Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity limitations and participation restrictions in people with multiple sclerosis: a detailed 10-year perspective

Abstract Aim To conduct a detailed investigation into changes in activity limitations and participation restrictions over 10 years in people with mild, moderate and severe multiple sclerosis. Methods This study was a 10-year longitudinal study of 264 people with multiple sclerosis living in Stockholm County, Sweden. Ten-year changes in personal and instrumental activities in daily living were assessed using the Katz Activities in Daily Living Index Extended and participation in social/lifestyle activities using the Frenchay Activities Index. Results While people with moderate multiple sclerosis, compared to baseline, demonstrated significantly higher proportions of dependency in most activities of personal and instrumental activities in daily living at the 10-year follow-up, the mild group primarily increased their dependency in instrumental activities and the severe group in personal activities. Significantly higher proportions of the moderate group showed restricted participation in domestic and outdoor activities whereas the mild group only showed restrictions in a few domains of participation. A majority of people with severe multiple sclerosis showed restricted participation in all social/lifestyle activities at baseline and the 10-year follow-up. Conclusions Prominent long-term increases in activity limitations and participation restrictions occurred across the spectrum of disease severity but was most pronounced in those more moderately affected. Implications for rehabilitation This study provides guidance with regard to specific activities that are prone to deteriorate across 10 years and thereby reflect important targets and outcomes for interventions. Increases in activity limitations and participation restrictions were most pronounced in those moderately affected by multiple sclerosis. Those mildly affected by multiple sclerosis primarily increased their dependency in instrumental activities of daily living while those severely affected increased their dependency in personal activities of daily living.
Costs and benefits of realism and optimism

Purpose of review What is the relationship between rationality and mental health? By considering the psychological literature on depressive realism and unrealistic optimism, it was hypothesized that, in the context of judgments about the self, accurate cognitions are psychologically maladaptive and inaccurate cognitions are psychologically adaptive. Recent studies recommend being cautious in drawing any general conclusion about the style of thinking and mental health. Recent findings Recent investigations suggest that people with depressive symptoms are more accurate than controls in tasks involving time perception and estimates of personal circumstances, but not in other tasks. Unrealistic optimism remains a robust phenomenon across a variety of tasks and domains, and researchers are starting to explore its neural bases. However, the challenge is to determine to what extent and in what way unrealistic optimism is beneficial. Summary We should revisit the hypothesis that optimistic cognitions are psychologically adaptive, whereas realistic thinking is not. Realistic beliefs and expectations can be conducive to wellbeing and good functioning, and wildly optimistic cognitions have considerable psychological costs.
Interleukin‐1 and nitric oxide protect against tumor necrosis factor α‐induced liver injury through distinct pathways

Mice sensitized with D‐galactosamine (GalN) and challenged with recombinant murine tumor necrosis factor α (TNFα) developed severe apoptotic and secondary necrotic liver injury as assessed by histology, measurement of cytosolic DNA fragments, and determination of liver specific enzymes in plasma. Pretreatment with recombinant human interleukin‐1β (IL‐1) rendered mice insensitive to this TNFα toxicity. Coadministration of the liver‐specific transcriptional inhibitor GalN with IL‐1 prevented the development of tolerance, implicating de novo synthesis of liver specific proteins in the induction of tolerance. Pretreatment of mice with IL‐1 resulted in elevated levels of nitrite/nitrate in serum and in enhanced nitric oxide synthase (NOS) activity in liver cells isolated from these animals. In addition, pharmacological doses of the nitric oxide (NO) donor sodium nitroprusside conferred complete protection against TNFα‐induced liver injury in galactosamine‐sensitized mice, suggesting a possible link between IL‐1‐ and NO‐in‐duced protection. However, prevention of NO‐synthesis by NG‐monomethyl‐L‐arginine (NMMA) did not abolish IL‐1‐induced tolerance to TNFα in vivo. Cytotoxicity of TNFα to isolated hepatocytes sensitized with actinomycin D (ActD) was not significantly altered by inhibition of endogenous nitrite release. Also, enhanced NO production elicited in vitro by glycerol trinitrate or ex vivo by pretreatment with IL‐1 had no significant effect in this system. We conclude that IL‐1‐ and NO‐induced protection of mice against TNFα‐mediated liver damage follow distinct pathways. (Hepatology 1995; 22:1829‐1837).
Outcome following Nerve Repair of High Isolated Clean Sharp Injuries of the Ulnar Nerve

Objective The detailed outcome of surgical repair of high isolated clean sharp (HICS) ulnar nerve lesions has become relevant in view of the recent development of distal nerve transfer. Our goal was to determine the outcome of HICS ulnar nerve repair in order to create a basis for the optimal management of these lesions. Methods High ulnar nerve lesions are defined as localized in the area ranging from the proximal forearm to the axilla just distal to the branching of the medial cord of the brachial plexus. A meta-analysis of the literature concerning high ulnar nerve injuries was performed. Additionally, a retrospective study of the outcome of nerve repair of HICS ulnar nerve injuries at our institution was performed. The Rotterdam Intrinsic Hand Myometer and the Rosén-Lundborg protocol were used. Results The literature review identified 46 papers. Many articles presented outcomes of mixed lesion groups consisting of combined ulnar and median nerves, or the outcome of high and low level injuries was pooled. In addition, outcome was expressed using different scoring systems. 40 patients with HICS ulnar nerve lesions were found with sufficient data for further analysis. In our institution, 15 patients had nerve repair with a median interval between trauma and reconstruction of 17 days (range 0–516). The mean score of the motor and sensory domain of the Rosen's Scale instrument was 58% and 38% of the unaffected arm, respectively. Two-point discrimination never reached less then 12 mm. Conclusion From the literature, it was not possible to draw a definitive conclusion on outcome of surgical repair of HICS ulnar nerve lesions. Detailed neurological function assessment of our own patients showed that some ulnar nerve function returned. Intrinsic muscle strength recovery was generally poor. Based on this study, one might cautiously argue that repair strategies of HICS ulnar nerve lesions need to be improved.
(Pro)renin Receptor Triggers Distinct Angiotensin II-Independent Extracellular Matrix Remodeling and Deterioration of Cardiac Function

Background Activation of the renin-angiotensin-system (RAS) plays a key pathophysiological role in heart failure in patients with hypertension and myocardial infarction. However, the function of (pro)renin receptor ((P)RR) is not yet solved. We determined here the direct functional and structural effects of (P)RR in the heart. Methodology/Principal Findings (P)RR was overexpressed by using adenovirus-mediated gene delivery in normal adult rat hearts up to 2 weeks. (P)RR gene delivery into the anterior wall of the left ventricle decreased ejection fraction (P<0.01), fractional shortening (P<0.01), and intraventricular septum diastolic and systolic thickness, associated with approximately 2–fold increase in left ventricular (P)RR protein levels at 2 weeks. To test whether the worsening of cardiac function and structure by (P)RR gene overexpression was mediated by angiotensin II (Ang II), we infused an AT1 receptor blocker losartan via osmotic minipumps. Remarkably, cardiac function deteriorated in losartan-treated (P)RR overexpressing animals as well. Intramyocardial (P)RR gene delivery also resulted in Ang II-independent activation of extracellular-signal-regulated kinase1/2 phosphorylation and myocardial fibrosis, and the expression of transforming growth factor-β1 and connective tissue growth factor genes. In contrast, activation of heat shock protein 27 phosphorylation and apoptotic cell death by (P)RR gene delivery was Ang II-dependent. Finally, (P)RR overexpression significantly increased direct protein–protein interaction between (P)RR and promyelocytic zinc-finger protein. Conclusions/Significance These results indicate for the first time that (P)RR triggers distinct Ang II-independent myocardial fibrosis and deterioration of cardiac function in normal adult heart and identify (P)RR as a novel therapeutic target to optimize RAS blockade in failing hearts.
The Cosmic Lens All‐Sky Survey: statistical strong lensing, cosmological parameters, and global properties of galaxy populations

Extensive analyses of statistical strong gravitational lensing are performed based on the final Cosmic Lens All-Sky Survey (CLASS) well-defined statistical sample of flat-spectrum radio sources and current estimates of galaxy luminosity functions per morphological type. The analyses are carried out under the assumption that galactic lenses are well-approximated by singular isothermal ellipsoids and early-type galaxies evolved passively since redshift z ∼ 1. Two goals of the analyses are: (i) to constrain cosmological parameters independently of other techniques (e.g. Type Ia supernovae magnitude-redshift relation, cosmic microwave background anisotropies, galaxy matter power spectra); and (ii) to constrain the characteristic line-of-sight velocity dispersion and the mean projected mass ellipticity for the early-type galaxy population. Depending on how the late-type galaxy population is treated (i.e. whether its characteristic velocity dispersion is constrained or not), we find for a flat universe with a classical cosmological constant that the matter fraction of the present critical density Ω m = 0.31 + 0 . 2 7 -0.14 (68 per cent) for the unconstrained case or 0.40 + 0 . 2 8 -0.16 (68 per cent) for the constrained case, with an additional systematic uncertainty of 0.11 arising from the present uncertainty in the distribution of CLASS sources in redshift and flux density. For a flat universe with a constant equation of state for dark energy w = p x (pressure)/ρ x (energy density) and the prior constraint ω ≥ -1, we find that -1 ≤ ω < -0.55 + 0 . 1 8 -0.11 (68 per cent) for the unconstrained case or -1 ≤ w < -0.41 + 0 . 2 8 -0.16 (68 per cent) for the constrained case, where w = -1 corresponds to a classical cosmological constant. The determined value of the early-type characteristic velocity dispersion [σ ( e ) *] depends on the faint-end slope of the early-type luminosity function [α ( 3 ) ] and the intrinsic shape distribution of galaxies; for equal frequencies of oblates and prolates, we find that σ ( e ) *(0.3 ≤ z ≤ 1) = 198 + 2 2 -18 km s - 1 (68 per cent) for a 'steep' α ( 3 ) = -1 or σ ( e ) *(0.3 ≤ z ≤ 1) = 181 + 1 8 -15 km s - 1 (68 per cent) for a 'shallow' α ( e ) = -0.54. Finally, from the relative frequencies of doubly imaged sources and quadruply imaged sources, we find that a mean projected mass ellipticity of early-type galaxies ∈ m a s s = 0.42 with a 68 per cent lower limit of 0.28 assuming equal frequencies of oblates and prolates.
WIVSS: a new methodology for scoring information systems vulnerabilities

Vulnerabilities of information systems constitute an ever-increasing problem that IT security management must solve. As the number of vulnerabilities is growing exponentially, their ranking and prioritization is a crucial task for organizations and researchers that are involved with the security of computer systems. The open standard to score and rank the vulnerabilities is the Common Vulnerability Scoring System (CVSS) while the focus of this research is to investigate ways to improve it by achieving higher diversity of values and better accuracy. In this paper it is introduced a new vulnerability scoring system, called WIVSS (Weighted Impact Vulnerability Scoring System). The methodology uses a different approach to score vulnerabilities, depending on the different impact of vulnerabilities characteristics. The methodology WIVSS is applied to the most recent 9455 vulnerabilities and the results show improvement in comparison with CVSS.
Full-duplex transmission in small area radio communication systems

Full-duplex transmission is an attractive air interface technology to improve spectral efficiency in future wireless systems. This paper introduces potential use cases for full-duplex transmission in small area radio communication systems, and evaluates the achievable performance gains of full-duplex transmission over half-duplex transmission in different network set-ups. Additionally, this paper introduces DUPLO full-duplex transceiver hardware demonstrator and characterizes with practical measurements the achievable performance in short-range communications.
Physico- Chemical Analysis of Well Water at Eloor Industrial Area-Seasonal Study

Seasonal variation on physico-chemical quality of well water at Eloor industrial area, Kerala was studied. A total of 100 samples, 25 each during four different seasons, viz. summer, pre- monsoon, monsoon and post monsoon were collected during the year 2009 and analyzed for temperature, pH, total hardness, Chemical Oxygen Demand, concentration of nitrate, fluoride, iron, heavy metals like lead, mercury, zinc, and cadmium. Significant difference between seasons was observed for temperature, Chemical Oxygen Demand, concentration of nitrate, zinc and cadmium. Highest temperature (28.96±0.16) was recorded during pre- monsoon. Chemical Oxygen Demand and zinc concentration was recorded maximum during summer (150.56±14.07, 0.21±0.04 mg/l respectively). Highest nitrate (5.96±1.10 mg/l) and cadmium (0.05±0.005 mg/l) concentrations were recorded during post monsoon and monsoon respectively The results were compared with WHO guidelines, 2006 and IS: 10500, 1991, desirable limits for drinking water and found that pH, total hardness, concentration of iron, lead and cadmium were not within the acceptable rage.
Blind Source Separation of Postnonlinear Convolutive Mixture

In this paper, a novel solution is developed to solve blind source separation of postnonlinear convolutive mixtures. The proposed model extends the conventional linear instantaneous mixture model to include both convolutive mixing and postnonlinear distortion. The maximum-likelihood (ML) approach solution based on the expectation-maximization (EM) algorithm is developed to estimate the source signals and the parameters in the proposed nonlinear model. In the proposed solution, the sufficient statistics associated with the source signals are estimated in the E-step, while the model parameters are optimized through these statistics in the M-step. However, the complication resulted from the postnonlinear function associated with the mixture renders these statistics difficult to be formulated in a closed form and hence causes intractability in the parameter optimization. A computationally efficient algorithm is proposed which uses the extended Kalman smoother (EKS) to facilitate the E-step tractable and a set of self-updated polynomials is used as the nonlinearity estimator to facilitate closed form estimations of the parameters in the M-step. The theoretical foundation of the proposed solution has been rigorously developed and discussed in details. Both simulations and recorded speech signals have been carried out to verify the success and efficacy of the proposed algorithm. Remarkable improvement has been obtained when compared with the existing algorithms.
Drugs and drug delivery systems targeting amyloid-β in Alzheimer's disease

Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no cure and limited treatment solutions that are unable to target any of the suspected causes. Increasing evidence suggests that one of the causes of neurodegeneration is the overproduction of amyloid beta (Aβ) and the inability of Aβ peptides to be cleared from the brain, resulting in self-aggregation to form toxic oligomers, fibrils and plaques. One of the potential treatment options is to target Aβ and prevent self-aggregation to allow for a natural clearing of the brain. In this paper, we review the drugs and drug delivery systems that target Aβ in relation to Alzheimer's disease. Many attempts have been made to use anti-Aβ targeting molecules capable of targeting Aβ (with much success in vitro and in vivo animal models), but the major obstacle to this technique is the challenge posed by the blood brain barrier (BBB). This highly selective barrier protects the brain from toxic molecules and pathogens and prevents the delivery of most drugs. Therefore novel Aβ aggregation inhibitor drugs will require well thought-out drug delivery systems to deliver sufficient concentrations to the brain.
One-Class Novelty Detection for Seizure Analysis from Intracranial EEG

This paper describes an application of one-class support vector machine (SVM) novelty detection for detecting seizures in humans. Our technique maps intracranial electroencephalogram (EEG) time series into corresponding novelty sequences by classifying short-time, energy-based statistics computed from one-second windows of data. We train a classifier on epochs of interictal (normal) EEG. During ictal (seizure) epochs of EEG, seizure activity induces distributional changes in feature space that increase the empirical outlier fraction. A hypothesis test determines when the parameter change differs significantly from its nominal value, signaling a seizure detection event. Outputs are gated in a . one-shot. manner using persistence to reduce the false alarm rate of the system. The detector was validated using leave-one-out cross-validation (LOO-CV) on a sample of 41 interictal and 29 ictal epochs, and achieved 97.1% sensitivity, a mean detection latency of -7.58 seconds, and an asymptotic false positive rate (FPR) of 1.56 false positives per hour (Fp/hr). These results are better than those obtained from a novelty detection technique based on Mahalanobis distance outlier detection, and comparable to the performance of a supervised learning technique used in experimental implantable devices (Echauz et al., 2001). The novelty detection paradigm overcomes three significant limitations of competing methods: the need to collect seizure data, precisely mark seizure onset and offset times, and perform patient-specific parameter tuning for detector training.
User-centric evaluation of a K-furthest neighbor collaborative filtering recommender algorithm

Collaborative filtering recommender systems often use nearest neighbor methods to identify candidate items. In this paper we present an inverted neighborhood model, k-Furthest Neighbors, to identify less ordinary neighborhoods for the purpose of creating more diverse recommendations. The approach is evaluated two-fold, once in a traditional information retrieval evaluation setting where the model is trained and validated on a split train/test set, and once through an online user study (N=132) to identify users' perceived quality of the recommender. A standard k-nearest neighbor recommender is used as a baseline in both evaluation settings. Our evaluation shows that even though the proposed furthest neighbor model is outperformed in the traditional evaluation setting, the perceived usefulness of the algorithm shows no significant difference in the results of the user study.
Comparison of myxobacterial diversity and evaluation of isolation success in two niches: Kiritimati Island and German compost

Myxobacteria harbor an enormous potential for new bioactive secondary metabolites and therefore the isolation of in particular new groups is of great interest. The diversity of myxobacteria present in two ecological habitats, namely sand from Kiritimati Island and German compost, was evaluated by both cultivation‐based and cultivation‐independent methods. Phylogenetic analyses of the strains in comparison with 16S rRNA gene sequences from cultured and uncultured material in GenBank revealed a great potential of undescribed myxobacteria in both sampling sites. Several OTUs (operational taxonomic units) represent unknown taxa and were detected by clone bank analyses, but not by cultivation. Clone bank analyses indicated that the myxobacterial community is predominantly indigenous. The 16S rDNA libraries from the two samples were generated from total community DNA with myxobacterial specific forward and universal reverse primer sets. The clones were partially sequenced. Cultivation was successful for exclusively bacteriolytic, but not for cellulolytic myxobacteria and revealed 42 strains from the genera Corallococcus, Myxococcus, and Polyangium. The genera of Myxococcaceae family were represented by both approaches. But, even in this well studied family, as well as in the suborders Sorangiineae and Nannocystineae, a considerable number of clones were assigned to, if any, uncultivated organisms. Our study shows an overrepresentation of the genera Myxococcus spp. and Corallococcus spp. with standard cultivation methods. However, high deficits are demonstrated in the cultivation success of the myxobacterial diversity detected by exclusively cultivation‐independent approaches. Especially, clades which are exclusively represented by clones are of high interest with regard to the cultivation of new bioactive secondary metabolite producers.
Pathway and mechanism of drug binding to G-protein-coupled receptors

How drugs bind to their receptors—from initial association, through drug entry into the binding pocket, to adoption of the final bound conformation, or “pose”—has remained unknown, even for G-protein-coupled receptor modulators, which constitute one-third of all marketed drugs. We captured this pharmaceutically critical process in atomic detail using the first unbiased molecular dynamics simulations in which drug molecules spontaneously associate with G-protein-coupled receptors to achieve final poses matching those determined crystallographically. We found that several beta blockers and a beta agonist all traverse the same well-defined, dominant pathway as they bind to the β1- and β2-adrenergic receptors, initially making contact with a vestibule on each receptor’s extracellular surface. Surprisingly, association with this vestibule, at a distance of 15 Å from the binding pocket, often presents the largest energetic barrier to binding, despite the fact that subsequent entry into the binding pocket requires the receptor to deform and the drug to squeeze through a narrow passage. The early barrier appears to reflect the substantial dehydration that takes place as the drug associates with the vestibule. Our atomic-level description of the binding process suggests opportunities for allosteric modulation and provides a structural foundation for future optimization of drug–receptor binding and unbinding rates.