Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of the Addition of Eicosapentaenoic Acid to Strong Statin Therapy on Inflammatory Cytokines and Coronary Plaque Components Assessed by Integrated Backscatter Intravascular Ultrasound.

BACKGROUND The effects of eicosapentaenoic acid (EPA) on coronary artery disease have been previously reported; however, those of the addition of EPA to strong statins on coronary plaque components and local inflammatory cytokines are not known. METHODSANDRESULTS A total of 95 patients who had been treated with strong statin for at least 6 months were randomized into 2 groups: an EPA group (additional treatment with EPA at 1,800 mg/day, n=48) or a control group (no additional treatment, n=47), for 6 months. The tissue characteristics of target coronary plaque in each patient were analyzed using IB-IVUS before and after treatment. We also measured plasma levels of inflammatory cytokines sampled in the coronary sinus (CS) and peripheral vein.A significant reduction in lipid volume (18.5 ± 1.3 to 15.0 ± 1.5 mm(3), P=0.007) and a significant increase in fibrous volume (22.9 ± 0.8 to 25.6 ± 1.1 mm(3), P=0.01) were observed in IB-IVUS image analyses in the EPA group, but no significant changes in the plaque components in the control group. CS levels of pentraxin 3 and monocyte chemoattractant protein-1 were lower after than before treatment with EPA (3.3 ± 2.1 to 2.6 ± 1.2 ng/ml, 120.4 ± 26.2 to 110.2 ± 26.8 pg/ml, P=0.015 and P=0.008, respectively); however, there were no significant changes in those inflammatory cytokines between pre- and post-treatment in the control group. CONCLUSIONS The addition of EPA was associated with reduced lipid volume in coronary plaques and decreased inflammatory cytokines.
Body Image in Eating Disorders: The Influence of Exposure to Virtual-Reality Environments

The aim of this article was to study the effect of virtual-reality exposure to situations that are emotionally significant for patients with eating disorders (ED) on the stability of body-image distortion and body-image dissatisfaction. A total of 85 ED patients and 108 non-ED students were randomly exposed to four experimental virtual environments: a kitchen with low-calorie food, a kitchen with high-calorie food, a restaurant with low-calorie food, and a restaurant with high-calorie food. In the interval between the presentation of each situation, body-image distortion and body-image dissatisfaction were assessed. Several 2 x 2 x 2 repeated measures analyses of variance (high-calorie vs. low-calorie food x presence vs. absence of people x ED group vs. control group) showed that ED participants had significantly higher levels of body-image distortion and body dissatisfaction after eating high-calorie food than after eating low-calorie food, while control participants reported a similar body image in all situations. The results suggest that body-image distortion and body-image dissatisfaction show both trait and state features. On the one hand, ED patients show a general predisposition to overestimate their body size and to feel more dissatisfied with their body image than controls. On the other hand, these body-image disturbances fluctuate when participants are exposed to virtual situations that are emotionally relevant for them.
Acute Stress Suppresses Synaptic Inhibition and Increases Anxiety via Endocannabinoid Release in the Basolateral Amygdala

Stress and glucocorticoids stimulate the rapid mobilization of endocannabinoids in the basolateral amygdala (BLA). Cannabinoid receptors in the BLA contribute to anxiogenesis and fear-memory formation. We tested for rapid glucocorticoid-induced endocannabinoid regulation of synaptic inhibition in the rat BLA. Glucocorticoid application to amygdala slices elicited a rapid, nonreversible suppression of spontaneous, but not evoked, GABAergic synaptic currents in BLA principal neurons; the effect was also seen with a membrane-impermeant glucocorticoid, but not with intracellular glucocorticoid application, implicating a membrane-associated glucocorticoid receptor. The glucocorticoid suppression of GABA currents was not blocked by antagonists of nuclear corticosteroid receptors, or by inhibitors of gene transcription or protein synthesis, but was blocked by inhibiting postsynaptic G-protein activity, suggesting a postsynaptic nongenomic steroid signaling mechanism that stimulates the release of a retrograde messenger. The rapid glucocorticoid-induced suppression of inhibition was prevented by blocking CB1 receptors and 2-arachidonoylglycerol (2-AG) synthesis, and it was mimicked and occluded by CB1 receptor agonists, indicating it was mediated by the retrograde release of the endocannabinoid 2-AG. The rapid glucocorticoid effect in BLA neurons in vitro was occluded by prior in vivo acute stress-induced, or prior in vitro glucocorticoid-induced, release of endocannabinoid. Acute stress also caused an increase in anxiety-like behavior that was attenuated by blocking CB1 receptor activation and inhibiting 2-AG synthesis in the BLA. Together, these findings suggest that acute stress causes a long-lasting suppression of synaptic inhibition in BLA neurons via a membrane glucocorticoid receptor-induced release of 2-AG at GABA synapses, which contributes to stress-induced anxiogenesis. SIGNIFICANCE STATEMENT We provide a cellular mechanism in the basolateral amygdala (BLA) for the rapid stress regulation of anxiogenesis in rats. We demonstrate a nongenomic glucocorticoid induction of long-lasting suppression of synaptic inhibition that is mediated by retrograde endocannabinoid release at GABA synapses. The rapid glucocorticoid-induced endocannabinoid suppression of synaptic inhibition is initiated by a membrane-associated glucocorticoid receptor in BLA principal neurons. We show that acute stress increases anxiety-like behavior via an endocannabinoid-dependent mechanism centered in the BLA. The stress-induced endocannabinoid modulation of synaptic transmission in the BLA contributes, therefore, to the stress regulation of anxiety, and may play a role in anxiety disorders of the amygdala.
An Introduction to Sequence Similarity (“Homology”) Searching

Sequence similarity searching, typically with BLAST, is the most widely used and most reliable strategy for characterizing newly determined sequences. Sequence similarity searches can identify “homologous” proteins or genes by detecting excess similarity— statistically significant similarity that reflects common ancestry. This unit provides an overview of the inference of homology from significant similarity, and introduces other units in this chapter that provide more details on effective strategies for identifying homologs. Curr. Protoc. Bioinform. 42:3.1. 1‐3.1. 8. © 2013 by John Wiley & Sons, Inc.
Application of the bispectrum to glottal pulse analysis

Higher order spectral (HOS) techniques, such as the bispectrum, offer robustness to Gaussian noise and the ability to recover phase information. However, their drawbacks, such as the high variance of estimates and the need for long data records, have limited their use in conventional speech processing applications. As in glottal pulse estimation, all existing inverse filtering approaches use second-order statistics, it is of interest to explore the potential of HOS in this area. Using the theory of HOS factorization and the linear bispectrum, it is shown how voiced speech can be modelled as a nonGaussian coloured noise driven system. The linear bispectrum approach can be used to obtain alternative glottal pulse and vocal tract estimates in hybrid Iterative Adaptive Inverse Filtering (hIAIF) and the results are compared with traditional IAIF. Finally, a new technique which involves joint estimation of the glottal pulse and vocal tract followed by inverse filtering is presented. This new technique shows good preliminary results and is much simpler than previous techniques.
Clostridium difficile Toxin A Attenuates Wnt/β-Catenin Signaling in Intestinal Epithelial Cells

ABSTRACT Clostridium difficile toxins A and B (TcdA and TcdB) are homologous glycosyltransferases that inhibit a group of small GTPases within host cells, but several mechanisms underlying their pathogenic activity remain unclear. In this study, we evaluated the effects of TcdA on the Wnt/β-catenin pathway, the major driving force behind the proliferation of epithelial cells in colonic crypts. IEC-6 and RKO cells stimulated with Wnt3a-conditioned medium were incubated with 10, 50, and 100 ng/ml of TcdA for 24 h, resulting in a dose-dependent inhibition of the Wnt signaling, as demonstrated by a T-cell factor (TCF) reporter assay. This was further confirmed by immunofluorescence staining for nuclear localization of β-catenin and Western blotting for β-catenin and c-Myc (encoded by a Wnt target gene). Moreover, our Western blot analysis showed a decrease in the β-catenin protein levels, which was reversed by z-VAD-fmk, a pan-caspase inhibitor. Nonetheless, TcdA was still able to inhibit the Wnt/β-catenin pathway even in the presence of z-VAD-fmk, lithium chloride (a GSK3β inhibitor), or constitutively active β-catenin, as determined by a TCF reporter assay. Furthermore, preincubation of RKO cells with TcdA for 12 h also attenuated Wnt3a-mediated activation of Wnt signaling, suggesting that inactivation of Rho GTPases plays a significant role in that inhibition. Taken together, these findings suggest that attenuation of the Wnt signaling by TcdA is important for TcdA antiproliferative effects.
Knapp-Stein Type Intertwining Operators for Symmetric Pairs II. - The Translation Principle and Intertwining Operators for Spinors

Abstract For a symmetric pair ( G , H ) of reductive groups we construct a family of intertwining operators between spherical principal series representations of G and H that are induced from parabolic subgroups satisfying certain compatibility conditions. The operators are given explicitly in terms of their integral kernels and we prove convergence of the integrals for an open set of parameters and meromorphic continuation. In particular, this establishes lower bounds for multiplicities of intertwining operators. We further discuss uniqueness of intertwining operators, and for the rank one cases ( G , H ) = ( SU ( 1 , n ; F ) , S ( U ( 1 , m ; F ) × U ( n − m ; F ) ) ) , with F = R , C , H , O , and for the pair ( G , H ) = ( GL ( 4 n , R ) , GL ( 2 n , C ) ) we show that for a certain choice of maximal parabolic subgroups our operators generically span the space of intertwiners.
Molecular Framework of a Regulatory Circuit Initiating Two-Dimensional Spatial Patterning of Stomatal Lineage

Stomata, valves on the plant epidermis, are critical for plant growth and survival, and the presence of stomata impacts the global water and carbon cycle. Although transcription factors and cell-cell signaling components regulating stomatal development have been identified, it remains unclear as to how their regulatory interactions are translated into two-dimensional patterns of stomatal initial cells. Using molecular genetics, imaging, and mathematical simulation, we report a regulatory circuit that initiates the stomatal cell-lineage. The circuit includes a positive feedback loop constituting self-activation of SCREAMs that requires SPEECHLESS. This transcription factor module directly binds to the promoters and activates a secreted signal, EPIDERMAL PATTERNING FACTOR2, and the receptor modifier TOO MANY MOUTHS, while the receptor ERECTA lies outside of this module. This in turn inhibits SPCH, and hence SCRMs, thus constituting a negative feedback loop. Our mathematical model accurately predicts all known stomatal phenotypes with the inclusion of two additional components to the circuit: an EPF2-independent negative-feedback loop and a signal that lies outside of the SPCH•SCRM module. Our work reveals the intricate molecular framework governing self-organizing two-dimensional patterning in the plant epidermis.
Family, Community and Long-Term Earnings Inequality

This paper studies the influence of family, schools and neighborhoods on life-cycle earnings inequality. We develop an earnings dynamics model linking brothers, schoolmates and teenage parish neighbors using population register data for Denmark. We exploit differences in the timing of family mobility and the partial overlap of schools and neighborhoods to separately identify sorting from community and family effects. We find that family is far more important than community in influencing earnings inequality over the life cycle. Neighborhoods and schools influence earnings only early in the working life and this influence falls rapidly and becomes negligible after age 30.
Lynch Syndrome-associated Mutations in MSH2 Alter DNA Repair and Checkpoint Response Functions In Vivo

The DNA mismatch repair (MMR) pathway is essential in maintaining genomic stability through its role in DNA repair and the checkpoint response. Loss of DNA MMR underlies the hereditary cancer disease Lynch Syndrome (LS). Germline mutations in MSH2 account for approximately 40% of LS patients and of these, 18% are missense variants. One important clinical challenge has been discriminating between missense variants that are pathogenic and those that are not. Current analysis of missense mutations in MSH2 is performed using a combination of clinical, biochemical, and functional data; however, suitable cell culture models to test the various functions of the DNA MMR proteins are lacking. Here, we have generated human cell lines stably expressing a subset of MSH2 missense mutants and tested their effect on DNA repair and checkpoint response functions. We have expanded on previous biochemical and functional analyses performed in non‐human systems to further understand defects conferred by this subset of single amino acid alterations. The functional characterization of MSH2 missense mutants combined with clinical and biochemical data is essential for appropriate patient management and genetic counseling decisions. ©2010 Wiley‐Liss, Inc.
Genetic Variants of Nucleotide Excision Repair Genes Are Associated with DNA Damage in Coke Oven Workers

We explored the effects of single nucleotide polymorphisms (SNP) of nucleotide excision repair (NER) genes on DNA damage caused by exposure to carcinogenic polycyclic aromatic hydrocarbons (PAH) in 475 Chinese workers. We quantified urinary 1-hydroxypyrene using high-performance liquid chromatography, and the DNA damage level of lymphocytes was examined by the comet assay and represented as the Olive tail moment (OTM) value. We genotyped 38 tagSNPs in 10 NER genes. The SNP function was further investigated using luciferase reporter assay in three cell lines. Our results showed that two promoter SNPs, XPA rs1800975 and XPC rs3731055, were associated with lower OTM values (Ptrend = 0.01 and 0.02 respectively). However, another missense SNP rs2228001 in the XPC gene was positively associated with OTM value (Ptrend = 0.01). A stratified analysis found that the association between this SNP and DNA damage was only observed among subjects with higher PAH exposure levels but not among those with lower exposure levels (Pinteraction = 0.018). A dose-response association was found between the combined risk alleles of the above three genetic variants and increased DNA damage levels (Ptrend = 0.004). This association was more pronounced in subjects with higher PAH exposure than those with lower exposure levels (Pinteraction = 0.046). Our functional study indicated that XPA rs1800975G and XPC rs3731055A alleles had a higher luciferase expression than their corresponding SNP alleles (P < 0.05). These results suggested that genetic variations in key NER genes, especially in XPA and XPC genes, may modulate DNA damage levels when exposed to PAHs. Cancer Epidemiol Biomakers Prev; 19(1); 211–8
Association of peroxisome proliferator-activated receptor-gamma gene polymorphisms and gene-gene interaction with asthma risk in a Chinese adults population.

AIMS To investigate the association between single nucleotide polymorphism (SNP) of peroxisome proliferator-activated receptors γ (PPAR γ) and additional gene-gene interactions on asthma risk. METHODS A total of 882 subjects (602 males, 280 females), with a mean age of 61.3±14.8 years old, including 430 asthma patients and 452 normal subjects were selected in this study, including the genotyping of polymorphisms. Logistic regression was performed to investigate association between SNP and asthma. Generalized MDR (GMDR) was used to analysis the interaction among four SNP. RESULTS Asthma risk was significantly lower in carriers of Ala allele of the rs1805192 polymorphism than those with Pro/Pro (Pro/Ala+ Ala/Ala versus Pro/Pro, adjusted OR (95% CI)=0.70 (0.51-0.94). In addition, we also found a significant association between rs10865710 and asthma, asthma risk was significantly lower in carriers of G allele of the rs10865710 polymorphism than those with CC (CG+ GG versus CC, adjusted OR (95% CI)=0.68 (0.55-0.95). There was a significant three-locus model (P=0.0107) involving rs1805192, rs10865710 and rs709158, indicating a potential gene-gene interaction among rs1805192, rs10865710 and rs709158. Overall, the three-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 60.72% after covariates adjustment. CONCLUSIONS Our results support an important association of rs1805192 and rs10865710 with asthma, and additional interaction among rs1805192, rs10865710 and rs709158.
It starts with iGaze: visual attention driven networking with smart glasses

In this work, we explore a new networking mechanism with smart glasses, through which users can express their interest and connect to a target simply by a gaze. Doing this, we attempt to let wearable devices understand human attention and intention, and pair devices carried by users according to such attention and intention. To achieve this ambitious goal, we propose a proof-of-concept system iGaze, a visual attention driven networking suite: an iGaze glass (hardware), and a networking protocol VAN (software). Our glass, iGaze glass, is a low-cost head-mounted glass with a camera, orientation sensors, microphone and speakers, which are embedded with our software for visual attention capture and networking. A visual attention driven networking protocol (VAN) is carefully designed and implemented. In VAN, we design an energy efficient and highly accurate visual attention determination scheme using single camera to capture user's communication interest and a double-matching scheme based on visual direction detection and Doppler effect of acoustic signal to lock the target devices. Using our system, we conduct a series of trials for various application scenarios to demonstrate the effectiveness of our system.
Protection of 3'-Azido-3'-Deoxythymidine Induced Toxicity to Murine Hematopoietic Progenitors (CFU-GM, BFU-E and CFU-MEG) with Interleukin-1

3'-Azido-3'-deoxythymidine (AZT) has attained wide clinical utility in the treatment of acquired immunodeficiency syndrome (AIDS). Unfortunately, associated with AZT use, is the development pf severe hematopoietic toxicity as manifested by anemia, neutropenia and overall bone marrow suppression. Interleukin-1 (IL-1), a cytokine, primarily produced by activated macrophages, has been involved in the control of hematopoiesis by acting synergistically with other hematopoietic growth factors, and has been demonstrated to be an effective agent in reducing the myelosuppression associated with the therapy for malignant disease. We report here the ability of recombinant human IL-1 alpha to protect normal murine hematopoietic progenitors (CFU-GM, BFU-E, and CFU-Meg) from the toxic effects of AZT. Following the determination of the LD5Q dose for each progenitor, IL-1 was added in co-culture studies (10 - 1000 units; 0.001 - 1.0 yg/ml protein) with adherent cell depleted marrow. Marrow progenitors expressed differences in AZT sensitivity, e.g., BFU-E, LD50 5 x 10′9M; CFU-Meg, LD50 10′7M; CFU-GM, 5 x 10′5M respectively. IL-1 inhibited AZT induced toxicity. The maximum IL-1 dose effect was observed for CFU-GM and CFU-Meg at 300 units, 0.3 yg protein; however BFU-E required a dose of 600 units, 0.6 yg/ml protein to reverse the effects of AZT. These results demonstrate marrow progenitors respond differently to AZT and identifies the potential efficacy of IL-I to minimize the hematopoietic toxicity associated with AZT treatment.
The Wernicke area

The term “Wernicke's area” is most often used as an anatomical label for the gyri forming the lower posterior left sylvian fissure. Although traditionally this region was held to support language comprehension, modern imaging and neuropsychological studies converge on the conclusion that this region plays a much larger role in speech production. This evidence is briefly reviewed, and a simple schematic model of posterior cortical language processing is described.
Preoperative Ultrasonic Assessment of Thin Melanocytic Skin Lesions Using a 100‐MHz Ultrasound Transducer: A Comparative Study

BACKGROUND It has been shown that tumor thickness (TT) of melanocytic skin lesions (MSL) of less than 1 mm vertical thickness assessed by 20 MHz are often incorrectly evaluated. OBJECTIVE We aimed to evaluate the accuracy of 100-MHz ultrasound for the determination of TT of thin MSL, compared with conventional 20-MHz ultrasound and histologic findings. METHODS Thirty-seven patients with 50 suspicious MSL, including tumor diameter up to 1 cm and maximum vertical TT of less than 1 mm, were recruited. The agreement between the histologically and ultrasographically measured TT was analyzed using Bland and Altman plots. RESULTS Compared to histology, 20-MHz ultrasound (33.9 μm) as well as 100-MHz (16 μm) resulted in overestimation of TT that was twofold higher for 20-MHz ultrasound. The latter also revealed wider 95% limits of agreement (4.9 to 63 μm) than 100-MHz ultrasound (3.5 to 28.7 μm). CONCLUSION Analysis of agreement clearly demonstrated that the performance of 100-MHz ultrasound is superior to conventional 20-MHz ultrasound, even though a relatively small positive bias was observed in 100-MHz ultrasound, indicating a systematic error. We consider 100-MHz ultrasound a useful tool for the noninvasive determination of TT of thin MSL in vivo.
Licofelone Modulates Neuroinflammation and Attenuates Mechanical Hypersensitivity in the Chronic Phase of Spinal Cord Injury

Inflammation is a major factor shaping outcome during the early, acute phase of traumatic spinal cord injury (SCI). It is known that pro-inflammatory signaling within the injured spinal cord drives pathological alterations in neurosensory processing and shapes functional outcome early after injury. However, it is unclear whether inflammation persists into the chronic phase of injury or shapes sensory processing long after injury. To investigate these possibilities, we have performed biochemical and behavioral assessments 9 months after moderate thoracic spinal contusion injury in the rat. We have found that levels of the pro-inflammatory lipid mediators leukotriene B4 and prostaglandin E2 are elevated in the chronic spinal cord lesion site. Additionally, using metabolomic profiling, we have detected elevated levels of pro-oxidative and inflammatory metabolites, along with alterations in multiple biological pathways within the chronic lesion site. We found that 28 d treatment of chronically injured rats with the dual COX/5-LOX inhibitor licofelone elevated levels of endogenous anti-oxidant and anti-inflammatory metabolites within the lesion site. Furthermore, licofelone treatment reduced hypersensitivity of hindpaws to mechanical, but not thermal, stimulation, indicating that mechanical sensitivity is modulated by pro-inflammatory signaling in the chronic phase of injury. Together, these findings provide novel evidence of inflammation and oxidative stress within spinal cord tissue far into the chronic phase of SCI, and demonstrate a role for inflammatory modulation of mechanical sensitivity in the chronic phase of injury.