Miracle-dz/UniFAR-FTUs huggingface dataset:
Spastic Paraplegia Type 7 Is Associated with Multiple Mitochondrial DNA Deletions

Spastic paraplegia 7 is an autosomal recessive disorder caused by mutations in the gene encoding paraplegin, a protein located at the inner mitochondrial membrane and involved in the processing of other mitochondrial proteins. The mechanism whereby paraplegin mutations cause disease is unknown. We studied two female and two male adult patients from two Norwegian families with a combination of progressive external ophthalmoplegia and spastic paraplegia. Sequencing of SPG7 revealed a novel missense mutation, c.2102A>C, p.H 701P, which was homozygous in one family and compound heterozygous in trans with a known pathogenic mutation c. 1454_1462del in the other. Muscle was examined from an additional, unrelated adult female patient with a similar phenotype caused by a homozygous c.1047insC mutation in SPG7. Immunohistochemical studies in skeletal muscle showed mosaic deficiency predominantly affecting respiratory complex I, but also complexes III and IV. Molecular studies in single, microdissected fibres showed multiple mitochondrial DNA deletions segregating at high levels (38–97%) in respiratory deficient fibres. Our findings demonstrate for the first time that paraplegin mutations cause accumulation of mitochondrial DNA damage and multiple respiratory chain deficiencies. While paraplegin is not known to be directly associated with the mitochondrial nucleoid, it is known to process other mitochondrial proteins and it is possible therefore that paraplegin mutations lead to mitochondrial DNA deletions by impairing proteins involved in the homeostasis of the mitochondrial genome. These studies increase our understanding of the molecular pathogenesis of SPG7 mutations and suggest that SPG7 testing should be included in the diagnostic workup of autosomal recessive, progressive external ophthalmoplegia, especially if spasticity is present.
Intranasal lorazepam delivery 1 1 Vinyl polymers-coated lorazepam particles for potential intrananal delivery

25 A particle engineering method that adsorbs a microfine vinyl polymer coat to crystalline drug 26 microparticles has been shown to be an effective way to control delivery. However, the means by 27 which the functional performance of such microparticles is altered by the behaviour of the 28 polymers in the microparticle coat remains unclear. The aim of this study was to determine the 29 influence of vinyl polymer coating on the in vitro delivery characteristics of intranasal lorazepam 30 microparticles. A series of four, similarly sized (ca. 10 µm), lorazepam-rich microparticles with 31 different polymer coats were generated. The absorption of the polymer coats appeared to disrupt 32 lorazepam solid state dimer formation in the microparticles, which manifested in a reduction in 33 drug melting point. Mildly cohesive particles (aerodynamic diameter of 32 µm) that allowed rapid 34 drug release (ca. 80% in 5 min) were generated when partially hydrolysed PVA dominated the 35 microparticle coat, whilst fully hydrolysed PVA reduced particle cohesion and retarded drug 36 release (ca. 15% release in 5 min). Infrared analysis showed that the properties of the 37 microparticles were dictated by the strength of the hydrogen bonding in the polymer coat and not 38 the strength of coat adsorption that was facilitated by hydrogen bond formation between the 39 hydroxyl groups of the PVA and the hydroxyl group at position C3 of the lorazepam diazepine 40 ring.
The effect of hydroalcoholic extract of Stachys lavandulifolia vahl on pregnant mice

Objectives: Stachys lavandulifolia is commonly used for many health problems including anxiety. A couple of reports indicate that this plant might have an abortifacient effect on pregnant women. Here we examined this effect on pregnant mice. Materials and methods: Incremental doses of 0, 50, 100, 150 and 200 mg/kg of the extracts or normal saline (control group) were injected intraperitoneally to the pregnant mice between 7th to 12th days of pregnancy. On day 16, uterine tubes were resected and absorbed fetuses were counted. Results: Our study showed that the different average of absorbed fetuses between treated and control groups is significant (P < 0.05). S. lavandulifolia changes the activity level of hypothalamus-pituitary gland-gonad axis due to flavonoid compounds. Also, S. lavandulifolia decreases progesterone concentration resulting in a significant difference between treated and control groups (P < 0.05) and gives rise to failure in fetus survival and consequently, abortion. The length and weight of fetuses decreased in treated groups and there was a significant difference between treated and control groups (P < 0.05). Conclusion: Owing to the possible abortive effect of Stachys lavandulifolia, it is highly recommended to use it cautiously during pregnancy.
Six months of exercise programe twice a week seems to be not enought to improve cognitive function in older people

Aging is a natural process that implies a physical and cognitive decline. In the last two decades, physical exercise has emerged as a powerful modulator of these processes, and an important lifestyle to reduce frailty and dependence. This study measure physical and cognitive performance of sixteen old people who participated in a six-month physical exercise program, twice a week. Our results show an improvement in strength and agility with the exercise program, and a tendency to improve cognitive outcomes depending of assistance. The variable assistance or maybe the exercise program leads to not find significant improvements in endurance, neither in cognitive responses, when all group is taken in care, and these two variables maybe are related.
Older patients have the most to gain from orthopaedic enhanced recovery programmes.

BACKGROUND Between August 2007 and May 2009, 2128 consecutive patients underwent either primary hip or knee joint replacement surgery at our institute on an enhanced recovery pathway. We aimed to investigate the potential benefits of this pathway in patients over the age of 85 years. METHODS Data extracted from Hospital Episode Statistics were analysed. This data are prospectively collected and independently collated. RESULTS In all patients median length of stay was reduced when compared with both our own data before the introduction of the pathway (6 to 4 days) and national averages over the same time period for both hip and knee replacements (5 to 4 days). Difference in length of stay was most pronounced in the group of patients aged 85 years and over (9 to 5 days for total hip replacement and 8 to 5 days for total knee replacement). Nearly all patients were discharged directly home (97.4%). Readmission rates were over 45% lower in patients aged 85 and over when compared with national averages (5.2 vs. 9.4%). CONCLUSIONS This is the first series in the literature to assess the role of enhanced recovery pathways in the very elderly. This study not only shows that successful fast track rehabilitation can be achieved in the very elderly population undergoing elective joint replacement surgery, but that it is this cohort of vulnerable patients who have the most to gain from such multidisciplinary recovery programmes.
Dysfunctional breathing and reaching one’s physiological limit as causes of exercise-induced dyspnoea

Key points Excessive exercise-induced shortness of breath is a common complaint. For some, exercise-induced bronchoconstriction is the primary cause and for a small minority there may be an alternative organic pathology. However for many, the cause will be simply reaching their physiological limit or be due to a functional form of dysfunctional breathing, neither of which require drug therapy. The physiological limit category includes deconditioned individuals, such as those who have been through intensive care and require rehabilitation, as well as the unfit and the fit competitive athlete who has reached their limit with both of these latter groups requiring explanation and advice. Dysfunctional breathing is an umbrella term for an alteration in the normal biomechanical patterns of breathing that result in intermittent or chronic symptoms, which may be respiratory and/or nonrespiratory. This alteration may be due to structural causes or, much more commonly, be functional as exemplified by thoracic pattern disordered breathing (PDB) and extrathoracic paradoxical vocal fold motion disorder (pVFMD). Careful history and examination together with spirometry may identify those likely to have PDB and/or pVFMD. Where there is doubt about aetiology, cardiopulmonary exercise testing may be required to identify the deconditioned, unfit or fit individual reaching their physiological limit and PDB, while continuous laryngoscopy during exercise is increasingly becoming the benchmark for assessing extrathoracic causes. Accurate assessment and diagnosis can prevent excessive use of drug therapy and result in effective management of the cause of the individual’s complaint through cost-effective approaches such as reassurance, advice, breathing retraining and vocal exercises. This review provides an overview of the spectrum of conditions that can present as exercise-induced breathlessness experienced by young subjects participating in sport and aims to promote understanding of the need for accurate assessment of an individual’s symptoms. We will highlight the high incidence of nonasthmatic causes, which simply require reassurance or simple interventions from respiratory physiotherapists or speech pathologists. Breathlessness: accurate assessment and diagnosis is essential in order to provide correct advice and assistance http://ow.ly/4nrW8z
Refringence, field theory and normal modes

In a previous paper [Barceló C et al 2001 Class. Quantum Grav. 18 3595–610 (Preprint gr-qc/0104001)] we have shown that the occurrence of curved spacetime ‘effective Lorentzian geometries’ is a generic result of linearizing an arbitrary classical field theory around some nontrivial background configuration. This observation explains the ubiquitous nature of the ‘analogue models’ for general relativity that have recently been developed based on condensed matter physics. In the simple (single scalar field) situation analysed in our previous paper, there is a single unique effective metric; more complicated situations can lead to bi-metric and multi-metric theories. In the present paper we will investigate the conditions required to keep the situation under control and compatible with experiment—either by enforcing a unique effective metric (as would be required to be strictly compatible with the Einstein equivalence principle), or at the worst by arranging things so that there are multiple metrics that are all ‘close’ to each other (in order to be compatible with the Eötvös experiment). The algebraically most general situation leads to a physical model whose mathematical description requires an extension of the usual notion of Finsler geometry to a Lorentzian-signature pseudo-Finsler geometry; while this is possibly of some interest in its own right, this particular case does not seem to be immediately relevant for either particle physics or gravitation. The key result is that wide classes of theories lend themselves to an effective metric description. This observation provides further evidence that the notion of ‘analogue gravity’ is rather generic.
Emotional Perception and Distortion Correlates With Rorschach Cognitive and Interpersonal Variables

Although emotional intelligence is frequently measured with performance tasks, they are often correlated with self-report measures of personality. The present research compared the scores of two performance tests: the Rorschach Inkblot Method for personality (scored using R-PAS), and the Computerized Test of Primary Emotions Perception for emotional perception and understanding, branches of emotional intelligence. Participants were 93 Brazilian people, including undergraduates and psychiatric outpatients. Significant correlations were found, ranging from . 20 to . 37. The results indicate that the ability to perceive emotional expressions in people’s faces is related to empathy and interest in human interaction, attention to details, integrative thinking, and complex cognitive processing. Distortion in emotional perception, that is perceiving emotions that were not present, correlated with thought and perception disturbances.
Adoption and diffusion of collaborative technology in interorganizational networks

The results from two longitudinal case studies on the implementation of collaborative technology in interorganizational networks of small and medium sized enterprises are presented. Several issues influencing the adoption and diffusion processes in these cases are identified and discussed. These issues are related to the strategic importance of the collaborative arrangement as perceived by the member organizations, the characteristics of the technology and the adopting environment, and the organization of the implementation activities. The interorganizational adoption context is found to imply additional complexity compared to previous studies of intraorganizational implementation, due to a larger degree of autonomy among the actors and heterogeneity in technological platforms. The results emphasize a need for further research on the influence of the local context of each member organization in the network on the implementation process.
Mining Data Streams with Labeled and Unlabeled Training Examples

In this paper, we propose a framework to build prediction models from data streams which contain both labeled and unlabeled examples. We argue that due to the increasing data collection ability but limited resources for labeling, stream data collected at hand may only have a small number of labeled examples, whereas a large portion of data remain unlabeled but can be beneficial for learning. Unleashing the full potential of the unlabeled instances for stream data mining is, however, a significant challenge, consider that even fully labeled data streams may suffer from the concept drifting, and inappropriate uses of the unlabeled samples may only make the problem even worse. To build prediction models, we first categorize the stream data into four different categories, each of which corresponds to the situation where concept drifting may or may not exist in the labeled and unlabeled data. After that, we propose a relational k-means based transfer semi-supervised SVM learning framework (RK-TS3VM), which intends to leverage labeled and unlabeled samples to build prediction models. Experimental results and comparisons on both synthetic and real-world data streams demonstrate that the proposed framework is able to help build prediction models more accurate than other simple approaches can offer.
Interaction of Z form poly(dG-dC).poly(dG-dC) with divalent metal ions: localization of the binding sites by I.R. spectroscopy.

The secondary structures of poly(dG-dC). poly(dG-dC) in the presence of alcaline , alcaline earth and first row transition metal ions (Na+, Mg2+, Co2+, Ni2+) are investigated by infrared spectroscopy. The conformational transitions are studied as a function of the hydration of the polynucleotide and counter-ion nature and content. The use of selectively deuterated poly(dG-dC). poly(dG-dC) on the 8-carbon of guanines allows to show that a direct interaction occurs between the N7 site of guanines and the transition metal ions Co2+ and Ni2+. In the case of Mg2+, for high ion/nucleotide ratios, the interaction occurs essentially at the level of the phosphate groups. This interaction leads to a modification of the left-handed conformation. Based on the IR spectroscopy results, an explanation is proposed for the different efficiencies of these various ions to induce the B----Z transition.
Social interaction learning strategies, motivation, first-year students’ experiences and permanence in university studies*

Abstract Applying a structural equations modelling methodology, the study analyses the relationships and effects of self-regulated learning (social interaction learning strategies and motivation) and first-year university experiences on permanence in the sophomore year. The participants are 239 first-year students in different Engineering degrees at a public university in south-eastern Spain. Two alternative structural models are evaluated, showing the superiority of the model where first-year university experiences completely mediate the effects of self-regulated learning on permanence. Motivation and social interaction learning strategies show direct effects on first-year university experiences, and first-year university experiences, in turn, show direct effects on permanence; additionally, both motivation and social interaction learning strategies have indirect effects on permanence via first-year university experiences. The noteworthy theoretical implications of the results are discussed, as well as the teaching methodology and support services provided to first-year university students.
In the Yeast Heat Shock Response, Hsf1-Directed Induction of Hsp90 Facilitates the Activation of the Slt2 (Mpk1) Mitogen-Activated Protein Kinase Required for Cell Integrity

ABSTRACT Yeast is rendered temperature sensitive with loss of the C-terminal (CT) domain of heat shock transcription factor (Hsf1). This domain loss was found to abrogate heat stimulation of Slt2 (Mpk1), the mitogen-activated protein kinase that directs the reinforced cell integrity gene expression needed for high-temperature growth. In Hsf1 CT domain-deficient cells, Slt2 still undergoes Mkk1/2-directed dual-Thr/Tyr phosphorylation in response to the heat stimulation of cell integrity pathway signaling, but the low Hsp90 expression level suppresses any corresponding increase in Slt2 kinase activity due to Slt2 being a “client” of the Hsp90 chaperone. A non-Hsf1-directed Hsp90 overexpression restored the heat induction of Slt2 activity in these cells, as well as both Slt2-dependent (Rlm1, Swi4) and Slt2-independent (MBF) transcriptional activities. Their high-temperature growth was also rescued, not just by this Hsp90 overexpression but by osmotic stabilization, by the expression of a Slt2-independent form of the Rlm1 transcriptional regulator of cell integrity genes, and by a multicopy SLT2 gene vector. In providing the elevated Hsp90 needed for an efficient activation of Slt2, heat activation of Hsf1 indirectly facilitates (Slt2-directed) heat activation of yet another transcription factor (Rlm1). This provides an explanation as to why, in earlier transcript analysis compared to chromatin immunoprecipitation studies, many more genes of yeast displayed an Hsf1-dependent transcriptional activation by heat than bound Hsf1 directly. The levels of Hsp90 expression affecting transcription factor regulation by Hsp90 client protein kinases also provides a mechanistic model for how heat shock factor can influence the expression of several non-hsp genes in higher organisms.
Projection pursuit mixture density estimation

In this paper we seek a Gaussian mixture model (GMM) of an n-variate probability density function. Usually the parameters of GMMs are determined in the original n-dimensional space by optimizing a maximum likelihood (ML) criterion. A practical deficiency of this method of fitting GMMs is its poor performance when dealing with high-dimensional data since a large sample size is needed to match the accuracy that is possible in low dimensions. We propose a method for fitting the GMM based on the projection pursuit strategy. This GMM is highly constrained and hence its ability to model structure in subspaces is enhanced, compared to a direct ML fitting of a GMM in high dimensions. Our method is closely related to recently developed independent factor analysis (IFA) mixture models. The comparisons with ML fitting of GMM in n-dimensions and IFA mixtures show that the proposed method is an attractive choice for fitting GMMs using small sizes of training sets.
Richness of Side-Chain Liquid-Crystal Polymers: From Isotropic Phase towards the Identification of Neglected Solid-Like Properties in Liquids

Very few studies concern the isotropic phase of Side-Chain Liquid-Crystalline Polymers (SCLCPs). However, the interest for the isotropic phase appears particularly obvious in flow experiments. Unforeseen shear-induced nematic phases are revealed away from the N-I transition temperature. The non-equilibrium nematic phase in the isotropic phase of SCLCP melts challenges the conventional timescales described in theoretical approaches and reveal very long timescales, neglected until now. This spectacular behavior is the starter of the present survey that reveals long range solid-like interactions up to the sub-millimetre scale. We address the question of the origin of this solid-like property by probing more particularly the non-equilibrium behavior of a polyacrylate substituted by a nitrobiphenyl group (PANO2). The comparison with a polybutylacrylate chain of the same degree of polymerization evidences that the solid-like response is exacerbated in SCLCPs. We conclude that the liquid crystal moieties interplay as efficient elastic connectors. Finally, we show that the “solid” character can be evidenced away from the glass transition temperature in glass formers and for the first time, in purely alkane chains above their crystallization temperature. We thus have probed collective elastic effects contained not only in the isotropic phase of SCLCPs, but also more generically in the liquid state of ordinary melts and of ordinary liquids.