Miracle-dz/UniFAR-FTUs huggingface dataset:
Tanshinone IIA induces apoptosis via inhibition of Wnt/β-catenin/MGMT signaling in AtT-20 cells

A strategy to suppress the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) by inhibition of Wnt/β-catenin signaling may be useful as a novel treatment for pituitary adenoma. Previous studies have reported that Tanshinone IIA (TSA), a major quinone compound isolated from Salvia miltiorrhiza, had antitumor effects. However, whether TSA has antitumor effects against pituitary adenoma and whether the mechanisms are associated with the Wnt/β-catenin/MGMT pathway remains to be clarified. In the present study, TSA treatment caused apoptosis in AtT-20 cells in a concentration-dependent manner, as demonstrated by cell viability reduction, phophatidylserine externalization detected by Annexin V staining and mitochondrial membrane potential disruption detected by JC-1 staining, which were associated with activation of caspase-3 and DNA fragmentation detected by TUNEL in AtT-20 cells. T-cell factor (TCF)-lymphoid-enhancing factor (LEF) reporter activity was determined by dual luciferase reporter assay and the interaction between β-catenin and TCF-4 were detected using a co-immunoprecipitation kit. The results indicated TSA treatment increased β-catenin phosphorylation, inhibited β-catenin nuclear translocation, reduced β-catenin/TCF-4 complex formation and TCF-LEF luciferase reporter activity, and subsequently reduced the expression of cyclin D1 and MGMT. Notably, overexpression of MGMT in β-catenin knock down AtT-20 cells abrogated the TSA-mediated effects in AtT-20 cells. In conclusion, TSA induced apoptosis via inhibition of Wnt/β-catenin-dependent MGMT expression, which may provide novel insights into the understanding of the mechanism of the antitumor effects of Salvia miltiorrhiza.
Adenoviral hemorrhagic disease in California mule deer, 1990–2014

We reviewed case records from the California Animal Health and Food Safety (CAHFS) laboratory and the California Department of Fish and Wildlife (CDFW) spanning 25 years (1990–2014) for all deer accessions submitted to CAHFS for pathology and/or histopathology, with and without a diagnosis of adenoviral hemorrhagic disease (AHD), in order to determine the prevalence of AHD in California. We also examined spatial and temporal distribution, age, and mule deer subspecies in deer that died from AHD. Of 483 deer submitted to CAHFS for diagnostic testing in 1990–2014, 17.2% were diagnosed with confirmed AHD, and 26.5% were confirmed plus suspected cases of AHD. Columbian black-tailed deer (Odocoileus hemionus columbianus), particularly fawns and juveniles, were most frequently affected. Deer adenovirus (Odocoileus adenovirus 1; OdAdV-1) was detected by immunohistochemistry in archived CDFW formalin-fixed, paraffin-embedded tissues from deer that died in mortality events in 1981, 1983, and 1986–1987. OdAdV-1 is a common cause of hemorrhagic disease mortality events in California deer, and mortality as a result of AHD is documented as early as 1981.
Generation of intense 100 fs solitons tunable from 2 to 4.3 μm in fluoride fiber

There is great interest in sources of coherent radiation in the mid-wave infrared (3–5 μm), and instruments based on fiber can offer major practical advantages. This range, and much broader, can be covered easily by supercontinuum generation in soft glass fibers, but with low power spectral density. For applications that require intense ultrashort pulses, fiber sources are quite limited. In this Letter, we report a fiber-based system that generates 100 fs pulses with 5 nJ energy, continuously wavelength-tunable over 2–4.3 μm through the soliton self-frequency shift (SSFS) in fluoride fibers. The pulse energies are 2 orders of magnitude higher than those previously achieved by SSFS, around 3 μm, and the range of wavelengths is extended by 1000 nm. Peak power ranges from 20 to 75 kW are achieved across the tuning range. Numerical simulations are in good agreement with the experimental results, and indicate the potential for few-cycle soliton generation out to 5.6 μm. Fiber-integrated sources of femtosecond pulses tunable across this region should be valuable for mid-infrared applications.
A Neurodynamic Model of Feature-Based Spatial Selection

Huang and Pashler (2007) suggested that feature-based attention creates a special form of spatial representation, which is termed a Boolean map. It partitions the visual scene into two distinct and complementary regions: selected and not selected. Here, we developed a model of a recurrent competitive network that is capable of state-dependent computation. It selects multiple winning locations based on a joint top-down cue. We augmented a model of the WTA circuit that is based on linear-threshold units with two computational elements: dendritic non-linearity that acts on the excitatory units and activity-dependent modulation of synaptic transmission between excitatory and inhibitory units. Computer simulations showed that the proposed model could create a Boolean map in response to a featured cue and elaborate it using the logical operations of intersection and union. In addition, it was shown that in the absence of top-down guidance, the model is sensitive to bottom-up cues such as saliency and abrupt visual onset.
Smartphone-Enabled Otoscopy in Neurotology/Otology

Objective A smartphone-enabled otoscope (SEO) can capture tympanic membrane (TM) images. We sought to compare a SEO to microscopic otoscopy in the detection and evaluation of TM pathology in an otology/neurotology practice. Study Design Prospective single-site study in adults presenting over a 3-month period. Setting Neurotology clinic within a tertiary care academic medical center. Subjects and Methods Following consent, 57 patients underwent a medical and microscopic ear examination. Afterward, clinicians photographed bilateral TMs using a SEO. A second “blinded” neurotologist received a SEO-acquired image of each TM and a brief patient history. Our primary end point was identification of TM pathology (or lack thereof) and the blinded neurotologists’ corresponding diagnosis. Secondary end points included patient-reported SEO comfort levels. Results A single SEO-acquired TM image and brief patient history resulted in correct diagnosis of 96% (23/24) of normal TMs and identification of 100% (33/33) of microscope-confirmed abnormal TMs. When pathology was identified by the “blinded” physician, the diagnosis was identical to that made by the primary treating physician 82% (27/33) of the time. On patient surveys, 93% (53/57) of patients felt “very comfortable” with SEO utilization, and 88% (50/57) reported viewing acquired images was “very useful” in understanding their condition. Conclusion A SEO is 96% specific in identifying normal TMs and 100% sensitive in identifying pathology. Its 97% positive predictive value and small false-positive rate makes it a useful screening tool. Furthermore, patients are receptive to this technology and felt comfortable with its utilization in a health care or possible telemedicine setting.
Using Stochastic Roadmap Simulation to Predict Experimental Quantities in Protein Folding Kinetics: Folding Rates and Phi-Values

This paper presents a new method for studying protein folding kinetics. It uses the recently introduced Stochastic Roadmap Simulation (SRS) method to estimate the transition state ensemble (TSE) and predict the rates and the Phi-values for protein folding. The new method was tested on 16 proteins, whose rates and Phi-values have been determined experimentally. Comparison with experimental data shows that our method estimates the TSE much more accurately than an existing method based on dynamic programming. This improvement leads to better folding-rate predictions. We also compute the mean first passage time of the unfolded states and show that the computed values correlate with experimentally determined folding rates. The results on Phi-value predictions are mixed, possibly due to the simple energy model used in the tests. This is the first time that results obtained from SRS have been compared against a substantial amount of experimental data. The results further validate the SRS method and indicate its potential as a general tool for studying protein folding kinetics.
Association study of LIN28B in girls with precocious puberty

Abstract Background: Central precocious puberty (CPP), predominant in girls, is defined by early development of secondary sexual characteristics driven by the early secretion of hypothalamic gonadotropin releasing hormone (GnRH) and subsequent gonadotropin. Recent studies have shown variation in the LIN28B gene is associated with timing of puberty, but only a few have show it to be associated with CPP. Methods: This study attempted to investigate the relation between single-nucleotide polymorphisms (SNPs) in LIN28B and girls with precocious puberty. Genotype and alleles frequencies of selected SNPs were compared between 116 girls with CPP and 102 controls. Results: We found genotype frequencies in rs314276 and rs221634 were significantly correlated with girls with CPP; while the C allele frequency in rs314276 showed the dominant trait. Standard deviation score (SDS) of weight and body mass index (BMI) were higher in CC homozygotes of rs314276 in girls with CPP. Conclusions: Our results demonstrate that the genotype of rs314276 in LIN28B is associated with girls with CPP, carrying dominant trait in the C allele.
Engineered Protein Polymer-Gold Nanoparticle Hybrid Materials for Small Molecule Delivery

We have fabricated protein polymer-gold nanoparticle (P-GNP) nanocomposites that exhibit enhanced binding and delivery properties of the small hydrophobic molecule drug, curcumin, to the model breast cancer cell line, MCF-7. These hybrid biomaterials are constructed via in situ GNP templated-synthesis with genetically engineered histidine tags. The P-GNP nanocomposites exhibit enhanced small molecule loading, sustained release and increased uptake by MCF-7 cells. When compared to the proteins polymers alone, the P-GNPs demonstrate a greater than 7-fold increase in curcumin binding, a nearly 50% slower release profile and more than 2-fold increase in cellular uptake of curcumin. These results suggest that P-GNP nanocomposites serve as promising candidates for drug delivery vehicles.
Phase-resolved pulse propagation through metallic photonic crystal slabs: plasmonic slow light

We characterized the electromagnetic field of ultra-short laser pulses after propagation through metallic photonic crystal structures featuring photonic and plasmonic resonances. The complete pulse information, i.e. the envelope and phase of the electromagnetic field, was measured using the technique of cross-correlation frequency resolved optical gating. In good agreement, measurements and scattering matrix simulations show a dispersive behaviour of the spectral phase at the position of the resonances. Asymmetric Fano-type resonances go along with asymmetric phase characteristics. Furthermore, the spectral phase is used to calculate the dispersion of the sample and possible applications in dispersion compensation are investigated. Group refractive indices of 700 and 70 and group delay dispersion values of 90 000 fs2 and 5000 fs2 are achieved in transverse electric and transverse magnetic polarization, respectively. The behaviour of extinction and spectral phase can be understood from an intuitive model using the complex transmission amplitude. An associated depiction in the complex plane is a useful approach in this context. This method promises to be valuable also in photonic crystal and filter design, for example, with regards to the symmetrization of the resonances. This article is part of the themed issue ‘New horizons for nanophotonics’.
Debonding Resistance of NSM CFRP Strips Bonded to Masonry under Various Environmental Exposures.

WILLIAMS, MARGARET KATHERINE. Debonding Resistance of NSM CFRP Strips Bonded to Masonry under Various Environmental Exposures. (Under the direction of Dr. Rudolf Seracino). Much research has been done on the repair or strengthening of masonry walls with both externally bonded and near-surface mounted FRP systems. However, research is needed to determine the durability of an FRP-reinforced masonry wall subjected to environmental conditions similar to what it may witness over its lifespan. The pull-test is commonly used to determine the bond behavior of the FRP and the masonry prism as it simulates the critical intermediate crack debonding failure mode. This thesis describes the results of pull-tests performed on hollow core clay brick prisms strengthened with NSM carbon FRP. Three series of tests were performed at approximately four-month intervals during which the prisms were exposed to varying environmental conditions. While a portion of the constructed prisms remained in a controlled humidity and temperature setting, others were weathered outside in a natural environmental condition. The remaining prisms were placed in an extreme environmental condition, in which the prisms were subjected to large temperature ranges through the use of an environmental chamber. The change in debonding behavior due to varying the masonry pattern bond and exposure to environmental conditions was experimentally determined and compared to existing models. Further, a numerical analysis using the Applied Element Method was completed on six different pull-test specimens in an effort to determine the suitability of using such a program to accurately model the pull-test. The resulting pull-test behavior exhibited a significant change in the debonding failure of a naturally conditioned specimen due to exposure to high temperatures and moisture. The failure mechanism changed to shear failure in the adhesive. Further, the debonding resistances of the control specimens and specimens placed in the environmental chamber were also compromised by premature splitting of the prisms through the cores. This is turn lessened the debonding resistance of FRP-reinforced prisms. However, the numerical analysis program utilized in this research was able to capture the splitting failure of the control prisms with accuracy. Debonding Resistance of NSM CFRP Strips Bonded to Masonry under Various Environmental Exposures by Margaret Katherine Williams A thesis submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the degree of Master of Science
Optimal feeding frequency of captive head‐started green turtles (Chelonia mydas)

Optimal feeding frequency was investigated to improve head-started propagation programme of juvenile green turtles (Chelonia mydas). The 15-day-old turtles (25-26 g body weight) were fed for ad libitum intake at one (1MD), two (2MD), three (3MD) or four (4MD) meals daily over a 3-month trial. Responses in growth, feed utilization, faecal characteristics, haematological parameters and carapace elemental composition were used to compare treatment effects. At the end of the feeding trial, no treatment had induced mortality. Growth performance in terms of weight gain and specific growth rate was similar in turtles fed 2MD, 3MD or 4MD (p > 0.05), but 1MD differed from these (p < 0.05), and feeding at excess frequency (3MD and 4MD) increased the within-group size variation. Turtles fed 2MD had significantly lower feed intake than in 3MD and 4MD groups, but the feed conversion ratios were similar. Faecal digestive enzyme analysis indicated higher catabolism of lipid and protein in the deprivation group (1MD), when compared with turtles fed at least twice daily. The feeding frequency did not affect the specific activities of carbohydrate-digesting enzymes. The results on enzymes activities were corroborated by the transition enthalpy characteristics of faeces, indicating nutrients remaining after digestion. The 2MD treatment also improved the haematological characteristics and the carapace quality, relative to low or excess feeding. Overall, the findings indicate that feeding juvenile green turtles twice a day is the preferred option in their head-started propagation. This promotes growth, reduces feed consumption, and improves health and carapace quality.
ACETYLATED RUBBERWOOD FLAKEBOARD RESISTANCE TO BIO-DETERIORATION

Flakeboards made from rubberwood (Hevea brasiliensis Muell. Arg.) and phenol-formaldehyde resin were used to test for resistance to dry wood termites, subterranean termites, and fungal attacks. Dried flakes were immersed in acetic anhydride and subsequently heated at 120°C to give specimens of 7 and 18 weight percent gains. Control flakeboards were also prepared for comparison. Flakeboards were put in the boxes containing 50 healthy and active dry wood nymphae of Cryptotermes cynocephalus Light for 4 weeks. Nymphae mortality and weight loss were determined for each sample. Flakeboards were also stacked in an arboretum for 12 weeks and protection level and weight loss of flakeboard caused by Macrotermes gilvus Hagen attack were determined. Flakeboards were also innoculated with Schizophyllum commune for 10 weeks and moisture content, weight loss, and modulus of rupture loss of flakeboard were determined. The results showed that the acetylation of the flakes increased the resistance to dry wood termite, subterranean termite, and fungal attacks. The higher the acetylation level, the greater the resistance.
Visualizing and comparing results of different peptide identification methods

In mass spectrometry-based proteomics, peptides are typically identified from tandem mass spectra using spectrum comparison. A sequence search engine compares experimentally obtained spectra with those predicted from protein sequences, applying enzyme cleavage and fragmentation rules. To this, there are two main alternatives: spectral libraries and de novo sequencing. The former compares measured spectra with a collection of previously acquired and identified spectra in a library. De novo attempts to sequence peptides from the tandem mass spectra alone. We here present a theoretical framework and a data processing workflow for visualizing and comparing the results of these different types of algorithms. The method considers the three search strategies as different dimensions, identifies distinct agreement classes and visualizes the complementarity of the search strategies. We have included X! Tandem, SpectraST and PepNovo, as they are in common use and representative for algorithms of each type. Our method allows advanced investigation of how the three search methods perform relatively to each other and shows the impact of the currently used decoy sequences for evaluating the false discovery rates.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe multiorgan hypersensitivity reaction mostly caused by a limited number of eliciting drugs in patients with a genetic predisposition. Patients with DRESS syndrome present with characteristic but variable clinical and pathological features. Reactivation of human herpesviruses (HHV), especially HHV-6, is the hallmark of the disease. Anti-viral immune responses intertwined with drug hypersensitivity make the disease more complicated and protracted. In recent years, emerging studies have outlined the disease more clearly, though several important questions remain unresolved. In this review, we provide an overview of DRESS syndrome, including clinical presentations, histopathological features, pathomechanisms, and treatments.
Dietary diversity and nutritional status among children in rural Burkina Faso.

Background Burkina Faso has a seasonal malnutrition pattern, with higher malnutrition prevalence during the rainy season when crop yields are low. We investigated the association between dietary diversity and nutritional status among children aged 6-59 mo during the low crop yield season in rural Burkina Faso to assess the role of dietary diversity during the lean season on childhood nutritional status. Methods Caregivers reported the dietary diversity of the past 7 d, consisting of 11 food groups, summed into a scale. Anthropometric measurements were taken from all children. Height-for-age (HAZ), weight-for-height (WHZ) and weight-for-age (WAZ) z-scores were calculated based on 2006 WHO standards. Stunting, wasting and underweight were defined as HAZ, WHZ and WAZ <-2 SD, respectively. Multivariable regression models adjusting for potential confounders including household food insecurity and animal ownership were used to assess the relationship between anthropometric indices and dietary diversity. Results Of 251 children enrolled in the study, 20.6% were stunted, 10.0% wasted and 13.9% underweight. Greater dietary diversity was associated with greater HAZ (SD 0.14, 95% CI 0.04 to 0.25) among all children. There was no association between dietary diversity and wasting or mid-upper arm circumference in this study. Conclusions Increasing dietary diversity may be an approach to reduce the burden of stunting and chronic malnutrition among young children in regions with seasonal food insecurity.
Time to Endovascular Treatment and Outcome in Acute Ischemic Stroke: MR CLEAN Registry Results

Background: Randomized, clinical trials in selected acute ischemic stroke patients reported that for every hour delay of endovascular treatment (EVT), chances of functional independence diminish by up to 3.4%. These findings may not be fully generalizable to clinical practice because of strict in- and exclusion criteria in these trials. Therefore, we aim to assess the association of time to EVT with functional outcome in current, everyday clinical practice. Methods: The MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands) is an ongoing, prospective, observational study in all centers that perform EVT in The Netherlands. Data were analyzed from patients treated between March 2014 and June 2016. In the primary analysis we assessed the association of time from stroke onset to start of EVT and time from stroke onset to successful reperfusion with functional outcome (measured with the modified Rankin Scale), by means of ordinal logistic regression. Results: We analyzed 1488 patients with acute ischemic stroke who underwent EVT. An increased time to start of EVT was associated with worse functional outcome (adjusted common odds ratio, 0.83 per hour; 95% confidence interval, 0.77–0.89) and a 2.2% increase in mortality. Every hour increase from stroke onset to EVT start resulted in a 5.3% decreased probability of functional independence (modified Rankin Scale, 0–2). In the 742 patients with successful reperfusion, every hour increase from stroke onset to reperfusion was associated with a 7.7% decreased probability of functional independence. Conclusions: Time to EVT for acute ischemic stroke in current clinical practice is strongly associated with functional outcome. Our data suggest that this association might be even stronger than previously suggested in reports on more selected patient populations from randomized, controlled trials. These findings emphasize that functional outcome of EVT patients can be greatly improved by shortening onset to treatment times.