Miracle-dz/UniFAR-FTUs huggingface dataset:
Orexin (hypocretin) gene transfer diminishes narcoleptic sleep behavior in mice

Gene transfer has proven to be an effective neurobiological tool in a number of neurodegenerative diseases, but it is not known if it can correct a sleep disorder. Narcolepsy is a neurodegenerative sleep disorder linked to the loss of neurons containing the neuropeptide orexin, also known as hypocretin. Here, a replication‐defective herpes simplex virus‐1 amplicon‐based vector was constructed to transfer the gene for mouse prepro‐orexin into mice with a genetic deletion of the orexin gene. After in vitro tests confirmed successful gene transfer into cells, the gene vector was delivered to the lateral hypothalamus of orexin knockout (KO) mice where the orexin peptide was robustly expressed in the somata and processes of numerous neurons, and the peptide product was detected in the cerebrospinal fluid. During the 4‐day life‐span of the vector the incidence of cataplexy declined by 60%, and the levels of rapid eye movement sleep during the second half of the night were similar to levels in wild‐type mice, indicating that narcoleptic sleep–wake behavior in orexin KO mice can be improved by targeted gene transfer.
IMPACT OF FLUORESCEIN ANGIOGRAPHIC CHARACTERISTICS OF MACULAR LESIONS ON OUTCOMES AFTER MACULAR TRANSLOCATION 360° SURGERY IN EYES WITH AGE-RELATED MACULAR DEGENERATION

Purpose: To evaluate the relationship between preoperative lesion size and composition and visual outcomes at 1 year after macular translocation surgery with 360° peripheral retinectomy (MT360) for neovascular age-related macular degeneration (AMD). Methods: A prospective, interventional, consecutive, noncomparative case series of 64 patients with bilateral neovascular AMD treated with MT360 in the eye with more recent vision loss. Masked reviewers graded preoperative fluorescein angiograms for lesion size in Macular Photocoagulation Study disk areas (MPS DAs) and predominant lesion composition (classic or occult choroidal neovascularization or subretinal hemorrhage). Median changes in distance and near visual acuities and reading speed at 12 months after surgery were analyzed with respect to lesion size and composition. Results: There was no significant difference between the outcomes for small-, medium- or large-sized preoperative lesions. Patients in each predominant lesion composition group had median improvement in visual outcomes with significant improvement in near visual acuity and reading speed for predominantly classic and occult lesions. Conclusion: MT360 stabilizes or improves visual function in patients with neovascular AMD irrespective of lesion size categories and with a variety of lesion compositions. Removal of the subretinal lesion and repositioning of the fovea over a healthier retinal pigment epithelial bed may account for these improvements.
Plantar fascia anatomy and its relationship with Achilles tendon and paratenon

Although the plantar fascia (PF) has been studied quite well from a biomechanical viewpoint, its microscopic properties have been overlooked: nothing is known about its content of elastic fibers, the features of the extracellular matrix or the extent of innervation. From a functional and clinical standpoint, the PF is often correlated with the triceps surae muscle, but the anatomical grounds for this link are not clear. The aim of this work was to focus on the PF macroscopic and microscopic properties and study how Achilles tendon diseases might affect it. Twelve feet from unembalmed human cadavers were dissected to isolate the PF. Specimens from each PF were tested with various histological and immunohistochemical stains. In a second stage, 52 magnetic resonance images (MRI) obtained from patients complaining of aspecific ankle or foot pain were analyzed, dividing the cases into two groups based on the presence or absence of signs of degeneration and/or inflammation of the Achilles tendon. The thickness of PF and paratenon was assessed in the two groups and statistical analyses were conducted. The PF is a tissue firmly joined to plantar muscles and skin. Analyzing its possible connections to the sural structures showed that this fascia is more closely connected to the paratenon of Achilles tendon than to the Achilles tendon, through the periosteum of the heel. The PF extended medially and laterally, continuing into the deep fasciae enveloping the abductor hallucis and abductor digiti minimi muscles, respectively. The PF was rich in hyaluronan, probably produced by fibroblastic‐like cells described as ‘fasciacytes’. Nerve endings and Pacini and Ruffini corpuscles were present, particularly in the medial and lateral portions, and on the surface of the muscles, suggesting a role for the PF in the proprioception of foot. In the radiological study, 27 of the 52 MRI showed signs of Achilles tendon inflammation and/or degeneration, and the PF was 3.43 ± 0.48 mm thick (99%CI and SD = 0.95), as opposed to 2.09 ± 0.24 mm (99%CI, SD = 0.47) in the patients in which the MRI revealed no Achilles tendon diseases; this difference in thickness of 1.29 ± 0.57 mm (99%CI) was statistically significant (P < 0.001). In the group of 27/52 patients with tendinopathies, the PF was more than 4.5 mm thick in 5, i.e. they exceeded the threshold for a diagnosis of plantar fasciitis. None of the other 25/52 paitents had a PF more than 4 mm thick. There was a statistically significant correlation between the thicknesses of the PF and the paratenon. These findings suggest that the plantar fascia has a role not only in supporting the longitudinal arch of the foot, but also in its proprioception and peripheral motor coordination. Its relationship with the paratenon of the Achilles tendon is consistent with the idea of triceps surae structures being involved in the PF pathology, so their rehabilitation can be considered appropriate. Finally, the high concentration of hyaluronan in the PF points to the feasibility of using hyaluronan injections in the fascia to treat plantar fasciitis.
Combining Measurements and Physical Model Outputs for the Spatial Prediction of Hourly Ozone Space-Time Fields ∗

This technical report extends to a spatial setting, an existing temporal two-step linear regression recalibration procedure designed to make the outputs from a deterministic time series simulator comparable with measurements of that series. The result, which Kriges the site specific coefficients of that procedure, enables both temporal forecasting and spatial prediction. Although the extension is somewhat ad hoc, unlike an alternative in work now in preparation, it is computationally simple and fairly transparent. Moreover, in an application where the procedure is used to combing measurements of and simulated model outputs for an hourly ozone field over the eastern and central regions of the United States, we find that it outperforms the model output alone and Kriging, a purely spatial method. ∗The work was supported in part by grants from the Natural Science and Engineering Research Council of Canada (NSERC) and the Pacific Institute for the Mathematical Sciences (PIMS). †Department of Statistics, U. of British Columbia. Email: zliu@stat.ubc. ca ‡British Columbia Cancer Research Centre. Email: nle@bccrc.ca §Department of Statistics, U. of British Columbia. Email: jim@stat.ubc. ca
Cumulative Effects of Stressful Childhood Experiences on Delusions and Hallucinations

The association between stressful childhood experiences (SCE) and psychotic symptoms is still not clearly understood, and different causal pathways have been proposed. Generalized estimating equation modeling was used to test the dose–response relationship between SCE and delusions and hallucinations at baseline and follow-up periods and the possible confounding effects of dissociation on this relationship. The prevalence of SCE in individuals with psychotic disorders was high, with more co-occurring SCE categories being positively associated with more types of delusions and hallucinations. Each additional SCE was associated with a 1.20 increase in the incidence rate ratio (95% confidence interval [CI; 1.09, 1.32]) for hallucinations and a 1.19 increase (CI [1.09, 1.29]) for delusions, supporting a dose–response association. After we controlled for the mediating effects of dissociative symptoms at follow-up, SCE remained independently associated with delusions. We propose that cumulative SCE can result in complex trauma reactions that present with a broad range of symptomatology, including dissociative, posttraumatic stress disorder, and psychotic symptoms.
INFLUENCE OFGELSOLIN DEFICIENCYON EXCITATION CONTRACTION COUPLING INADULT MURINE CARDIOMYOCYTES

The cytoskeleton is an important constituent to maintain the shape and integrity of cardiomyocytes. Furthermore ion channels involved in cardiac excitation-contraction coupling are linked to the cytoskeleton. Therefore changes in the actin filaments of the cytoskeleton may influence both, the morphology and the physiology of cardiomyocytes. Actin polymerisation and depolymerisation is brought about by the actin filament serving and capping protein gelsolin (gsn) (1). Gsn is Ca2+-activated and is involved in dynamic changes of the cytoskeleton by depolymerization of cytosolic actin filaments, and thereby substantially influencing cellular architecture (2), excitability (3) and cell function (4). The tight regulation of gsn by Ca2+ and phosphoinositol-bisphosphate (PIP 2) is crucial for its physiological role (5, 6). Furthermore, elevated gsn-levels in human failing hearts and animal models of heart failure have been found (7). It has been shown, that gsn is a contributor to heart failure progression via hypoxia inducible factor -1 (HIF-1) and DNase I activation as well as downregulation of antiapoptotic survival factors in a model of myocardial infarction where the end-diastolic volume decreased in the absence of gsn (8). Various investigations have been performed to clarify the role of the cytoskeleton in excitation-contraction coupling. Pharmacological depolymersation of the microfilaments by cytochalasin D application led to an acute 75% reduction of the L-type Ca2+-current in adult guinea pig cardiomyocytes (9), while another study could not show an influence of cytochalasin D on L-type Ca2+ currents in adult rat cardiomyocytes (10). In cultured neonatal cardiomyocytes gsn deficiency , which causes higher polymerisation of actin resulted in a 300% increase in Ca 2+
Dietary Lupin Protein Lowers Triglyceride Concentrations in Liver and Plasma in Rats by Reducing Hepatic Gene Expression of Sterol Regulatory Element-Binding Protein-1c

Background: Recently, it has been shown that dietary lupin protein lowers plasma triglyceride concentrations in rats. In this study, we investigated the hypothesis that this effect is due to a downregulation of sterol regulatory element-binding protein (SREBP)-1c, a transcription factor that regulates the expression of lipogenic enzymes in the livers of rats. Methods: Two groups of 12 rats each were fed semisynthetic diets containing 200 g/kg of either casein (control group) or lupin protein from Lupinus albus for 22 days. Results: Rats fed the diet containing lupin protein had lower concentrations of triglycerides in the liver, plasma and VLDL + chylomicrons (p < 0.05). The concentration of protein in VLDL + chylomicrons was also lower in rats fed lupin protein than in rats fed casein (p < 0.05). The mRNA concentrations of SREBP-1c and fatty acid synthase in the liver were lower in rats fed lupin protein than in rats fed casein (p < 0.05). The mRNA concentrations of lipoprotein lipase in the liver did not differ between both groups of rats. Conclusion: This study confirms that a protein isolated from L. albus is strongly hypotriglyceridemic in rats. It is shown for the first time that this effect is at least in part due to a downregulation of SREBP-1c in the liver which in turn leads to a reduction in hepatic fatty acid synthesis.
Daunomycin, an antitumor DNA intercalator, influences histone–DNA interactions

Although daunomycin and adriamycin are considered effective antitumor drugs and have been used in the clinic for over 40 years, their mechanism of action is still a matter of debate. We investigated the influence of daunomycin on interaction between linker or core histones and DNA in live HeLa cells in vitro, using image and flow cytometry. Exposure to daunomycin at clinically relevant concentrations (25–250 nM) caused dissociation of wild-type H1.1 as well as 4 H1 point mutants from DNA, followed by their accumulation in nucleoli and aggregation of chromatin. A detectable dissociation of H2B core histones occurred only at much higher concentrations of the drug (500 nM). Replication of DNA and synthesis of RNA were not halted by daunomycin (up to 2500 nM); however the characteristic subnuclear distribution of sites of transcription and replication was lost. Dissociation of the H1.1 linker histones and subsequent loss of higher order chromatin structures may constitute an important component of the mechanism of cytotoxicity of daunomycin.
Flexible Coping Psychotherapy for Functional Dyspeptic Patients: A Randomized, Controlled Trial

Objective: This study tested the efficacy of a new psychotherapy, flexible coping psychotherapy (FCP), specifically designed for enhancing coping flexibility of patients with functional dyspepsia (FD). The design of this psychotherapy is based on the general cognitive–behavioral model and previous findings on FD. Methods: We adopted a randomized, controlled design to examine the differences between the target (FCP) and control (supportive psychotherapy [SPP]) conditions. Coping flexibility and outcome measures reported by 75 Chinese FD patients (18–65 years; 35% men) were assessed before and 12 months after treatment. Results: Results revealed that participants who received the FCP reported an increase in coping flexibility as well as reductions in self-rated dyspeptic symptom severity (SDSS), gastroenterologist-rated dyspeptic symptom severity, and anxiety levels (p values <.01). Participants who received the SPP reported reductions in SDSS and anxiety levels (p values <.0001). Although both groups reported a decrease in SDSS, only the SDSS level of the FCP group was comparable to that of a healthy community sample (p = .28). Conclusions: These findings suggest that FCP is a potentially effective intervention for treating FD symptoms. Its effectiveness may be attributable to the specific components of FCP rather than common psychotherapeutic factors such as emotional support and empathy per se. CFQ = Cognitive Flexibility Questionnaire; DSQ = Dyspeptic Symptom Questionnaire; FCP = flexible coping psychotherapy; FD = functional dyspepsia; GDSS = gastroenterologist-rated dyspeptic symptom severity; MANOVA = multivariate analysis of variance; RCI = reliable change index; SDSS = self-rated dyspeptic symptom severity; SPP = supportive psychotherapy; STAI = State-Trait Anxiety Inventory.
Reactive oxygen species and the role of inflammatory markers (IL-6 and TNF-α) in the causation of insulin resistance in type 2 obese diabetics

Oxidative stress is increased in diabetes and the overproduction of the reactive oxygen species in diabetes is a direct consequence of hyperglycemia. Inflammatory cytokines such as tumor necrosis factor (TNF α) and interleukin (IL 6), and free radicals are believed to play key roles in the causation of insulin resistance in obese type 2 diabetes subjects. Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes. Different vascular cells like vascular smooth muscle, adipose tissue, renal cells, and endothelial cells are able to produce ROS under hyperglycemic condition. Both NADPH oxidase and mitochondrial electron gradient play roles in hyperglycemia induced ROS generation with increased lipid peroxidation, and production of inflammatory markers (IL 6 and Tnf α) leading to the development of insulin resistance. Cytokines produced by high fat in adipocytes acts as a signaling molecule for the activation of signal transduction cascades in which activate IKK inhibitor of nF κB kinase and nuclear factor κB (IKKβ/nF kβ) and Janus kinases (JNK) pathways in adipocytes, hepatocytes, mesangial cells and associated macrophages. These factors activate transcription factors leading to the transcriptional activation of the inflammatory cytokines TNF α, which impairs insulin signaling through serine phosphorylation of IRS 1 and can reduce GLUT4 gene expression, plausible cellular basis for inflammatory markers as a mediator of insulin resistance in type 2 obese diabetes subjects. Abbreviations: ROS: Reactive oxygen species, IL 6: Interleukin 6, Tnf α: Tumor necrosis factor alpha, IR: Insulin resistance, SOCS: suppressor of cytokine signaling, nF κB: nuclear factor κB, IKK inhibitor of nF κB kinase , JNK Janus kinases, FABPs: fatty acid– binding proteins, AP 1: activator protein, LXR: liver X receptor, PPAR: Peroxisome proliferator activated receptor γ,
Electromagnetic Performance Analysis of Wind Power Generator With Outer Permanent Magnet Rotor Based on Turbine Characteristics Variation Over Nominal Wind Speed

In this paper, we investigate the electromagnetic performance of wind power generators with outer permanent magnet rotors on the bases of variations in the turbine characteristics over nominal wind speeds by employing various proposed analytical techniques. We have employed an electromagnetic analytical method for calculating electrical parameters such as back EMF constant, synchronous inductance, and phase resistance on the basis of the magnetic field distribution calculated in previous studies. Moreover, curve fitting and finite element methods have been used for core losses analysis, while the d-q model employing the coordinate transformation theorem has been used for analyzing generation performances. To validate our techniques, we compared the performance results obtained using our analytical methods with those obtained by experimental setups. In addition, we propose optimized wind turbine characteristics for our model from the analysis results of electromagnetic performances obtained by considering three types of turbine characteristics.
Reconnaissance de critères de comparabilité dans un corpus multilingue spécialisé

Notre objectif est d'automatiser la construction de corpus comparables specialises a partir du Web. La comparabilite se base sur trois niveaux : le domaine, le theme et le type de discours. Le domaine et le theme peuvent etre filtres grâce aux mots-cles utilises lors de la recherche. Nous presentons dans cet article la reconnaissance automatique du type de discours dans des documents specialises francais et japonais, qui necessite une analyse linguistique poussee. Une analyse contrastive des documents nous permet de determiner quelles informations paraissent discriminantes. En s'inspirant des travaux classiques de recherche d'information, nous creons une typologie robuste et linguistiquement motivee basee sur trois niveaux d'analyse : structurel, modal et lexical. Cette typologie nous permet d'apprendre des modeles de classification qui donnent de bons resultats, ce qui montre l'efficacite de cette typologie. Our goal is to automate the compilation of smart specialized comparable corpora. The comparability is based on three levels: domain, topic and type of discourse. Domain and topic can be filtered with the keywords used through web search. We present in this paper the automatic detection of the type of discourse in French and Japanese documents, which needs a wide linguistic analysis. A contrastive analysis of the documents leads us to specify which information is relevant to distinguish them. Referring to classical studies on information retrieval, we create a robust and linguistically motivated typology based on three analysis levels: structural, modal and lexical. This typology is used to learn classification models using shallow parsing. We obtain good results, that demonstrates the efficiency of this typology.
Validation by Computer Simulation of Two Indirect Methods for Quantification of Free Water Transport in Peritoneal Dialysis

Background In peritoneal dialysis, approximately 40% of the total osmotic ultrafiltration (UF) induced by glucose can be predicted to be due to “free” water transport across aquaporin-1 (APQ-1). Theoretically, it would be possible to assess the fraction of free water transport in the early phase of a hypertonic dwell, when UF rate is high and the relative contribution of Na+ diffusion is low. La Milia et al. [La Milia V. et al. Fast-fast peritoneal equilibration test (FAST-FAST-PET): a simple method for peritoneal hydraulic permeability study [Abstract]. Nephrol Dial Transplant 2002; 17 (Suppl 1):17–18] suggested a technique to assess sodium-associated water transport based on sodium removal (Na+R) divided by the plasma Na+ concentration during a “fast-fast” (60 minute) peritoneal equilibration test (PET) for 3.86% glucose, yielding an estimate of the UF passing through the small pores (UFSP). Free water transport (UF through ultrasmall pores; UFUSP) was obtained by subtracting UFSP from total UF. Although peritoneal Na+ transport is almost totally convective, this technique will slightly overestimate small-pore UF due to the presence of some small-pore Na+ diffusion from the circulation during the dwell. A way of dealing with this problem was presented recently by Smit (Smit W. et al. Quantification of free water transport in peritoneal dialysis. Kidney Int 2004; 66:849–854). Methods In the present study we used the three-pore model of peritoneal transport to predict the degree of overestimation of UFSP for the technique presented by La Milia et al., and any potential deviations from theory for the technique presented by Smit et al. Simulations were performed under ordinary conditions and during simulated UF failure for 3.86% glucose. The fractional UF coefficient accounted for by APQ-1 was set at 2%. Results Estimating the UFSP from the sodium-associated water transport according to the method by La Milia et al. consistently overestimated UFSP and underestimated UFUSP. These errors were, however, minimal for dwells lasting between 30 and 80 minutes. The technique by Smit et al. to calculate aquaporin-mediated water flow (UFUSP), using an elaborate correction for Na+ diffusion from the circulation during the dwell, seemed accurate in most situations but, in general, tended to moderately overestimate UFUSP at early dwell times (<30 minutes) and underestimate UFUSP at long dwell times (4 hours). Conclusions The technique presented by La Milia et al. to calculate free water transport during a fast-fast PET was found to be surprisingly accurate, although the procedure would further improve by the introduction of a correction algorithm. The technique by Smit is even more accurate for dwells up to 4 hours’ duration. However, since the Smit technique is elaborate, it is less practical for routine determinations of aquaporin-mediated water transport in peritoneal dialysis.
Atherosclerosis, biomarkers of atherosclerosis and Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent type of dementia, involving progressive deterioration of neuronal networks. Although the pathophysiological mechanism of AD is not fully elucidated, apart from β-amyloid and tau protein, a diverse number of factors such as cardiovascular risk factors, inflammation, and lipids metabolism may play a significant role. Numerous epidemiological and laboratory studies support vascular injury and inflammation, as key pathological processes. The present review is focused on cardiovascular risk factors, lipids, and circulating biomarkers of inflammation, discussing them as independent mechanisms converging to the same final pathogenetic cascade of AD.