Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model

Objective(s): Exposing to stress may be associated with increased production of reactive oxygen species (ROS). Therefore, high level of oxidative stress may eventually give rise to accumulation of oxidative damage and development of numerous neurodegenerative diseases. It has been presented that brain-derived neurotrophic factor (BDNF) supports neurons against various neurodegenerative conditions. Lately, there has been growing evidence that changes in the cerebral neurotrophic support and especially in the BDNF expression and its engagement with ROS might be important in various disorders and neurodegenerative diseases. Hence, we aimed to investigate protective effects of BDNF against stress-induced oxidative damage. Materials and Methods: Five- to six-month-old male wild-type and BDNF knock-down mice were used in this study. Activities of catalase (CAT) and superoxide dismutase (SOD) enzymes, and the amount of malondialdehyde (MDA) were assessed in the cerebral homogenates of studied groups in response to acute restraint stress. Results: Exposing to acute physiological stress led to significant elevation in the markers of oxidative stress in the cerebral cortexes of experimental groups. Conclusion: As BDNF-deficient mice were observed to be more susceptible to stress-induced oxidative damage, it can be suggested that there is a direct interplay between oxidative stress indicators and BDNF levels in the brain.
An evolutionary algorithm for performance optimization at software architecture level

Architecture-based software performance optimization can not only significantly save time but also reduce cost. A few rule-based performance optimization approaches at software architecture (SA) level have been proposed in recent years. However, in these approaches, the number of rules being used and the order of application of each rule are uncertain in the optimization process and these uncertainties have not been fully considered so far. As a result, the search space for performance improvement is limited, possibly excluding optimal solutions. Aiming to solve this problem, we propose an evolutionary algorithm for rule-based performance optimization at SA level named EA4PO. First, the rule-based software performance optimization at SA level is abstracted into a mathematical model called RPOM. RPOM can precisely characterize the mathematical relation between the usage of rules and the optimal solution in the performance improvement space. Then, a framework named RSEF is designed to support the execution of rule sequences. Based on RPOM and RSEF, EA4PO is proposed to find the optimal performance improvement solution. In EA4PO, an adaptive mutation operator is designed to guide the search direction by fully considering heuristic information of rule usage during the evolution. Finally, the effectiveness of EA4PO is validated by comparing EA4PO with a typical rule-based approach. The results show that EA4PO can explore a relatively larger space and get better solutions.
Securing passfaces for description

One common practice in relation to alphanumeric passwords is to write them down or share them with a trusted friend or colleague. Graphical password schemes often claim the advantage that they are significantly more secure with respect to both verbal disclosure and writing down. We investigated the reality of this claim in relation to the Passfaces graphical password scheme. By collecting a corpus of naturalistic descriptions of a set of 45 faces, we explored participants' ability to associate descriptions with faces across three conditions in which the decoy faces were selected: (1) at random; (2) on the basis of their visual similarity to the target face; and (3) on the basis of the similarity of the verbal descriptions of the decoy faces to the target face. Participants were found to perform significantly worse when presented with visual and verbally grouped decoys, suggesting that Passfaces can be further secured for description. Subtle differences in both the nature of male and female descriptions, and male and female performance were also observed.
Multiscale Modelling Of Platelet Aggregation

During clotting under flow, platelets bind and activate on collagen and release autocrinic factors such ADP and thromboxane, while tissue factor (TF) on the damaged wall leads to localized thrombin generation. Toward patient-specific simulation of thrombosis, a multiscale approach was developed to account for: platelet signaling (neural network trained by pairwise agonist scanning, PAS-NN), platelet positions (lattice kinetic Monte Carlo, LKMC), wall-generated thrombin and platelet-released ADP/thromboxane convectiondiffusion (PDE), and flow over a growing clot (lattice Boltzmann). LKMC included shear-driven platelet aggregate restructuring. The PDEs for thrombin, ADP, and thromboxane were solved by finite element method using cell activation-driven adaptive triangular meshing. At all times, intracellular calcium was known for each platelet by PAS-NN in response to its unique exposure to local collagen, ADP, thromboxane, and thrombin. The model accurately predicted clot morphology and growth with time on collagen/TF surface as compared to microfluidic blood perfusion experiments. The model also predicted the complete occlusion of the blood channel under pressure relief settings. Prior to occlusion, intrathrombus concentrations reached 50 nM thrombin, ~1 μM thromboxane, and ~10 μM ADP, while the wall shear rate on the rough clot peaked at ~1000-2000 sec-1. Additionally, clotting on TF/collagen was accurately simulated for modulators of platelet cyclooxygenase-1, P2Y1, and IP-receptor. The model was then extended to a rectangular channel with symmetric Gaussian obstacles representative of a coronary artery with severe stenosis. The upgraded stenosis model was able to predict platelet deposition dynamics at the post-stenotic segment corresponding to development of artery thrombosis prior to severe myocardial infarction. The presence of stenosis conditions alters the hemodynamics of normal hemostasis, showing a different thrombus growth mechanism. The model was able to recreate the platelet aggregation process under the complex recirculating flow features and make reasonable prediction on the clot morphology with flow separation. The model also detected recirculating transport dynamics for diffusible species in response to vortex features, posing interesting questions on the interplay between biological signaling and prevailing hemodynamics. In future work, the model will be extended to clot growth with a patient cardiovasculature under pulsatile flow conditions. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Chemical and Biomolecular Engineering First Advisor Scott L. Diamond Second Advisor Talid R. Sinno This dissertation is available at ScholarlyCommons: https://repository.upenn. edu/edissertations/2452
Functional Analysis Of Histamine Receptor Subtypes Involved In Endothelium‐Mediated Relaxation Of The Human Uterine Artery

1. This work was designed to introduce human uterine arteries as a new model for cardiovascular research. Advantages of this model include considerable availability of tissue because of the appearance of uterus myomatosus in post‐menopausal women who undergo surgery and the chance to work on dysfunctional and healthy vessels.
Mutations in the Effector Binding Loops in the C2A and C2B Domains of Synaptotagmin I Disrupt Exocytosis in a Nonadditive Manner*

The secretory vesicle protein synaptotagmin I (syt) plays a critical role in Ca2+-triggered exocytosis. Its cytoplasmic domain is composed of tandem C2 domains, C2A and C2B; each C2 domain binds Ca2+. Upon binding Ca2+, positively charged residues within the Ca2+-binding loops are thought to interact with negatively charged phospholipids in the target membrane to mediate docking of the cytoplasmic domain of syt onto lipid bilayers. The C2 domains of syt also interact with syntaxin and SNAP-25, two components of a conserved membrane fusion complex. Here, we have neutralized single positively charged residues at the membrane-binding interface of C2A (R233Q) and C2B (K366Q). Either of these mutations shifted the Ca2+ requirements for syt-liposome interactions from ∼20 to ∼40 μm Ca2+. Kinetic analysis revealed that the reduction in Ca2+-sensing activity was associated with a decrease in affinity for membranes. These mutations did not affect sytsyntaxin interactions but resulted in a ∼50% loss in SNAP-25 binding activity, suggesting that these residues lie at an interface between membranes and SNAP-25. Expression of full-length versions of syt that harbored these mutations reduced the rate of exocytosis in PC12 cells. In both biochemical and functional assays, effects of the R233Q and K366Q mutations were not additive, indicating that mutations in one domain affect the activity of the adjacent domain. These findings indicate that the tandem C2 domains of syt cooperate with one another to trigger release via loop-mediated electrostatic interactions with effector molecules.
Nicotinic Acetylcholine Receptor α9 and α10 Subunits Are Expressed in the Brain of Mice

The α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits are likely to be the evolutionary precursors to the entire cys-loop superfamily of ligand-gated ion channels, which includes acetylcholine, GABA, glycine and serotonin ionotropic receptors. nAChRs containing α9 and α10 subunits are found in the inner ear, dorsal root ganglia and many non-excitable tissues, but their expression in the central nervous system has not been definitely demonstrated. Here we show the presence of both α9 and α10 nAChR subunits in the mouse brain by RT-PCR and immunochemical approaches with a range of nAChR subunit-selective antibodies, which selectivity was demonstrated in the brain preparations of α7−/−, α9−/− and α10−/− mice. The α9 and α10 RNA transcripts were found in medulla oblongata (MO), cerebellum, midbrain (MB), thalamus and putamen (TP), somatosensory cortex (SC), frontal cortex (FC) and hippocampus. High α9-selective signal in ELISA was observed in the FC, SC, MO, TP and hippocampus and α10-selective signal was the highest in MO and FC. The α9 and α10 proteins were found in the brain mitochondria, while their presence on the plasma membrane has not been definitely confirmed The α7-, α9- and α10-selective antibodies stained mainly neurons and hypertrophied astrocytes, but not microglia. The α9- and α10-positive cells formed ordered structures or zones in cerebellum and superior olive (SO) and were randomly distributed among α7-positive cells in the FC; they were found in CA1, CA3 and CA4, but not in CA2 region of the hippocampus. The α9 and α10 subunits were up-regulated in α7−/− mice and both α7 and α9 subunits were down-regulated in α10−/− mice. We conclude that α9 and α10 nAChR subunits are expressed in distinct neurons of the mouse brain and in the brain mitochondria and are compensatory up-regulated in the absence of α7 subunits.
A TOA-based location algorithm reducing the errors due to non-line-of-sight (NLOS) propagation

An effective location algorithm, which considers non-line-of-sight (NLOS) propagation, is presented. By using a new variable to replace the square term and adding the loose variable, the problem becomes a mathematical programming problem, and then the NLOS propagation's effect can be evaluated. This method is simple and does not add much computation time. Compared with other methods, it has high accuracy.
Relational Recognition for Information Extraction in Free Text Documents

Information extraction tools provide an important means for distilling content from free text documents, and knowledgebased tools provide an important means for automatically reasoning over statements expressed as well-formed tuples. A number of techniques deliver reliable extraction of entities, less reliable extraction of relations, and poor extraction on entity-entity-relation tuples. However, tuple extraction is needed to bridge the gap between free text and knowledge-based applications. We describe an information extraction system and experiment that demonstrates accurate tuple extraction in a selected domain.
The Structure of the Ca\(^{2+}\)-binding, Glycosylated F-spondin Domain of F-spondin - A C2-Domain Variant in an Extracellular Matrix Protein

Background: F-spondin is a multi-domain extracellular matrix (ECM) protein and a contact-repellent molecule that directs axon outgrowth and cell migration during development. The reelin_N domain and the F-spondin domain (FS domain) comprise a proteolytic fragment that interacts with the cell membrane and guides the projection of commissural axons to floor plate. The FS domain is found in F-spondins, mindins, M-spondin and amphiF-spondin. Results: We present the crystal structure of human F-spondin FS domain at 1. 95Å resolution. The structure reveals a Ca 2+ -binding C2 domain variant with an 8-stranded antiparallel b -sandwich fold. Though the primary sequences of the FS domains of F-spondin and mindin are less than 36% identical, their overall structures are very similar. The unique feature of F-spondin FS domain is the presence of three disulfide bonds associated with the N- and C-termini of the domain and a highly conserved N-linked glycosylation site. The integrin-binding motif found in mindin is not conserved in the F-spondin FS domain. Conclusion: The structure of the F-spondin FS domain completes the structural studies of the multiple-domain ECM molecule. The homology of its core structure to a common Ca 2+ - and lipid-binding C2 domain suggests that the F-spondin FS domain may be responsible for part of the membrane targeting of F-spondin in its regulation of axon development. The structural properties of the FS domain revealed in this study pave the way for further exploration into the functions of F-spondin.
Glucocorticoid Receptor 1B and 1C mRNA Transcript Alterations in Schizophrenia and Bipolar Disorder, and Their Possible Regulation by GR Gene Variants

Abnormal patterns of HPA axis activation, under basal conditions and in response to stress, are found in individuals with schizophrenia and bipolar disorder. Altered glucocorticoid receptor (GR) mRNA and protein expression in the dorsolateral prefrontal cortex (DLPFC) in psychiatric illness have also been reported, but the cause of these abnormalities is not known. We quantified expression of GR mRNA transcript variants which employ different 5′ promoters, in 35 schizophrenia cases, 31 bipolar disorder cases and 34 controls. We also explored whether sequence variation within the NR3C1 (GR) gene is related to GR mRNA variant expression. Total GR mRNA was decreased in the DLPFC in schizophrenia cases relative to controls (15.1%, p<0.0005) and also relative to bipolar disorder cases (8.9%, p<0.05). GR-1B mRNA was decreased in schizophrenia cases relative to controls (20.2%, p<0.05), while GR-1C mRNA was decreased in both schizophrenia and bipolar disorder cases relative to controls (16.1% and 17.2% respectively, both p<0.005). A dose-dependent effect of rs10052957 genotype on GR-1B mRNA expression was observed, where CC homozygotes displayed 18.4% lower expression than TC heterozygotes (p<0.05), and 31.8% lower expression than TT homozygotes (p<0.005). Similarly, a relationship between rs6190 (R23K) genotype and GR-1C expression was seen, with 24.8% lower expression in GG homozygotes than GA heterozygotes (p<0.01). We also observed an effect of rs41423247 (Bcl1) SNP on expression of 67 kDa GRα isoform, the most abundant GRα isoform in the DLPFC. These findings suggest possible roles for the GR-1B and GR-1C promoter regions in mediating GR gene expression changes in psychotic illness, and highlight the potential importance of sequence variation within the NR3C1 gene in modulating GR mRNA expression in the DLPFC.
The Term Structure of Interest Rates in a DSGE Model with Recursive Preferences

We solve a dynamic stochastic general equilibrium (DSGE) model in which the representative household has Epstein and Zin recursive preferences. The parameters governing preferences and technology are estimated by means of maximum likelihood using macroeconomic data and asset prices, with a particular focus on the term structure of interest rates. We estimate a large risk aversion, an elasticity of intertemporal substitution higher than one, and substantial adjustment costs. Furthermore, we identify the tensions within the model by estimating it on subsets of these data. We conclude by pointing out potential extensions that might improve the model's fit.
Increased Activation of the Supragenual Anterior Cingulate Cortex during Visual Emotional Processing in Male Subjects with High Degrees of Alexithymia: An Event-Related fMRI Study

Background: One of the most prominent neurobiological models of alexithymia assumes an altered function of the anterior cingulate cortex (ACC) as the crucial neural correlate of alexithymia. So far functional imaging studies have yielded inconclusive results. Therefore, we tested this hypothesis in healthy alexithymics and nonalexithymics in an event-related fMRI study. Methods:Thirty high- and 30 low-alexithymic right-handed male subjects (selected by the 20-item Toronto Alexithymia Scale, TAS-20) were investigated with event-related fMRI using a picture viewing paradigm. The stimuli consisted of happy, fearful and neutral facial expressions (Ekman-Friesen) as well as positive, negative and neutral pictures from the International Affective Picture System. Results: Contrasting the high-alexithymic with the low-alexithymic group we observed increased activation of the supragenual ACC for different emotional valences as well as for different emotional stimuli. Moreover, there was a positive correlation of the ACC with the individual TAS-20 scores but no correlations with the individual Beck Depression Inventory scores. Additionally, there was no difference in activity of the amygdala. Conclusions: We demonstrated that the supragenual ACC is constantly activated more strongly in alexithymic subjects and that this activation is related to the symptoms of alexithymia and not to associated symptoms such as depression. Therefore, our findings support the hypothesis of an altered function of the ACC in alexithymia.
The role of stratum corneum and dermal microvascular perfusion in penetration and tissue levels of water‐soluble drugs investigated by microdialysis

Background Hydrophilic drugs are poorly absorbed when applied topically, due to low partitioning through the lipid matrix of the stratum corneum. Cutaneous blood flow rapidly clears the absorbed drug, which may result in low tissue levels. This is of importance for topically applied drugs whose site of action is within the epidermis or dermis. Dermal drug levels can be measured using cutaneous microdialysis, which is a means of continuously sampling substances from the dermal extracellular fluid.
Approach in Nonintrusive Type I Load Monitoring Using Subtractive Clustering

In this paper, a low-sampling-rate and nonintrusive appliance loads monitoring (NIALM), which required only few tuning parameters and which is little sensitive to the grid power noise, is presented. Using transformed active power transitions as features, the proposed approach is based on the subtractive clustering and the maximum likelihood classifier. In order to validate the NIALM, a 1 Hz sampling rate experimental data from the reference energy disaggregation dataset is selected. The validation results with six commonly found ON/OFF residential appliances indicate that the proposed approach is effective. In addition, the obtained results from a Monte Carlo simulation suggest that this approach is less sensitive to power grid noise than a $K$ -mean-based NIALM method.
Respective contributions of intestinal Niemann-Pick C1-like 1 and scavenger receptor class B type I to cholesterol and tocopherol uptake: in vivov. in vitro studies

The intestinal absorption of cholesterol and lipid micronutrients such as vitamin E has been shown to share some common pathways. The present study aims to further compare the uptake of cholesterol ([3H]cholesterol v. 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3-ol (NBD-cholesterol)) and tocopherol in Caco-2 TC-7 cells and in mouse intestine, with special focus on the respective roles of scavenger receptor class B type I (SR-BI) and Niemann-Pick C1-like 1 (NPC1L1). Conversely to NBD-cholesterol, the uptakes of [3H]cholesterol and tocopherol by Caco-2 cells were impaired by both block lipid transport-1 and ezetimibe, which inhibit SR-BI and NPC1L1, respectively. These inhibitions occurred only when cholesterol or tocopherol was delivered to cells included in micelles that contained biliary acid and at least oleic acid as a lipid. In vivo, after 2 h of digestion in mice, the uptake of the two cholesterol analogues and of tocopherol all showed distinct patterns along the duodenum–jejunum axis. [3H]Cholesterol uptake, which correlated closely to NPC1L1 mRNA expression in wild-type (wt) mice, was strongly inhibited by ezetimibe. Intestinal SR-BI overexpression did not change NPC1L1 expression and led to a significant increase in [3H]cholesterol uptake in the distal jejunum. Conversely, neither ezetimibe treatment nor SR-BI overexpression had an effect on NBD-cholesterol uptake. However, in contrast with SR-BI mRNA expression, tocopherol absorption increased strongly up to the distal jejunum in wt mice where it was specifically inhibited by ezetimibe, and was increased in the proximal intestine of intestinal SR-BI-overexpressing mice. Thus, cholesterol and tocopherol uptakes share common pathways in cell culture models, but display different in vivo absorption patterns associated with distinct contributions of SR-BI and NPC1L1.
Privacy-preserving Query-by-Example Speech Search

This paper investigates a new privacy-preserving paradigm for the task of Query-by-Example Speech Search using Secure Binary Embeddings, a hashing method that converts vector data to bit strings through a combination of random projections followed by banded quantization. The proposed method allows performing spoken query search in an encrypted domain, by analyzing ciphered information computed from the original recordings. Unlike other hashing techniques, the embeddings allow the computation of the distance between vectors that are close enough, but are not perfect matches. This paper shows how these hashes can be combined with Dynamic Time Warping based on posterior derived features to perform secure speech search. Experiments performed on a sub-set of the Speech-Dat Portuguese corpus showed that the proposed privacy-preserving system obtains similar results to its non-private counterpart.