bluuebunny/crossref_metadata_2025 huggingface dataset:
Proofreading-Deficient Coronaviruses Adapt for Increased Fitness over Long-Term Passage without Reversion of Exoribonuclease-Inactivating Mutations
Authors: Graepel Kevin W. , Lu Xiaotao , Case James Brett , Sexton Nicole R. , Smith Everett Clinton , Denison Mark R.
Published: November 2017

The coronavirus (CoV) RNA genome is the largest among the single-stranded positive-sense RNA viruses. CoVs encode a proofreading 3′-to-5′ exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is responsible for CoV high-fidelity replication. Alanine substitution of ExoN catalytic residues [ExoN(-)] in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and murine hepatitis virus (MHV) disrupts ExoN activity, yielding viable mutant viruses with defective replication, up to 20-fold-decreased fidelity, and increased susceptibility to nucleoside analogues. To test the stability of the ExoN(-) genotype and phenotype, we passaged MHV-ExoN(-) 250 times in cultured cells (P250), in parallel with wild-type MHV (WT-MHV). Compared to MHV-ExoN(-) P3, MHV-ExoN(-) P250 demonstrated enhanced replication and increased competitive fitness without reversion at the ExoN(-) active site. Furthermore, MHV-ExoN(-) P250 was less susceptible than MHV-ExoN(-) P3 to multiple nucleoside analogues, suggesting that MHV-ExoN(-) was under selection for increased replication fidelity. We subsequently identified novel amino acid changes within the RNA-dependent RNA polymerase and nsp14 of MHV-ExoN(-) P250 that partially accounted for the reduced susceptibility to nucleoside analogues. Our results suggest that increased replication fidelity is selected in ExoN(-) CoVs and that there may be a significant barrier to ExoN(-) reversion. These results also support the hypothesis that high-fidelity replication is linked to CoV fitness and indicate that multiple replicase proteins could compensate for ExoN functions during replication.

IMPORTANCE
Uniquely among RNA viruses, CoVs encode a proofreading exoribonuclease (ExoN) in nsp14 that mediates high-fidelity RNA genome replication. Proofreading-deficient CoVs with disrupted ExoN activity [ExoN(-)] either are nonviable or have significant defects in replication, RNA synthesis, fidelity, fitness, and virulence. In this study, we showed that ExoN(-) murine hepatitis virus can adapt during long-term passage for increased replication and fitness without reverting the ExoN-inactivating mutations. Passage-adapted ExoN(-) mutants also demonstrate increasing resistance to nucleoside analogues that is explained only partially by secondary mutations in nsp12 and nsp14. These data suggest that enhanced resistance to nucleoside analogues is mediated by the interplay of multiple replicase proteins and support the proposed link between CoV fidelity and fitness.
Dynamic Proteomics of Herpes Simplex Virus Infection
Authors: Drayman Nir , Karin Omer , Mayo Avi , Danon Tamar , Shapira Lev , Rafael Dor , Zimmer Anat , Bren Anat , Kobiler Oren , Alon Uri
Published: November 2017

The cellular response to viral infection is usually studied at the level of cell populations. Currently, it remains an open question whether and to what extent cell-to-cell variability impacts the course of infection. Here we address this by dynamic proteomics—imaging and tracking 400 yellow fluorescent protein (YFP)-tagged host proteins in individual cells infected by herpes simplex virus 1. By quantifying time-lapse fluorescence imaging, we analyze how cell-to-cell variability impacts gene expression from the viral genome. We identify two proteins, RFX7 and geminin, whose levels at the time of infection correlate with successful initiation of gene expression. These proteins are cell cycle markers, and we find that the position in the cell cycle at the time of infection (along with the cell motility and local cell density) can reasonably predict in which individual cells gene expression from the viral genome will commence. We find that the onset of cell division dramatically impacts the progress of infection, with 70% of dividing cells showing no additional gene expression after mitosis. Last, we identify four host proteins that are specifically modulated in infected cells, of which only one has been previously recognized. SUMO2 and RPAP3 levels are rapidly reduced, while SLTM and YTHDC1 are redistributed to form nuclear foci. These modulations are dependent on the expression of ICP0, as shown by infection with two mutant viruses that lack ICP0. Taken together, our results provide experimental validation for the long-held notion that the success of infection is dependent on the state of the host cell at the time of infection.

IMPORTANCE
High-throughput assays have revolutionized many fields in biology, both by allowing a more global understanding of biological processes and by deciphering rare events in subpopulations. Here we use such an assay, dynamic proteomics, to study viral infection at the single-cell level. We follow tens of thousands of individual cells infected by herpes simplex virus using fluorescence live imaging. Our results link the state of a cell at the time of virus infection with its probability to successfully initiate gene expression from the viral genome. Further, we identified three cellular proteins that were previously unknown to respond to viral infection. We conclude that dynamic proteomics provides a powerful tool to study single-cell differences during viral infection.
Near-Cognate Codons Contribute Complexity to Translation Regulation
Authors: Glass N. Louise
Published: November 2017

The interplay between translation initiation, modification of translation initiation factors, and selection of start sites on mRNA for protein synthesis can play a regulatory role in the cellular response to stress, development, and cell fate in eukaryotic species by shaping the proteome. As shown by Ivanov et al. (mBio 8:e00844-17, 2017,
https://doi.org/10.1128/mBio.00844-17
), in the filamentous fungus
Neurospora crassa
, both upstream open reading frames (uORFs) and near-cognate start codons negatively or positively regulate the translation of the transcription factor CPC1 and production of CPC1 isoforms, which mediate the cellular response to amino acid starvation. Dissecting the physiological roles that differentiate cellular choice of translation initiation is an important parameter to understanding mechanisms that determine cell fate via gene regulation and protein synthesis.
Subtle Microbiome Manipulation Using Probiotics Reduces Antibiotic-Associated Mortality in Fish
Authors: Schmidt Victor , Gomez-Chiarri Marta , Roy Chelsea , Smith Katherine , Amaral-Zettler Linda
Published: November 2017

Prophylactic antibiotics are widespread in the aquaculture industry and are used where vaccination is impossible or overly expensive. If antibiotics impact fish as they do mice and humans, prophylactic administrations in aquaculture and ornamental fish farms may increase downstream disease susceptibility in target hosts, despite short-term pathogen control benefits. Recent research has suggested that their use exacerbates bacterial outbreaks by creating sterile, nutrient-rich environments for invading pathogens to colonize and could help to explain rising economic costs of bacterial outbreaks in aquaculture. Our findings suggest a long-term cost of prophylactic antibiotic use and demonstrate a probiotic-based solution that does not rely on full microbiome community transplantation.
Diagnostic accuracy of the D-dimer in children
Authors: Kanis Jessica , Hall Cassandra L , Pike Jonathan , Kline Jeffrey A
Published: November 2017

Background

We sought to measure the diagnostic accuracy of D-dimer in children with suspected pulmonary embolism (PE).

Methods

We queried our electronic medical record for quantitative D-dimer values obtained in all children ages 5–17 over 10 years in our 10-hospital system. Patients who had a D-dimer obtained in the evaluation of PE underwent supervised chart review to extract baseline demographics (age, sex, ethnicity), medical history, laboratory data and imaging results. PE was confirmed by imaging positive for deep vein thrombosis (DVT) or PE and excluded by imaging or no DVT or PE diagnosis within 90 days.

Results

Over a 10-year period, we identified 13 792 orders for D-dimer testing in 2554 unique patients. Chart review indicated that 526 (20.6%) unique patients had D-dimer testing performed in the evaluation of PE (Cohen’s kappa=0.95, 95% CI 0.85 to 1.0). Most D-dimers (465/526, 88%) were ordered in children aged >12 years. Of these 526 children, 34 (6.4%, 95% CI) had a criterion standard positive for new or recurrent PE. The mean D-dimer value was 2104±1394 ng/mL in the 34/34 PE+ children and 586±962 ng/mL in PE− children with a sensitivity of 34/34 (100%, 89% to 100%) and a specificity of 290/492 (58%, 54% to 63%). The area under the receiver operating characteristic curve was 0.90 ((0.9)87–0.94).

Conclusions

D-dimer is currently ordered in children for suspected PE in the emergency care setting, mostly in teenagers. The observed lower limit 95% CIs of 89% and 54% for diagnostic sensitivity and the specificity, respectively, suggest if used in patients with low-clinical probability, a normal D-dimer can safely exclude PE in children.
Longitudinal deformation bench testing using a coronary artery model: a new standard?
Authors: Choudhury Tawfiq R , Al-Saigh Salwan , Burley Steve , Li Lin , Shakhshir Nizar , Mirhosseini Nazanin , Wang Tao , Arnous Samer , Khan Muhammad A , Mamas Mamas A , Fraser Douglas G W
Published: November 2017

Objectives

To compare susceptibility of five different stent platforms with longitudinal stent deformation (LSD) using a clinically relevant bench testing model simulating both short and long malapposed lengths.

Background

Recent data suggest that design modifications to the Promus Element stent which led to the Promus Premier stent has reduced susceptibility to LSD. However, susceptibility to LSD at long malapposed lengths has not been tested. Furthermore, the mechanisms behind susceptibility to LSD are as yet unclear.

Methods

The Omega, Integrity, Multilink 8, Biomatrixand Promus Premier stent platforms were tested. The Omega, Integrity and Multilink 8 platforms were used in place of their drug-eluting equivalents. 3.5 mm stents were deployed in a stepped tube with the distal portion fixed and the proximal test section exposed. The force required to compress stents by a fixed distance at different exposed lengths was compared. Symmetrical and point loading were used.

Results

The Promus Premier was longitudinally as strong as Multilink and Integrity at a short exposed length (4 mm) but weaker, in between Omega and the other platforms, at longer exposed lengths (12 mm). As previously noted, the Omega (Promus Element) platform was significantly weaker than the other stents and Biomatrix was the strongest stent.

Conclusion

Susceptibility to LSD varies depending on length of malapposed segment when tested using a clinically relevant model as in this study. The mechanisms behind the susceptibility are likely multifactorial, including connector number, strut thickness, connector alignment and ring orientation but remain to be elucidated.
Small-strain behaviour and crushability of Ballyconnelly carbonate sand under monotonic and cyclic loading
Authors: Nanda S. , Sivakumar V. , Donohue S. , Graham S.
Published: November 2017

In various parts of the globe, carbonate sands are found at shallow sea water depth. These types of sands are very susceptible to large-scale particle breakage. Offshore structures like wind turbines and sea defences are constructed on these types of soils. From a design perspective, it is essential to assess the extent of particle breakage and the subsequent change in soil properties that occur under working load conditions. This paper presents the data obtained from a number of drained monotonic and cyclic triaxial tests on crushable carbonate sand (“Ballyconnelly sand”) in conjunction with small-strain shear stiffness (Gmax) measurements using the bender element technique. The soils were allowed to shear under three different loading patterns to understand the factors influencing the breakage of particles. The degree of crushing was quantified and analysed based on the total energy input. It was observed that, apart from applied stress, the total strain accumulation governs the amount of particle breakage. It was observed that Gmaxincreased significantly under high stress ratio. Gmaxalso increased noticeably during resting periods without any change in loading conditions as a result of creep, and subsequently during cyclic loading although at a reduced rate.
Why is there a discrepancy in shear wave velocity – cone tip resistance (Vs–qc) correlations’ trends with respect to grain size?
Authors: Karray Mourad , Hussien Mahmoud N.
Published: November 2017

Although many regression equations of cone penetration test tip resistance, qc-CPT, versus shear wave velocity, Vs, are available in the literature resulting from a substantial research effort in this topic area, the outcome of these research efforts with respect to the influence of grain size on the Vs–qc correlations is in fact inconclusive because some of the suggested relationships, in common use today, either utilize irrelevant parameters or they are rather crude approximations of the Vs–qc trend over a wide range of grain sizes. A closer examination of this effect would be important for better assessment of the reliability and limitations of the proposed correlations. This note discusses the plausible reasons for the inconsistency in the existing Vs–qc correlations with respect to grain size through a detailed comparison of two well-known discrepant correlations referring to comparable experimental and field data. This note then goes further in its contribution to the practice of geotechnics by providing some useful recommendations to be considered in the prospective construction of Vs–qc correlations, especially when particle characteristics are taken into account.
Coordinated Search for a Random Walk Target Motion
Authors: El-Hadidy Mohamed Abd Allah , Abou-Gabal Hamdy M.
Published: November 2017

This paper presents the cooperation between two searchers at the origin to find a Random Walk moving target on the real line. No information is not available about the target’s position all the time. Rather than finding the conditions that make the expected value of the first meeting time between one of the searchers and the target is finite, we show the existence of the optimal search strategy which minimizes this first meeting time. The effectiveness of this model is illustrated using a numerical example.
The linear canonical wavelet transform on some function spaces
Authors: Guo Yong , Li Bing-Zhao
Published: November 2017

It is well known that the domain of Fourier transform (FT) can be extended to the Schwartz space [Formula: see text] for convenience. As a generation of FT, it is necessary to detect the linear canonical transform (LCT) on a new space for obtaining the similar properties like FT on [Formula: see text]. Therefore, a space [Formula: see text] generalized from [Formula: see text] is introduced firstly, and further we prove that LCT is a homeomorphism from [Formula: see text] onto itself. The linear canonical wavelet transform (LCWT) is a newly proposed transform based on the convolution theorem in LCT domain. Moreover, we propose an equivalent definition of LCWT associated with LCT and further study some properties of LCWT on [Formula: see text]. Based on these properties, we finally prove that LCWT is a linear continuous operator on the spaces of [Formula: see text] and [Formula: see text].
Wavelet spectra and filtering of tropical cyclone forecast errors
Authors: Smith D. H.
Published: November 2017

Ensemble mean forecast errors during a tropical cyclone event are probed with a spherical wavelet transform constructed by the lifting scheme. Coefficient spectra and associated filtered error components are examined during the forecast, with an emphasis on feature detection, for mean sea level pressure and wind components. Leading wavelet coefficients within a reference circle centered on the estimated cyclone track demonstrate a clear affinity for local error extrema, reflecting the transform’s feature detection capacity. Compression performance of the transform is also demonstrated by truncated wavelet expansions, which exhibit contrasting behavior reflecting fundamental structural differences between the wind and pressure error fields.
The Origin of Life on Earth and the Design of Alternative Life Forms
Authors: Szostak Jack W.
Published: November 2017

To understand the origin of life on Earth, and to evaluate the potential for life on exoplanets, we must understand the pathways that lead from chemistry to biology. Recent experiments suggest that a chemically rich environment that provides the building blocks of membranes, nucleic acids and peptides, along with sources of chemical energy, could result in the emergence of replicating, evolving cells. The broad scope of synthetic chemistry suggests that it may be possible to design and construct artificial life forms based upon a very different biochemistry than that of existing biology.
Endocannabinoid-mediated potentiation of nonnociceptive synapses contributes to behavioral sensitization
Authors: Wang Yanqing , Burrell Brian D.
Published: November 2017

Endocannabinoids, such as 2-arachidonoyl glycerol (2-AG) and anandamide, can elicit long-term depression of both excitatory and inhibitory synapses. This latter effect will result in disinhibition and would therefore be expected to produce an increase in neural circuit output. However, there have been no examples directly linking endocannabinoid-mediated disinhibition to a change in a functional neurobehavioral circuit. The present study uses the well-characterized central nervous system of the medicinal leech, Hirudo verbana, to examine the functional/behavioral relevance of endocannabinoid modulation of an identified afferent synapse. Bath application of 2-AG potentiates synaptic transmission by pressure-sensitive sensory neurons (P cells) as well as the magnitude of the defensive shortening reflex elicited by P-cell stimulation. This potentiation requires activation of TRPV-like channels. Endocannabinoid/TRPV signaling was found to produce sensitization of the shortening reflex elicited by either direct stimulation of nearby nociceptive afferents (N cells) or noxious stimulation applied to skin several segments away. In both cases, heterosynaptic potentiation of P-cell synapses was observed in parallel with an increase in the magnitude of elicited shortening and both synaptic and behavioral effects were blocked by pharmacological inhibition of 2-AG synthesis or TRPV-like channel activation. Serotonin (5-HT) is known to play a critical role in sensitization in Hirudo and other animals, and the 5-HT2receptor antagonist ritanserin also blocked behavioral sensitization and the accompanying synaptic potentiation. These findings suggest a novel, endocannabinoid-mediated contribution to behavioral sensitization that may interact with known 5-HT-dependent modulatory processes.

NEW & NOTEWORTHY There is considerable interest in the analgesic potential of cannabinoids. However, there is evidence that the cannabinoid system can have both pro- and antinociceptive effects. This study examines how an endogenous cannabinoid transmitter can potentiate nonnociceptive synapses and enhance their capacity to elicit a nocifensive behavioral response.
Binocular deprivation induces both age-dependent and age-independent forms of plasticity in parvalbumin inhibitory neuron visual response properties
Authors: Feese Berquin D. , Pafundo Diego E. , Schmehl Meredith N. , Kuhlman Sandra J.
Published: November 2017

Activity of cortical inhibitory interneurons is rapidly reduced in response to monocular deprivation during the critical period for ocular dominance plasticity and in response to salient events encountered during learning. In the case of primary sensory cortex, a decrease in mean evoked firing rate of parvalbumin-positive (PV) inhibitory neurons is causally linked to a reorganization of excitatory networks following sensory perturbation. Converging evidence indicates that it is deprivation, and not an imbalance between open- and closed-eye inputs, that triggers rapid plasticity in PV neurons. However, this has not been directly tested in vivo. Using two-photon guided cell-attached recording, we examined the impact of closing both eyes for 24 h on PV neuron response properties in mouse primary visual cortex. We found that binocular deprivation induces a 30% reduction in stimulus-evoked mean firing rate and that this reduction is specific to critical period-aged mice. The number of PV neurons showing detectable tuning to orientation increased after 24 h of deprivation, and this effect was also specific to critical period-aged mice. In contrast to evoked mean firing rate and orientation tuning, measurements of trial-to-trial variability revealed that stimulus-driven decreases in variability are significantly dampened by deprivation during both the critical period and the postcritical period. These data establish that open-eye inputs are not required to drive deprivation-induced weakening of PV neuron evoked activity and that other aspects of in vivo PV neuron activity are malleable throughout life.

NEW & NOTEWORTHY Parvalbumin-positive (PV) neurons in sensory cortex are generally considered to be mediators of experience-dependent plasticity, and their plasticity is restricted to the critical period. However, in regions outside of sensory cortex, accumulating evidence demonstrates that PV neurons are plastic in adults, raising the possibility that aspects of PV response properties may be plastic throughout life. Here we identify a feature of in vivo PV neuron activity that remains plastic past the critical period.
Control of saccadic latency in a dynamic environment: allocation of saccades in time follows the matching law
Authors: Vullings Cécile , Madelain Laurent
Published: November 2017

When exploring the visual environment, one uses saccades to shift gaze and fixation to gather spatially and temporally localized information. We propose that the temporal structure of our environment should constrain the temporal allocation of saccades. Here we probe the possibility of learning to control saccadic latencies in a choice paradigm. Six participants made saccades within 80–300 ms following a target horizontally stepping by 10° between two fixed locations. For each participant we constructed two classes of latencies, “short” and “long,” using the first and last quartiles of the individual baseline distribution (e.g., [80;152] ms and [185;300] ms, respectively). We then concurrently reinforced each class in three blocked conditions across ~60 experimental sessions per participant, using different reinforcement probabilities such that the relative ratio of reinforcement rates for short vs. long latencies was 9/1, 1/9, or 1/1. Latency distributions followed the reinforcement conditions: distributions shifted toward the shorter or longer values or became strongly bimodal. Moreover, the relative rates of short over long latencies matched the relative rates of reinforcers earned for the corresponding latencies (slope up to 0.95), which reveals the ability to choose when to saccade. Our results reveal that learned contingencies considerably affect the allocation of saccades in time and are in line with recent studies on the temporal adjustment of behavior to dynamic environments. This study provides strong evidence for fine operant control of saccadic latency, supporting the hypothesis of a cost-benefit control of saccade latencies.

NEW & NOTEWORTHY Saccades may be regarded as an information-foraging behavior mostly concerned with the spatial localization of objects, yet our world is dynamic and environmental temporal regularities should also affect saccade decisions. We present behavioral data from a choice task establishing that humans can learn to choose their saccadic latencies depending on the reinforcement contingencies. This suggests a cost-benefit-based policy that takes into account the learned temporal properties of the environmental contingencies for controlling saccade triggering.
Vestibular short-latency evoked potential abolished by low-frequency noise exposure in rats
Authors: Stewart Courtney E. , Kanicki Ariane C. , Altschuler Richard A. , King W. M.
Published: November 2017

The vestibular system plays a critical role in detection of head movements and is essential for normal postural control. Because of their anatomical proximity to the cochlea, the otolith organs are selectively exposed to sound pressure and are at risk for noise overstimulation. Clinical reports suggest a link between noise exposure and balance problems, but the structural and physiological basis for this linkage is not well understood. The goal of this study was to determine the effects of low-frequency noise (LFN) on the otolith organs by correlating changes in vestibular short-latency evoked potentials (VsEPs) with changes in saccular afferent endings following noise exposure. LFN exposure transiently abolished the VsEP and reduced the number of stained calyces within the sacculus. Although some recovery of the VsEP waveform could be observed within 3 days after noise, at 3 wk recovery was only partial in most animals, consistent with a reduced number of afferents with calyceal endings. These data show that a single intense noise exposure is capable of causing a vestibular deficit that appears to mirror the synaptic deficit associated with hidden hearing loss after noise-induced cochlear injury.

NEW & NOTEWORTHY This is the first study to explore the effects of low-frequency high-intensity noise on vestibular short-latency evoked potential (VsEP) responses, which shows a linkage between attenuated noise-induced VsEPs and pathological changes to otolith organ afferents. This finding suggests a potential limitation of the VsEP for evaluation of vestibular dysfunction, since the VsEP measurement may assess the activity of a specific class rather than all afferents.
A Comparison of Screening Tools for the Early Detection of Peripheral Neuropathy in Adults with and without Type 2 Diabetes
Authors: Brown Jennifer J. , Pribesh Shana L. , Baskette Kimberly G. , Vinik Aaron I. , Colberg Sheri R.
Published: November 2017

Objective. Examine the effectiveness of the 128 Hz tuning fork, two monofilaments, and Norfolk Quality of Life Diabetic Neuropathy (QOL-DN) questionnaire as tools for the early detection of diabetic peripheral neuropathy (DPN) in overweight, obese, and inactive (OOI) adults or those who have prediabetes (PD) or type 2 diabetes (T2D). Research Design and Methods. Thirty-four adults (mean age 58.4 years ± 12.1) were divided by glycemia (10 OOI normoglycemic, 13 PD, and 11 T2D). Sural nerves were tested bilaterally with the NC-stat DPNCheck to determine sural nerve amplitude potential (SNAP) and sural nerve conduction velocity (SNCV). All other testing results were compared to SNAP and SNCV. Results. Total 1 g monofilament scores significantly correlated with SNAP values and yielded the highest sensitivity and specificity combinations of tested measures. Total QOL-DN scores negatively correlated with SNAP values, as did QOL-DN symptoms. QOL-DN activities of daily living correlated with the right SNAP, and the QOL-DN small fiber subscore correlated with SNCV. Conclusions. The 1 g monofilament and total QOL-DN are effective, low-cost tools for the early detection of DPN in OOI, PD, and T2D adults. The 128 Hz tuning fork and 10 g monofilament may assist DPN screening as a tandem, but not primary, early DPN detection screening tools.
Cytotoxicity and Proapoptotic Effects of Allium atroviolaceum Flower Extract by Modulating Cell Cycle Arrest and Caspase‐Dependent and p53‐Independent Pathway in Breast Cancer Cell Lines
Authors: Khazaei Somayeh , Abdul Hamid Roslida , Ramachandran Vasudevan , Mohd Esa Norhaizan , Pandurangan Ashok Kumar , Danazadeh Fatemeh , Ismail Patimah
Published: November 2017

Breast cancer is the second leading cause of cancer death among women and despite significant advances in therapy, it remains a critical health problem worldwide. Allium atroviolaceum is an herbaceous plant, with limited information about the therapeutic capability. We aimed to study the anticancer effect of flower extract and the mechanisms of action in MCF‐7 and MDA‐MB‐231. The extract inhibits the proliferation of the cells in a time‐ and dose‐dependent manner. The underlying mechanism involved the stimulation of S and G2/M phase arrest in MCF‐7 and S phase arrest in MDA‐MB‐231 associated with decreased level of Cdk1, in a p53‐independent pathway. Furthermore, the extract induces apoptosis in both cell lines, as indicated by the percentage of sub‐G0 population, the morphological changes observed by phase contrast and fluorescent microscopy, and increase in Annexin‐V‐positive cells. The apoptosis induction was related to downregulation of Bcl-2 and also likely to be caspase‐dependent. Moreover, the combination of the extract and tamoxifen exhibits synergistic effect, suggesting that it can complement current chemotherapy. LC‐MS analysis displayed 17 major compounds in the extract which might be responsible for the observed effects. Overall, this study demonstrates the potential applications of Allium atroviolaceum extract as an anticancer drug for breast cancer treatment.
Encapsulation of Nicardipine Hydrochloride and Release from Biodegradable Poly(D,L-lactic-co-glycolic acid) Microparticles by Double Emulsion Process: Effect of Emulsion Stability and Different Parameters on Drug Entrapment
Authors: Soomherun Nopparuj , Kreua-ongarjnukool Narumol , Chumnanvej Sorayouth , Thumsing Saowapa
Published: November 2017

Poly(D,L-lactic-co-glycolic acid) (PLGA) is an important material used in drug delivery when controlled release is required. The purpose of this research is to design and characterize PLGA microparticles (PLGA MPs) implants for the controlled release of nicardipine hydrochloride (NCH) in vitro. This study used the water-in-oil-in-water (w1/o/w2) double emulsion and solvent diffusion/evaporation approach to prepare PLGA MPs. Optimal processing conditions were found, such as polymer content, surfactant type, stabilizer concentration, inner and outer aqueous phase volumes, and stirring speed. The PLGA MPs for use as nicardipine hydrochloride (NCH) loading and release had spherical morphology, and the average diameter was smaller than 5.20±0.25 μm. The release kinetics were modeled to elucidate the possible mechanism of drug release. In vitro release studies indicated that the NCH release rate is slow and continuous. PLGA MPs are an interesting alternative drug delivery system, especially for use with NCH for biomedical applications.
Modeling of Two-Phase Flow in Rough-Walled Fracture Using Level Set Method
Authors: Dai Yunfeng , Zhou Zhifang , Lin Jin , Han Jiangbo
Published: November 2017

To describe accurately the flow characteristic of fracture scale displacements of immiscible fluids, an incompressible two-phase (crude oil and water) flow model incorporating interfacial forces and nonzero contact angles is developed. The roughness of the two-dimensional synthetic rough-walled fractures is controlled with different fractal dimension parameters. Described by the Navier–Stokes equations, the moving interface between crude oil and water is tracked using level set method. The method accounts for differences in densities and viscosities of crude oil and water and includes the effect of interfacial force. The wettability of the rough fracture wall is taken into account by defining the contact angle and slip length. The curve of the invasion pressure-water volume fraction is generated by modeling two-phase flow during a sudden drainage. The volume fraction of water restricted in the rough-walled fracture is calculated by integrating the water volume and dividing by the total cavity volume of the fracture while the two-phase flow is quasistatic. The effect of invasion pressure of crude oil, roughness of fracture wall, and wettability of the wall on two-phase flow in rough-walled fracture is evaluated.
Feature Selection and ANN Solar Power Prediction
Authors: O’Leary Daniel , Kubby Joel
Published: November 2017

A novel method of solar power forecasting for individuals and small businesses is developed in this paper based on machine learning, image processing, and acoustic classification techniques. Increases in the production of solar power at the consumer level require automated forecasting systems to minimize loss, cost, and environmental impact for homes and businesses that produce and consume power (prosumers). These new participants in the energy market, prosumers, require new artificial neural network (ANN) performance tuning techniques to create accurate ANN forecasts. Input masking, an ANN tuning technique developed for acoustic signal classification and image edge detection, is applied to prosumer solar data to improve prosumer forecast accuracy over traditional macrogrid ANN performance tuning techniques. ANN inputs tailor time-of-day masking based on error clustering in the time domain. Results show an improvement in prediction to target correlation, the R2 value, lowering inaccuracy of sample predictions by 14.4%, with corresponding drops in mean average error of 5.37% and root mean squared error of 6.83%.
Optical Design of Porous ZnO/TiO2 Films for Highly Transparent Glasses with Broadband Ultraviolet Protection
Authors: Song Han Sung , Yoo Young Jin , Lee Gil Ju , Chang Ki Soo , Song Young Min
Published: November 2017

We present a design of a bilayer porous film structure on a glass substrate for the highly efficient ultraviolet (UV) protection with high visible-light transparency. To effectively block UVB (280–315 nm) and UVA (315–400 nm), titanium dioxide (TiO2) and zinc oxide (ZnO) are used as absorbing layers having the appropriate coverages in different UV ranges with extinction coefficients, respectively. We show the process of refractive index (RI) matching by controlling porosity (Pr). Effective RIs of porous media with TiO2 and ZnO were calculated based on volume averaging theory. Transmittances of the designed films with different effective RIs were calculated using rigorous coupled-wave analysis method. Using admittance loci method, the film thickness was optimized in center wavelengths from 450 to 550 nm. The results show that the optimal design provides high UV shielding performance at both UVA and UVB with high transparency in the visible range. We also analyze electrical field distributions in each layer and angle dependency with 3D HSV color map.
Xanthine-Catechin Mixture Enhances Lithium-Induced Anti-Inflammatory Response in Activated Macrophages In Vitro
Authors: Barbisan Fernanda , Azzolin Verônica Farina , Teixeira Cibele Ferreira , Mastella Moisés Henrique , Ribeiro Euler Esteves , do Prado-Lima Pedro Antonio Schmidt , Praia Raquel de Souza , Medeiros Frescura Duarte Marta Maria , da Cruz Ivana Beatrice Mânica
Published: November 2017

Lithium (Li) is a chemical element used for treating and preventing bipolar disorder (BD) and exerts positive effects such as anti-inflammatory effects as well as undesirable side effects. These effects of Li can be influenced by interaction with some nutritional elements. Therefore, we investigated the potential effects of xanthine (caffeine and theobromine) and catechin molecules present in some food beverages broadly consumed worldwide, such as coffee and tea, on Li-induced anti-inflammatory effects. In the present study, we concomitantly exposed RAW 264.7 macrophages to Li, isolated xanthine and catechin molecules, and a xanthine-catechin mixture (XC mixture). We evaluated the effects of these treatments on cell proliferation, cell cycle progression, oxidative and antioxidant marker expression, cytokine levels, gene expression, and GSK-3β enzyme expression. Treatment with the XC mixture potentialized Li-induced anti-inflammatory effects by intensification of the following: GSK-3β inhibitory action, lowering effect on proinflammatory cytokines (IL-1β, IL-6, and TNFα), and increase in the levels of IL-10 that is an anti-inflammatory cytokine. Despite the controversial nature of caffeine consumption by BD patients, these results suggested that consumption of caffeine, in low concentrations, mixed with other bioactive molecules along with Li may be safe.
Gene Prediction in Metagenomic Fragments with Deep Learning
Authors: Zhang Shao-Wu , Jin Xiang-Yang , Zhang Teng
Published: November 2017

Next generation sequencing technologies used in metagenomics yield numerous sequencing fragments which come from thousands of different species. Accurately identifying genes from metagenomics fragments is one of the most fundamental issues in metagenomics. In this article, by fusing multifeatures (i.e., monocodon usage, monoamino acid usage, ORF length coverage, and Z-curve features) and using deep stacking networks learning model, we present a novel method (called Meta-MFDL) to predict the metagenomic genes. The results with 10 CV and independent tests show that Meta-MFDL is a powerful tool for identifying genes from metagenomic fragments.
Impact of Blood Vessel Quantity and Vascular Expression of CD133 and ICAM-1 on Survival of Glioblastoma Patients
Authors: Minajeva Ave , Kase Marju , Saretok Mikk , Adamson-Raieste Aidi , Kase Sandra , Niinepuu Kristi , Vardja Markus , Asser Toomas , Jaal Jana
Published: November 2017

Glioblastoma (GB) is the most angiogenic tumor. Nevertheless, antiangiogenic therapy has not shown significant clinical efficacy. The aim of this study was to assess blood vessel characteristics on survival of GB patients. Surgically excised GB tissues were histologically examined for overall proportion of glomeruloid microvascular proliferation (MP) and the total number of blood vessels. Also, immunohistochemical vascular staining intensities of CD133 and ICAM-1 were determined. Vessel parameters were correlated with patients’ overall survival. The survival time depended on the number of blood vessels (p=0.03) but not on the proportion of MP. Median survival times for patients with low (<median) and high (≥median) number of blood vessels were 9.0 months (95% CI: 7.5–10.5) and 12.0 months (95% CI: 9.3–14.7). Also, median survival times for patients with low (<median) and high (≥median) vascular expression level of CD133 were 9.0 months (95% CI: 8.0–10.1) and 12.0 months (95% CI: 10.3–13.7). In contrast, the staining intensity of vascular ICAM-1 did not affect survival. In multivariate analysis, the number of blood vessels emerged as an independent predictor for longer overall survival (HR: 2.4, 95% CI: 1.2–5.0, p=0.02). For success in antiangiogenic therapy, better understanding about tumor vasculature biology is needed.
Episodic Frequency of Energy-Dense Food Consumption in Women with Excessive Adiposity
Authors: Laguna-Camacho Antonio , Castro-Nava Gustavo A. , López-Arriaga Jerónimo A.
Published: November 2017

Each episode of fatty or sugary food consumption contributes to the pathophysiological alterations found in obesity. The present study estimated episodic frequency of energy-dense food (EDF) consumption in 348 adult women with excessive adiposity. Participants reported in open questions their habitual exercise and EDF consumption per week. Body fat percentage was measured using electric impedance analysis. Variations in EDF consumption by age, fat mass, and exercise levels were examined by factorial analysis of variance. The frequency of consumption of EDF was on average 12 times per week and it did not vary significantly across subgroups. It is argued that, to reduce obesity and its comorbidities, lowering a high episodic frequency of EDF consumption could be recommended in clinical settings.
Efficacy and Mechanism of Preoperative Simvastatin Therapy on Myocardial Protection after Extracorporeal Circulation
Authors: Hua Ping , Liu Jianyang , Tao Jun , Zou Rongjun , Lin Xifeng , Zhang Dingwen , Yang Songran
Published: November 2017

Background. Cardiopulmonary bypass (CPB) causes systemic inflammatory response and ischemia-reperfusion (IR) injury. Objective. To investigate the effect and mechanism of simvastatin on myocardial injury in cardiac valve surgery with CPB. Methods. One hundred thirty patients were randomly assigned to the statin group (n=65) or control group (n=65). Simvastatin was administered preoperatively and postoperatively. Duration of intensive care unit stay, duration of assisted ventilation, and left ventricular ejection fraction were recorded. Plasma was analysed for troponin T (cTnT), isoenzyme of creatine kinase (CK-MB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). Ultrastructure of the myocardium and autophagosomes were observed. Beclin-1, LC3-II/I, P62, AMPK, and the phosphorylation of AMPK in cardiomyocytes were detected. Results. Simvastatin significantly reduced the duration of assisted ventilation (P=0.030) and ejection fraction was significantly higher in the statin group (P=0.024). Simvastatin significantly reduced the levels of cTnT, CK-MB, TNF-α, IL-6, and IL-8 (P<0.05), reduced the expression of LC3-II/LC3-I and Beclin 1, and increased the expression of phosphorylation of AMPK. Simvastatin reduced the generation of autophagosomes and the ultrastructural injuries to myocardium. Conclusion. Perioperative statin therapy reduced myocardial injury by regulating myocardial autophagy and activating the phosphorylation of AMPK. The registration number of this study is ChiCTR-TRC-14005164.
Polydatin Protects Rat Liver against Ethanol‐Induced Injury: Involvement of CYP2E1/ROS/Nrf2 and TLR4/NF‐κB p65 Pathway
Authors: Huang Qiong-Hui , Xu Lie-Qiang , Liu Yu-Hong , Wu Jia-Zhen , Wu Xue , Lai Xiao-Ping , Li Yu-Cui , Su Zi-Ren , Chen Jian-Nan , Xie You-Liang
Published: November 2017

Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD) exerted antioxidant and anti‐inflammatory effects and attenuated ethanol‐induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol‐induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in the serum, suppressed the malonaldehyde (MDA) and triglyceride (TG) content and the production of reactive oxygen species (ROS), and enhanced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), catalase (CAT), andalcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH), paralleled by an improvement of histopathology alterations. The protective effect of PD against oxidative stress was probably associated with downregulation of cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2) and its target gene haem oxygenase‐1 (HO‐1). Moreover, PD inhibited the release of proinflammatory cytokines (TNF‐α, IL‐1β, and IL‐6) via downregulating toll‐like receptor 4 (TLR4) and nuclear factor kappa B (NF‐κB) p65. To conclude, PD pretreatment protects against ethanol‐induced liver injury via suppressing oxidative stress and inflammation.
Taenia crassiceps Antigens Control Experimental Type 1 Diabetes by Inducing Alternatively Activated Macrophages
Authors: Espinoza-Jiménez Arlett , De Haro Roberto , Terrazas Luis I.
Published: November 2017

Type 1 diabetes (T1D) is an autoimmune disease caused by the selective destruction of the pancreatic β-cells, causing inability to produce insulin. Proinflammatory cytokines such as IL-1β, IL-6, TNF-α, IFN-γ, IL-12, IL-17, and NO can be released by CD4 and CD8+ lymphocytes as well as by classically activated macrophages (CAMϕs), which are important in the development of T1D. Helminth infections have been shown to prevent T1D, mainly through Th2-biased responses and increased recruitment of regulatory cell populations. Previously, we have shown that Taenia crassiceps infection in mice significantly reduces hyperglycemia, insulitis, and the incidence of T1D. In this study, we determined whether T. crassiceps-derived products such as soluble (TcS) or excreted/secreted (TcES) antigens might have a beneficial influence on the development of experimental T1D. Treatment with different doses before or after induction of T1D was analyzed. Mice that were pretreated with TcS were unable to develop T1D, whereas those receiving TcES early after T1D induction displayed significantly reduced insulitis and hyperglycemia along with increased recruitment of alternatively activated macrophages (AAMϕs) and myeloid-derived suppressor cells (MDSCs). Finally, we examined the modulatory role of AAMϕs on T1D by depleting macrophages with clodronate-loaded liposomes, demonstrating that AAMϕs are key cells in T1D regulation.
High Performance Implementation of 3D Convolutional Neural Networks on a GPU
Authors: Lan Qiang , Wang Zelong , Wen Mei , Zhang Chunyuan , Wang Yijie
Published: November 2017

Convolutional neural networks have proven to be highly successful in applications such as image classification, object tracking, and many other tasks based on 2D inputs. Recently, researchers have started to apply convolutional neural networks to video classification, which constitutes a 3D input and requires far larger amounts of memory and much more computation. FFT based methods can reduce the amount of computation, but this generally comes at the cost of an increased memory requirement. On the other hand, the Winograd Minimal Filtering Algorithm (WMFA) can reduce the number of operations required and thus can speed up the computation, without increasing the required memory. This strategy was shown to be successful for 2D neural networks. We implement the algorithm for 3D convolutional neural networks and apply it to a popular 3D convolutional neural network which is used to classify videos and compare it to cuDNN. For our highly optimized implementation of the algorithm, we observe a twofold speedup for most of the 3D convolution layers of our test network compared to the cuDNN version.
Multiobjective Location Model Design Based on Government Subsidy in the Recycling of CDW
Authors: Fu Peihua , Li Hongxuan , Wang Xiaohua , Luo Juanjuan , Zhan Sha-lei , Zuo Chao
Published: November 2017

With the generation of a large amount of construction and demolition waste (CDW), many scholars have recently paid more attention to the recycling of CDW. In this paper, we design a classification recycling method based on the degree of CDW availability in the recycling of CDW. Considering the important role of the government in reverse logistics, a model of reverse logistics network based on the trade‐off between cost and recycling rate is put forward, which is subject to government subsidy. The model includes the location of classification processing center and ensures the best route of transportation. Then, the improved particle swarm optimization algorithm is applied to solve the model to get Pareto frontier by transforming it into a multiobjective integer‐programming problem. As a case study, the results of the statistical modeling used in this study indicate the feasibility of the model. Finally, according to the sensitivity analysis of government’s subsidy, we evaluate the effectiveness of this program and its applicability.