Miracle-dz/UniFAR-FTUs huggingface dataset:
Amyloid β-Induced Impairments in Hippocampal Synaptic Plasticity Are Rescued by Decreasing Mitochondrial Superoxide

Generation of reactive oxygen species (ROS) causes cellular oxidative damage and has been implicated in the etiology of Alzheimer's disease (AD). In contrast, multiple lines of evidence indicate that ROS can normally modulate long-term potentiation (LTP), a cellular model for memory formation. We recently showed that decreasing the level of superoxide through the overexpression of mitochondrial superoxide dismutase (SOD-2) prevents memory deficits in the Tg2576 mouse model of AD. In the current study, we explored whether AD-related LTP impairments could be prevented when ROS generation from mitochondria was diminished either pharmacologically or via genetic manipulation. In wild-type hippocampal slices treated with exogenous amyloid β peptide (Aβ1-42) and in slices from APP/PS1 mutant mice that model AD, LTP was impaired. The LTP impairments were prevented by MitoQ, a mitochondria-targeted antioxidant, and EUK134, an SOD and catalase mimetic. In contrast, inhibition of NADPH oxidase either by diphenyliodonium (DPI) or by genetically deleting gp91phox, the key enzymatic component of NADPH oxidase, had no effect on Aβ-induced LTP blockade. Moreover, live staining with MitoSOX Red, a mitochondrial superoxide indicator, combined with confocal microscopy, revealed that Aβ-induced superoxide production could be blunted by MitoQ, but not DPI, in agreement with our electrophysiological findings. Finally, in transgenic mice overexpressing SOD-2, Aβ-induced LTP impairments and superoxide generation were prevented. Our data suggest a causal relationship between mitochondrial ROS imbalance and Aβ-induced impairments in hippocampal synaptic plasticity.
Quantitative analysis of over 20 years of golf course monitoring studies

The purpose of the present study was to comprehensively evaluate available golf course water quality data and assess the extent of impacts, as determined by comparisons with toxicologic and ecologic reference points. Most water quality monitoring studies for pesticides have focused on agriculture and often the legacy chemicals. There has been increased focus on turf pesticides since the early 1990s, due to the intense public scrutiny proposed golf courses receive during the local permitting process, as well as pesticide registration evaluations by the U.S. Environmental Protection Agency under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Results from permit‐driven studies are frequently not published and knowledge about them is usually not widespread. Forty‐four studies involving 80 courses from a 20‐year period passed our quality control and other review criteria. A total of 38,827 data entries (where one analysis for one substance in one sample equals a data entry) from pesticide, pesticide metabolite, total phosphorus, and nitrate analyses of surface water and groundwater were evaluated. Analytes included 161 turf‐related pesticides and pesticide metabolites. Widespread and/or repeated water quality impacts by golf courses had not occurred at the sites studied, although concerns are raised herein about phosphorus. Individual pesticide database entries that exceed toxicity reference points for groundwater and surface water are 0.15 and 0.56%, respectively. These percentages would be higher if they could be expressed in terms of samples collected rather than chemicals analyzed. The maximum contaminant level ([MCL]; 10 mg/L) for nitrate‐nitrogen was exceeded in 16/1,683 (0.95%) of the groundwater samples. There were 1,236 exceedances of the total phosphorus ecoregional criteria in five ecoregions for 1,429 (86.5%) data entries. (This comparison is conservative because many of the results in the database are derived from storm flow events.) Thus, phosphorus appears to present the greatest water quality problem in these studies. Pesticides detected in wells had longer soil metabolism half‐lives (49 d) compared with those not detected (22 d), although the means were not significantly different. Environ. Toxicol. Chem. 2010;29:1224–1236. © 2010 SETAC
Microvascular function is impaired in ankylosing spondylitis and improves after tumour necrosis factor α blockade

Objectives: Ankylosing spondylitis (AS) is associated with increased cardiovascular morbidity and mortality. Microvascular function has been linked to several risk factors for cardiovascular disease. Inflammation in AS may cause microvascular dysfunction. To test this, we assessed microvascular function in (a) patients with AS compared to healthy controls and (b) patients with AS before and after 1 month of anti-tumour necrosis factor (TNF)α treatment with etanercept. Methods: A total of 15 consecutive patients with AS, who were scheduled for etanercept treatment according to the Assessment in Ankylosing Spondylitis (ASAS) group guidelines, and 12 healthy controls matched for age and sex, were recruited. Endothelium-dependent and independent vasodilatation in skin were evaluated with laser Doppler fluxmetry after iontophoresis of acetylcholine and sodium nitroprusside, respectively. Videomicroscopy was used to measure recruitment of skin capillaries after arterial occlusion. Results: Compared to healthy controls, patients with AS had impaired endothelium-dependent vasodilatation and capillary recruitment. Following anti-TNFα treatment, microvascular function improved significantly for endothelium-dependent vasodilatation (p = 0.03) and capillary recruitment (p = 0.006). A significant correlation was observed between changes in endothelium-dependent vasodilatation and changes in erythrocyte sedimentation rate (ESR) (r = −0.56; p = 0.03). Conclusion: Microvascular dysfunction is present in patients with AS with active disease, but improves as inflammation regresses after TNFα blockade.
Computational and Imaging Methods for Studying Neuronal Populations during Behavior

Computational and Imaging Methods for Studying Neuronal Populations during Behavior Shuting Han One of the central questions in neuroscience is how the nervous system generates and regulates behavior. To understand the neural code for any behavior, an ideal experiment would entail (i) quantitatively defining that behavior, (ii) recording neuronal activity in relevant brain regions to identify the underlying neuronal circuits and eventually (iii) manipulating them to test their function. Novel methods in neuroscience have greatly advanced our abilities to conduct such experiments but are still insufficient. In this thesis, I developed methods for these three goals. In Chapter 2, I describe an automatic behavior identification and classification method for the cnidarian Hydra vulgaris using machine learning. In Chapter 3, I describe a fast volumetric two-photon microscope with dual-color laser excitation that can image in 3D the activity of populations of neurons from visual cortex of awake mice. In Chapter 4, I present a machine learning method that identifies cortical ensembles and pattern completion neurons in mouse visual cortex, using two-photon calcium imaging data. These methods advance current technologies, providing opportunities for new discoveries.
Differential expression of Galα1,3Gal epitopes on fetal and adult porcine hematopoietic cells

Galα1‐3Gal (Gal) is the major epitope on pig tissues bound by human natural antibodies. Xenogeneic hematopoietic cell transplantation is being investigated to induce immunological tolerance to xenografts. We have investigated the level of Gal expression on pig hematopoietic cells. Cells were collected from pig fetal liver and bone marrow (BM), and also from adult BM and peripheral blood, before and after treatment with pig‐specific hematopoietic growth factors. Fluorescent activated cell sorting (FACS) analysis was performed with the M86 monoclonal antibody (specific for Gal), lineage markers, and biotinylated stem cell factor (SCF) to detect c‐kit expression. In fetal pig BM and liver, there was no significant difference in Gal expression between monocytes/macrophages (myeloid cells) and lymphocytes. In adult hematopoietic cells from all sources, Gal‐positive subpopulations in T cells showed weak expression of Gal, whereas B cells demonstrated higher expression, and myeloid cells showed highest expression. Adult BM and mobilized peripheral blood progenitor cells contained small populations with very low or negligible expression of Gal. A very small population of c‐kit‐positive cells, indicating progenitor cells, were Gal‐negative. The small Gal‐negative population that exists in progenitor cells might explain why some pig colony forming units (CFU) can be resistant to human serum.
Verification of real-time WSA-ENLIL+Cone simulations of CME arrival-time at the CCMC from 2010-2016

The Wang-Sheeley-Arge (WSA)-ENLIL+Cone model is used extensively in space weather operations world-wide to model CME propagation. As such, it is important to assess its performance. We present validation results of the WSA-ENLIL+Cone model installed at the Community Coordinated Modeling Center (CCMC) and executed in real-time by the CCMC space weather team. CCMC uses the WSA-ENLIL+Cone model to predict CME arrivals at NASA missions throughout the inner heliosphere. In this work we compare model predicted CME arrival-times to in-situ ICME leading edge measurements at STEREO-A, STEREO-B, and Earth (Wind and ACE) for simulations completed between March 2010-December 2016 (over 1,800 CMEs). We report hit, miss, false alarm, and correct rejection statistics for all three locations. For all predicted CME arrivals, the hit rate is 0.5, and the false alarm rate is 0.1. For the 273 events where the CME was predicted to arrive at Earth, STEREO-A, or STEREO-B, and was actually observed (hit event), the mean absolute arrival-time prediction error was 10.4 +/- 0.9 hours, with a tendency to early prediction error of -4.0 hours. We show the dependence of the arrival-time error on CME input parameters. We also explore the impact of the multi-spacecraft observations used to initialize the model CME inputs by comparing model verification results before and after the STEREO-B communication loss (since September 2014) and STEREO-A sidelobe operations (August 2014-December 2015). There is an increase of 1.7 hours in the CME arrival time error during single, or limited two-viewpoint periods, compared to the three-spacecraft viewpoint period. This trend would apply to a future space weather mission at L5 or L4 as another coronagraph viewpoint to reduce CME arrival time errors compared to a single L1 viewpoint.
Topographical Analysis of the Subependymal Zone Neurogenic Niche

The emerging model for the adult subependymal zone (SEZ) cell population indicates that neuronal diversity is not generated from a uniform pool of stem cells but rather from diverse and spatially confined stem cell populations. Hence, when analysing SEZ proliferation, the topography along the anterior-posterior and dorsal-ventral axes must be taken into account. However, to date, no studies have assessed SEZ proliferation according to topographical specificities and, additionally, SEZ studies in animal models of neurological/psychiatric disorders often fail to clearly specify the SEZ coordinates. This may render difficult the comparison between studies and yield contradictory results. More so, by focusing in a single spatial dimension of the SEZ, relevant findings might pass unnoticed. In this study we characterized the neural stem cell/progenitor population and its proliferation rates throughout the rat SEZ anterior-posterior and dorsal-ventral axes. We found that SEZ proliferation decreases along the anterior-posterior axis and that proliferative rates vary considerably according to the position in the dorsal-ventral axis. These were associated with relevant gradients in the neuroblasts and in the neural stem cell populations throughout the dorsal-ventral axis. In addition, we observed spatially dependent differences in BrdU/Ki67 ratios that suggest a high variability in the proliferation rate and cell cycle length throughout the SEZ; in accordance, estimation of the cell cycle length of the neuroblasts revealed shorter cell cycles at the dorsolateral SEZ. These findings highlight the need to establish standardized procedures of SEZ analysis. Herein we propose an anatomical division of the SEZ that should be considered in future studies addressing proliferation in this neural stem cell niche.
Convergent Pathways for Utilization of the Amino Sugars N-Acetylglucosamine,N-Acetylmannosamine, and N-Acetylneuraminic Acid by Escherichia coli

ABSTRACT N-Acetylglucosamine (GlcNAc) andN-acetylneuraminic acid (NANA) are good carbon sources forEscherichia coli K-12, whereasN-acetylmannosamine (ManNAc) is metabolized very slowly. The isolation of regulatory mutations which enhanced utilization of ManNAc allowed us to elucidate the pathway of its degradation. ManNAc is transported by the manXYZ-encoded phosphoenolpyruvate-dependent phosphotransferase system (PTS) transporter producing intracellular ManNAc-6-P. This phosphorylated hexosamine is subsequently converted to GlcNAc-6-P, which is further metabolized by the nagBA-encoded deacetylase and deaminase of the GlcNAc-6-P degradation pathway. Two independent mutations are necessary for good growth on ManNAc. One mutation maps tomlc, and mutations in this gene are known to enhance the expression of manXYZ. The second regulatory mutation was mapped to the nanAT operon, which encodes the NANA transporter and NANA lyase. The combined action of thenanAT gene products converts extracellular NANA to intracellular ManNAc. The second regulatory mutation defines an open reading frame (ORF), called yhcK, as the gene for the repressor of the nan operon (nanR). Mutations in the repressor enhance expression of the nanAT genes and, presumably, three distal, previously unidentified genes,yhcJIH. Expression of just one of these downstream ORFs,yhcJ, is necessary for growth on ManNAc in the presence of an mlc mutation. The yhcJ gene appears to encode a ManNAc-6-P-to-GlcNAc-6-P epimerase (nanE). Another putative gene in the nan operon, yhcI, likely encodes ManNAc kinase (nanK), which should phosphorylate the ManNAc liberated from NANA by the NanA protein. Use of NANA as carbon source by E. coli also requires thenagBA gene products. The existence of a ManNAc kinase and epimerase within the nan operon allows us to propose that the pathways for dissimilation of the three amino sugars GlcNAc, ManNAc, and NANA, all converge at the step of GlcNAc-6-P.
The Problem with Kappa

It is becoming clear that traditional evaluation measures used in Computational Linguistics (including Error Rates, Accuracy, Recall, Precision and F-measure) are of limited value for unbiased evaluation of systems, and are not meaningful for comparison of algorithms unless both the dataset and algorithm parameters are strictly controlled for skew (Prevalence and Bias). The use of techniques originally designed for other purposes, in particular Receiver Operating Characteristics Area Under Curve, plus variants of Kappa, have been proposed to fill the void. This paper aims to clear up some of the confusion relating to evaluation, by demonstrating that the usefulness of each evaluation method is highly dependent on the assumptions made about the distributions of the dataset and the underlying populations. The behaviour of a number of evaluation measures is compared under common assumptions. Deploying a system in a context which has the opposite skew from its validation set can be expected to approximately negate Fleiss Kappa and halve Cohen Kappa but leave Powers Kappa unchanged. For most performance evaluation purposes, the latter is thus most appropriate, whilst for comparison of behaviour, Matthews Correlation is recommended.
Neuronal Injuries Induced by Perinatal Hypoxic-Ischemic Insults Are Potentiated by Prenatal Exposure to Lipopolysaccharide: Animal Model for Perinatally Acquired Encephalopathy

We developed an original rat model for neonatal brain lesions whereby we explored the sequential effects of infectious and hypoxic-ischemic aggressions. We investigated the influence of combined exposure to prenatal infection with neonatal hypoxic-ischemic insult. Infectious effect was produced by administrating lipopolysaccharide (LPS) intraperitoneally to pregnant rats starting on embryonic day 17. Hypoxia-ischemia (H/I) was induced in the pups at postnatal day 1 (P1) by ligature of the right common carotid artery followed by exposure to hypoxia (8% O2) for 3.5 h. Animals were randomized into four groups: (1) control group: pups born to mothers subjected to intraperitoneal saline injection; (2) LPS group: pups exposed in utero to LPS; (3) H/I group: pups exposed to postnatal hypoxia after ligation of the right carotid artery, and (4) H/I plus LPS group: in utero exposure to LPS followed by postnatal hypoxia after ligation of the right carotid artery. Neuropathological findings in pups examined at P3 and P8 showed that groups 2, 3, and 4 presented a pattern of neuronal injury similar to those characterized as ‘selective neuronal necrosis’ within the context of human perinatal encephalopathy. Neuronal cellular injuries were particularly seen in the neocortex, mainly in parasagittal areas. The extent of neuronal cell injury in the brain of rats exposed to postnatal H/I was significantly increased by antenatal exposure to LPS. This animal model provides an experimental means to explore the respective roles of anoxic and infectious components in the pathogenesis of perinatal brain lesions and consequent cerebral palsy.
Short- and long-term subjective medical treatment outcome of trauma surgery patients: the importance of physician empathy

Purpose To investigate accident casualties’ long-term subjective evaluation of treatment outcome 6 weeks and 12 months after discharge and its relation to the experienced surgeon’s empathy during hospital treatment after trauma in consideration of patient-, injury-, and health-related factors. The long-term results are compared to the 6-week follow-up outcomes. Patients and methods Two hundred and seventeen surgery patients were surveyed at 6 weeks, and 206 patients at 12 months after discharge from the trauma surgical general ward. The subjective evaluation of medical treatment outcome was measured 6 weeks and 12 months after discharge with the respective scale from the Cologne Patient Questionnaire. Physician Empathy was assessed with the Consultation and Relational Empathy Measure. The correlation between physician empathy and control variables with the subjective evaluation of medical treatment outcome 12 months after discharge was identified by means of logistic regression analysis under control of sociodemographic and injury-related factors. Results One hundred and thirty-six patients were included within the logistic regression analysis at the 12-month follow-up. Compared to the 6-week follow-up, the level of subjective evaluation of medical treatment outcome was slightly lower and the association with physician empathy was weaker. Compared to patients who rated the empathy of their surgeon lower than 31 points, patients with ratings of 41 points or higher had a 4.2-fold higher probability to be in the group with a better medical treatment outcome (3.5 and above) on the Cologne Patient Questionnaire scale 12 months after discharge from hospital (P=0.009, R2=33.5, 95% confidence interval: 1.440–12.629). Conclusion Physician empathy is the strongest predictor for a higher level of trauma patients’ subjective evaluation of treatment outcome 6 weeks and 12 months after discharge from the hospital. Interpersonal factors between surgeons and their patients are possible key levers for improving patient outcomes in an advanced health system. Communication trainings for surgeons might prepare them to react appropriately to their patients’ needs and lead to satisfactory outcomes for both parties.
Evaluation of Apelin, and Tartrate-Resistant Acid Phosphatase-5b in Ankylosing Spondylitis Male Patients With and Without Osteoporosis

Osteoporosis is a common complication of ankylosing spondylitis (AS), and it is related to the high levels of biochemical markers such as tartrate-resistant acid phosphates (TRACP)-5b and other proinflammatory cytokines. In early AS, osteoporosis may appear due to the action proinflammatory cytokines, however spinal osteoporosis commonly observed in those patients with severe AS of long duration but it can occur as a result of ankylosis and lack of movement. Apelin is a new adipokine that has a negative impact on bone formation and can act as an anti-anabolic agent. The aim of this study is to evaluate serum (apelin and TRACP-5b) levels in ankylosing spondylitis (AS) male patients with and without osteoporosis and look for the relation between osteoporosis and the studied parameters. About fifty-eight male AS patients were included in this study. Serum (apelin and tartrate-resistant acid phosphates (TRACP)-5b) were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Bone mineral density (BMD)(Z-score)of Lumbar spine was determined using dual-energy X-ray absorptiometry (DXA). This study shows that AS male patients with osteoporosis had significantly high serum TRACP-5b level (P-value <0.001) while no significant differences of serum apelin level (P-value=0.06) between AS male patients with and without osteoporosis. A significant correlation has been found between BMD (Z-score) and serum TRACP-5b level while no correlation has been found between BMD (Z-score) and serum apelin level. The results of this study suggest that serum TRACP-5b is could be used in detection of AS disease with osteoporosis, while serum Apelin level is would not be effected.
Cognitive deficit induced by acute tryptophan depletion in patients with Alzheimer's disease.

OBJECTIVE The study assessed the effects on global cognitive function and mood of a reduction of brain serotonin by means of acute tryptophan depletion in 16 patients with dementia of the Alzheimer type and in 16 cognitively intact comparison subjects. METHOD In a double-blind, crossover design, subjects received a tryptophan-free amino acid drink to induce acute tryptophan depletion and, on a separate occasion, a placebo drink containing a balanced mixture of amino acids. On each occasion, ratings of depressed mood were made at baseline and 4 and 7 hours later, and the Modified Mini-Mental State was administered at baseline and 4 hours later. RESULTS Patients with dementia of the Alzheimer type had a significantly lower mean score on the Modified Mini-Mental State after acute tryptophan depletion than after receiving placebo. The comparison group showed no difference in mean score on the Modified Mini-Mental State after acute tryptophan depletion and after receiving placebo. No significant changes in mood were found in either group. CONCLUSIONS Acute tryptophan depletion significantly impaired cognitive function in patients with dementia of the Alzheimer type. Compromised serotonergic function, in combination with cholinergic deficit, may make an important contribution to cognitive decline in dementia of the Alzheimer type.