Miracle-dz/UniFAR-FTUs huggingface dataset:
Arterial wall chondroitin sulfate proteoglycans: diverse molecules with distinct roles in lipoprotein retention and atherogenesis

Chondroitin sulfate proteoglycans (CSPGs) of the arterial wall are generally considered to be atherogenic because of their ability to trap cholesterol-rich lipoproteins in vitro. Nevertheless, CSPGs are a diverse group of molecules with a long evolutionary history and distinct biologic functions. The three principal CSPGs in the arterial wall are versican, which is part of the hyalectan gene family; and decorin and biglycan, which are members of a separate gene family, the small leucine-rich proteoglycans. Importantly, there is now substantial evidence that the different molecular species of CSPGs participate unequally in lipoprotein retention, and that they exert unequal regulatory effects that are related to atherogenesis. Recently available murine models with genetic manipulations that affect CSPGs now allow causal studies of the roles of these molecules to be conducted in vivo, with occasionally surprising results. Moreover, tools are being developed to examine human genetic variations that are relevant to CSPGs, which may provide additional important insights into the human disease. The era in which proteoglycans are regarded as a nondescript backdrop, playing purely nonspecific structural roles, is over. Studies in manipulated animals and in human populations will continue to reveal precise, dynamic roles for these fascinating and ancient molecules.
Human Host Defense Peptide LL-37 Prevents Bacterial Biofilm Formation

ABSTRACT The ability to form biofilms is a critical factor in chronic infections by Pseudomonas aeruginosa and has made this bacterium a model organism with respect to biofilm formation. This study describes a new, previously unrecognized role for the human cationic host defense peptide LL-37. In addition to its key role in modulating the innate immune response and weak antimicrobial activity, LL-37 potently inhibited the formation of bacterial biofilms in vitro. This occurred at the very low and physiologically meaningful concentration of 0.5 μg/ml, far below that required to kill or inhibit growth (MIC = 64 μg/ml). LL-37 also affected existing, pregrown P. aeruginosa biofilms. Similar results were obtained using the bovine neutrophil peptide indolicidin, but no inhibitory effect on biofilm formation was detected using subinhibitory concentrations of the mouse peptide CRAMP, which shares 67% identity with LL-37, polymyxin B, or the bovine bactenecin homolog Bac2A. Using microarrays and follow-up studies, we were able to demonstrate that LL-37 affected biofilm formation by decreasing the attachment of bacterial cells, stimulating twitching motility, and influencing two major quorum sensing systems (Las and Rhl), leading to the downregulation of genes essential for biofilm development.
Headcounts, Expectations, and Presidential Coalitions in Congress

This paper examines presidential influence in Congress. Three questions are answered: Do members change their positions? Is the administration successful at building coalitions? Are members converted by administration influence? In answering these three questions, a new set of data that identifies the positions of members during coalition building is introduced and a baseline model of members' preferences is utilized. With the baseline model, the "normal" positions of members are predicted. A distinction is made between those members who could be expected to change their positions in the normal course of events and those members who are true converts. Critical members are also identified along with members who probably are acting strategically. Although the nature of this investigation is exploratory, the results support several conjectures. First, there is substantial change during the legislative process. Second, they suggest that the legislative successes of the Johnson administration depended heavily upon its large core of initial support. And third, the data suggest that the Johnson administration actually did build coalitions by converting hard-core opponents. Two measures of how much conversion took place are proposed.
Cardiac Neuronal Nitric Oxide Synthase Isoform Regulates Myocardial Contraction and Calcium Handling

Abstract— A neuronal isoform of nitric oxide synthase (nNOS) has recently been located to the cardiac sarcoplasmic reticulum (SR). Subcellular localization of a constitutive NOS in the proximity of an activating source of Ca2+ suggests that cardiac nNOS-derived NO may regulate contraction by exerting a highly specific and localized action on ion channels/transporters involved in Ca2+ cycling. To test this hypothesis, we have investigated myocardial Ca2+ handling and contractility in nNOS knockout mice (nNOS−/−) and in control mice (C) after acute nNOS inhibition with 100 &mgr;mol/L L-VNIO. nNOS gene disruption or L-VNIO increased basal contraction both in left ventricular (LV) myocytes (steady-state cell shortening 10.3±0.6% in nNOS−/− versus 8.1±0.5% in C;P <0.05) and in vivo (LV ejection fraction 53.5±2.7 in nNOS−/− versus 44.9±1.5% in C;P <0.05). nNOS disruption increased ICa density (in pA/pF, at 0 mV, −11.4±0.5 in nNOS−/− versus −9.1±0.5 in C;P <0.05) and prolonged the slow time constant of inactivation of ICa by 38% (P <0.05), leading to an increased Ca2+ influx and a greater SR load in nNOS−/− myocytes (in pC/pF, 0.78±0.04 in nNOS−/− versus 0.64±0.03 in C;P <0.05). Consistent with these data, [Ca2+]i transient (indo-1) peak amplitude was greater in nNOS−/− myocytes (410/495 ratio 0.34±0.01 in nNOS−/− versus 0.31±0.01 in C;P <0.05). These findings have uncovered a novel mechanism by which intracellular Ca2+ is regulated in LV myocytes and indicate that nNOS is an important determinant of basal contractility in the mammalian myocardium. The full text of this article is available at http://www.circresaha. org.
Using deep learning to quantify the beauty of outdoor places

Beautiful outdoor locations are protected by governments and have recently been shown to be associated with better health. But what makes an outdoor space beautiful? Does a beautiful outdoor location differ from an outdoor location that is simply natural? Here, we explore whether ratings of over 200 000 images of Great Britain from the online game Scenic-Or-Not, combined with hundreds of image features extracted using the Places Convolutional Neural Network, might help us understand what beautiful outdoor spaces are composed of. We discover that, as well as natural features such as ‘Coast’, ‘Mountain’ and ‘Canal Natural’, man-made structures such as ‘Tower’, ‘Castle’ and ‘Viaduct’ lead to places being considered more scenic. Importantly, while scenes containing ‘Trees’ tend to rate highly, places containing more bland natural green features such as ‘Grass’ and ‘Athletic Fields’ are considered less scenic. We also find that a neural network can be trained to automatically identify scenic places, and that this network highlights both natural and built locations. Our findings demonstrate how online data combined with neural networks can provide a deeper understanding of what environments we might find beautiful and offer quantitative insights for policymakers charged with design and protection of our built and natural environments.
A HYPOTHESIS FOR PLASTID EVOLUTION IN CHROMALVEOLATES 1

Four eukaryotic lineages, namely, haptophytes, alveolates, cryptophytes, and heterokonts, contain in most cases photosynthetic and nonphotosynthetic members—the photosynthetic ones with secondary plastids with chl c as the main photosynthetic pigment. These four photosynthetic lineages were grouped together on the basis of their pigmentation and called chromalveolates, which is usually understood to imply loss of plastids in the nonphotosynthetic members. Despite the ecological and economic importance of this group of organisms, the phylogenetic relationships among these algae are only partially understood, and the so‐called chromalveolate hypothesis is very controversial. This review evaluates the evidence for and against this grouping and summarizes the present understanding of chromalveolate evolution. We also describe a testable hypothesis that is intended to accommodate current knowledge based on plastid and nuclear genomic data, discuss the implications of this model, and comment on areas that require further examination.
Testing the usability of a personalized system: comparing the use of interviews, questionnaires and thinking-aloud

Personalized systems present each user with tailored content or output. Testing the usability of such a system must take some specific usability issues and the suitability of the personalized output into account. In this study, we evaluated a personalized search engine to compare the use of interviews, questionnaires and concurrent thinking- aloud to this avail. The interview and the questionnaire are the best methods to elicit comments on usability issues. Concurrent thinking-aloud turned out to be the best method to elicit comments on the perceived relevance of search results. When testing the usability of a personalized system it is wise to use a combination of concurrent thinking-aloud and the interview or the questionnaire.
Neural Correlates of Self-Generated Imagery and Cognition Throughout the Sleep Cycle

Humans have been aware for thousands of years that sleep comes in many forms, accompanied by different kinds of mental content. We review the first-person report literature on the frequency and type of content experienced in various stages of sleep, showing that different sleep stages are dissociable at the subjective level. We then relate these subjective differences to the growing literature differentiating the various sleep stages at the neurophysiological level, including evidence from electrophysiology, neurochemistry, and functional neuroimaging. We suggest that there is emerging evidence for relationships between sleep stage, neurophysiological activity, and subjective experiences. Specifically, we emphasize that functional neuroimaging work suggests a parallel between activation and deactivation of default network and visual network brain areas and the varying frequency and intensity of imagery and dream mentation across sleep stages; additionally, frontoparietal control network activity across sleep stages may parallel levels of cognitive control and meta-awareness. Together these findings suggest intriguing brain-mind isomorphisms and may serve as a first step toward a comprehensive understanding of the relationship between neurophysiology and psychology in sleep and dreaming.
A novel metamaterial-inspired electrically small antenna fed by CPW

This article presents the design of an inexpensive, efficient, and electrically small antenna based on metamaterial- inspired structure fed by the coplanar waveguide (CPW). The size of the proposed antenna is 12 mm x 12 mm with the resonant frequency of 1.47 GHz. Details of the proposed antenna are presented, with full-wave simulation results to support the design.
Nonlinearity Analysis and Parameters Optimization for an Inductive Angle Sensor

Using the finite element method (FEM) and particle swarm optimization (PSO), a nonlinearity analysis based on parameter optimization is proposed to design an inductive angle sensor. Due to the structure complexity of the sensor, understanding the influences of structure parameters on the nonlinearity errors is a critical step in designing an effective sensor. Key parameters are selected for the design based on the parameters' effects on the nonlinearity errors. The finite element method and particle swarm optimization are combined for the sensor design to get the minimal nonlinearity error. In the simulation, the nonlinearity error of the optimized sensor is 0.053% in the angle range from −60° to 60°. A prototype sensor is manufactured and measured experimentally, and the experimental nonlinearity error is 0.081% in the angle range from −60° to 60°.
Comparison of multi-port converter topologies with bidirectional energy flow for automotive energy net applications

Three-port converters with bidirectional energy flow have been investigated for the 14V/42V automotive energy net. The three-port converters are designed to interlink the two energy nets and a double-layer capacitor to relieve the battery from current stress and to stabilize the energy net voltages. The investigated converter topologies include a three-port converter that requires only three MOSFETS as switching devices. Analyses of the converter topologies have been performed and a prototype converter of the most promising converter, the three-switch topology, has been built and tested to prove theoretical predictions. Measurements are in good correlations with results from the analyses.
RNA-Seq of the Caribbean reef-building coral Orbicella faveolata (Scleractinia-Merulinidae) under bleaching and disease stress expands models of coral innate immunity

Climate change-driven coral disease outbreaks have led to widespread declines in coral populations. Early work on coral genomics established that corals have a complex innate immune system, and whole-transcriptome gene expression studies have revealed mechanisms by which the coral immune system responds to stress and disease. The present investigation expands bioinformatic data available to study coral molecular physiology through the assembly and annotation of a reference transcriptome of the Caribbean reef-building coral, Orbicella faveolata. Samples were collected during a warm water thermal anomaly, coral bleaching event and Caribbean yellow band disease outbreak in 2010 in Puerto Rico. Multiplex sequencing of RNA on the Illumina GAIIx platform and de novo transcriptome assembly by Trinity produced 70,745,177 raw short-sequence reads and 32,463 O. faveolata transcripts, respectively. The reference transcriptome was annotated with gene ontologies, mapped to KEGG pathways, and a predicted proteome of 20,488 sequences was generated. Protein families and signaling pathways that are essential in the regulation of innate immunity across Phyla were investigated in-depth. Results were used to develop models of evolutionarily conserved Wnt, Notch, Rig-like receptor, Nod-like receptor, and Dicer signaling. O. faveolata is a coral species that has been studied widely under climate-driven stress and disease, and the present investigation provides new data on the genes that putatively regulate its immune system.
A Structural Basis for the Biochemical Behavior of Activation-induced Deoxycytidine Deaminase Class-switch Recombination-defective Hyper-IgM-2 Mutants*

Background: HIGM-2 syndrome results from mutations spanning AID. Results: AID mutations are characterized biochemically and analyzed using a surrogate Apo3G structure. Conclusion: Catalytically active mutants retain salient enzymatic properties of WT AID; catalytically inactive mutants retain salient ssDNA binding properties of WT AID. Significance: We identify four structural classes of mutants and discuss the catalytic consequences of each mutation. Hyper-IgM syndrome type 2 stems from mutations in activation-induced deoxycytidine deaminase (AID) that abolish immunoglobulin class-switch recombination, causing an accumulation of IgM and absence of IgG, IgA, and IgE isotypes. Although hyper-IgM syndrome type 2 is rare, the 23 missense mutations identified in humans span almost the entire gene for AID resulting in a recessive phenotype. Using high resolution x-ray structures for Apo3G-CD2 as a surrogate for AID, we identify three classes of missense mutants as follows: catalysis (class I), substrate interaction (class II), and structural integrity (class III). Each mutant was expressed and purified from insect cells and compared biochemically to wild type (WT) AID. Four point mutants retained catalytic activity at 1/3rd to 1/200th the level of WT AID. These “active” point mutants mimic the behavior of WT AID for motif recognition specificity, deamination spectra, and high deamination processivity. We constructed a series of C-terminal deletion mutants (class IV) that retain catalytic activity and processivity for deletions ≤18 amino acids, with ΔC10 and ΔC15 having 2–3-fold higher specific activities than WT AID. Deleting 19 C-terminal amino acids inactivates AID. WT AID and active and inactive point mutants bind cooperatively to single-stranded DNA (Hill coefficients ∼1.7–3.2) with microscopic dissociation constant values (KA) ranging between 10 and 250 nm. Active C-terminal deletion mutants bind single-stranded DNA noncooperatively with KA values similar to wild type AID. A structural analysis is presented that shows how localized defects in different regions of AID can contribute to loss of catalytic function.
Morphological Changes in Degenerative Disc Disease on Magnetic Resonance Imaging: Comparison Between Young and Elderly.

BACKGROUND Morphological changes implicated in low back are complicated by additional age related degenerative changes in spine, which increases with aging. This study aims to compare the morphological MRI findings in young and elderly patients with low back pain and also correlate them with the clinical symptoms. METHODS The study was a retrospective hospital record based comparative study carried out in a Teaching Hospital. MRI performed for patients with low back pain during May 2012 to October 2012 were reviewed. The MRI findings were compared between below 60 years and at and above 60 years and were also correlated with symptoms. RESULTS A total of 301 MRI met the inclusion criteria out of which 228(75.74%) were young adults and 73(24.25%) were elderly adults. Degenerative changes and disc bulge was more common in elderly. Disc herniations including disc prolapse was more common in young adults. Disc protrusion involving L4-L5 was most common in the elderly while L5-S1 was most common in young adults. Nerve root compression was noted more commonly in the young adults. Radiculopathy was associated with grade III nerve root compression and paramedian disc protrusion in young adults while no such association was noted in elderly. No association of radiculopathy with presence of degenerative changes, spinal stenosis was noted in both groups. CONCLUSIONS Degenerative changes are more common in elderly while disc herniations are more common in young adults. Morphologic changes do correlate with symptoms in young adults to some extent while they do not correlate in elderly.
Promoted Interaction of Nuclear Factor-κB with Demethylated Cystathionine-β-Synthetase Gene Contributes to Gastric Hypersensitivity in Diabetic Rats

Patients with long-standing diabetes frequently demonstrate gastric hypersensitivity with an unknown mechanism. The present study was designed to investigate roles for nuclear factor-κB (NF-κB) and the endogenous H2S-producing enzyme cystathionine-β-synthetase (CBS) signaling pathways by examining cbs gene methylation status in adult rats with diabetes. Intraperitoneal injection of streptozotocin (STZ) produced gastric hypersensitivity in female rats in response to gastric balloon distention. Treatment with the CBS inhibitor aminooxyacetic acid significantly attenuated STZ-induced gastric hypersensitivity in a dose-dependent fashion. Aminooxyacetic acid treatment also reversed hyperexcitability of gastric-specific dorsal root ganglion (DRG) neurons labeled by the dye DiI in diabetic rats. Conversely, the H2S donor NaHS enhanced neuronal excitability of gastric DRG neurons. Expression of CBS and p65 were markedly enhanced in gastric DRGs in diabetic rats. Blockade of NF-κB signaling using pyrrolidine dithiocarbamate reversed the upregulation of CBS expression. Interestingly, STZ treatment led to a significant demethylation of CpG islands in the cbs gene promoter region, as determined by methylation-specific PCR and bisulfite sequencing. STZ treatment also remarkably downregulated the expression of DNA methyltransferase 3a and 3b. More importantly, STZ treatment significantly enhanced the ability of cbs to bind DNA at the p65 consensus site, as shown by chromatin immunoprecipitation assays. Our findings suggest that upregulation of cbs expression is attributed to cbs promoter DNA demethylation and p65 activation and that the enhanced interaction of the cbs gene and p65 contributes to gastric hypersensitivity in diabetes. This finding may guide the development and evaluation of new treatment modalities for patients with diabetic gastric hypersensitivity.
Traffic Receipts for Network Transparency

Today’s Internet is not transparent: when packets get lost or delayed, there is typically no information about where the problem occurred, hence no information about who is responsible. This results in Internet service providers (ISPs) offering service level agreements (SLAs) that cannot be verified, and governments enacting neutrality regulations that cannot be enforced. To remedy this, we propose a “transparency system,” where each participating network emits receipts for traffic it receives and delivers; an independent monitor collects these receipts and makes decisions regarding the network’s performance and neutrality (or lack thereof). The main challenge we face is misbehavior: On the one hand, a network that participates in such a system has a clear incentive to game the system and influence the monitor’s decisions to its advantage, by manipulating either the receipts it emits or the corresponding traffic. On the other hand, the monitor (or, more precisely, an adversary who has access to the same information as the monitor, e.g., a government that has subpoenaed the monitor’s records) may have an incentive to use the receipts emitted by a network in order to infer information that is otherwise private to the network, in particular, its internal topology. We make three contributions, each one to prevent a different type of misbehavior: (1) Incentive-compatible reporting, which ensures that networks have no incentive to manipulate the receipts they emit in order to claim better performance or fake neutrality. The key to our solution is a trade-off that we discover between network performance and neutrality: we design our system such that the more a network tries to exaggerate its estimated performance the more likely it is to be perceived to violate neutrality (and vice versa). (2) Unbiased reporting, which ensures that networks cannot manipulate the traffic for which they emit receipts in order to claim better performance. The key to our solution is delayed disclosure: we design receipt generation such that, by the time a network has all the information it needs to emit a correct receipt, the network has already forwarded the traffic that this receipt concerns, hence cannot manipulate it. (3) Topology-obfuscation reporting, which enables networks to emit the information that is necessary for the monitor to make correct decisions without leaking any information about internal network topology. The key to our solution is the observation that topology inference exploits the diversity of pairwise similarities between the delay vectors of different network paths; hence, we design receipt generation such that any delay vectors that the monitor might compute have almost 0 pairwise similarities. We conclude that it is possible to design a transparency system that enables networks to report on their own performance such that networks have no incentive to game the system and no fear of leaking information about their private topology.