bluuebunny/crossref_metadata_2025 huggingface dataset:
Enterococcus faecalis Demonstrates Pathogenicity through Increased Attachment in anEx VivoPolymicrobial Pulpal Infection
Authors: Nishio Ayre Wayne , Melling Genevieve , Cuveillier Camille , Natarajan Madhan , Roberts Jessica L. , Marsh Lucy L. , Lynch Christopher D. , Maillard Jean-Yves , Denyer Stephen P. , Sloan Alastair J.
Published: February 2018

This study investigated the host response to a polymicrobial pulpal infection consisting ofStreptococcus anginosusandEnterococcus faecalis, bacteria commonly implicated in dental abscesses and endodontic failure, using a validatedex vivorat tooth model. Tooth slices were inoculated with planktonic cultures ofS. anginosusorE. faecalisalone or in coculture atS. anginosus/E. faecalisratios of 50:50 and 90:10. Attachment was semiquantified by measuring the area covered by fluorescently labeled bacteria. Host response was established by viable histological cell counts, and inflammatory response was measured using reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemistry. A significant reduction in cell viability was observed for single and polymicrobial infections, with no significant differences between infection types (∼2,000 cells/mm2for infected pulps compared to ∼4,000 cells/mm2for uninfected pulps).E. faecalisdemonstrated significantly higher levels of attachment (6.5%) thanS. anginosusalone (2.3%) and mixed-species infections (3.4% for 50:50 and 2.3% for 90:10), with a remarkable affinity for the pulpal vasculature. Infections withE. faecalisdemonstrated the greatest increase in tumor necrosis factor alpha (TNF-α) (47.1-fold forE. faecalis, 14.6-fold forS. anginosus, 60.1-fold for 50:50, and 25.0-fold for 90:10) and interleukin 1β (IL-1β) expression (54.8-fold forE. faecalis, 8.8-fold forS. anginosus, 54.5-fold for 50:50, and 39.9-fold for 90:10) compared to uninfected samples. Immunohistochemistry confirmed this, with the majority of inflammation localized to the pulpal vasculature and odontoblast regions. Interestingly,E. faecalissupernatant and heat-killedE. faecalistreatments were unable to induce the same inflammatory response, suggestingE. faecalispathogenicity in pulpitis is linked to its greater ability to attach to the pulpal vasculature.
Electron Transfer to Nitrogenase in Different Genomic and Metabolic Backgrounds
Authors: Poudel Saroj , Colman Daniel R. , Fixen Kathryn R. , Ledbetter Rhesa N. , Zheng Yanning , Pence Natasha , Seefeldt Lance C. , Peters John W. , Harwood Caroline S. , Boyd Eric S.
Published: February 2018

Nitrogenase catalyzes the reduction of dinitrogen (N
2
) using low-potential electrons from ferredoxin (Fd) or flavodoxin (Fld) through an ATP-dependent process. Since its emergence in an anaerobic chemoautotroph, this oxygen (O
2
)-sensitive enzyme complex has evolved to operate in a variety of genomic and metabolic backgrounds, including those of aerobes, anaerobes, chemotrophs, and phototrophs. However, whether pathways of electron delivery to nitrogenase are influenced by these different metabolic backgrounds is not well understood. Here, we report the distribution of homologs of Fds, Flds, and Fd-/Fld-reducing enzymes in 359 genomes of putative N
2
fixers (diazotrophs). Six distinct lineages of nitrogenase were identified, and their distributions largely corresponded to differences in the host cells' ability to integrate O
2
or light into energy metabolism. The predicted pathways of electron transfer to nitrogenase in aerobes, facultative anaerobes, and phototrophs varied from those in anaerobes at the levels of Fds/Flds used to reduce nitrogenase, the enzymes that generate reduced Fds/Flds, and the putative substrates of these enzymes. Proteins that putatively reduce Fd with hydrogen or pyruvate were enriched in anaerobes, while those that reduce Fd with NADH/NADPH were enriched in aerobes, facultative anaerobes, and anoxygenic phototrophs. The energy metabolism of aerobic, facultatively anaerobic, and anoxygenic phototrophic diazotrophs often yields reduced NADH/NADPH that is not sufficiently reduced to drive N
2
reduction. At least two mechanisms have been acquired by these taxa to overcome this limitation and to generate electrons with potentials capable of reducing Fd. These include the bifurcation of electrons or the coupling of Fd reduction to reverse ion translocation.

IMPORTANCE
Nitrogen fixation supplies fixed nitrogen to cells from a variety of genomic and metabolic backgrounds, including those of aerobes, facultative anaerobes, chemotrophs, and phototrophs. Here, using informatics approaches applied to genomic data, we show that pathways of electron transfer to nitrogenase in metabolically diverse diazotrophic taxa have diversified primarily in response to host cells' acquired ability to integrate O
2
or light into their energy metabolism. The acquisition of two key enzyme complexes enabled aerobic and facultatively anaerobic phototrophic taxa to generate electrons of sufficiently low potential to reduce nitrogenase: the bifurcation of electrons via the Fix complex or the coupling of Fd reduction to reverse ion translocation via the
Rhodobacter
nitrogen fixation (Rnf) complex.
Long Noncoding RNA uc002yug.2 Activates HIV-1 Latency through Regulation of mRNA Levels of Various RUNX1 Isoforms and Increased Tat Expression
Authors: Huan Chen , Li Zhaolong , Ning Shanshan , Wang Hong , Yu Xiao-Fang , Zhang Wenyan
Published: February 2018

The HIV-1 reservoir is a major obstacle to complete eradication of the virus. Although many proteins and RNAs have been characterized as regulators in HIV-1/AIDS pathogenesis and latency, only a few long noncoding RNAs (lncRNAs) have been shown to be closely associated with HIV-1 replication and latency. In this study, we demonstrated that lncRNA uc002yug.2 plays a key role in HIV-1 replication and latency. uc002yug.2 potentially enhances HIV-1 replication, long terminal repeat (LTR) activity, and the activation of latent HIV-1 in both cell lines and CD4
+
T cells from patients. Further investigation revealed that uc002yug.2 activates latent HIV-1 through downregulating RUNX1b and -1c and upregulating Tat protein expression. The accumulated evidence supports our model that the Tat protein has the key role in the uc002yug.2-mediated regulatory effect on HIV-1 reactivation. Moreover, uc002yug.2 showed an ability to activate HIV-1 similar to that of suberoylanilide hydroxamic acid or phorbol 12-myristate 13-acetate using latently infected cell models. These findings improve our understanding of lncRNA regulation of HIV-1 replication and latency, providing new insights into potential targeted therapeutic interventions.

IMPORTANCE
The latent viral reservoir is the primary obstacle to curing HIV-1 disease. To date, only a few lncRNAs, which play major roles in various biological processes, including viral infection, have been identified as regulators in HIV-1 latency. In this study, we demonstrated that lncRNA uc002yug.2 is important for both HIV-1 replication and activation of latent viruses. Moreover, uc002yug.2 was shown to activate latent HIV-1 through regulating alternative splicing of RUNX1 and increasing the expression of Tat protein. These findings highlight the potential merit of targeting lncRNA uc002yug.2 as an activating agent for latent HIV-1.
Enhanced Human-Type Receptor Binding by Ferret-Transmissible H5N1 with a K193T Mutation
Authors: Peng Wenjie , Bouwman Kim M. , McBride Ryan , Grant Oliver C. , Woods Robert J. , Verheije Monique H. , Paulson James C. , de Vries Robert P.
Published: February 2018

All human influenza pandemics have originated from avian influenza viruses. Although multiple changes are needed for an avian virus to be able to transmit between humans, binding to human-type receptors is essential. Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets. Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding. We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer. In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193. Thus, we hypothesized that a K193T mutation would improve binding to branched N-linked receptors. Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.

IMPORTANCE
Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans. Fortunately, H5N1 viruses do not transmit between humans because they do not bind to human-type receptors. In 2012, three seminal papers have shown how these viruses can be engineered to transmit between ferrets, the human model for influenza virus infection. Receptor binding, among others, was changed, and the viruses now bind to human-type receptors. Receptor specificity was still markedly different compared to that of human influenza viruses. Here we report an additional mutation in ferret-transmissible H5N1 that increases human-type receptor binding. K193T seems to be a common receptor specificity determinant, as it increases human-type receptor binding in multiple subtypes. The K193T mutation can now be used as a marker during surveillance of emerging viruses to assess potential pandemic risk.
Neurofilament light chain and tau concentrations are markedly increased in the serum of patients with sporadic Creutzfeldt-Jakob disease, and tau correlates with rate of disease progression
Authors: Thompson Andrew Geoffrey Bourne , Luk Connie , Heslegrave Amanda J , Zetterberg Henrik , Mead Simon H , Collinge John , Jackson Graham S
Published: February 2018

Objectives

A blood-based biomarker of neuronal damage in sporadic Creutzfeldt-Jakob disease (sCJD) will be extremely valuable for both clinical practice and research aiming to develop effective therapies.

Methods

We used an ultrasensitive immunoassay to measure two candidate biomarkers, tau and neurofilament light (NfL), in serum from patients with sCJD and healthy controls. We tested longitudinal sample sets from six patients to investigate changes over time, and examined correlations with rate of disease progression and associations with known phenotype modifiers.

Results

Serum concentrations of both tau and NfL were increased in patients with sCJD. NfL distinguished patients from controls with 100% sensitivity and 100% specificity. Tau did so with 91% sensitivity and 83% specificity. Both tau and NfL appeared to increase over time in individual patients, particularly in those with several samples tested late in their disease. Tau, but not NfL, was positively correlated with rate of disease progression, and was particularly increased in patients homozygous for methionine at codon 129 of PRNP.

Conclusions

These findings independently replicate other recent studies using similar methods and offer novel insights. They show clear promise for these blood-based biomarkers in prion disease. Future work should aim to fully establish their potential roles for monitoring disease progression and response to therapies.
Does HIV pre-exposure prophylaxis use lead to a higher incidence of sexually transmitted infections? A case-crossover study of men who have sex with men in Los Angeles, California
Authors: Beymer Matthew R , DeVost Michelle A , Weiss Robert E , Dierst-Davies Rhodri , Shover Chelsea L , Landovitz Raphael J , Beniasians Corinne , Talan Ali J , Flynn Risa P , Krysiak Robyn , McLaughlin Kayla , Bolan Robert K
Published: February 2018

Background

Pre-exposure prophylaxis (PrEP) is an effective method for reducing HIV incidence among at-risk populations. However, concerns exist over the potential for an increase in STIs following PrEP initiation. The objective of this study is to compare the STI incidence before and after PrEP initiation within subjects among a cohort of men who have sex with men in Los Angeles, California.

Methods

The present study used data from patients who initiated PrEP services at the Los Angeles LGBT Center between October 2015 and October 2016 (n=275). A generalised linear mixed model was used with a case-crossover design to determine if there was a significant difference in STIs within subjects 365 days before (before-PrEP period) and 365 days after PrEP initiation (after-PrEP period).

Results

In a generalised linear mixed model, there were no significant differences in urethral gonorrhoea (P=0.95), rectal gonorrhoea (P=0.33), pharyngeal gonorrhoea (P=0.65) or urethral chlamydia (P=0.71) between periods. There were modest increases in rectal chlamydia (rate ratio (RR) 1.83; 95% CI 1.13 to 2.98; P=0.01) and syphilis diagnoses (RR 2.97; 95% CI 1.23 to 7.18; P=0.02).

Conclusions

There were significant increases in rectal chlamydia and syphilis diagnoses when comparing the periods directly before and after PrEP initiation. However, only 28% of individuals had an increase in STIs between periods. Although risk compensation appears to be present for a segment of PrEP users, the majority of individuals either maintain or decrease their sexual risk following PrEP initiation.
Myocardial depression in a calf with septic shock
Authors: Naseri Amir , Turgut Kursad , Sen Ismail , Ider Merve , Akar Aybars
Published: February 2018

A 10‐day‐old, 32‐kg Simmental heifer calf was presented with a 2‐day history of diarrhoea and anorexia. The diagnosis of septic shock was based on the presence of severe sepsis and hypotension that could not be reversed with fluid resuscitation. Echocardiographic findings included a hypokinetic left ventricle with decreased left ventricle ejection fraction, stroke volume and cardiac index. The end‐systolic volume index (ESVI) was elevated to 36.14 ml/m2 and a depressed end‐diastolic volume index (EDVI) (51.31 ml/m2). Left ventricular depression was normalised 24 hours after resuscitation. It was concluded that myocardial depression could be reversible in the calf with septic shock; however, according to the postresuscitation echocardiographic findings, a decreased ESVI suggests vasomotor dysregulation and a decreased EDVI suggests alterations in vascular permeability. These were the major implications of sepsis and resulted in multiple organ dysfunction and death.
Weierstrass points of order three on smooth quartic curves
Authors: Kamel Alwaleed , Elshareef Waleed Khaled
Published: February 2018

In this paper, we study the [Formula: see text]-Weierstrass points on smooth projective plane quartic curves and investigate their geometry. Moreover, we use a technique to determine in a very precise way the distribution of such points on any smooth projective plane quartic curve. We also give a variety of examples that illustrate and enrich the subject.
Weighted Castelnuovo–Mumford regularity and weighted global generation
Authors: Malaspina F. , Sankaran G. K.
Published: February 2018

We introduce and study a notion of Castelnuovo–Mumford regularity suitable for weighted projective spaces.
V-Rings versus Σ-V rings
Authors: Davvaz Bijan , Nazemian Zahra , Srivastava Ashish K.
Published: February 2018

This paper studies similarities and differences between the classes of rings over which each simple module is injective and rings over which each simple module is [Formula: see text]-injective. The rings in the former class are called [Formula: see text]-rings and the rings in the latter class are called [Formula: see text]-[Formula: see text] rings. We point out some inaccuracies in the literature on [Formula: see text]-rings and raise some questions.
Quantum cost optimized design of 4-bit reversible universal shift register using reduced number of logic gate
Authors: Maity H. , Biswas A. , Bhattacharjee A. K. , Pal A.
Published: February 2018

In this paper, we have proposed the design of quantum cost (QC) optimized 4-bit reversible universal shift register (RUSR) using reduced number of reversible logic gates. The proposed design is very useful in quantum computing due to its low QC, less no. of reversible logic gate and less delay. The QC, no. of gates, garbage outputs (GOs) are respectively 64, 8 and 16 for proposed work. The improvement of proposed work is also presented. The QC is 5.88% to 70.9% improved, no. of gate is 60% to 83.33% improved with compared to latest reported result.
Collapse and revival of entanglement between qubits coupled to a spin coherent state
Authors: Bahari Iskandar , Spiller Timothy P. , Dooley Shane , Hayes Anthony , McCrossan Francis
Published: February 2018

We extend the study of the Jayne–Cummings (JC) model involving a pair of identical two-level atoms (or qubits) interacting with a single mode quantized field. We investigate the effects of replacing the radiation field mode with a composite spin, comprising [Formula: see text] qubits, or spin-1/2 particles. This model is relevant for physical implementations in superconducting circuit QED, ion trap and molecular systems. For the case of the composite spin prepared in a spin coherent state, we demonstrate the similarities of this set-up to the qubits-field model in terms of the time evolution, attractor states and in particular the collapse and revival of the entanglement between the two qubits. We extend our analysis by taking into account an effect due to qubit imperfections. We consider a difference (or “mismatch”) in the dipole interaction strengths of the two qubits, for both the field mode and composite spin cases. To address decoherence due to this mismatch, we then average over this coupling strength difference with distributions of varying width. We demonstrate in both the field mode and the composite spin scenarios that increasing the width of the “error” distribution increases suppression of the coherent dynamics of the coupled system, including the collapse and revival of the entanglement between the qubits.
Severe hypoglycemia-induced sudden death is mediated by both cardiac arrhythmias and seizures
Authors: Reno Candace M. , Skinner Allie , Bayles Justin , Chen Y. Stefanie , Daphna-Iken Dorit , Fisher Simon J.
Published: February 2018

We previously demonstrated that insulin-induced severe hypoglycemia-associated sudden death is largely mediated by fatal cardiac arrhythmias. In the current study, a pharmacological approach was taken to explore the potential contribution of hypoglycemic seizures and the sympathoadrenergic system in mediating severe hypoglycemia-associated sudden death. Adult Sprague-Dawley rats were randomized into one of four treatment groups: 1) saline (SAL), 2) anti-arrhythmic (β1 blocker atenolol), 3) antiseizure (levetiracetam), and 4) combination antiarrhythmic and antiseizure (β1 Blocker+Levetiracetam). All rats underwent hyperinsulinemic severe hypoglycemic clamps for 3.5 h. When administered individually during severe hypoglycemia, β1 blocker reduced 2nd and 3rd degree heart block by 7.7- and 1.6-fold, respectively, and levetiracetam reduced seizures 2.7-fold, but mortality in these groups did not decrease. However, it was combined treatment with both β1 blocker and levetiracetam that remarkably reduced seizures and completely prevented respiratory arrest, while also eliminating 2nd and 3rd degree heart block, leading to 100% survival. These novel findings demonstrate that, in mediating sudden death, hypoglycemia elicits two distinct pathways (seizure-associated respiratory arrest and arrhythmia-associated cardiac arrest), and therefore, prevention of both seizures and cardiac arrhythmias is necessary to prevent severe hypoglycemia-induced mortality.
Delayed Appearance of a Traumatic Fetal Intracranial Hemorrhage
Authors: Yamasato Kelly , Kurata Nicole , Towner Dena
Published: February 2018

Background. Fetal intracranial injury is a potentially devastating sequelae of maternal trauma, but there is little guidance regarding fetal evaluation in this setting. Case. A 23-year-old woman at 27-week gestation was admitted after a high-speed motor vehicle accident. The initial obstetrical ultrasound was unremarkable, but persistently minimal fetal heart rate variability was observed. Ultrasound on day 3 after the accident showed an intracranial hyperechogenic lesion and subdural fluid collection. The neonate, following an uneventful birth at 39 weeks, had seizures and abnormal muscle tone. MRI was consistent with in utero intracranial hemorrhage. Conclusion. Serial fetal imaging following maternal trauma, particularly when accompanied by abnormal fetal heart rate tracings, should be considered when fetal injury is a concern, even in the setting of a normal initial ultrasound.
Enhancing Antidepressant Effect of Poloxamer/Chitosan Thermosensitive Gel Containing Curcumin-Cyclodextrin Inclusion Complex
Authors: Zhang Ye
Published: February 2018

Poor solubility and bioavailability are limiting factors for the clinical application of curcumin. This study seeks to develop poloxamer/chitosan thermosensitive gel containing curcumin-cyclodextrin inclusion complex with enhanced brain bioavailability and antidepressant effect. The optimized gel had shorter gelation time and produced sustained release in vitro characterized with non-Fickian diffusion. Pharmacokinetics of gel were evaluated using male Sprague-Dawley rats receiving 240 μg/kg of curcumin and curcumin-cyclodextrin inclusion complex through intranasal administration, compared against a control group receiving intravenous curcumin (240 μg/kg). The intranasal administration of gel provided sustained release by maintaining plasma concentrations of curcumin above 21.27 ± 3.26 ng/mL for up to 8 h. Compared to intranasal administration of the inclusion complex, AUC0–8 h of curcumin from thermoreversible gel in plasma and hippocampus was increased 1.62- and 1.28-fold, respectively. The gel exhibited superior antidepressant activity in mice. The findings reported here suggested that the clinical application of curcumin can be better exploited through an intranasal administration of the thermosensitive gel.
Morphological and Molecular Identification of the Causal Agent of Anthracnose Disease of Avocado in Kenya
Authors: Kimaru S. K. , Monda E. , Cheruiyot R. C. , Mbaka J. , Alakonya A.
Published: February 2018

Anthracnose disease of avocado contributes to a huge loss of avocado fruits due to postharvest rot in Kenya. The causal agent of this disease has not been clear but presumed to beColletotrichum gloeosporioidesas reported in other regions where avocado is grown. The fungus mainly infects fruits causing symptoms such as small blackish spots, “pepper spots,” and black spots with raised margin which coalesce as infection progresses. Due to economic losses associated with the disease and emerging information of other species of fungi as causal agents of the disease, this study was aimed at identifying causal agent(s) of the disease. A total of 80 fungal isolates were collected from diseased avocado fruits in Murang’a County, the main avocado growing region in Kenya. Forty-six isolates were morphologically identified asColletotrichumspp. based on their cultural characteristics, mainly whitish, greyish, and creamish colour and cottony/velvety mycelia on the top side of the culture and greyish cream with concentric zonation on the reverse side. Their spores were straight with rounded end and nonseptate. Thirty-four isolates were identified asPestalotiopsisspp. based on their cultural characteristics: whitish grey mycelium with black fruiting structure on the upper side and greyish black one on the lower side and septate spores with 3-4 septa and 2 or 3 appendages at one end. Further molecular studies using ITS indicatedColletotrichum gloeosporioides,Colletotrichum boninense, andPestalotiopsis microsporaas the causal agents of anthracnose disease in avocado. However, with this being the first report, there is a need to conduct further studies to establish whether there is coinfection or any interaction thereof.
Endovascular Embolization of Spontaneous Iliopsoas Hematoma: First Experience with Squidperi
Authors: Torcia Pierluca , Squarza Silvia , Rossi Umberto G. , Rigamonti Paolo , Pescatori Lorenzo Carlo , Damiani Giovanni , Cariati Maurizio
Published: February 2018

A 79-year-old man, suffering from atrial fibrillation and on anticoagulation therapy, was admitted at the emergency department of our institution because of a worsening respiratory insufficiency. After a diagnostic work-up, he was found to suffer from pneumonia, and antibiotic therapy was settled. He was kept under observation for his pulmonary conditions but, within a week, he developed a spontaneous iliopsoas hematoma, due to a sudden dysregulation of anticoagulation therapy subsequent to new in-hospital treatments. An endovascular approach was attempted and the bleeding vessels were embolized with a new liquid agent, named Squidperi (Emboflu, Switzerland). Complete exclusion of the diseased vessels was obtained and no complications occurred after the procedure. We conclude that Squidperi can be considered as an option for treatment of spontaneous iliopsoas hematomas.
Higher Income and Integration into the Workforce Are the Main Factors Associated with Quality of Life in Acromegalic Patients in Northeastern Brazil
Authors: GuimarãesSá Adriana Maria , Ferreira Pedro Antônio Muniz , Souza Marinilde Teles , Nascimento Gilvan Cortês , da Silva Pereira Damianse Sabrina , de Carvalho Rocha Viviane Chaves , dos Santos Faria Manuel , de Souza Paiva Ferreira Adalgisa
Published: February 2018

Objective. To identify the factors associated with quality of life in patients with acromegaly with follow-up at the referral service in neuroendocrinology of the state of Maranhão, northeast Brazil. Methods. The Acromegaly Quality of Life Questionnaire (Acro-QoL) was used. Factors independently associated with quality of life were identified using multivariate linear regression, with p values < 0.05 considered significant. Results. The multivariate linear regression analysis indicated a positive association between being integrated into the job market and quality of life scores in the overall domain (β=0.288, p=0.003), psychological domain (β=0.291, p=0.032), and personal relationship domain (β=0.314, p=0.019). We also observed a positive association with income and the quality of life scores in all domains as follows: overall domain (β=0.037, p=0.003), physical domain (β=0.988, p=0.001), psychological domain (β=0.342, p=0.008), physical appearance domain (β=0.270, p=0.049), and personal relationship domain (β=0.315, p=0.012). Conclusion. For patients with acromegaly living in one of the least developed regions of Brazil, integration into the job market and a higher income were associated with a better quality of life.
Heterogeneous Rock Simulation Using DIP‐Micromechanics‐Statistical Methods
Authors: Molladavoodi H. , RahimiRezaei Y.
Published: February 2018

Rock as a natural material is heterogeneous. Rock material consists of minerals, crystals, cement, grains, and microcracks. Each component of rock has a different mechanical behavior under applied loading condition. Therefore, rock component distribution has an important effect on rock mechanical behavior, especially in the postpeak region. In this paper, the rock sample was studied by digital image processing (DIP), micromechanics, and statistical methods. Using image processing, volume fractions of the rock minerals composing the rock sample were evaluated precisely. The mechanical properties of the rock matrix were determined based on upscaling micromechanics. In order to consider the rock heterogeneities effect on mechanical behavior, the heterogeneity index was calculated in a framework of statistical method. A Weibull distribution function was fitted to the Young modulus distribution of minerals. Finally, statistical and Mohr–Coulomb strain‐softening models were used simultaneously as a constitutive model in DEM code. The acoustic emission, strain energy release, and the effect of rock heterogeneities on the postpeak behavior process were investigated. The numerical results are in good agreement with experimental data.
Targeting Polo-like Kinase 1 by a Novel Pyrrole-Imidazole Polyamide–Hoechst Conjugate Suppresses Tumor Growth In Vivo
Authors: Liu Ke , Fang Lijing , Sun Haiyan , Pan Zhengyin , Zhang Jianchao , Chen Juntao , Shao Ximing , Wang Wei , Tan Yuanyan , Ding Zhihao , Ao Lijiao , Wu Chunlei , Liu Xiaoqi , Li Huashun , Wang Rui , Su Wu , Li Hongchang
Published: February 2018

The serine/threonine kinase Polo-like kinase 1 (Plk1) plays a pivotal role in cell proliferation and has been validated as a promising anticancer drug target. However, very limited success has been achieved in clinical applications using existing Plk1 inhibitors, due to lack of sufficient specificity toward Plk1. To develop a novel Plk1 inhibitor with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide–Hoechst conjugate, PIP3, targeted to specific DNA sequence in the PLK1 promoter. PIP3 could specifically inhibit the cell cycle–regulated Plk1 expression and consequently retard tumor cell growth. Cancer cells treated with PIP3 exhibited severe mitotic defects and increased apoptosis, whereas normal cells were not affected by PIP3 treatment. Furthermore, subcutaneous injection of PIP3 into mice bearing human cancer xenografts induced significant tumor growth suppression with low host toxicity. Therefore, PIP3 exhibits the potential as an effective agent for targeted cancer therapy. Mol Cancer Ther; 17(5); 988–1002. ©2018 AACR.
Inhibition of the Histone H3K27 Demethylase UTX Enhances Tumor Cell Radiosensitivity
Authors: Rath Barbara H. , Waung Isabella , Camphausen Kevin , Tofilon Philip J.
Published: February 2018

The processes mediating the repair of DNA double-strand breaks (DSB) are critical determinants of radiosensitivity and provide a source of potential targets for tumor radiosensitization. Among the events required for efficient DSB repair are a variety of post-translational histone modifications, including methylation. Because trimethylation of histone H3 on lysine 27 (H3K27me3) has been associated with chromatin condensation, which can influence DSB repair, we determined the effects of radiation on H3K27me3 levels in tumor and normal cell lines. Irradiation of tumor cells resulted in a rapid loss of H3K27me3, which was prevented by the siRNA-mediated knockdown of the H3K27 demethylase UTX. Knockdown of UTX also enhanced the radiosensitivity of each tumor cell line. Treatment of tumor cells with the H3K27 demethylase inhibitor GSKJ4 immediately before irradiation prevented the radiation-induced decrease in H3K27me3 and enhanced radiosensitivity. As determined by neutral comet analysis and γH2AX expression, this GSKJ4 treatment protocol inhibited the repair of radiation-induced DSBs. Consistent with in vitro results, treatment of mice bearing leg tumor xenografts with GSKJ4 significantly enhance radiation-induce tumor growth delay. In contrast with results generated from tumor cell lines, radiation had no effect on H3K27me3 levels in normal fibroblast cell lines and GSKJ4 did not enhance their radiosensitivity. These data suggest that H3K27me3 demethylation contributes to DSB repair in tumor cells and that UTX, the demethylase responsible, provides a target for selective tumor cell radiosensitization. Mol Cancer Ther; 17(5); 1070–8. ©2018 AACR.
Physicochemical Properties of Magnetic Nanoparticles: Implications for Biomedical Applications In Vitro and In Vivo
Authors: Belanova Anna A. , Gavalas Nikos , Makarenko Yuriy M. , Belousova Mariya M. , Soldatov Alexander V. , Zolotukhin Peter V.
Published: February 2018

Magnetic and superparamagnetic iron oxide nanoparticles are emerging as promising candidates for various applications in biology and medicine, and especially in oncology. These applications, however, require that a specific set of physical, chemical, and biological properties be combined in a given sample of nanoparticles for them to act as intended. Some of these properties are fundamental: They strictly determine the nanoparticles' behavior both in vitro and in vivo. These properties are the charge, the solution stability and zeta potential, and the coating of the nanoparticles. A certain combination of these properties may satisfy a researcher in an in vitro study, but other properties should also be considered when in vivo applications are planned. For in vivo experiments, additional determinants of the quality of nanoparticles are their size, shape, modifications with targeting moieties, and degradation/excretion pathways. All these properties are in the focus of the present review.
The Association between Serum 25-Hydroxyvitamin D and Cancer Risk: Results from the Prospective KORA F4 Study
Authors: Cheney Catherine P. , Thorand Barbara , Huth Cornelia , Berger Katja , Peters Annette , Seifert-Klauss Vanadin , Kiechle Marion , Strauch Konstantin , Quante Anne S.
Published: February 2018

Background: Many studies have examined the relationship between vitamin D and specific types of cancer with inconsistent results. Furthermore, to date, no observational studies have demonstrated a clear relationship between vitamin D and total cancer risk. Methods: We analyzed data from a population-based prospective cohort study including 2,003 initially cancer-free participants from the KORA F4 study with baseline serum 25-hydroxyvitamin D (25(OH)D) measurements (surveyed between 2006 and 2008). We used Cox proportional hazard models to assess the association between 25(OH)D levels and incident cancer risk. Results: Within a follow-up period of 7 years, 69 of the participants developed cancer. Overall, we observed no significant relationship between serum 25(OH)D levels and cancer risk. The hazard ratio (HR) per 1 ng/ml increase in 25 (OH)D for this relationship was 1.00 (95% confidence interval (CI) 0.97-1.04) adjusting for age, sex, body mass index, and season of blood draw. This was also true in subgroup analysis for prostate cancer (HR 0.95, 95% CI 0.88-1.03), breast cancer (HR 1.03, 95% CI 0.97-1.09), and colorectal cancer (HR 0.97, 95% CI 0.88-1.07). Conclusion: Our study found no protective effect of 25(OH)D against developing cancer. However, studies with more participants and additional measurements of 25(OH)D are still needed to accurately clarify the relationship between 25(OH)D and total cancer risk.
Enhanced Delignification of Lignocellulosic Biomass by Recombinant Fungus Phanerochaete chrysosporium Overexpressing Laccases and Peroxidases
Authors: Coconi Linares Nancy , Fernández Francisco , Loske Achim M. , Gómez-Lim Miguel A.
Published: February 2018

Ligninolytic enzyme production and lignin degradation are typically the rate-limiting steps in the biofuel industry. To improve the efficiency of simultaneous bio-delignification and enzyme production, Phanerochaete chrysosporium was transformed by shock wave-induced acoustic cavitation to co-overexpress 3 peroxidases and 1 laccase and test it on the degradation of sugarcane bagasse and wheat bran. Lignin depolymerization was enhanced by up to 25% in the presence of recombinant fungi in comparison with the wild-type strain. Sugar release on lignocellulose was 2- to 6-fold higher by recombinant fungi as compared with the control. Wheat bran ostensibly stimulated the production of ligninolytic enzymes. The highest peroxidase activity from the recombinant strains was 2.6-fold higher, whereas the increase in laccase activity was 4-fold higher in comparison to the control. The improvement of lignin degradation was directly proportional to the highest peroxidase and laccase activity. Because various phenolic compounds released during lignocellulose degradation have proven to be toxic to cells and to inhibit enzyme activity, a significant reduction (over 40%) of the total phenolic content in the samples treated with recombinant strains was observed. To our knowledge, this is the first report that engineering P. chrysosporium enhances biodegradation of lignocellulosic biomass.
Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome
Authors: Thomas Anub Mathew , Schjalm Camilla , Nilsson Per H. , Lindenskov Paal H.H. , Rørtveit Runa , Solberg Rønnaug , Saugstad Ola Didrik , Berglund Magnus M. , Strömberg Patrik , Lau Corinna , Espevik Terje , Jansen Johan Høgset , Castellheim Albert , Mollnes Tom Eirik , Barratt-Due Andreas
Published: February 2018

Background: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a piglet MAS model. Additionally, we showed ex vivo that meconium-induced inflammation was dependent on complement and Toll-like receptors. Objectives: To assess the efficacy of the combined inhibition of complement (C5) and CD14 on systemic inflammation induced in a forceful piglet MAS model. Methods: Thirty piglets were randomly allocated to a treatment group receiving the C5-inhibitor SOBI002 and anti-CD14 (n = 15) and a nontreated control group (n = 15). MAS was induced by intratracheal meconium instillation, and the piglets were observed for 5 h. Complement, cytokines, and myeloperoxidase (MPO) were measured by ELISA. Results: SOBI002 ablated C5 activity and the formation of the terminal complement complex in vivo. The combined inhibition attenuated the inflammasome cytokines IL-1β and IL-6 by 60 (p = 0.029) and 44% (p = 0.01), respectively, and also MPO activity in the bronchoalveolar fluid by 42% (p = 0.017). Ex vivo experiments in human blood revealed that the combined regimen attenuated meconium-induced MPO release by 64% (p = 0.008), but there was only a negligible effect with single inhibition, indicating a synergic cross-talk between the key molecules C5 and CD14. Conclusion: Combined inhibition of C5 and CD14 attenuates meconium-induced inflammation in vivo and this could become a future therapeutic regimen for MAS.
Short-Term Effects of a Multimodal 3-Week Inpatient Pulmonary Rehabilitation Programme for Patients with Sarcoidosis: The ProKaSaRe Study
Authors: Lingner Heidrun , Buhr-Schinner Heike , Hummel Stefan , van der Meyden Jochen , Grosshennig Anika , Nowik Daniel , Schultz Konrad
Published: February 2018

Background: Real-world data on the effects of a multicomponent pulmonary rehabilitation (PR) for patients with sarcoidosis are scarce. Objective: To describe characteristics of patients with sarcoidosis referred for a 3-week inpatient PR, to assess the effects of PR on their quality of life (QoL) and clinical outcomes, and to investigate whether there are specific subgroups who particularly benefit from PR. Methods: Using a prospective multicentre study design, data regarding 6-min walking distance (6MWD), QoL (Saint George’s Respiratory Questionnaire, SGRQ), and the secondary outcomes of dyspnoea and psychological burden (fatigue, anxiety, and depression) were collected. Results: We included 296 patients in the study (average age 49.1 ± 9.7 years, 47% female, average vital capacity 3.5 ± 1.0 L [87.0 ± 20.6 predicted]). The 6MWD improved by the end of the rehabilitation by 39.8 m on average (p < 0.0001; standardised response mean, SRM = 0.61), SGRQ showed significant improvements in all 3 domains, and the total score (p < 0.001) improved by 5.69–8.28 points (SRM 0.46–0.62). For the secondary outcomes, significant improvement (p < 0.001) was seen for all measured parameters, e.g., dyspnoea (modified Medical Research Council Scale, mMRC), fatigue (Fatigue Assessment Scale [FAS]; SRM = –0.71), anxiety and depression (Hospital Anxiety and Depression Scale [HADS]; SRM –0.58/–0.38), and generic QoL (measured by the SF-36 scales of physical and mental health; SRM 0.31/0.55). Conclusions: Our results provide the first documented evidence that PR is a promising complementary therapy option for sarcoidosis patients who remain subjectively symptomatic despite optimised outpatient medical treatment.
A New Peircean Response to Radical Skepticism
Authors: Remhof Justin
Published: February 2018

The radical skeptic argues that I have no knowledge of things I ordinarily claim to know because I have no evidence for or against the possibility of being systematically fed illusions. Recent years have seen a surge of interest in pragmatic responses to skepticism inspired by C.S. Peirce. This essay challenges one such influential response and presents a better Peircean way to refute the skeptic. The account I develop holds that although I do not know whether the skeptical hypothesis is true, I still know things I ordinarily claim to know. It will emerge that although this reply appears similar to a classic contextualist response to radical skepticism, it avoids two central problems facing that response.
John Dewey’s Reconstructed Conception of Growth
Authors: Popp Jerome A.
Published: February 2018

John Dewey’s analysis of the role of emotion in moral reasoning, presented in the later Ethics, led him to conclude that our development of moral reasoning should be less focused on the secondary interest of attention to ourselves or others, and attend to the more complete interests of the welfare and integrity of the social groups in which we participate. In that analysis, Dewey identified the essential role of empathic understanding in moral decisions, referred to by neuroscientists as social intelligence. Dewey’s discussion of the essential role of emotion in these decisions is further supported by research in neuroscience which has established that general intelligence is located in an area of the brain distinct from the area that supports social intelligence, our capacity for empathic experience. These findings suggest that the presence of individuals with developed social intelligence in the groups in which we participate provide increased opportunities for growth.
Plant diversity of the Heydari Wildlife Refuge in northeastern Iran, with a checklist of vascular plants
Authors: ATASHGAHI ZOHREH , EJTEHADI HAMID , MESDAGHI MANSOOR , GHASSEMZADEH FERESHTEH
Published: February 2018

Heydari Wildlife Refuge (HWR) is located in Binalood mountain range of the Razavi Khorassan Province in Northeastern Iran. The area belongs to the central part of Khorassan-Kopet Dagh floristic province, which is a transitional zone between different phytogeographical units in the Irano-Turanian region. We investigated the floristic composition, life-form spectrum and the phytogeography of the area during 2014–2017 by collecting vascular plants and establishing 443 random-quadrats in representative stands of different vegetation types. A total of 588 vascular plant taxa (species and subspecies) belonging to 304 genera and 65 families are recorded as native and naturalized in the study area. The richest plant families are Asteraceae (40 genera/87 species), Fabaceae (15/72), Poaceae (33/60), Brassicaceae (33/49), Lamiaceae (19/32), and Apiaceae (18/27). The genera Astragalus (44 species), Cousinia (17), and Allium (10) are the richest ones. However, the dominant canopy cover belongs to Acantholimon, Astragalus, Artemisia, and Acanthophyllum species. Raunkiaer’s plant life-form spectrum in the area is dominated by hemicryptophytes (41.50%) and therophytes (28.06%). The core flora of HWR has the Irano-Turanian origin; the widespread elements are also well represented in the study area. Based on the Sørensen dissimilarity index, the HWR has about 50% dissimilarity to the adjacent areas. The study area is inhabited by several Iranian and/or Khorassan-Kopet Dagh endemic (19%), threatened (16%), and narrow-range plant species. The results indicate the importance of the HWR in the plant diversity of NE Iran.
Taxonomic and geographic novelties in the genus Plantago (Plantaginaceae) in Chile, including the description of a new species
Authors: HASSEMER GUSTAVO , SHIPUNOV ALEXEY B. , RØNSTED NINA , MEUDT HEIDI M.
Published: February 2018

We present taxonomic and geographic novelties in the genus Plantago from Chile. More specifically, we describe P. nebularis, a new species endemic to Cerro Moreno, Antofagasta region, and propose P. zoellneriana, a new name for P. sericea subsp. araucana. We also lectotypify the name P. sericea, expand the recorded distribution of P. lanceolata and P. pachyneura to the Tarapacá region, and argue that the narrowly endemic species P. johnstonii, known only from the type which was collected in Taltal, Antofagasta region, is likely extinct.
A taxonomic account of species in the tribe Spongoclonieae (Ceramiaceae, Ceramiales, Rhodophyta) reported from Atlantic and Pacific Mexico
Authors: MATEO-CID LUZ ELENA , MENDOZA-GONZÁLEZ A. CATALINA , NORRIS JAMES N. , GARCÍA-LÓPEZ DEISY Y.
Published: February 2018

The tribe Spongoclonieae (Ceramiaceae subfam. Spongoclonioideae) is represented on the Atlantic and Pacific coasts of Mexico by two genera: Pleonosporium with eight species and Spongoclonium with a single species. Pleonosporium boergesenii and P. borreri are both new records for Atlantic Mexico. Known in Pacific and Atlantic Mexico, P. rhizoideum has the widest distribution, while P. pygmaeum and P. vancouverianum have only a few records in the study area. Pleonosporium mexicanum is found mainly in tropical Pacific Mexico, and P. globuliferum has a discontinuous distribution in the Gulf of California and then in Salina Cruz, Oaxaca. In the case of P. squarrulosum morphological and genetic comparisons are needed to verify its presence in Mexico. The report of Spongoclonium caribaeum from intertidal Veracruz (Gulf of Mexico) represents the second record of this species for the Atlantic coast of Mexico. Detailed descriptions, information on nomenclature, collections studied, distribution and habitat are provided for each of the species. Measurements of vegetative characters and reproductive structures provide a consistent basis for identifying Atlantic and Pacific Mexican species of Pleonosporium and Spongoclonium.
Polygala azizsancarii (Polygalaceae), a new species from Mardin Province, SE Turkey
Authors: DÖNMEZ ALİ A. , UĞURLU AYDIN ZÜBEYDE
Published: February 2018

Polygala azizsancarii Dönmez (Polygalaceae) is herein described and illustrated as a new species from Mardin province in SE Turkey. This new species is similar to P. kurdica and P. supina, but it clearly differs by several morphological characters. Diagnostic characters of this new species are discussed with respect to taxonomy and illustrations. Conservation status of the new species is also assessed according to field observations. An updated identification key is presented for the Turkish species of the genus, which currently includes 18 taxa.