficient hosts. These preclinical data suggest that an anti-CD40+MPL combined regimen is appropriate for clinical testing in human patients, including cancer patients who may be immunosuppressed from prior chemotherapy.
Dynamics and control of twisting bi-stable structures

Compliance-based morphing structures have the potential to offer large shape adaptation, high stiffness and low weight, while reducing complexity, friction, and scalability problems of mechanism based systems. A promising class of structure that enables these characteristics are multi-stable structures given their ability to exhibit large deflections and rotations without the expensive need for continuous actuation, with the latter only required intermittently. Furthermore, multi-stable structures exhibit inherently fast response due to the snap-through instability governing changes between stable states, enabling rapid configuration switching between the discrete number of programmed shapes of the structure. In this paper, the design and utilisation of the inherent nonlinear dynamics of bi-stable twisting I-beam structures for actuation with low strain piezoelectric materials is presented. The I-beam structure consists of three compliant components assembled into a monolithic single element, free of moving parts, and showing large deflections between two stable states. Finite element analysis is utilised to uncover the distribution of strain across the width of the flange, guiding the choice of positioning for piezoelectric actuators. In addition, the actuation authority is maximised by calculating the generalised coupling coefficient for different positions of the piezoelectric actuators. The results obtained are employed to tailor and test I-beam designs exhibiting desired large deflection between stable states, while still enabling the activation of snap-through with the low strain piezoelectric actuators. To this end, the dynamic response of the I-beams to piezoelectric excitation is investigated, revealing that resonant excitations are insufficient to dynamically trigger snap-through. A novel bang–bang control strategy, which exploits the nonlinear dynamics of the structure successfully triggers both single and constant snap-through between the stable states of the bi-stable twisting I-beam structures. The obtained optimal piezoelectric actuator positioning is not necessarily intuitive and when used with the proposed dynamic actuation strategy serve as a blueprint for the actuation of such multi-stable compliant structures to produce fast and large deflections with highly embeddable actuators. This class of structures has potential applications in aerospace systems and soft/compliant robotics.
Arabidopsis NAC45/86 direct sieve element morphogenesis culminating in enucleation

Removing the nucleus in sieve elements Although a cell's nucleus performs critical command and control functions, some cell types, such as enucleated red blood cells, seem to do without. Sieve element cells in plants similarly carry out their function of transporting nutrients and signals from one end of the plant to the other without the guidance of a nucleus. Furuta et al. watched how the nucleus self-destructs during the development of sieve element cells (see the Perspective by Geldner). The process is regulated under the control of transcription factors, even as the entire nuclear edifice crumbles into nothingness. Science, this issue p. 933; see also p. 875 Cellular remodeling to develop phloem cells orchestrates degradation of the cell’s nucleus. [Also see Perspective by Geldner] Photoassimilates such as sugars are transported through phloem sieve element cells in plants. Adapted for effective transport, sieve elements develop as enucleated living cells. We used electron microscope imaging and three-dimensional reconstruction to follow sieve element morphogenesis in Arabidopsis. We show that sieve element differentiation involves enucleation, in which the nuclear contents are released and degraded in the cytoplasm at the same time as other organelles are rearranged and the cytosol is degraded. These cellular reorganizations are orchestrated by the genetically redundant NAC domain–containing transcription factors, NAC45 and NAC86 (NAC45/86). Among the NAC45/86 targets, we identified a family of genes required for enucleation that encode proteins with nuclease domains. Thus, sieve elements differentiate through a specialized autolysis mechanism.
Characterization of Soft Tissue Tumors by Diffusion-Weighted Imaging

Background: Diffusion-weighted imaging (DWI) is a noninvasive method for investigation of tumor histological content. It has been applied for some musculoskeletal tumors and reported to be useful. Objectives: The aim of the present study was to prospectively evaluate the apparent diffusion coefficient (ADC) values of benign and malignant soft tissue tumors and to determine if ADC can help differentiate these tumors. Patients and Methods: DWI was performed on 25 histologically proven soft tissue masses. It was obtained with a single-shot echo-planar imaging technique using a 1.5T magnetic resonance (MR) machine. The mean ADC values were calculated. We grouped soft tissue tumors as benign cystic, benign solid or mixed, malignant cystic and malignant solid or mixed tumors and compared mean ADC values between these groups. Results: There was only one patient with a malignant cystic tumor and was not included in the statistical analysis. The median ADC values of benign and malignant tumors were 2.31 ± 1.29 and 0.90 ± 0.70 (median ± interquartile range), respectively. The mean ADC values were different between benign and malignant tumors (P = 0.031). Benign cystic tumors had significantly higher ADC values than benign solid or mixed tumors and malignant solid or mixed tumors (p values were < 0.001 and 0.003, respectively). Malignant solid or mixed tumors had lower ADC values than benign solid or mixed tumors (P = 0.02). Conclusion: Our preliminary results have shown that although there is some overlap between benign and malignant tumors, adding DWI, MR imaging to routine soft tissue tumor protocols may improve diagnostic accuracy.
Rare Event Detection in a Spatiotemporal Environment

In this paper we explore the use of Extensible Markov Models (EMM) to detect rare events in a spatiotemporal environment. This initial work shows that an EMM is scalable, dynamic, and can detect rare events based on spatial values, temporal values, or transitions between real world states. The core of the EMM approach is a combination of clustering and dynamic Markov Chain. Keywords—Extensible Markov Model (EMM), rare event
SEM resolution improvement using semi-blind restoration with hybrid L1-L2 regularization

Scanning electron microscopy (SEM) resolution is limited by many factors that include sample specific properties, microscope stability, noise, the three dimensional nature of the sample and the excitation volume, and the spatial distribution of electrons in the probe known as the point spread function (PSF). If all, but the latter are optimized, the loss of resolution is principally due to blurring by the convolution of the PSF with the structure of interest. Image resolution can then be increased by deconvolution combined with the mathematical process known as regularization. To accomplish this task, a novel high resolution semi-blind image restoration technique incorporating hybrid L1 and L2 regularization terms has been developed. The original optimization is divided into the efficient solution of three subproblems, and has been validated with a variety of actual SEM images.
Frequency-Shift Offset-QAM for GFDM

This paper presents a novel perspective to apply the offset quadrature amplitude modulation (OQAM) scheme on top of the multicarrier waveform termed Generalized Frequency Division Multiplexing (GFDM). The conventional time-shift OQAM is described for GFDM and, with the introducing of the general use of unitary transform, an interesting counterpart, i.e., frequency-shift OQAM, is proposed. The conventional long prototype pulse with time-shift of one half subsymbol becomes a short prototype pulse with frequency-shift of one half subcarrier. The frequency-shift OQAM scheme offers advantages such as low out-of-band emission and low implementation complexity. The concept can be applied to the broader scope of filtered OFDM without penalties in terms of performance in time variant frequency-selective channels.
Almost-Sure Model-Checking of Reactive Timed Automata

We consider the model of stochastic timed automata, a model in which both delays and discrete choices are made probabilistically. We are interested in the almost-sure model-checking problem, which asks whether the automaton satisfies a given property with probability 1. While this problem was shown decidable for single-clock automata few years ago, it was also proven that the algorithm for this decidability result could not be used for general timed automata. In this paper we describe the subclass of reactive timed automata, and we prove decidability of the almost-sure model-checking problem under that restriction. Decidability relies on the fact that this model is almost-surely fair. As a desirable property of real systems, we show that reactive automata are almost-surely non-Zeno. Finally we show that the almost-sure model-checking problem can be decided for specifications given as deterministic timed automata.
Effects of sodium hydroxide and polydopamine pretreatment and calcium phosphate coating on the properties of biodegradable magnesium

Magnesium (Mg) has shown great promise as a potential biocompatible and biodegradable implant material. Some of its unique properties include high strength/weight ratio and closer elastic modulus to that of the human bone. However, in a pure state, its in-vivo corrosion is too rapid to be used for implants. Hydrogen evolution during degradation leads to the elevation of body fluid pH which causes infection or inflammation and delaying tissue healing process. Despite many studies to improve the corrosion resistance of pure Mg, reports on sodium hydroxide (NaOH) and polydopamine (PDA) pre-treated Mg followed by calcium-phosphate (Ca-P) coating using electrodeposition (ED) technique are hardly found in the literature especially fluoridated hydroxyapatite (FHA) coating. This research is aimed to improve the corrosion resistance of Mg by NaOH and PDA pre-treatment followed by different phases of Ca-P coatings. In the first stage, pure Mg was pre-treated with NaOH (1M, 30 minutes) and PDA (2 mg/ml in 10 mM Tris buffer, pH 8.5). In the second stage, different phases of Ca-P were coated on the pre-treated specimens using ED technique with two different electrolytes at current density equal to 1 mA/cm2 for 60 minutes at room temperature. The pre-treated and coated specimens were analysed using X-ray photoelectron spectroscopy, grazing incidence X-ray diffraction, attenuated total reflectance-Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and optical microscopy. The specimens were also evaluated on their surface roughness, water contact angle and scratch hardness. In addition, corrosion behaviours of specimens were analysed using potentiodynamic polarization and in-vitro immersion tests. Results in the first stage showed that both pre-treatments decreased the corrosion rate of Mg, in particular coated substrates with PDA by almost 27 folds. PDA pre-treatment also improved surface properties by reducing water contact angle and increasing surface roughness by 2.3 and 4.5 folds respectively as compared to pure Mg. In the second stage, the results showed that dicalcium-phosphate dihydrate (DCPD) and FHA were formed on NaOH pre-treated specimens. It was found that DCPD coatings required posttreatment to convert DCPD to hydroxyapatite (HA). However, HA and FHA were able to be deposited directly on the PDA pre-treated specimens without requiring any post-treatment. In terms of adhesion strength between the Ca-P coatings and the substrates, PDA pre-treatment specimens were superior than NaOH pre-treatment. Comparing between FHA and HA coatings on both pre-treatments, FHA coated specimens demonstrated higher corrosion resistance and surface roughness. It is believed that by introducing fluorine into the coating, it stabilizes and increases the crystalline structure of FHA. The corrosion resistance of FHA-PDA coated Mg improved significantly (approximately 62 folds) as compared to uncoated pure Mg.
An Immersive Virtual Environment for Special Relativity

In this paper, an immersive virtual environment is presented which allows the user to virtually explore and experience special relativity, including phenomena such as Lorentz contraction, time dilation, aberration, and finite speed of light. The relativistic-vehicle-control metaphor—a physically based camera control technique—is introduced for navigating at high velocities. Acceleration of the relativistic observer is investigated. Furthermore, tracking of both the position and velocity of the user is considered. A geometric approach to relativistic polygon rendering is described. The rendering pipeline is extended to accomplish the relativistic transformations in parallel. The implementation supports multiprocessor and multipipe systems for fast rendering and the same frame rates can be achieved for relativistic visualization as for non-relativistic rendering.
Alkoxy-auxins Are Selective Inhibitors of Auxin Transport Mediated by PIN, ABCB, and AUX1 Transporters*

Polar auxin movement is a primary regulator of programmed and plastic plant development. Auxin transport is highly regulated at the cellular level and is mediated by coordinated transport activity of plasma membrane-localized PIN, ABCB, and AUX1/LAX transporters. The activity of these transporters has been extensively analyzed using a combination of pharmacological inhibitors, synthetic auxins, and knock-out mutants in Arabidopsis. However, efforts to analyze auxin-dependent growth in other species that are less tractable to genetic manipulation require more selective inhibitors than are currently available. In this report, we characterize the inhibitory activity of 5-alkoxy derivatives of indole 3-acetic acid and 7-alkoxy derivatives of naphthalene 1-acetic acid, finding that the hexyloxy and benzyloxy derivatives act as potent inhibitors of auxin action in plants. These alkoxy-auxin analogs inhibit polar auxin transport and tropic responses associated with asymmetric auxin distribution in Arabidopsis and maize. The alkoxy-auxin analogs inhibit auxin transport mediated by AUX1, PIN, and ABCB proteins expressed in yeast. However, these analogs did not inhibit or activate SCFTIR1 auxin signaling and had no effect on the subcellular trafficking of PIN proteins. Together these results indicate that alkoxy-auxins are inactive auxin analogs for auxin signaling, but are recognized by PIN, ABCB, and AUX1 auxin transport proteins. Alkoxy-auxins are powerful new tools for analyses of auxin-dependent development.