Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic mutations linked to Parkinson's disease differentially control nucleolar activity in pre-symptomatic mouse models

ABSTRACT Genetic mutations underlying neurodegenerative disorders impair ribosomal DNA (rDNA) transcription suggesting that nucleolar dysfunction could be a novel pathomechanism in polyglutamine diseases and in certain forms of amyotrophic lateral sclerosis/frontotemporal dementia. Here, we investigated nucleolar activity in pre-symptomatic digenic models of Parkinson's disease (PD) that model the multifactorial aetiology of this disease. To this end, we analysed a novel mouse model mildly overexpressing mutant human α-synuclein (hA53T-SNCA) in a PTEN-induced kinase 1 (PINK1/PARK6) knockout background and mutant mice lacking both DJ-1 (also known as PARK7) and PINK1. We showed that overexpressed hA53T-SNCA localizes to the nucleolus. Moreover, these mutants show a progressive reduction of rDNA transcription linked to a reduced mouse lifespan. By contrast, rDNA transcription is preserved in DJ-1/PINK1 double knockout (DKO) mice. mRNA levels of the nucleolar transcription initiation factor 1A (TIF-IA, also known as RRN3) decrease in the substantia nigra of individuals with PD. Because loss of TIF-IA, as a tool to mimic nucleolar stress, increases oxidative stress and because DJ-1 and PINK1 mutations result in higher vulnerability to oxidative stress, we further explored the synergism between these PD-associated genes and impaired nucleolar function. By the conditional ablation of TIF-IA, we blocked ribosomal RNA (rRNA) synthesis in adult dopaminergic neurons in a DJ-1/PINK1 DKO background. However, the early phenotype of these triple knockout mice was similar to those mice exclusively lacking TIF-IA. These data sustain a model in which loss of DJ-1 and PINK1 does not impair nucleolar activity in a pre-symptomatic stage. This is the first study to analyse nucleolar function in digenic PD models. We can conclude that, at least in these models, the nucleolus is not as severely disrupted as previously shown in DA neurons from PD patients and neurotoxin-based PD mouse models. The results also show that the early increase in rDNA transcription and nucleolar integrity may represent specific homeostatic responses in these digenic pre-symptomatic PD models. Summary: Genetic mutations linked to Parkinson's disease lead to stage-specific deregulation of the nucleolus, a major integrator of the cellular stress response.
Classical complement activation induced by pregnancy: implications for management of connective tissue diseases.

AIMS: To determine the effect of pregnancy on C4d concentrations and to assess whether C4d remains a useful disease activity marker in the management of connective tissue diseases during pregnancy. METHODS: Plasma C3, C4, and C4d concentrations were measured in 83 women at various stages of normal pregnancy and compared with those in 80 non-pregnant controls. RESULTS: C3 concentrations in the pregnant women were significantly raised (p = 0.0001) and the C4 concentrations were reduced (p = 0.0007), and accompanied by a significant increase in C4d (p = 0.0001). The C4d:C4 ratio was higher in the pregnant women (p = 0.0001). CONCLUSIONS: Pregnancy induces activation of the classical complement pathway. C4d concentrations cannot be used to monitor disease activity in patients with connective tissue diseases during pregnancy.
The first theory about hemispheric specialization: fresh light on an old codex.

La premiere theorie concernant l'asymetrie des hemispheres droit et gauche du cerveau decrite dans un manuscrit ancien du Moyen Age est discutee et a permis de conduire, au XIX e siecle, a la decouverte de la specialisation de chaque hemisphere
Multiseed lossless filtration

We study a method of seed-based lossless filtration for approximate string matching and related bioinformatics applications. The method is based on a simultaneous use of several spaced seeds rather than a single seed as studied by Burkhardt and Karkkainen. We present algorithms to compute several important parameters of seed families, study their combinatorial properties, and describe several techniques to construct efficient families. We also report a large-scale application of the proposed technique to the problem of oligonucleotide selection for an EST sequence database.
Education and Use of Dementia Drugs: A Register-Based Study of Over 600,000 Older People

Background/Aims: Low education has been shown to be a risk factor for dementia. However, little is known about the association between educational level and dementia drugs. Methods: We conducted a register-based study in Sweden of 645,973 people aged 75–89 years. Data on age, sex, type of residential area (urban/rural), dispensed drugs and education were analyzed from people aged 75–89 years registered in the Swedish Prescribed Drug Register during July to October 2005. The 3 main outcome measures were dispensed dementia drugs, cholinesterase inhibitors (donepezil, rivastigmine and galantamine) and memantine. Results: Dementia drugs were used by 3% of the study population, cholinesterase inhibitors by almost 3% and memantine by 0.4%. High education was associated with dementia drugs (OR: 1.26; 95% CI: 1.19–1.34 for ≧15 years of education compared with ≤9 years), cholinesterase inhibitors (OR: 1.25; 95% CI: 1.17–1.33 for ≧15 years of education compared with ≤9 years) and, especially, memantine (OR: 1.46; 95% CI: 1.26–1.68 for ≧15 years of education compared with ≤9 years), after adjustment for age, sex, type of residential area and number of dispensed drugs. Conclusion: The results indicate that there may be inequalities in the use of dementia drugs among elderly Swedes. Future research is required to explain why educational level has the opposite relationship to dementia drugs than to dementia diagnosis.
Dynamic Model Interpolation for Statistical Machine Translation

This paper presents a technique for class-dependent decoding for statistical machine translation (SMT). The approach differs from previous methods of class-dependent translation in that the class-dependent forms of all models are integrated directly into the decoding process. We employ probabilistic mixture weights between models that can change dynamically on a segment-by-segment basis depending on the characteristics of the source segment. The effectiveness of this approach is demonstrated by evaluating its performance on travel conversation data. We used the approach to tackle the translation of questions and declarative sentences using class-dependent models. To achieve this, our system integrated two sets of models specifically built to deal with sentences that fall into one of two classes of dialog sentence: questions and declarations, with a third set of models built to handle the general class. The technique was thoroughly evaluated on data from 17 language pairs using 6 machine translation evaluation metrics. We found the results were corpus-dependent, but in most cases our system was able to improve translation performance, and for some languages the improvements were substantial.
3D room geometry estimation from measured impulse responses

Estimation of the room geometry from spatial room impulse responses is studied. An algorithm for estimating the geometry is presented. The algorithm does not require any a priori information on the room shape, number of walls, or order of the reflections, but deduces the set of planes that explain the measured source and image-source locations and covariances iteratively. The algorithm is demonstrated with real data experiments.
Electroencephalogram measurement using polymer-based dry microneedle electrode

In this paper, we report a successful electroencephalogram (EEG) measurement using polymer-based dry microneedle electrodes. The electrodes consist of needle-shaped substrates of SU-8, a silver film, and a nanoporous parylene protective film. Differently from conventional wet electrodes, microneedle electrodes do not require skin preparation and a conductive gel. SU-8 is superior as a structural material to poly(dimethylsiloxane) (PDMS; Dow Corning Toray Sylgard 184) in terms of hardness, which was used in our previous work, and facilitates the penetration of needles through the stratum corneum. SU-8 microneedles can be successfully inserted into the skin without breaking and could maintain a sufficiently low skin-electrode contact impedance for EEG measurement. The electrodes successfully measured EEG from the frontal pole, and the quality of acquired signals was verified to be as high as those obtained using commercially available wet electrodes without any skin preparation or a conductive gel. The electrodes are readily applicable to record brain activities for a long period with little stress involved in skin preparation to the users.
Reaction Time to Spatial Frequencies Using Yellow and Luminance‐Matched Neutral Goggles

ABSTRACT The popularity of yellow goggles for outdoor activities has long been a paradox to visual scientists as previous tests of their effectiveness have failed to show any visual advantage. The achromatic/chromatic theory of color vision suggests a possible solution to the paradox which was tested by measuring reaction times to spatial frequencies of varying contrast. Reaction times were faster with yellow goggles than with luminance‐matched neutrals under certain conditions. These conditions included frequencies in the middle of the range of human sensitivity and, specifically, the lower contrasts of these frequencies. The theoretical and practical applications of the results are discussed.
The Pre-S2 Domain of the Hepatitis B Virus Is Dispensable for Infectivity but Serves a Spacer Function for L-Protein-Connected Virus Assembly

ABSTRACT The envelope of the human hepatitis B virus (HBV) contains three membrane proteins (L, M, and S). They accomplish different functions in HBV infectivity and nucleocapsid envelopment. Infectivity determinants have been assigned to the N-terminal part of the pre-S1 domain of the L protein and the antigenic loop of the S domain in the L and/or S protein. Nucleocapsid envelopment requires a C-terminal sequence within pre-S1, including the five N-terminal amino acids of pre-S2 as part of the L protein. However, the role of the M protein and the pre-S2 domain of the L protein are not entirely understood. We addressed this question and analyzed assembly competence and infectivity of viruses that lack the M protein and, at the same time, carry alterations in the pre-S2 domain of L. These include deletions, in part frameshift mutations and a randomization of virtually the entire pre-S2 sequence. We found that the M protein is dispensable for HBV in vitro infectivity. Viruses that lack the M protein and contain a mostly randomized pre-S2 sequence assemble properly and are infectious in HepaRG cells and primary human hepatocytes. While deletions of 20 amino acids in the pre-S2 domain of L protein allowed the production of infectious virions, more extended deletions interfered with assembly. This indicates that the pre-S2 domain of the L protein serves an important role for virus assembly, presumably as a spacer that supports conformational changes of L protein but does not participate as part of the M protein or as a subdomain of the L protein in virus entry.
Modulation of the expression of components of the metabolic stress response by dietary 1 arachidonic acid in European sea bass ( Dicentrarchus labrax ) larvae 2

52 This study reports for the first time in European sea bass, Dicentrarchus labrax (L.), larvae, 53 the effect of different levels of dietary arachidonic acid (ARA; 20:4n-6) on the expression of 54 genes related to the fish stress response. Copies of mRNA from genes related to 55 steroidogenesis (StAR (steroidogenic acute regulatory protein), c-Fos, and CYP11β (11β56 hydroxylase gene)), glucocorticoid receptor complex (GR (glucorticoid receptor) and HSP 57 (heat shock proteins) 70 and 90) and antioxidative stress (catalase (CAT), superoxide 58 dismutase (SOD), and glutathione peroxidase (GPX)) were quantified. Eighteen day-old 59 larvae were fed for 14 days with three experimental diets with increasing levels of ARA 60 (0.3, 0.6 and 1.2% d.w.) and similar levels of docosahexaenoic (DHA; 22:6n-3) and 61 eicosapentaenoic (EPA; 20:5n-3) acids (5 and 3%, respectively). The quantification of 62 stress-related genes transcripts was conducted by One-Step TaqMan real time RT-PCR 63 with the standard curve method (absolute quantification). Increase dietary levels of ARA 64 induced a significantly (p<0.05) down-regulation of genes related to cortisol synthesis, 65 such as StAR and CYP11β and up-regulated genes related to glucocorticoid receptor 66 complex, such as HSP70 and GR. No effects were observed on antioxidant enzymes gene 67 expression. These results revealed the regulatory role of dietary ARA on the expression of 68 stress-related genes in European sea bass larvae. 69
Fusarin C production by North American isolates of Fusarium moniliforme

A liquid culture medium was developed to screen North American isolates of Fusarium moniliforme Sheldon and Fusarium subglutinans (Wollenw. and Reink.) Nelson, Toussoun, and Marasas for their ability to produce fusarin C. Parameters which were important for the optimal biosynthesis of fusarin C included pH (3.0 to 4.0), aeration, and sugar concentration (30 to 40%). Of seven sugars tested, sucrose and glucose were the best carbohydrate sources for mycotoxin production, resulting in levels of fusarin C of greater than 60 ppm (greater than 60 micrograms/g) in liquid culture (28 degrees C; 7 days). A time-course study of fusarin C production was done over a 21-day period, during which time pH values, glucose concentrations, nitrogen levels, and fungal biomass were determined. Of the two Fusarium spp. studied, 13 of 16 isolates of F. moniliforme produced fusarin C in liquid medium (14 of 16 in corn), while none of the 15 isolates of F. subglutinans studied was found to produce the compound. Levels of fusarin C produced by Fusarium sp. isolates growing on corn ranged from 18.7 to 332.0 micrograms/g.
Alternative Strategies to Inpatient Hospitalization for Acute Medical Conditions: A Systematic Review.

Importance Determining innovative approaches that better align health needs to the appropriate setting of care remains a key priority for the transformation of US health care; however, to our knowledge, no comprehensive assessment exists of alternative management strategies to hospital admission for acute medical conditions. Objective To examine the effectiveness, safety, and cost of managing acute medical conditions in settings outside of a hospital inpatient unit. Evidence Review MEDLINE, Scopus, CINAHL, and the Cochrane Database of Systematic Reviews (January 1995 to February 2016) were searched for English-language systematic reviews that evaluated alternative management strategies to hospital admission. Two investigators extracted data independently on trial design, eligibility criteria, clinical outcomes, patient experience, and health care costs. The quality of each review was assessed using the revised AMSTAR tool (R-AMSTAR) and the strength of evidence from primary studies was graded according to the Oxford Centre for Evidence-Based Medicine. Findings Twenty-five systematic reviews (representing 123 primary studies) met inclusion criteria. For outpatient management strategies, several acute medical conditions had no significant difference in mortality, disease-specific outcomes, or patient satisfaction compared with inpatient admission. For quick diagnostic units, the evidence was more limited but did demonstrate low mortality rates and high patient satisfaction. For hospital-at-home, a variety of acute medical conditions had mortality rates, disease-specific outcomes, and patient and caregiver satisfaction that were either improved or no different compared with inpatient admission. For observation units, several acute medical conditions were found to have no difference in mortality, a decreased length of stay, and improved patient satisfaction compared to inpatient admission; results for some conditions were more limited. Across all alternative management strategies, cost data were heterogeneous but showed near-universal savings when assessed. Conclusions and Relevance For low-risk patients with a range of acute medical conditions, evidence suggests that alternative management strategies to inpatient care can achieve comparable clinical outcomes and patient satisfaction at lower costs. Further study and application of such opportunities for health system redesign is warranted.
Neuroplasticity of excitatory and inhibitory cortical circuits in schizophrenia

Schizophrenia is a neurodevelopmental disorder characterized by deficits in cognitive processes mediated by the circuitry of the dorsolateral prefrontal cortex (DLPFC). These deficits are associated with a range of alterations in DLPFC circuitry, some of which reflect the pathology of the illness and others of which reflect the neuroplasticity of the brain in response to the underlying disease process. This article reviews disturbances in excitatory and inhibitory components of DLPFC circuitry from the perspective of developmental neuroplasticity and discusses their implications for the identification of novel therapeutic targets.
Computer Estimation of Vocabulary in a Protolanguage from Word Lists in Four Daughter Languages

Even if no written records of a protolanguage remain, it is possible to estimate what some of the words in that language might have been, by comparison of its reflexes in the more recent daughter languages. This method of protolanguage reconstruction is called the ‘comparative method’, and is described by Crowley (1992, Chapter 5). Although long practiced by human linguists, the comparative method is extremely time consuming, and only a few parts of the process have previously been automated. This paper describes a program which attempts to replicate the methodology described by Crowley almost in its entirety.
DETERMINANTS AND BEHAVIORAL CORRELATES OF STATE-LEVEL ANXIETY IN CLINICAL COUPLE INTERACTIONS

Title of Document: DETERMINANTS AND BEHAVIORAL CORRELATES OF STATE-LEVEL ANXIETY IN CLINICAL COUPLE INTERACTIONS Taryn M. Dezfulian, M.S., 2005 Directed By: Professor Norman E. Epstein, Department of Family Studies Extant research demonstrated that clinically diagnosable disorders such as depression and anxiety have detrimental effects on dyadic satisfaction in couple relationships, but studies have focused almost exclusively on trait-level emotional responses. Consequently, little is known about state-level emotional responses, including factors influencing negative emotional states during couple interactions, and associations between emotional states and the partners’ subsequent communication behavior. This study investigated the associations between: (a) each partner’s attachment security and negative attributions about the other’s malicious intent for them; (b) the degree of state-level anxiety partners experience immediately before engaging in a discussion about a conflictual relationship issue; and (c) partners’ use of constructive and destructive behaviors during the discussion. State-level anxiety mediated the relationship between partners’ pre-existing attachment security and negative attributions about the partner and each partner’s use of constructive and destructive communication. Implications for clinical assessment and intervention with state-level anxiety responses in distressed couples are discussed. DETERMINANTS AND BEHAVIORAL CORRELATES OF STATE-LEVEL ANXIETY IN CLINICAL COUPLE INTERACTIONS
Characteristics of newly-formed cementum following emdogain application

Periodontal regenerative techniques have been proposed; however, the outcomes remain debatable. The present investigation assessed the regenerated cementum following enamel matrix derivative application in dehiscence‐type defects. Buccal osseous dehiscences were surgically created on the maxillary cuspid, and the second and fourth premolars in five female beagle dogs. The treatment group (n=15 sites) received the enamel matrix derived application, whereas the control groups (n=15) did not. The dogs were sacrificed 4 months following treatment and the specimens were histologically and histometrically examined. The newly formed cementum was uneven in thickness and mineralization, overlapped the old cementum and exhibited functional orientation, cementocyte lacunae and collagen fibril bundles. Most of the histological specimens showed the presence of a gap between the newly formed cementum and the underlying dentin. Control sites did not exhibit any cementum formation. The present study concluded that newly formed cementum is of cellular type and exhibits multiple characteristics.
Mutational analysis of the membrane-proximal cleavage site of L- selectin: relaxed sequence specificity surrounding the cleavage site

L-selectin expression is regulated in part by membrane-proximal cleavage from the cell surface of leukocytes and L-selectin-transfected cells. The downregulation of L-selectin from the surface of neutrophils is speculated to be a process involved in the adhesion cascade leading to neutrophil recruitment to sites of inflammation. We previously reported that L-selectin is cleaved between Lys321 and Ser322 in a region that links the second short consensus repeat (SCR) and the transmembrane domain. We demonstrate that replacing this cleavage domain of L-selectin with the corresponding region of E-selectin prevents L-selectin shedding, as judged by inhibiting the generation of the 68-kD soluble and 6-kD transmembrane cleavage products of L- selectin. Unexpectedly, we found that point mutations of the cleavage site, as well as mutations of multiple conserved amino acids within the cleavage domain, do not significantly affect L-selectin shedding. However, short deletions of four or five amino acids in the L-selectin cleavage domain inhibit L-selectin downregulation. Mutations that appeared to inhibit L-selectin shedding resulted in higher levels of cell surface expression, consistent with a lack of apparent proteolysis from the cell membrane. One deletion mutant, I327 delta N332, retains the native cleavage site yet inhibits L-selectin proteolysis as well. Restoring the amino acids deleted between I327 and N332 with five alanine residues restores L-selectin proteolysis. Thus, the proteolytic processing of L-selectin appears to have a relaxed sequence specificity at the cleavage site, and it may depend on the physical length or other secondary structural characteristics of the cleavage domain.