Miracle-dz/UniFAR-FTUs huggingface dataset:
Magnetic Nanoparticles in the Central Nervous System: Targeting Principles, Applications and Safety Issues

One of the most challenging goals in pharmacological research is overcoming the Blood Brain Barrier (BBB) to deliver drugs to the Central Nervous System (CNS). The use of physical means, such as steady and alternating magnetic fields to drive nanocarriers with proper magnetic characteristics may prove to be a useful strategy. The present review aims at providing an up-to-date picture of the applications of magnetic-driven nanotheranostics agents to the CNS. Although well consolidated on physical ground, some of the techniques described herein are still under investigation on in vitro or in silico models, while others have already entered in—or are close to—clinical validation. The review provides a concise overview of the physical principles underlying the behavior of magnetic nanoparticles (MNPs) interacting with an external magnetic field. Thereafter we describe the physiological pathways by which a substance can reach the brain from the bloodstream and then we focus on those MNP applications that aim at a nondestructive crossing of the BBB such as static magnetic fields to facilitate the passage of drugs and alternating magnetic fields to increment BBB permeability by magnetic heating. In conclusion, we briefly cite the most notable biomedical applications of MNPs and some relevant remarks about their safety and potential toxicity.
SelectionReceptor Ligation in B Cell-Negative Differential c-Myc Responsiveness to B Cell

Responsiveness of c- Myc oncogene to B cell receptor ligation has been implicated in the induction of apoptosis in transformed and normal immature B cells. These studies provided compelling evidence to link the c- Myc oncogene with the process of negative selection in B-lymphocytes. However, in addition to apoptosis, B cell-negative selection has been shown to occur by secondary Ig gene rearrangements, a mechanism called receptor editing. In this study, we assessed whether differential c- Myc responsiveness to B cell receptor (BCR) ligation is associated with the mechanism of negative selection in immature B cells. Using an in vitro bone marrow culture system and an Ig-transgenic mouse model (3-83) we show here that c- Myc is expressed at low levels throughout B cell development and that c- Myc responsiveness to BCR ligation is developmentally regulated and increased with maturation. Furthermore, we found that the competence to mount c- Myc responsiveness upon BCR ligation is important for the induction of apoptosis and had no effect on the process of receptor editing. Therefore, this study suggests an important role of c- Myc in promoting and/or maintaining B cell development and that compartmentalization of B cell tolerance may also be developmentally regulated by differential c- Myc responsiveness. The Journal of Immunology, 2003, 171: 2446–2452. 94°C, 40 s at 65°C, and 60 s at 72°C for 30 cycles. The PCR was performed using serial dilutions of cDNA and the PCR products were fractionated on 1% agarose gels. Gels were scanned using an UVIDoc Gel Documentation System and images were analyzed using UVIDoc software (UVItec, Cam-bridge, U.K.) to quantify signal intensity. The results are expressed as a semiquantitative estimate, where signal intensity of c- Myc or RAG-2 product was normalized to that of G (cid:3) s product signal, as we have described elsewhere (31).
The NuRD nucleosome remodelling complex and NHK-1 kinase are required for chromosome condensation in oocytes

ABSTRACT Chromosome condensation during cell division is one of the most dramatic events in the cell cycle. Condensin and topoisomerase II are the most studied factors in chromosome condensation. However, their inactivation leads to only mild defects and little is known about the roles of other factors. Here, we took advantage of Drosophila oocytes to elucidate the roles of potential condensation factors by performing RNA interference (RNAi). Consistent with previous studies, depletion of condensin I subunits or topoisomerase II in oocytes only mildly affected chromosome condensation. In contrast, we found severe undercondensation of chromosomes after depletion of the Mi-2-containing NuRD nucleosome remodelling complex or the protein kinase NHK-1 (also known as Ballchen in Drosophila). The further phenotypic analysis suggests that Mi-2 and NHK-1 are involved in different pathways of chromosome condensation. We show that the main role of NHK-1 in chromosome condensation is to phosphorylate Barrier-to-autointegration factor (BAF) and suppress its activity in linking chromosomes to nuclear envelope proteins. We further show that NHK-1 is important for chromosome condensation during mitosis as well as in oocytes.
A Nested-Loop Architecture for Mobile Robot Navigation

This paper describes a navigation architecture for mobile robots, structured as a set of nested control loops whose depth is related to their knowledge of the environment and the ability to drive the actuator, and involving as well competing behaviors that will ultimately generate the robot motion. The architecture has been successfully used on a mobile platform to support three-dimensional environment reconstruction tasks. The architecture may be classified as belonging to the hybrid type but made up of hybrid elements as well, allowing virtually any level of input awareness and ranging from high-level task planning to direct motion commands issued by external user or applications. A monitorized data path ensures the construction of the most adequate and safe motion, as well as an unlimited set of behaviors depending on the already known and perceived environment. Added concepts of path recovering and assisted navigation fulfill the demands for the three-dimensional acquisition scheme involved. Some comparison with existing architectures is carried out throughout the text. The versatility and robustness of the architecture are supported by extensive results.
Oesophageal dysmotility, delayed gastric emptying and gastrointestinal symptoms in patients with diabetes mellitus

Aims Gastroparesis is a common gastrointestinal complication in diabetes mellitus, whereas dysfunction in the other gastrointestinal organs has been less thoroughly investigated. Furthermore, it is not known whether there is any relationship between motility and dysmotility between these organs. The aim of this study was to examine whether diabetic patients with gastrointestinal symptoms also have motility disturbances in the oesophagus and stomach and, if so, whether there are any associations between these disturbances.
Release of telomeric DNA from chromosomes in immortal human cells lacking telomerase activity.

Some immortal human cell lines lack telomerase activity. These cell lines were found to contain small dispersed DNA hybridizing to TTAGGG repeats. Such DNA was located in their cytoplasm and nuclei. Normal human fibroblasts or telomerase-positive cell lines did not contain such DNA. Upon cloning and sequencing, it was shown to consist of TTAGGG repeats. When electrophoresed on neutral and alkaline agarose gels, it behaved as double-stranded and linear DNA. These results suggest that telomeric DNA is released from chromosomes in association with maintenance of telomeres in telomerase-negative cell lines.
Sequence-Based Genotyping for Marker Discovery and Co-Dominant Scoring in Germplasm and Populations

Conventional marker-based genotyping platforms are widely available, but not without their limitations. In this context, we developed Sequence-Based Genotyping (SBG), a technology for simultaneous marker discovery and co-dominant scoring, using next-generation sequencing. SBG offers users several advantages including a generic sample preparation method, a highly robust genome complexity reduction strategy to facilitate de novo marker discovery across entire genomes, and a uniform bioinformatics workflow strategy to achieve genotyping goals tailored to individual species, regardless of the availability of a reference sequence. The most distinguishing features of this technology are the ability to genotype any population structure, regardless whether parental data is included, and the ability to co-dominantly score SNP markers segregating in populations. To demonstrate the capabilities of SBG, we performed marker discovery and genotyping in Arabidopsis thaliana and lettuce, two plant species of diverse genetic complexity and backgrounds. Initially we obtained 1,409 SNPs for arabidopsis, and 5,583 SNPs for lettuce. Further filtering of the SNP dataset produced over 1,000 high quality SNP markers for each species. We obtained a genotyping rate of 201.2 genotypes/SNP and 58.3 genotypes/SNP for arabidopsis (n = 222 samples) and lettuce (n = 87 samples), respectively. Linkage mapping using these SNPs resulted in stable map configurations. We have therefore shown that the SBG approach presented provides users with the utmost flexibility in garnering high quality markers that can be directly used for genotyping and downstream applications. Until advances and costs will allow for routine whole-genome sequencing of populations, we expect that sequence-based genotyping technologies such as SBG will be essential for genotyping of model and non-model genomes alike.
Automatic Clustering Using Multi-objective Particle Swarm and Simulated Annealing

This paper puts forward a new automatic clustering algorithm based on Multi-Objective Particle Swarm Optimization and Simulated Annealing, “MOPSOSA”. The proposed algorithm is capable of automatic clustering which is appropriate for partitioning datasets to a suitable number of clusters. MOPSOSA combines the features of the multi-objective based particle swarm optimization (PSO) and the Multi-Objective Simulated Annealing (MOSA). Three cluster validity indices were optimized simultaneously to establish the suitable number of clusters and the appropriate clustering for a dataset. The first cluster validity index is centred on Euclidean distance, the second on the point symmetry distance, and the last cluster validity index is based on short distance. A number of algorithms have been compared with the MOPSOSA algorithm in resolving clustering problems by determining the actual number of clusters and optimal clustering. Computational experiments were carried out to study fourteen artificial and five real life datasets.
Credit Derivatives, Disintermediation and Investment Decisions

The credit derivatives market provides a liquid but opaque forum for secondary market trading of banking assets. I show that, when entrepreneurs rely on the certification value of bank debt to obtain cheap bond market finance, the existence of a credit derivatives market may cause them to issue sub-investment grade bonds instead and engage in second-best behavior. Credit derivatives can therefore cause disintermediation and thus reduce welfare. I argue that this effect can be most effectively countered by the introduction of reporting requirements for credit derivatives.
Decision-Theoretic Saliency: Computational Principles, Biological Plausibility, and Implications for Neurophysiology and Psychophysics

A decision-theoretic formulation of visual saliency, first proposed for top-down processing (object recognition) (Gao & Vasconcelos, 2005a), is extended to the problem of bottom-up saliency. Under this formulation, optimality is defined in the minimum probability of error sense, under a constraint of computational parsimony. The saliency of the visual features at a given location of the visual field is defined as the power of those features to discriminate between the stimulus at the location and a null hypothesis. For bottom-up saliency, this is the set of visual features that surround the location under consideration. Discrimination is defined in an information-theoretic sense and the optimal saliency detector derived for a class of stimuli that complies with known statistical properties of natural images. It is shown that under the assumption that saliency is driven by linear filtering, the optimal detector consists of what is usually referred to as the standard architecture of V1: a cascade of linear filtering, divisive normalization, rectification, and spatial pooling. The optimal detector is also shown to replicate the fundamental properties of the psychophysics of saliency: stimulus pop-out, saliency asymmetries for stimulus presence versus absence, disregard of feature conjunctions, and Weber's law. Finally, it is shown that the optimal saliency architecture can be applied to the solution of generic inference problems. In particular, for the class of stimuli studied, it performs the three fundamental operations of statistical inference: assessment of probabilities, implementation of Bayes decision rule, and feature selection.
Characterizing Unstructured Overlay Topologies in Modern P2P File-Sharing Systems

In recent years, peer-to-peer (P2P) file-sharing systems have evolved to accommodate growing numbers of participating peers. In particular, new features have changed the properties of the unstructured overlay topologies formed by these peers. Little is known about the characteristics of these topologies and their dynamics in modern file-sharing applications, despite their importance. This paper presents a detailed characterization of P2P overlay topologies and their dynamics, focusing on the modern Gnutella network. We present Cruiser, a fast and accurate P2P crawler, which can capture a complete snapshot of the Gnutella network of more than one million peers in just a few minutes, and show how inaccuracy in snapshots can lead to erroneous conclusions-such as a power-law degree distribution. Leveraging recent overlay snapshots captured with Cruiser, we characterize the graph-related properties of individual overlay snapshots and overlay dynamics across slices of back-to-back snapshots. Our results reveal that while the Gnutella network has dramatically grown and changed in many ways, it still exhibits the clustering and short path lengths of a small world network. Furthermore, its overlay topology is highly resilient to random peer departure and even systematic attacks. More interestingly, overlay dynamics lead to an ldquoonion-likerdquo biased connectivity among peers where each peer is more likely connected to peers with higher uptime. Therefore, long-lived peers form a stable core that ensures reachability among peers despite overlay dynamics.
Cognitive rehabilitation for elderly people with early-stage Alzheimer’s disease

[Purpose] The purpose of this study was to investigate the effect of cognitive rehabilitation including tasks of cognitive training on performance of everyday activities in elderly people with early-stage Alzheimer’s disease. [Subjects and Methods] Forty-three elderly people (15 men, 28 women) with a diagnosis of Alzheimer’s disease who had a Mini-Mental State Examination (MMSE) score of 18 or above were randomly assigned to two groups: the cognitive rehabilitation group (experimental) and control group. This study used a randomized controlled trial design. Cognitive rehabilitation is consisted of 8 sessions, each lasting 60 minutes (individual 30 min, group 30 min). The eight weekly individual sessions of cognitive rehabilitation were performed consisting of an individualized intervention focusing on a personally meaningful goal. The eight weekly group sessions involved practicing time-and-place orientation, matching faces and names, and learning memory and sustaining attention. [Results] Significant improvements were observed in rating of occupation performance and satisfaction, Quality of Life in Alzheimer’s Disease (QOL-AD), and the orientation subscale of the MMSE in the experimental group, whereas participants in the control group did not show any significant difference in any tests between before and after the intervention. [Conclusion] Cognitive rehabilitation including tasks of cognitive training is an effective intervention for improving performance and satisfaction with respect to activities of daily living and specific cognitive functions.
Sleep, Cognition, and Normal Aging

Sleep is implicated in cognitive functioning in young adults. With increasing age, there are substantial changes to sleep quantity and quality, including changes to slow-wave sleep, spindle density, and sleep continuity/fragmentation. A provocative question for the field of cognitive aging is whether such changes in sleep physiology affect cognition (e.g., memory consolidation). We review nearly a half century of research across seven diverse correlational and experimental domains that historically have had little crosstalk. Broadly speaking, sleep and cognitive functions are often related in advancing age, though the prevalence of null effects in healthy older adults (including correlations in the unexpected, negative direction) indicates that age may be an effect modifier of these associations. We interpret the literature as suggesting that maintaining good sleep quality, at least in young adulthood and middle age, promotes better cognitive functioning and serves to protect against age-related cognitive declines.
Disk Packing in a Square: A New Global Optimization Approach

We present a new computational approach to the problem of placing n identical nonoverlapping disks in the unit square in such a way that their radii are maximized. The problem has been studied in a large number of papers, from both a theoretical and a computational point of view. In this paper, we conjecture that the problem possesses a so-called funneling landscape, a feature that is commonly found in molecular conformation problems. Based on this conjecture, we develop a stochastic search algorithm that displays excellent numerical performance. Thanks to this algorithm, we could improve over previously known putative optima in the range n ≤ 130 in as many as 32 instances, the smallest of which is n = 53.
Intensity-Modulated and Image-Guided Radiotherapy in Patients with Locally Advanced Inoperable Pancreatic Cancer after Preradiation Chemotherapy

Background. Radiotherapy (RT) in patients with pancreatic cancer is still a controversial subject and its benefit in inoperable stages of locally advanced pancreatic cancer (LAPC), even after induction chemotherapy, remains unclear. Modern radiation techniques such as image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) may improve effectiveness and reduce radiotherapy-related toxicities. Methods. Patients with LAPC who underwent radiotherapy after chemotherapy between 09/2004 and 05/2013 were retrospectively analyzed with regard to preradiation chemotherapy (PRCT), modalities of radiotherapy, and toxicities. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves. Results. 15 (68%) women and 7 men (median age 64 years; range 40–77) were identified. Median duration of PRCT was 11.1 months (range 4.3–33.0). Six patients (27%) underwent conventional RT and 16 patients (73%) advanced IMRT and IGRT; median dosage was 50.4 (range 9–54) Gray. No grade III or IV toxicities occurred. Median PFS (estimated from the beginning of RT) was 5.8 months, 2.6 months in the conventional RT group (conv-RT), and 7.1 months in the IMRT/IGRT group (P = 0.029); median OS was 11.0 months, 4.2 months (conv-RT), and 14.0 months (IMRT/IGRT); P = 0.141. Median RT-specific PFS for patients with prolonged PRCT > 9 months was 8.5 months compared to 5.6 months for PRCT < 9 months (P = 0.293). This effect was translated into a significantly better median RT-specific overall survival of patients in the PRCT > 9 months group, with 19.0 months compared to 8.5 months in the PRCT < 9 months group (P = 0.049). Conclusions. IGRT and IMRT after PRCT are feasible and effective options for patients with LAPC after prolonged preradiation chemotherapy.
Ex Vivo Lung Perfusion in the Rat: Detailed Procedure and Videos

Ex vivo lung perfusion (EVLP) is a promising procedure for evaluation, reconditioning, and treatment of marginal lungs before transplantation. Small animal models can contribute to improve clinical development of this technique and represent a substantial platform for bio-molecular investigations. However, to accomplish this purpose, EVLP models must sustain a prolonged reperfusion without pharmacological interventions. Currently available protocols only partly satisfy this need. The aim of the present research was accomplishment and optimization of a reproducible model for a protracted rat EVLP in the absence of anti-inflammatory treatment. A 180 min, uninjured and untreated perfusion was achieved through a stepwise implementation of the protocol. Flow rate, temperature, and tidal volume were gradually increased during the initial reperfusion phase to reduce hemodynamic and oxidative stress. Low flow rate combined with open atrium and protective ventilation strategy were applied to prevent lung damage. The videos enclosed show management of the most critical technical steps. The stability and reproducibility of the present procedure were confirmed by lung function evaluation and edema assessment. The meticulous description of the protocol provided in this paper can enable other laboratories to reproduce it effortlessly, supporting research in the EVLP field.
Dominant Trees in a Subtropical Forest Respond to Drought Mainly via Adjusting Tissue Soluble Sugar and Proline Content

It is well-known that drought has considerable effects on plant traits from leaf to ecosystem scales; however, little is known about the relative contributions of various traits within or between tree species in determining the plant’s sensitivity or the tolerance to drought under field conditions. We conducted a field throughfall exclusion experiment to simulate short-term drought (∼67% throughfall exclusion during the dry season from October to March) and prolonged drought (∼67% throughfall exclusion prolonging the dry season from October to May) and to understand the effects of drought on two dominant tree species (Michelia macclurei and Schima superba) in subtropical forests of southern China. The morphological, physiological, and nutritional responses of the two species to the two types of drought were determined. There were significantly different morphological (leaf max length, max width, leaf mass per area), physiological (leaf proline) and nutritional (P, S, N, K, Ca, Mg) responses by M. macclurei and S. superba to prolonged drought. Comparison between the drought treatments for each species indicated that the trees responded species–specifically to the short-term and prolonged drought, with S. superba exhibiting larger plasticity and higher adaption than M. macclurei. M. macclurei responded more sensitively to prolonged drought in terms of morphology, proline content, and nutritional traits and to short-term drought with regard to soluble sugars content. The differential species-specific responses to drought will allow us to estimate the changes in dominant trees in subtropical forests of China that have experienced a decade’s worth of annual seasonal drought.