Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling Dopamine Activity in the Brain with Reinforcement Learning A case study

A serious problem of society today are the drug and their consequences. One approach to solve this problem is to administer a drug that will block the dopamine receptors in the brain. This approach originates in that increased dopamine level caused by drugs is believed to be one of the main reasons for why we become addicted to drugs. One way to study the mechanisms of craving, done by Professor Kenneth F. Green, is to utilize the Conditioned Place Preference method. The dopamine activity in the mesolimbic system has been studied and modeled with Temporal Difference (TD) methods. The focus of these studies has however been on the paring of a stimulus with a reward, i.e. classical conditioning. The purpose of this thesis is to examine whether one can use these existing models, to create a model of how a conditioned place preference among rats, due to amphetamine, is developed. By firstly analyzing and decomposing the existing TD model and then adapting it to the conditions of Green’s experiment, it does become possible to model the dopamine activity during the conditioning process that pairs a certain environment with the craving for amphetamine. Finally, different methods for improving the resulting model are tried out.
Inhaled hydrogen sulfide prevents endotoxin-induced systemic inflammation and improves survival by altering sulfide metabolism in mice.

AIMS The role of hydrogen sulfide (H(2)S) in endotoxin (lipopolysaccharide [LPS])-induced inflammation is incompletely understood. We examined the impact of H(2)S breathing on LPS-induced changes in sulfide metabolism, systemic inflammation, and survival in mice. RESULTS Mice that breathed air alone exhibited decreased plasma sulfide levels and poor survival rate at 72 h after LPS challenge. Endotoxemia markedly increased alanine aminotransferase (ALT) activity and nitrite/nitrate (NOx) levels in plasma and lung myeloperoxidase (MPO) activity in mice that breathed air. In contrast, breathing air supplemented with 80 ppm of H(2)S for 6 h after LPS challenge markedly improved survival rate compared to mice that breathed air alone (p<0.05). H(2)S breathing attenuated LPS-induced increase of plasma ALT activity and NOx levels and lung MPO activity. Inhaled H(2)S suppressed LPS-induced upregulation of inflammatory cytokines, while it markedly induced anti-inflammatory interleukin (IL)-10 in the liver. Beneficial effects of H(2)S inhalation after LPS challenge were associated with restored sulfide levels and markedly increased thiosulfate levels in plasma. Increased thiosulfate levels after LPS challenge were associated with upregulation of rhodanese, but not cystathionine-γ-lyase (CSE), in the liver. Administration of sodium thiosulfate dose-dependently improved survival after LPS challenge in mice. INNOVATION By measuring changes in plasma levels of sulfide and sulfide metabolites using an advanced analytical method, this study revealed a critical role of thiosulfate in the protective effects of H(2)S breathing during endotoxemia. CONCLUSION These observations suggest that H(2)S breathing prevents inflammation and improves survival after LPS challenge by altering sulfide metabolism in mice.
Applying Semantic Web Mining Technologies In Personalized E-Learning

The challenge of the Semantic Web Mining technologies in the e-Learning domain can relate to the provision of personalized experiences for the users. Particularly, these applications can take into consideration the individual needs and requirements of learners. In this paper, we propose a framework for personalised e-Learning based on aggregate usage profiles and a domain ontology. We have distinguished two stages in the whole process, one of offline tasks that includes data preparation, ontology creation and usage mining and one of online tasks that concerns the production of recommendations.
Characterization of a sustained-release delivery system for combined cytokine/peptide vaccination using a poly-N-acetyl glucosamine-based polymer matrix.

Identification of tumor-associated antigens (TAAs) and their class I MHC-restricted epitopes now allows for the rational design of peptide-based cancer vaccines. A biocompatible system capable of sustained release of biologically relevant levels of cytokine and TAA peptide could provide a more effective microenvironment for antigen presentation. Our goal was to test a sustained-release cytokine/TAA peptide-based formulation using a highly purified polysaccharide [poly-N-acetyl glucosamine (p-GlcNAc)] polymer. Granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 microgram) and MART-1(27-35) peptide (128 microgram in DMSO) were formulated into p-GlcNAc. Peptide release was assayed in vitro using interleukin 2 production from previously characterized MART-1(27-35)-specific Jurkat T cells (JRT22). GM-CSF release was assayed via ELISA and proliferation of M-07e (GM-CSF-dependent) cells. Local bioavailability of MART-1(27-35) peptide for uptake and presentation by antigen-presenting cells was demonstrated for up to 6 days (>0.5 microgram/ml). More than 1.0 microgram/ml GM-CSF was concomitantly released over the same period. Biocompatibility and local tissue response to p-GlcNAc releasing murine GM-CSF was determined in C57BL/6 mice via s.c. injection using murine GM-CSF (0. 2 microgram/ml) in 200 microliter of a 2.5% polymer gel. Significant lymphocytic and eosinophilic infiltration was observed 2-7 days after injection with polymer containing murine GM-CSF. The results of our studies show that this biocompatible system is capable of a sustained concomitant release of biologically active peptide and cytokine into the local microenvironment. These findings support further studies to validate a p-GlcNAc delivery system vehicle for a cytokine/TAA peptide-based cancer vaccine.
Automated measurement of bone-mineral-density (BMD) values of vertebral bones based on X-ray torso CT images

Bone is one of the most important anatomical structures in humans and osteoporosis is one of the major public health concerns in the world. Osteoporosis is a main target disease of bone, which can be detected by medical image techniques. The purpose of this study is to develop a fully automated computer scheme to measure bone-mineral-density (BMD) values for vertebral trabecular bones. This scheme will aid osteoporosis diagnosis performed using computer tomography (CT) images. This scheme includes the following processing steps: segmentation of the bone region, recognition of the skeletal structures and measurement of the BMD value in vertebral trabecular bone of each vertebral body. The proposed scheme was applied to 20 X-ray torso CT cases to measure the BMD values for vertebral trabecular bones. The experimental results show that the mean and standard deviation of the difference between the BMD values measured by using the proposed method and those measured using a manual segmentation method were 6.93 mg/cm3 and 6.82 mg/cm3 respectively. The accuracy of the proposed scheme satisfied the requirement for a computer-aided system used in osteoporosis diagnosis.
Two rapid pigmentation tests for identification of Cryptococcus neoformans

Two tests were developed for the rapid identification of Cryptococcus neoformans based on pigment produced by the organism's phenoloxidase activity. Caffeic acid was incorporated into cornmeal agar, a medium used routinely for yeast identification. When tested on this medium, only C. neoformans isolates produced brown pigment. All other yeasts maintained their normal morphology and did not produce the reaction product. A non-medium-based test was developed for same-day identification of C. neoformans isolates. Paper strips saturated with a buffered L-beta-3,4-dihydroxyphenylalanine-ferric citrate solution were inoculated with isolates and incubated at 37 degrees C. Pigment production occurred only with C. neoformans isolates, many within 60 to 90 min. All other yeasts remained negative.
The Association of Prolonged QT Interval on Electrocardiography and Chronic Lead Exposure

Objectives: The aim of this study was to examine the association of lead exposure with cardiac conduction disturbance among lead-exposed and nonexposed workers in Taiwan. Methods: The participants comprised 312 lead workers and 329 referents who had no known occupational lead exposure. During their annual health examination, they were invited to take part in the survey. Standard resting 12-lead electrocardiograms were obtained and the electrocardiographic features studied were related to blood lead levels (BLLs). Results: The mean BLLs were 26.05 (SD = 13.98) and 2.62 (SD = 1.42) &mgr;g/dL in lead-exposed and reference groups, respectively. Compared with the referents, lead workers had significantly shorter PR interval and longer QTc interval. Especially, workers with BLL > 30 &mgr;g/dL had the highest risk after adjusting for age, sex, body mass index, and other potential confounders. Conclusion: The data suggest that lead exposure is positively associated with prolonged QTc interval.
Blood–brain barrier disruption is associated with increased mortality after endovascular therapy

Objective: To evaluate the incidence, baseline characteristics, and clinical prognosis of blood–brain barrier (BBB) disruption after endovascular therapy in acute ischemic stroke patients. Methods: A total of 220 patients treated with endovascular therapy between April 2007 and October 2011 were identified from a prospective, clinical, thrombolysis registry. All patients underwent a nonenhanced CT scan immediately after treatment. CT scan or MRI was systematically realized at 24 hours to assess intracranial hemorrhage complications. BBB disruption was defined as a hyperdense lesion on the posttreatment CT scan. Results: BBB disruption was found in 128 patients (58.2%; 95% confidence interval [CI], 51.4%–64.9%). Cardioembolic etiology, high admission NIH Stroke Scale score, high blood glucose level, internal carotid artery occlusion, and use of combined endovascular therapy (chemical and mechanical revascularization) were independently associated with BBB disruption. Patients with BBB disruption had lower rates of early major neurologic improvement (8.6% vs 31.5%, p < 0.001), favorable outcome (39.8% vs 61.8%, p = 0.002), and higher rates of 90-day mortality (34.4% vs 14.6%, p = 0.001) and hemorrhagic complications (42.2% vs 8.7%, p < 0.001) than those without BBB disruption. By multivariable analysis, patients with BBB disruption remained with a lower rate of early neurologic improvement (adjusted odds ratio [OR], 0.28; 95% CI, 0.11–0.70) and with a higher rate of mortality (adjusted OR, 2.37; 95% CI, 1.06–5.32) and hemorrhagic complications (adjusted OR, 6.38; 95% CI, 2.66–15.28). Conclusion: BBB disruption has a detrimental effect on outcome and is independently associated with mortality after endovascular therapy. BBB disruption assessment may have a role in prognosis staging in these patients.
Use of Bacteriophages in Combination with Competitive Exclusion to Reduce Salmonella from Infected Chickens

Abstract Salmonella-specific bacteriophages (BP) and competitive exclusion (CE) were used to reduce Salmonella colonization in experimentally infected chickens. A “cocktail” of distinct phage (i.e., phage showing different host ranges and inducing different types of plaques on Salmonella Typhimurium [ST] cultures) was developed. The killing activity of the selected BPs on ST cultures differed significantly, as determined in in vitro killing assays. BPs were administered orally to the chickens several days prior and after ST challenge but not simultaneously. BPs were readily isolated from the feces of the BP-treated chickens approximately 48 hr after administration. A CE product consisting of a defined culture of seven different microbial species was used either alone or in combination with BP treatment. CE was administered orally at hatch. Salmonella counts in intestine, ceca, and a pool of liver/spleen were evaluated in Salmonella-challenged chickens treated with BP or with BP and CE. In both trials 1 and 2, a beneficial effect of the phage treatment on weight gain performance was evident. A reduction in Salmonella counts was detected in cecum and ileum of BP-, CE-, and BP+CE-treated chickens as compared with nontreated birds. In trial 1, BP treatment reduced ST counts to marginal levels in the ileum and reduced counts sixfold in the ceca. A reduction of Salmonella counts with BP, CE, and BP+CE treatments was evident in chickens from trial 2. Both CE and BP treatments showed differences in the reduction of Salmonella counts after challenge between specimens obtained at days 4 and 14 postchallenge in ceca, liver/spleen, and ileum. The preliminary data presented in this report show that isolation and characterization of Salmonella-specific BP is uncomplicated and feasible on a larger scale. Results indicate a protective effect of both Salmonella-specific BPs and a defined competitive exclusion product against Salmonella colonization of experimentally infected chickens. These results are encouraging for further work on the use of BP as an effective alternative to antibiotics to reduce Salmonella infections in poultry.
Graph-Grammar-Based Analog Circuit Topology Synthesis

Automatically constructing analog circuit topology according to specifications is always a challenging task, due to the high complexity and substantial design expertise required. This paper proposes a graph-grammar-based method that can efficiently and automatically generate analog circuit topologies, which can be applied to general analog circuit synthesis frameworks for analog circuit design. The topology generation process is encoded by constructing a binary tree, in which the leaf nodes are decomposed according to a set of grammar rules. In order to guarantee only unique circuit structures to be generated, double isomorphism checks are applied at both tree structure level and circuit transistor level. Our experimental results demonstrate the high efficiency and wide applicability of the proposed method.
Aided Cortical Auditory Evoked Potentials for Hearing Instrument Evaluation in Infants

With the widespread implementation of universal newborn hearing screening programs there is a need for reliable, objective techniques for fitting and evaluating hearing instruments in young infants. After hearing loss is diagnosed, fitting of hearing instruments can occur when infants are as young as five weeks old (Yoshinaga-Itano 2004). At this stage of development it is difficult to assess hearing using behavioral techniques and it is not yet known which hearing instrument fitting approach is optimal in such young infants (Snik and Stollman 1998). Because of the lack of reliable behavioral information audiologists may be tempted to fit hearing instruments “conservatively” in young infants, with less gain and output than would normally be prescribed for children and adults who are able to give reliable behavioral responses while wearing hearing instruments. Objective measures such as auditory evoked potentials offer the possibility of evaluating the effectiveness of hearing instruments in infants and other children who have a limited behavioral repertoire due to developmental delay or other disabilities. This chapter describes the range of auditory evoked potentials, previous research that attempted to use evoked potentials to evaluate hearing instruments, and recent work showing that cortical auditory
Spurious Tests and Sign Reversals in International Economics

Empirical tests of numerous theories in international economics, e.g., the monetary explanation of the balance of payments/exchange rate, the portfolio balance model of capital flows, purchasing power parity, and covered interest rate arbitrage, usually impose the subtractive linear constraint that corresponding foreign and domestic explanatory variables have equal but opposite effects on the dependent variable. ' Rasulo and Wilford [15] investigate empirically the bias in general caused by such a restriction in monetary models of the balance of payments/exchange rate.2 What is not recognized, however, is the peculiar nature and potential severity of the bias, including sign reversals, which results from subtracting (as opposed to aggregating) explanatory variables; and the wide range of tests in international economics which may be spurious because of this type of bias.
Contribution of L‐type Ca2+ channels to evoked transmitter release in cultured Xenopus nerve‐muscle synapses

1 Simultaneous pre‐ and postsynaptic patch recordings were obtained from the varicosity synapses formed by Xenopus motoneurons on muscle cells in embryonic cultures, in order to elucidate the contribution of N‐ and L‐type Ca2+ channels to the varicosity Ca2+ current (ICa) and evoked transmitter release. 2 Although N‐type channels are predominant in the varicosities and generally thought to be responsible for all evoked release, in most synapses a fraction of ICa and release could be reversibly blocked by the L‐type channel antagonist nifedipine, and enhanced by the agonist Bay K8644. Up to 50 % (mean, 21 %) of the ICa evoked by a voltage clamp waveform mimicking a normal presynaptic action potential (APWF) is composed of L‐type current. 3 Surprisingly, the nifedipine‐sensitive (L) channels activated more rapidly (time‐constant, 0.46 ms at +30 mV) than the nifedipine‐insensitive (N) channels (time constant, 1.42 ms). Thus the L‐type current would play a disproportionate role in the ICa linked to a normal action potential. 4 The relationship between ICa and release was the same for nifedipine‐sensitive and ‐resistant components. The N‐ and L‐components of ICa are thus equally potent in evoking release. This may represent an immature stage before N‐type channels become predominant. 5 Replacing Ca2+ in the medium with Ba2+ strongly enhanced the L‐type component, suggesting that L‐type channels may be inactivated at Ca2+ levels close to those at rest. 6 We speculate that populations of L‐type channels in different parts of the neuron may be recruited or inactivated by fluctuations of the cytosolic Ca2+ concentration within the physiological range.
Conserved Changes in the Dynamics of Metabolic Processes during Fruit Development and Ripening across Species1[C][W][OPEN]

STATIS analysis of metabolic profiles discerns conserved metabolic processes during development and ripening across fruits. Computational analyses of molecular phenotypes traditionally aim at identifying biochemical components that exhibit differential expression under various scenarios (e.g. environmental and internal perturbations) in a single species. High-throughput metabolomics technologies allow the quantification of (relative) metabolite levels across developmental stages in different tissues, organs, and species. Novel methods for analyzing the resulting multiple data tables could reveal preserved dynamics of metabolic processes across species. The problem we address in this study is 2-fold. (1) We derive a single data table, referred to as a compromise, which captures information common to the investigated set of multiple tables containing data on different fruit development and ripening stages in three climacteric (i.e. peach [Prunus persica] and two tomato [Solanum lycopersicum] cultivars, Ailsa Craig and M82) and two nonclimacteric (i.e. strawberry [Fragaria × ananassa] and pepper [Capsicum chilense]) fruits; in addition, we demonstrate the power of the method to discern similarities and differences between multiple tables by analyzing publicly available metabolomics data from three tomato ripening mutants together with two tomato cultivars. (2) We identify the conserved dynamics of metabolic processes, reflected in the data profiles of the corresponding metabolites that contribute most to the determined compromise. Our analysis is based on an extension to principal component analysis, called STATIS, in combination with pathway overenrichment analysis. Based on publicly available metabolic profiles for the investigated species, we demonstrate that STATIS can be used to identify the metabolic processes whose behavior is similarly affected during fruit development and ripening. These findings ultimately provide insights into the pathways that are essential during fruit development and ripening across species.
High resolution structure of streptavidin in complex with a novel high affinity peptide tag mimicking the biotin binding motif

A novel peptide was designed which possesses nanomolar affinity of less than 20 nM for streptavidin. Therefore it was termed Nano‐tag and has been used as an affinity tag for recombinant proteins. The minimized version of the wild type Nano‐tag is a seven‐amino acid peptide with the sequence fMDVEAWL. The three‐dimensional structure of wild type streptavidin in complex with the minimized Nano‐tag was analyzed at atomic resolution of 1.15 Å and the details of the binding motif were investigated. The peptide recognizes the same pocket of streptavidin where the natural ligand biotin is bound, but the peptide requires significantly more space than biotin. Therefore the binding loop adopts an “open” conformation in order to release additional space for the peptide. The conformation of the bound Nano‐tag corresponds to a 310 helix. However, the analysis of the intermolecular interactions of the Nano‐tag with residues of the binding pocket of streptavidin reveals astonishing similarities to the biotin binding motif. In principle the three‐dimensional conformation of the Nano‐tag mimics the binding mode of biotin. Our results explain why the use of the Nano‐tag in fusion with recombinant proteins is restricted to their N‐terminus and we describe the special significance of the fMet residue for the high affinity binding mode. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Origin of respiratory sinus arrhythmia in conscious humans. An important role for arterial carotid baroreceptors.

BACKGROUND We investigated whether respiratory sinus arrhythmia (RSA) in healthy humans originated from central neuronal oscillations or from peripheral baroreceptors responding to respiratory changes in venous return. METHODS AND RESULTS During subjects' controlled breathing we used sinusoidal neck suction to influence RSA (spectral analysis of RR interval). In 11 subjects, 20-second apnea greatly reduced RSA, which was restored by neck suction at the frequency of respiration. Counteracting the respiration-induced cycles of carotid blood pressure decreased RSA in 13 subjects (from 2136 +/- 682 to 1372 +/- 561 ms2, P < .01). The critical phase of this neck suction was constant for each subject at around the phase shift (with regard to respiration-related fluctuations of blood pressure) best for smoothing respiratory (mechanical) changes in blood pressure. Suction of a non-baroreceptor area (the thigh) did not affect RSA. In 4 subjects, to separate the effects of peripheral baroreceptor afferents from respiration-entrained central oscillation (15 breaths/min), we cycled the neck suction at 12 cycles/min. Increasing neck suction from -7 to -30 mm Hg increased the ratio of the power of the 12 cycles compared with the 15-cycle RSA oscillation in RR interval spectral analysis from 0.26 to 2.57. A 12-cycle/min suction of an area other than the neck had little effect on the RR interval spectrum. CONCLUSIONS RSA can be mimicked or reduced by stimulation of arterial baroreceptors with cycles of appropriately phased neck suction at the frequency of respiration. This suggests an important influence of the arterial baroreceptors in the generation of RSA in conscious humans.