Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Cost and Network Topology on Urban Mobility: A Study of Public Bicycle Usage in 2 U.S. Cities

Understanding the drivers of urban mobility is vital for epidemiology, urban planning, and communication networks. Human movements have so far been studied by observing people's positions in a given space and time, though most recent models only implicitly account for expected costs and returns for movements. This paper explores the explicit impact of cost and network topology on mobility dynamics, using data from 2 city-wide public bicycle share systems in the USA. User mobility is characterized through the distribution of trip durations, while network topology is characterized through the pairwise distances between stations and the popularity of stations and routes. Despite significant differences in station density and physical layout between the 2 cities, trip durations follow remarkably similar distributions that exhibit cost sensitive trends around pricing point boundaries, particularly with long-term users of the system. Based on the results, recommendations for dynamic pricing and incentive schemes are provided to positively influence mobility patterns and guide improved planning and management of public bicycle systems to increase uptake.
Establishing a hematopoietic genetic network through locus-specific integration of chromatin regulators

Significance Broadly expressed enzymes commonly change chromatin structure and function. How ubiquitous chromatin regulators establish specialized patterns of gene activity is not understood. We identified an important link between a histone methyltransferase and a transcription factor (GATA-1) that controls red blood cell development. We found that distinct combinations of this enzyme and additional chromatin regulators are required for GATA-1 to control transcription at different genetic loci. The resulting regulatory “matrix” provides a conceptual framework for understanding how cell-restricted factors use broadly expressed chromatin regulators to confer specialized gene-expression patterns that control important biological processes. The establishment and maintenance of cell type-specific transcriptional programs require an ensemble of broadly expressed chromatin remodeling and modifying enzymes. Many questions remain unanswered regarding the contributions of these enzymes to specialized genetic networks that control critical processes, such as lineage commitment and cellular differentiation. We have been addressing this problem in the context of erythrocyte development driven by the transcription factor GATA-1 and its coregulator Friend of GATA-1 (FOG-1). As certain GATA-1 target genes have little to no FOG-1 requirement for expression, presumably additional coregulators can mediate GATA-1 function. Using a genetic complementation assay and RNA interference in GATA-1–null cells, we demonstrate a vital link between GATA-1 and the histone H4 lysine 20 methyltransferase PR-Set7/SetD8 (SetD8). GATA-1 selectively induced H4 monomethylated lysine 20 at repressed, but not activated, loci, and endogenous SetD8 mediated GATA-1–dependent repression of a cohort of its target genes. GATA-1 used different combinations of SetD8, FOG-1, and the FOG-1–interacting nucleosome remodeling and deacetylase complex component Mi2β to repress distinct target genes. Implicating SetD8 as a context-dependent GATA-1 corepressor expands the repertoire of coregulators mediating establishment/maintenance of the erythroid cell genetic network, and provides a biological framework for dissecting the cell type-specific functions of this important coregulator. We propose a coregulator matrix model in which distinct combinations of chromatin regulators are required at different GATA-1 target genes, and the unique attributes of the target loci mandate these combinations.
Faculty Perception of and Resistance to Online Education in the Fields of Acupuncture, Chiropractic, and Massage Therapy

This paper reports findings of a research study undertaken to determine the attitudes and perceptions of acupuncture, chiropractic, and massage therapy faculty with regard to online learning within their respective disciplines, and to determine how they might be persuaded to teach online. The study surveyed faculty teaching at schools in these three fields and followed up with additional interviews. The study results indicate that, in general, acupuncture, chiropractic, and massage therapy faculty lack awareness of the capabilities of online education and the elements of good online learning. There is also a perception that what they teach cannot be taught online because of its kinesthetic requirements. The faculty hold this perception in spite of the success of medical science and related health care fields in the online environment, and they do not seem to separate the kinesthetic from the didactic. The present study indicates that faculty opinions about online instruction in this alternative type of education range from being willing to look at the potential of online education to outright dismissing it.
The fine structure of positive lightning return-stroke radiation fields

The electric fields generated by lightning flashes striking the North Sea were measured, with a time resolution better than a few tens of nanoseconds, at Fano island in Denmark. The measuring station was located a few tens of meters away from the high water mark at the west coast of the island. This particular location made it possible to capture, with minimal propagation effects, the electromagnetic fields from lightning flashes striking the North Sea. The waveforms were recorded by a measuring system that could provide a time resolution of about 10 ns. The data recorded had the following features. The initial rising part of the positive return-stroke fields contains a slow front followed by a fast transition. The duration of the slow front of the positive return-stroke fields had an average of 8.3 /spl mu/s and its amplitude, measured as a fraction of the initial peak, had an average of 0.61. The 10%-90% rise time of the fast rising portion of the positive return-stroke fields was about 0.26 /spl mu/s, on average. The average peak value of the measured radiation fields normalized to 100 km was 15.7 V/m. The mean of the peak value of the time derivative of the radiation fields was 25 V/m//spl mu/s. The full width at half maximum of the radiation field derivative had a mean of 170 ns.
ANTI-HBC IgG SUBCLASSES IN DIFFERENT POPULATIONS BY COMPARING A VARIETY OF ELISA PLATES

The number of IgG subclasses for hepatitis B virus (HBV) core antigen (anti-HBc), demonstrated for HBV-infected individuals, was measured by enzyme-linked immunosorbent assay (ELISA). Four commercially available hepatitis B core antigen (HBcAg) plates and one prepared plate were tested for ELISA sensitivity by the detection of 14 serum samples drawn from HBV chronic carriers, cured patients, vaccinees, and non-infected individuals. Differences in optical density (OD) values were obtained by comparing data gathered from the five plate types, suggesting that different plates may have different binding capabilities for each anti-HBc IgG subclass and, thus, contribute to the different ELISA sensitivities. Of these plates, the GB plate showed the most obvious absorbance changes for anti-HBc subclasses in different populations. These data also indicated different patterns for IgG-specific subclasses for various populations. For HBsAg+ carriers, the OD for IgG1 was greater than for IgG3. By contrast, the OD for IgG3 was higher than that for IgG1 in those subjects who were negative for HBsAg.
The zero age main sequence of WIMP burners

We modify a stellar structure code to estimate the effect upon the main sequence of the accretion of weakly-interacting dark matter onto stars and its subsequent annihilation. The effect upon the stars depends upon whether the energy generation rate from dark matter annihilation is large enough to shut off the nuclear burning in the star. Main sequence weakly-interacting massive particles (WIMP) burners look much like proto-stars moving on the Hayashi track, although they are in principle completely stable. We make some brief comments about where such stars could be found, how they might be observed and more detailed simulations which are currently in progress. Finally we comment on whether or not it is possible to link the paradoxically hot, young stars found at the galactic center with WIMP burners.
Gonadal Steroids Negatively Modulate Oxidative Stress in CBA/Ca Female Mice Infected with P. berghei ANKA

We decreased the level of gonadal steroids in female and male mice by gonadectomy. We infected these mice with P. berghei ANKA and observed the subsequent impact on the oxidative stress response. Intact females developed lower levels of parasitaemia and lost weight faster than intact males. Gonadectomised female mice displayed increased levels of parasitaemia, increased body mass, and increased anaemia compared with their male counterparts. In addition, gonadectomised females exhibited lower specific catalase, superoxide dismutase, and glutathione peroxidase activities in their blood and spleen tissues compared with gonadectomised males. To further study the oxidative stress response in P. berghei ANKA-infected gonadectomised mice, nitric oxide levels were assessed in the blood and spleen, and MDA levels were assessed in the spleen. Intact, sham-operated, and gonadectomised female mice exhibited higher levels of nitric oxide in the blood and spleen compared with male mice. MDA levels were higher in all of the female groups. Finally, gonadectomy significantly increased the oxidative stress levels in females but not in males. These data suggest that differential oxidative stress is influenced by oestrogens that may contribute to sexual dimorphism in malaria.
A Robust Method to Analyze Copy Number Alterations of Less than 100 kb in Single Cells Using Oligonucleotide Array CGH

Comprehensive genome wide analyses of single cells became increasingly important in cancer research, but remain to be a technically challenging task. Here, we provide a protocol for array comparative genomic hybridization (aCGH) of single cells. The protocol is based on an established adapter-linker PCR (WGAM) and allowed us to detect copy number alterations as small as 56 kb in single cells. In addition we report on factors influencing the success of single cell aCGH downstream of the amplification method, including the characteristics of the reference DNA, the labeling technique, the amount of input DNA, reamplification, the aCGH resolution, and data analysis. In comparison with two other commercially available non-linear single cell amplification methods, WGAM showed a very good performance in aCGH experiments. Finally, we demonstrate that cancer cells that were processed and identified by the CellSearch® System and that were subsequently isolated from the CellSearch® cartridge as single cells by fluorescence activated cell sorting (FACS) could be successfully analyzed using our WGAM-aCGH protocol. We believe that even in the era of next-generation sequencing, our single cell aCGH protocol will be a useful and (cost-) effective approach to study copy number alterations in single cells at resolution comparable to those reported currently for single cell digital karyotyping based on next generation sequencing data.
Functional Characterization of EpsC, a Component of the Type II Secretion System, in the Pathogenicity of Vibrio vulnificus

ABSTRACT EpsC, one of the components comprising the type II secretion system (T2SS), was isolated from a human-pathogenic bacterium, Vibrio vulnificus, to evaluate its role in eliciting virulence. An espC-deleted mutant of V. vulnificus displayed a reduced cytotoxicity to the human cell line HEp-2 and an attenuated virulence in a mouse model. This mutant exhibited dramatic defects in the secretion of diverse extracellular proteins, such as outer membrane proteins, transporters, and the known secreted factors, notably, a hemolysin (VvhA) and an elastase (VvpE). A defect in its secretion of proteins was restored by in trans complementation of the intact epsC gene. Analyses of cellular fractions revealed that VvhA and VvpE of the ΔepsC mutant were not excreted outside the cell but were present mainly in the periplasmic space. Examination of a V. vulnificus mutant deficient in TolC, a component of the T1SS, showed that it is not involved in the secretion of VvhA and VvpE but that it is necessary for the secretion of another major toxin of V. vulnificus, RtxA. Therefore, the T2SS is required for V. vulnificus pathogenicity, which is mediated by at least two secreted factors, VvhA and VvpE, via facilitating the secretion and exposure of these factors to host cells.
A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker.

BACKGROUND Circulating tumor DNA (ctDNA) has emerged as a good candidate for tracking tumor dynamics in different cancer types, potentially avoiding repeated tumor biopsies. Many different genes can be mutated within a tumor, complicating procedures for tumor monitoring, even with highly sensitive next-generation sequencing (NGS) strategies. Droplet-based digital PCR (dPCR) is a highly sensitive and quantitative procedure, allowing detection of very low amounts of circulating tumor genetic material, but can be limited in the total number of target loci monitored. METHODS We analyzed hypermethylation of 3 genes, by use of droplet-based dPCR in different stages of colorectal cancer (CRC), to identify universal markers for tumor follow-up. RESULTS Hypermethylation of WIF1 (WNT inhibitory factor 1) and NPY (neuropeptide Y) genes was significantly higher in tumor tissue compared to normal tissue, independently of tumor stage. All tumor tissues appeared positive for one of the 2 markers. Methylated ctDNA (MetctDNA) was detected in 80% of metastatic CRC and 45% of localized CRC. For samples with detectable mutations in ctDNA, MetctDNA and mutant ctDNA (MutctDNA) fractions were correlated. During follow-up of different stage CRC patients, MetctDNA changes allowed monitoring of tumor evolution. CONCLUSIONS These results indicate that MetctDNA could be used as a universal surrogate marker for tumor follow-up in CRC patients, and monitoring MetctDNA by droplet-based dPCR could avoid the need for monitoring mutations.
Priming Children’s Use of Intentions in Moral Judgement with Metacognitive Training

Typically, adults give a primary role to the agent’s intention to harm when performing a moral judgment of accidental harm. By contrast, children often focus on outcomes, underestimating the actor’s mental states when judging someone for his action, and rely on what we suppose to be intuitive and emotional processes. The present study explored the processes involved in the development of the capacity to integrate agents’ intentions into their moral judgment of accidental harm in 5 to 8-year-old children. This was done by the use of different metacognitive trainings reinforcing different abilities involved in moral judgments (mentalising abilities, executive abilities, or no reinforcement), similar to a paradigm previously used in the field of deductive logic. Children’s moral judgments were gathered before and after the training with non-verbal cartoons depicting agents whose actions differed only based on their causal role or their intention to harm. We demonstrated that a metacognitive training could induce an important shift in children’s moral abilities, showing that only children who were explicitly instructed to “not focus too much” on the consequences of accidental harm, preferentially weighted the agents’ intentions in their moral judgments. Our findings confirm that children between the ages of 5 and 8 are sensitive to the intention of agents, however, at that age, this ability is insufficient in order to give a “mature” moral judgment. Our experiment is the first that suggests the critical role of inhibitory resources in processing accidental harm.
One does not simply produce funny memes! - Explorations on the Automatic Generation of Internet humor

This paper reports on the automatic generation of image macro based Internet memes – potentially funny combinations of an image and text, intended to be spread in social networks. Memes are produced for news headlines for which, based on linguistic features, a suitable macro is selected and the text is adapted. The generation method is described together with its current implementation, which integrates a variety of tools and resources. Illustrative examples are also presented. Results of a human evaluation showed that, despite positive and neutral assessments, overall, automatically-generated memes are still below those produced by humans.
The Influence of Language Proficiency on Lexical Semantic Processing in Native and Late Learners of English

We investigated the influence of English proficiency on ERPs elicited by lexical semantic violations in English sentences, in both native English speakers and native Spanish speakers who learned English in adulthood. All participants were administered a standardized test of English proficiency, and data were analyzed using linear mixed effects (LME) modeling. Relative to native learners, late learners showed reduced amplitude and delayed onset of the N400 component associated with reading semantic violations. As well, after the N400 late learners showed reduced anterior negative scalp potentials and increased posterior potentials. In both native and late learners, N400 amplitudes to semantically appropriate words were larger for people with lower English proficiency. N400 amplitudes to semantic violations, however, were not influenced by proficiency. Although both N400 onset latency and the late ERP effects differed between L1 and L2 learners, neither correlated with proficiency. Different approaches to dealing with the high degree of correlation between proficiency and native/late learner group status are discussed in the context of LME modeling. The results thus indicate that proficiency can modulate ERP effects in both L1 and L2 learners, and for some measures (in this case, N400 amplitude), L1–L2 differences may be entirely accounted for by proficiency. On the other hand, not all effects of L2 learning can be attributed to proficiency. Rather, the differences in N400 onset and the post-N400 violation effects appear to reflect fundamental differences in L1–L2 processing.
Effect of dilution rate and methanol‐glycerol mixed feeding on heterologous Rhizopus oryzae lipase production with Pichia pastoris Mut+ phenotype in continuous culture

The induction using substrate mixtures is an operational strategy for improving the productivity of heterologous protein production with Pichia pastoris. Glycerol as a cosubstrate allows for growth at a higher specific growth rate, but also has been reported to be repressor of the expression from the AOX1 promoter. Thus, further insights about the effects of glycerol are required for designing the induction stage with mixed substrates. The production of Rhizopus oryzae lipase (ROL) was used as a model system to investigate the application of methanol‐glycerol feeding mixtures in fast metabolizing methanol phenotype. Cultures were performed in a simple chemostat system and the response surface methodology was used for the evaluation of both dilution rate and methanol‐glycerol feeding composition as experimental factors. Our results indicate that productivity and yield of ROL are strongly affected by dilution rate, with no interaction effect between the involved factors. Productivity showed the highest value around 0.04–0.06 h−1, while ROL yield decreased along the whole dilution rate range evaluated (0.03–0.1 h−1). Compared to production level achieved with methanol‐only feeding, the highest specific productivity was similar in mixed feeding (0.9 UA g‐biomass−1 h−1), but volumetric productivity was 70% higher. Kinetic analysis showed that these results are explained by the effects of dilution rate on specific methanol uptake rate, instead of a repressor effect caused by glycerol feeding. It is concluded that despite the effect of dilution rate on ROL yield, mixed feeding strategy is a proper process option to be applied to P. pastoris Mut+ phenotype for heterologous protein production. © 2015 American Institute of Chemical Engineers Biotechnol. Prog. , 31:707–714, 2015
The Novel Desmin Mutant p.A120D Impairs Filament Formation, Prevents Intercalated Disk Localization, and Causes Sudden Cardiac Death

Background—The intermediate filament protein desmin is encoded by the gene DES and contributes to the mechanical stabilization of the striated muscle sarcomere and cell contacts within the cardiac intercalated disk. DES mutations cause severe skeletal and cardiac muscle diseases with heterogeneous phenotypes. Recently, DES mutations were also found in patients with arrhythmogenic right ventricular cardiomyopathy. Currently, the cellular and molecular pathomechanisms of the DES mutations leading to this disease are not exactly known. Methods and Results—We identified the 2 novel variants DES-p.A120D (c.359C>A) and DES-p.H326R (c.977A>G), which were characterized by cell culture experiments and atomic force microscopy. Family analysis indicated a broad spectrum of cardiomyopathies with a striking frequency of arrhythmias and sudden cardiac deaths. The in vitro experiments of desmin-p.A120D reveal a severe intrinsic filament formation defect causing cytoplasmic aggregates in cell lines and of the isolated recombinant protein. Model variants of codon 120 indicated that ionic interactions contribute to this filament formation defect. Ex vivo analysis of ventricular tissue slices revealed a loss of desmin staining within the intercalated disk and severe cytoplasmic aggregate formation, whereas z-band localization was not affected. The functional experiments of desmin-p.H326R did not demonstrate any differences from wild type. Conclusions—Because of the functional in vivo and in vitro characterization, DES-p.A120D has to be regarded as a pathogenic mutation and DES-p.H326R as a rare variant with unknown significance. Presumably, the loss of the desmin-p. A120D filament localization at the intercalated disk explains its clinical arrhythmogenic potential.
The Effect of Exogenous Zinc Concentration on the Responsiveness of MC3T3-E1 Pre-Osteoblasts to Surface Microtopography: Part II (Differentiation)

Osseointegration of bone implants is a vital part of the recovery process. Numerous studies have shown that micropatterned geometries can promote cell-substrate associations and strengthen the bond between tissue and the implanted material. As demonstrated previously, exogenous zinc levels can influence the responsiveness of pre-osteoblasts to micropatterns and modify their migratory behavior. In this study, we sought to determine the effect of exogenous zinc on differentiation of osteoblasts cultured on micropatterned vs. planar substrates. Levels of activated metalloproteinase-2 (MMP-2) and transforming growth factor-beta 1 (TGF-β1), as well as early stage differentiation marker alkaline phosphatase, were altered with the addition of zinc. These results suggest that exogenous zinc concentration and micropatterning may interdependently modulate osteoblast differentiation.