bluuebunny/crossref_metadata_2025 huggingface dataset:
One minute static stretch of plantar flexors transiently increases H reflex excitability and exerts no effect on corticospinal pathways
Authors: Budini Francesco , Gallasch Eugen , Christova Monica , Rafolt Dietmar , Rauscher Andreas Benedikt , Tilp Markus
Published: June 2017

New Findings

What is the central question of this study?

What mediates neural responses following static stretching, and how long do these influences last?

What is the main finding and its importance?

This study shows that 1 min of static stretching inhibits the tendon tap reflex and facilitates the H reflex without influencing motor‐evoked potentials. The results indicate that at least two different mechanisms mediate neural responses after static stretching.

The purpose of this study was to determine whether the neural responses observed after static stretching are mediated by sensitivity of muscle spindles, spinal excitability or cortical excitability and how long these influences last. Nineteen volunteers (25.7 ± 5.6 years old) were tested for the tendon tap reflex (T‐reflex), H reflex and motor‐evoked potentials on ankle flexors and extensors immediately, 5 and 10 min after 1 min static stretching applied at individual maximal ankle dorsiflexion, as well as immediately, 5 and 10 min after a control period of the same duration. Comparison of measurements collected immediately after stretching or control conditions revealed that the T‐reflex was weaker after stretching than after control (−59.2% P = 0.000). The T‐reflex showed a slow recovery rate within the first 150 s after stretching, but 5 min after the inhibition had disappeared. The H reflex increased immediately after stretching (+18.3%, P = 0.036), showed a quick tendency to recover and returned to control values within 5 min from stretching. Motor‐evoked potentials were not affected by the procedure. These results suggest that 1 min of static stretching primarily decreases muscle spindle sensitivity and facilitates the H reflex, whereas effects on the motor cortex can be excluded.
Toward the Virtual Benchmarking of Pneumatic Ventricular Assist Devices: Application of a Novel Fluid–Structure Interaction-Based Strategy to the Penn State 12 cc Device
Authors: Caimi Alessandro , Sturla Francesco , Good Bryan , Vidotto Marco , De Ponti Rachele , Piatti Filippo , Manning Keefe B. , Redaelli Alberto
Published: June 2017

The pediatric use of pneumatic ventricular assist devices (VADs) as a bridge to heart transplant still suffers for short-term major complications such as bleeding and thromboembolism. Although numerical techniques are increasingly exploited to support the process of device optimization, an effective virtual benchmark is still lacking. Focusing on the 12 cc Penn State pneumatic VAD, we developed a novel fluid–structure interaction (FSI) model able to capture the device functioning, reproducing the mechanical interplay between the diaphragm, the blood chamber, and the pneumatic actuation. The FSI model included the diaphragm mechanical response from uniaxial tensile tests, realistic VAD pressure operative conditions from a dedicated mock loop system, and the behavior of VAD valves. Our FSI-based benchmark effectively captured the complexity of the diaphragm dynamics. During diastole, the initial slow diaphragm retraction in the air chamber was followed by a more rapid phase; asymmetries were noticed in the diaphragm configuration during its systolic inflation in the blood chamber. The FSI model also captured the major features of the device fluid dynamics. In particular, during diastole, a rotational wall washing pattern is promoted by the penetrating inlet jet with a low-velocity region located in the center of the device. Our numerical analysis of the 12 cc Penn State VAD points out the potential of the proposed FSI approach well resembling previous experimental evidences; if further tested and validated, it could be exploited as a virtual benchmark to deepen VAD-related complications and to support the ongoing optimization of pediatric devices.
Suppression of Irregular Frequency Effect in Hydrodynamic Problems and Free-Surface Singularity Treatment
Authors: Liu Yujie , Falzarano Jeffrey M.
Published: June 2017

Multibody operations are routinely performed in offshore activities, for example, the floating liquefied natural gas (FLNG) and liquefied natural gas carrier (LNGC) side-by-side offloading case. To understand the phenomenon occurring inside the gap is of growing interest to the offshore industry. One important issue is the existence of the irregular frequency effect. The effect can be confused with the physical resonance. Thus, it needs to be removed. An extensive survey of the previous approaches to the irregular frequency problem has been undertaken. The matrix formulated in the boundary integral equations will become nearly singular for some frequencies. The existence of numerical round-off errors will make the matrix still solvable by a direct solver, however, it will result in unreasonably large values in some aspects of the solution, namely, the irregular frequency effect. The removal of the irregular effect is important especially for multibody hydrodynamic analysis in identifying the physical resonances caused by the configuration of floaters. This paper will mainly discuss the lid method on the internal free surface. To reach a higher accuracy, the singularity resulting from the Green function needs special care. Each term in the wave Green function will be evaluated using the corresponding analysis methods. Specifically, an analytical integral method is proposed to treat the log singularity. Finally, results with and without irregular frequency removal will be shown to demonstrate the effectiveness of our proposed method.
Jet Engine Gas Path Analysis Based on Takeoff Performance Snapshots
Authors: Putz A. , Staudacher S. , Koch C. , Brandes T.
Published: June 2017

Current engine condition monitoring (ECM) systems for jet engines include the analysis of on-wing gas path data using steady-state performance models. Such data, which are also referred to as performance snapshots, usually are taken during cruise flight and during takeoff. Using steady-state analysis, it is assumed that these snapshots have been taken under stabilized operating conditions. However, this assumption is reasonable only for cruise snapshots. During takeoff, jet engines operate in highly transient conditions with significant heat transfer occurring between the fluid and the engine structure. Hence, steady-state analysis of takeoff snapshots is subject to high uncertainty. Because of this, takeoff snapshots are not used for performance analysis in current ECM systems. We quantify the analysis uncertainty by transient simulation of a generic takeoff maneuver using a performance model of a medium size two-shaft turbofan engine with high bypass ratio. Taking into account the influence of the preceding operating regimes on the transient heat transfer effects, this takeoff maneuver is extended backward in time to cover the aircraft turnaround as well as the end of the last flight mission. We present a hybrid approach for thermal calculation of both the fired engine and the shutdown engine. The simulation results show that takeoff derate, ambient temperature, taxi-out (XO) duration and the duration of the preceding aircraft turnaround have a major influence on the transient effects occurring during takeoff. The analysis uncertainty caused by the transient effects is significant. Based on the simulation results, we propose a method for correction of takeoff snapshots to steady-state operating conditions. Furthermore, we show that the simultaneous analysis of cruise and corrected takeoff snapshots leads to significant improvements in observability.
Two new species of Hoplomegistidae (Acari: Mesostigmata) associated with passalid Beetles from China
Authors: Zhang Xin-Feng , Yi Tian-Ci , Guo Jian-Jun , Jin Dao-Chao
Published: June 2017

Stenosternum cordata sp. nov. and Stenosternum bifurcata sp. nov., new to science, are described, which is the first record of Hoplomegistidae from Asia. Stenosternum cordata sp. nov. is distinguished by its heart-shaped latigynal shield with two pairs of setae along the lateral margin, and two pairs of setae along the posterior margin of the sternal shield. Stenosternum bifurcata sp. nov. is distinguished by having remarkable bifurcate corniculus, six pairs of setae on the sternal shield and three pairs setae on the latigynal shield. The family Hoplomegistidae Camin & Gorirossi, 1955 is redefined and a key to adult females of species is provided.
Test of single degree of freedom acoustic treatment impedance models for multimodal acoustic propagation in duct with flow
Authors: Baccouche Ryan , Moreau Soléne , Ben Tahar Mabrouk
Published: June 2017

Passive acoustic treatments, also called liners, are the main solution to noise problems. The Single Degree Of Freedom (SDOF) acoustic treatment, composed of a thin material (perforated plate) affixed to air cavities with a rigid bottom, constitutes a solution. Predicting sound level reduction by an SDOF treatment requires reliable acoustic impedance models. An experimental/numerical method has been developed for a duct with an acoustic treatment to test acoustic impedance models of SDOF treatment with a multimodal propagation in the presence of a mean flow. This method is based on the comparison of experimental results from an aeroacoustic bench composed of a circular duct with a treated area, and numerical results from an FEM-PML axisymmetric model based on Galbrun's equation. The numerical results are confronted with experimental results to test impedance models up to M0=±0.25.
Acoustic levitation of an object larger than the acoustic wavelength
Authors: Andrade Marco A. B. , Okina Fábio T. A. , Bernassau Anne L. , Adamowski Julio C.
Published: June 2017

Levitation and manipulation of objects by sound waves have a wide range of applications in chemistry, biology, material sciences, and engineering. However, the current acoustic levitation techniques are mainly restricted to particles that are much smaller than the acoustic wavelength. In this work, it is shown that acoustic standing waves can be employed to stably levitate an object much larger than the acoustic wavelength in air. The levitation of a large slightly curved object weighting 2.3 g is demonstrated by using a device formed by two 25 kHz ultrasonic Langevin transducers connected to an aluminum plate. The sound wave emitted by the device provides a vertical acoustic radiation force to counteract gravity and a lateral restoring force that ensure horizontal stability to the levitated object. In order to understand the levitation stability, a numerical model based on the finite element method is used to determine the acoustic radiation force that acts on the object.
Influence of IS
256
on Genome Variability and Formation of Small-Colony Variants in Staphylococcus aureus
Authors: Kleinert Franziska , Kallies René , Hort Michael , Zweynert Annegret , Szekat Christiane , Nagel Michael , Bierbaum Gabriele
Published: June 2017

Staphylococcus aureus
has acquired resistance to nearly all antibiotics used in clinical practice. Whereas some resistance mechanisms are conferred by uptake of resistance genes, others evolve by mutation. In this study, IS
256
has been shown to play a role, e.g., in
S. aureus
strains displaying intermediate resistance to vancomycin (VISA). To characterize the IS
256
insertion sites in the genomes of two closely related sequence type 247 (ST247) VISA strains, all insertions were mapped in both VISA and a susceptible control strain. The results showed that the three ST247 strains contained the highest number so far of IS
256
insertions for all sequenced
S. aureus
strains. Furthermore, in contrast to the case with the other IS elements in these genomes, the IS
256
insertion sites were not identical in the closely related strains, indicating a high transposition frequency of IS
256
. When IS
256
was introduced into a laboratory strain which was then cultured in the presence of antibiotics, it was possible to isolate small-colony variants (SCVs) that possessed IS
256
insertions in
guaA
and
hemY
that displayed increased resistance to vancomycin and aminoglycosides, respectively. For these clones, a very rapid reversion to the wild type that resembled the fast reversion of clinical SCVs was observed. The reversion was caused by excision of IS
256
in a small number of fast-growing clones that quickly outcompeted the SCVs in broth cultures. In conclusion, the presence of IS
256
confers a strong genomic plasticity that is useful for adaptation to antibiotic stress.
Susceptibility of Colistin-Resistant, Gram-Negative Bacteria to Antimicrobial Peptides and Ceragenins
Authors: Hashemi Marjan M. , Rovig John , Weber Scott , Hilton Brian , Forouzan Mehdi M. , Savage Paul B.
Published: June 2017

The susceptibility of colistin-resistant clinical isolates of
Klebsiella pneumoniae
to ceragenins and antimicrobial peptides (AMPs) suggests that there is little to no cross-resistance between colistin and ceragenins/AMPs and that lipid A modifications are found in bacteria with modest changes in susceptibility to ceragenins and with high levels of resistance to colistin. These results suggest that there are differences in the resistance mechanisms to colistin and ceragenins/AMPs.
Targeted Metabolomics Analysis Identifies Intestinal Microbiota-Derived Urinary Biomarkers of Colonization Resistance in Antibiotic-Treated Mice
Authors: Obrenovich Mark E. , Tima MaryAnn , Polinkovsky Alex , Zhang Renliang , Emancipator Steven N. , Donskey Curtis J.
Published: June 2017

Antibiotics excreted into the intestinal tract may disrupt the microbiota that provide colonization resistance against enteric pathogens and alter normal metabolic functions of the microbiota. Many of the bacterial metabolites produced in the intestinal tract are absorbed systemically and excreted in urine. Here, we used a mouse model to test the hypothesis that alterations in levels of targeted bacterial metabolites in urine specimens could provide useful biomarkers indicating disrupted or intact colonization resistance. To assess
in vivo
colonization resistance, mice were challenged with
Clostridium difficile
spores orally 3, 6, and 11 days after the completion of 2 days of treatment with piperacillin-tazobactam, aztreonam, or saline. For concurrent groups of antibiotic-treated mice, urine samples were analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify the concentrations of 11 compounds targeted as potential biomarkers of colonization resistance. Aztreonam did not affect colonization resistance, whereas piperacillin-tazobactam disrupted colonization resistance 3 days after piperacillin-tazobactam treatment, with complete recovery by 11 days after treatment. Three of the 11 compounds exhibited a statistically significant and >10-fold increase (the tryptophan metabolite
N
-acetyltryptophan) or decrease (the plant polyphenyl derivatives cinnamoylglycine and enterodiol) in concentrations in urine 3 days after piperacillin-tazobactam treatment, followed by recovery to baseline that coincided with the restoration of
in vivo
colonization resistance. These urinary metabolites could provide useful and easily accessible biomarkers indicating intact or disrupted colonization resistance during and after antibiotic treatment.
Discovery and Characterization of a Novel CD4-Binding Adnectin with Potent Anti-HIV Activity
Authors: Wensel David , Sun Yongnian , Li Zhufang , Zhang Sharon , Picarillo Caryn , McDonagh Thomas , Fabrizio David , Cockett Mark , Krystal Mark , Davis Jonathan
Published: June 2017

A novel fibronectin-based protein (Adnectin) HIV-1 inhibitor was generated usingin vitroselection. This inhibitor binds to human CD4 with a high affinity (3.9 nM) and inhibits viral entry at a step after CD4 engagement and preceding membrane fusion. The progenitor sequence of this novel inhibitor was selected from a library of trillions of Adnectin variants using mRNA display and then further optimized for improved antiviral and physical properties. The final optimized inhibitor exhibited full potency against a panel of 124 envelope (gp160) proteins spanning 11 subtypes, indicating broad-spectrum activity. Resistance profiling studies showed that this inhibitor required 30 passages (151 days) in culture to acquire sufficient resistance to result in viral titer breakthrough. Resistance mapped to the loss of multiple potential N-linked glycosylation sites in gp120, suggesting that inhibition is due to steric hindrance of CD4-binding-induced conformational changes.
Capsid Assembly Modulators Have a Dual Mechanism of Action in Primary Human Hepatocytes Infected with Hepatitis B Virus
Authors: Berke Jan Martin , Dehertogh Pascale , Vergauwen Karen , Van Damme Ellen , Mostmans Wendy , Vandyck Koen , Pauwels Frederik
Published: June 2017

Hepatitis B virus (HBV) capsid assembly is a critical step in the propagation of the virus and is mediated by the core protein. Due to its multiple functions in the viral life cycle, core became an attractive target for new antiviral therapies. Capsid assembly modulators (CAMs) accelerate the kinetics of capsid assembly and prevent encapsidation of the polymerase-pregenomic RNA (Pol-pgRNA) complex, thereby blocking viral replication. CAM JNJ-632 is a novel and potent inhibitor of HBV replication
in vitro
across genotypes A to D. It induces the formation of morphologically intact viral capsids, as demonstrated by size exclusion chromatography and electron microscopy studies. Antiviral profiling in primary human hepatocytes revealed that CAMs prevented formation of covalently closed circular DNA in a dose-dependent fashion when the compound was added together with the viral inoculum, whereas nucleos(t)ide analogues (NAs) did not. This protective effect translated into a dose-dependent reduction of intracellular HBV RNA levels as well as reduced HBe/cAg and HBsAg levels in the cell culture supernatant. The same observation was made with another CAM (BAY41-4109), suggesting that mechanistic rather than compound-specific effects play a role. Our data show that CAMs have a dual mechanism of action, inhibiting early and late steps of the viral life cycle. These effects clearly differentiate CAMs from NAs and may translate into higher functional cure rates in a clinical setting when given alone or in combination with the current standard of care.
Transcriptional Regulator TetR21 Controls the Expression of the Staphylococcus aureus LmrS Efflux Pump
Authors: Truong-Bolduc Q. C. , Wang Y. , Chen C. , Hooper D. C.
Published: June 2017

TetR21 controls the expression of Tet38 and LmrS efflux pumps. A
tetR21
mutant, QT21, exhibited a 4-fold increase in the transcription level of
lmrS
.
Staphylococcus aureus
lmrS
overexpressor showed increases of 4-fold and 2-fold, respectively, in the MICs of chloramphenicol and erythromycin, while the MICs of
lmrS
mutant QT18 and
lmrS-tetR21
mutant QT1821 remained similar to those of parental strain RN6390. TetR21 does not bind to the promoter of
lmrS
, suggesting indirect regulation of
lmrS
.
Parasitic Protozoa and Interactions with the Host Intestinal Microbiota
Authors: Burgess Stacey L. , Gilchrist Carol A. , Lynn Tucker C. , Petri William A.
Published: June 2017

Parasitic protozoan infections represent a major health burden in the developing world and contribute significantly to morbidity and mortality. These infections are often associated with considerable variability in clinical presentation. An emerging body of work suggests that the intestinal microbiota may help to explain some of these differences in disease expression. The objective of this minireview is to synthesize recent progress in this rapidly advancing field. Studies of humans and animals and
in vitro
studies of the contribution of the intestinal microbiota to infectious disease are discussed. We hope to provide an understanding of the human-protozoal pathogen-microbiome interaction and to speculate on how that might be leveraged for treatment.
Metabolic heterogeneity of idiopathic pulmonary fibrosis: a metabolomic study
Authors: Zhao Yidan D , Yin Li , Archer Stephen , Lu Catherine , Zhao George , Yao Yan , Wu Licun , Hsin Michael , Waddell Thomas K , Keshavjee Shaf , Granton John , de Perrot Marc
Published: June 2017

Introduction

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown cause characterised by progressive fibrotic formation in lung tissue. We hypothesise that disrupted metabolic pathways in IPF contribute to disease pathogenesis.

Methods

Metabolomics of human IPF was performed using mass spectroscopy (IPF lung=8; donor lung=8). Gene expression of key metabolic enzymes was measured using microarrays. Of the 108 metabolites whose levels were found altered, 48 were significantly increased, whereas 60 were significantly decreased in IPF samples compared with normal controls.

Results

Specific metabolic pathways mediating the IPF remodelling were found with a downregulated sphingolipid metabolic pathway but an upregulated arginine pathway in IPF. In addition, disrupted glycolysis, mitochondrial beta-oxidation and tricarboxylic acid cycle, altered bile acid, haem and glutamate/aspartate metabolism were found in IPF samples compared with control.

Conclusions

Our results show alterations in metabolic pathways for energy consumption during lung structural remodelling, which may contribute to IPF pathogenesis. We believe that this is the first report of simultaneously and systemically measuring changes of metabolites involving nine metabolic pathways in human severe IPF lungs. The measurement of the metabolites may serve in the future diagnosis and prognosis of IPF.
Combining creative writing and narrative analysis to deliver new insights into the impact of pulmonary hypertension
Authors: Goddard Julia C , Armstrong Iain J , Kiely David G , Elliot Charlie A , Charalampopoulos Athanasios , Condliffe Robin , Stone Brendan J , Sabroe Ian
Published: June 2017

Introduction

Pulmonary hypertension is life limiting. Delays in diagnosis are common, and even after treatment has been initiated, pulmonary hypertension has marked effects on many aspects of social and physical function. We believed that a new approach to examining disease impact could be achieved through a combination of narrative research and creative writing.

Methods

Detailed unstructured narrative interviews with people with pulmonary hypertension were analysed thematically. Individual moments were also summarised and studied using creative writing, in which the interviewer created microstories from narrative and interview data. Stories were shared with their subjects, and with other patients, clinicians, researchers and the wider public. The study was carried out in hospital and in patients’ homes.

Results

Narrative analysis generated a rich data set which highlighted profound effects of pulmonary hypertension on identity, and demonstrated how the disease results in very marked personal change with ongoing and unpredictable requirement for adaptation. The novel methodology of microstory development proved to be an effective tool to summarise, communicate and explore the consequences of pulmonary hypertension and the clinical challenges of caring for patients with this illness.

Conclusions

A holistic approach to treatment of chronic respiratory diseases such as pulmonary hypertension requires and benefits from explicit exploration of the full impacts of the illness. Narrative analysis and the novel approach of targeted microstory development can form a valuable component of the repertoire of approaches to effectively comprehend chronic disease and can also facilitate patient-focused discussion and interventions.
Breathing–swallowing discoordination is associated with frequent exacerbations of COPD
Authors: Nagami Shinsuke , Oku Yoshitaka , Yagi Naomi , Sato Susumu , Uozumi Ryuji , Morita Satoshi , Yamagata Yoshie , Kayashita Jun , Tanimura Kazuya , Sato Atsuyasu , Takahashi Ryosuke , Muro Shigeo
Published: June 2017

Introduction

Impaired coordination between breathing and swallowing (breathing–swallowing discoordination) may be a significant risk factor for the exacerbation of chronic obstructive pulmonary disease (COPD). We examined breathing–swallowing discoordination in patients with COPD using a non-invasive and quantitative technique and determined its association with COPD exacerbation.

Methods

We recruited 65 stable outpatients with COPD who were enrolled in our prospective observational cohort study and did not manifest an apparent swallowing disorder. COPD exacerbation was monitored for 1 year before and 1 year after recruitment. Swallowing during inspiration (the I-SW pattern) and swallowing immediately followed by inspiration (the SW-I pattern) were identified.

Results

The mean frequency of the I-SW and/or SW-I patterns (I-SW/SW-I rate) was 21.5%±25.5%. During the 2-year observation period, 48 exacerbation incidents (25 patients) were identified. The I-SW/SW-I rate was significantly associated with the frequency of exacerbation. During the year following recruitment, patients with a higher I-SW/SW-I frequency using thicker test foods exhibited a significantly higher probability of future exacerbations (p=0.002, log-rank test).

Conclusions

Breathing–swallowing discoordination is strongly associated with frequent exacerbations of COPD. Strategies that identify and improve breathing–swallowing coordination may be a new therapeutic treatment for patients with COPD.
Initiation and duration of Grampian orogenesis constrained by refined Sm–Nd garnet geochronology of the Ballantrae ophiolite, Scotland
Authors: Stewart E. M. , Baxter Ethan F. , Ague Jay J.
Published: June 2017

We report the results of Sm–Nd garnet geochronology on a mafic granulite from the metamorphic sole of the Ballantrae Ophiolite, Scotland. The resultant age of 477.6 ± 1.9 Ma (2σ) is interpreted to represent the obduction of the Ballantrae Ophiolite and the onset of the Grampian phase of the Caledonian Orogeny in Scotland. Thermodynamic modelling indicates peak conditions of
c
. 825°C and at least 10 kbar for the unit. In conjunction with a biostratigraphic constraint on metamorphic garnet deposition in sediments at 465 ± 2.5 Ma, this new age more precisely constrains the duration of Grampian metamorphism in Scotland to 12.6 ± 3.1 myr (2σ). In combination with this new age, previous geochronological work on sillimanite-zone garnet indicates a time-averaged initial heating rate of 106 ± 78°C myr
−1
(2σ), a rapid rate that may be inconsistent with orogenic self-heating via crustal overthickening alone. The calculated heating rate for the associated garnet zone is also rapid and more precisely constrained at 47 ± 14°C myr
−1
(2σ). These results together with the short overall duration of the event support the idea that the Grampian phase of the Caledonian Orogeny in Scotland included both rapid heating and correspondingly fast exhumation.
Provenance of Lower Cretaceous clastic reservoirs in the Middle East
Authors: Wells Martin , Morton Andrew , Frei Dirk
Published: June 2017

Some of the world's largest oilfields contain reservoirs in Lower Cretaceous (Hauterivian–Albian) clastic successions of the Middle East. They comprise sandstone-prone intervals of hundreds of metres thickness deposited in non-marine to paralic settings on a very shallow gradient, otherwise carbonate-dominated, passive margin. This study integrates petrography, X-ray powder diffraction, heavy mineral analysis, mineral chemistry, zircon geochronology and palaeodrainage basin scale calculations to determine the likely provenance of the clastic deposits. Regional geological considerations are then used to suggest the likely driving mechanisms for the clastic influx. The sediments are highly texturally and chemically mature with low-diversity heavy mineral assemblages, suggesting extensive weathering and sediment recycling. The mixture of heavy minerals derived from metapelitic, metamafic and granitic domains at variable metamorphic grades is consistent with erosion of a complex heterogeneous basement or recycling of multiple earlier cycle sediments. Comparison with published data suggests an Arabian Shield provenance, with input from Precambrian basement and Palaeozoic sedimentary cover both possible. This is consistent with drainage basin scaling calculations. Large-scale tectonic reorganization associated with opening of the South and Equatorial Atlantic together with mantle plume related uplift in the northern Arabian Shield is postulated as the main driving mechanism of clastic influx.
FM-DBEM Simulation of 3D Microvoid and Microcrack Graphite Models
Authors: Lu Houdi , Wang Hongtao , Wang Haitao , Jin Lie , Wu Xinxin , Zhou Yu
Published: June 2017

The graphite is porous medium, and the geometry and size distribution of its structural deficiencies such as microcracks and microvoids at different oxidation degrees have a great influence on the overall performance. In this paper, we adopt the FM-DBEM to study 3D models which contain spheroidal microvoids and circular microcracks. The accuracy of this method is tested by a comparison to the theoretical solution to the problem of 2D microcrack and microvoid interaction problem. Two simulations are conducted: the simulation of graphite model containing a large number of randomly distributed microcracks and microvoids and the simulation of graphite model containing microcracks and growing microvoids. The simulations investigate the effective moduli versus the two microstructures’ density and the effect of microvoid’s growth on the SIF of microcrack.
Species Richness and Traditional Knowledge of Macrofungi (Mushrooms) in the Awing Forest Reserve and Communities, Northwest Region, Cameroon
Authors: Rosemary Kinge Tonjock , Apiseh Apalah Nkengmo , Mue Nji Theobald , Neh Acha Ache , Mathias Mih Afui
Published: June 2017

Macrofungi are diverse in their uses as food and medicine and several species serve as decomposers and also form mycorrhizal associations. Awing forest reserve is diverse in plants and fungi species. However, no work has been carried out to assess the diversity and traditional knowledge of macrofungi in the area. Diversity surveys were carried out in three altitudes using transects of 50×20 m for six months in 2015. Ethnomycology studies were carried out in fifteen communities using focus group discussion, pictorial presentation, and questionnaires. The data was analyzed using descriptive statistics in Microsoft Excel 2010. Seventy-five species belonging to thirty families were identified by morphology. Thirty-six species were found only in the low altitude, 16 in the mid altitude, and 16 species in high altitude. One species was common to low and mid altitude and also low and high altitude; five species were common to mid and high altitude while there was no species common to all three altitudes. The indigenes of the Awing communities commonly called mushroom “Poh” and use it mainly as food and medicine and in mythological beliefs. The most utilized species as food and medicine included Termitomyces titanicus, Laetiporus sulphureus, and Ganoderma sp.
Genetic Nrf2 Overactivation Inhibits the Deleterious Effects Induced by Hepatocyte‐Specific c‐met Deletion during the Progression of NASH
Authors: Ramadori Pierluigi , Drescher Hannah , Erschfeld Stephanie , Fragoulis Athanassios , Kensler Thomas W. , Wruck Christoph Jan , Cubero Francisco Javier , Trautwein Christian , Streetz Konrad L. , Kroy Daniela C.
Published: June 2017

We have recently shown that hepatocyte‐specific c‐met deficiency accelerates the progression of nonalcoholic steatohepatitis in experimental murine models resulting in augmented production of reactive oxygen species and accelerated development of fibrosis. The aim of this study focuses on the elucidation of the underlying cellular mechanisms driven by Nrf2 overactivation in hepatocytes lacking c‐met receptor characterized by a severe unbalance between pro‐oxidant and antioxidant functions. Control mice (c‐metfx/fx), single c‐met knockouts (c‐metΔhepa), and double c‐met/Keap1 knockouts (met/Keap1Δhepa) were then fed a chow or a methionine‐choline‐deficient (MCD) diet, respectively, for 4 weeks to reproduce the features of nonalcoholic steatohepatitis. Upon MCD feeding, met/Keap1Δhepa mice displayed increased liver mass albeit decreased triglyceride accumulation. The marked increase of oxidative stress observed in c‐metΔhepa was restored in the double mutants as assessed by 4‐HNE immunostaining and by the expression of genes responsible for the generation of free radicals. Moreover, double knockout mice presented a reduced amount of liver‐infiltrating cells and the exacerbation of fibrosis progression observed in c‐metΔhepa livers was significantly inhibited in met/Keap1Δhepa. Therefore, genetic activation of the antioxidant transcription factor Nrf2 improves liver damage and repair in hepatocyte‐specific c‐met‐deficient mice mainly through restoring a balance in the cellular redox homeostasis.
Mass Renormalization in the Nelson Model
Authors: Hiroshima Fumio , Osawa Susumu
Published: June 2017

The asymptotic behavior of the effective mass meff(Λ) of the so-called Nelson model in quantum field theory is considered, where Λ is an ultraviolet cutoff parameter of the model. Let m be the bare mass of the model. It is shown that for sufficiently small coupling constant α of the model, meff(Λ)/m can be expanded as meff(Λ)/m=1+∑n=1∞an(Λ)α2n. A physical folklore is that an(Λ)=O(logΛ(n-1)) as Λ→∞. It is rigorously shown that 0<limΛ→∞a1(Λ)<C,  C1≤limΛ→∞a2(Λ)/log⁡Λ≤C2 with some constants C, C1, and C2.
Detection of Enterocytozoon bieneusi in White Yaks in Gansu Province, China
Authors: Ma Jian-Gang , Zhang Nian-Zhang , Hou Jun-Ling , Zou Yang , Hu Gui-Xue , Zhu Xing-Quan , Zhou Dong-Hui
Published: June 2017

Enterocytozoon bieneusi, the most common zoonotic pathogen of microsporidiosis, has been found in various animals and humans, but no information is available concerning the prevalence and genotypes of E. bieneusi in white yaks (Bos grunniens). In the present study, 353 faecal samples from white yaks in Tianzhu Tibetan Autonomous County, Gansu Province, Northwestern China, were collected and examined by PCR amplification of the internal transcribed spacer gene to estimate E. bieneusi prevalence and identify their genotypes. Of the 353 faecal samples, 4 (1.13%) were tested E. bieneusi-positive. Sequences analysis revealed that two known genotypes, namely, I (n=1) and BEB4 (n=2), and a novel genotype, namely, WCY1 (n=1), were found in this study. Among them, genotype WCY1 was clustered into Group 1, and genotypes I and BEB4 belonged to Group 2. The present study firstly indicates the existence of E. bieneusi in yaks in Gansu Province, Northwestern China. This is also the first record of E. bieneusi in white yaks. Effective measures should be taken to control E. bieneusi infection in white yaks, other animals, and humans.
Innate Immune Response in Kidney Ischemia/Reperfusion Injury: Potential Target for Therapy
Authors: Kezić Aleksandra , Stajic Natasa , Thaiss Friedrich
Published: June 2017

Acute kidney injury caused by ischemia and subsequent reperfusion is associated with a high rate of mortality and morbidity. Ischemia/reperfusion injury in kidney transplantation causes delayed graft function and is associated with more frequent episodes of acute rejection and progression to chronic allograft nephropathy. Alloantigen-independent inflammation is an important process, participating in pathogenesis of injurious response, caused by ischemia and reperfusion. This innate immune response is characterized by the activity of classical cells belonging to the immune system, such as neutrophils, macrophages, dendritic cells, lymphocytes, and also tubular epithelial cells and endothelial cells. These immune cells not only participate in inflammation after ischemia exerting detrimental influence but also play a protective role in the healing response from ischemia/reperfusion injury. Delineating of complex mechanisms of their actions could be fruitful in future prevention and treatment of ischemia/reperfusion injury. Among numerous so far conducted experiments, observed immunomodulatory role of adenosine and adenosine receptor agonists in complex interactions of dendritic cells, natural killer T cells, and T regulatory cells is emphasized as promising in the treatment of kidney ischemia/reperfusion injury. Potential pharmacological approaches which decrease NF-κB activity and antagonize mechanisms downstream of activated Toll-like receptors are discussed.
Andrographolide Inhibits Inflammatory Cytokines Secretion in LPS‐Stimulated RAW264.7 Cells through Suppression of NF‐κB/MAPK Signaling Pathway
Authors: Li Yu , He Shengnan , Tang Jishun , Ding Nana , Chu Xiaoyan , Cheng Lianping , Ding Xuedong , Liang Ting , Feng Shibin , Rahman Sajid Ur , Wang Xichun , Wu Jinjie
Published: June 2017

Andrographolide, the main active component extracted from Andrographis paniculata (Burm.f.) Wall. ex Nees, exerts anti‐inflammatory effects; however, the principal molecular mechanisms remain unclear. The objective of this study was to investigate the molecular mechanisms of Andrographolide in modifying lipopolysaccharide‐ (LPS‐) induced signaling pathway in RAW264.7 cells. An in vitro model of inflammation was induced by LPS in mouse RAW264.7 cells in the presence of Andrographolide. The concentration and expression levels of proinflammatory cytokines were determined by an enzyme‐linked immunosorbent assay (ELISA) and quantitative real‐time polymerase chain reaction (qRT‐PCR), respectively. The nuclear level of NF‐κB was measured by an electrophoretic mobility shift assay (EMSA). The expression levels of NF‐κB, p38, ERK, and JNK were determined by western blot. Andrographolide dose‐dependently inhibited the release and mRNA expression of TNF‐α, IL‐6, and IL‐1β in LPS‐stimulated RAW264.7 cells. The nuclear level of p65 protein was decreased in Andrographolide treatment group. Western blot analysis showed that Andrographolide suppressed LPS‐induced NF‐κB activation and the phosphorylation of IkBa, ERK1/2, JNK, and p38. These results suggest that Andrographolide exerts an anti‐inflammatory effect by inhibiting the activation of NF‐κB/MAPK signaling pathway and the induction of proinflammatory cytokines.
On the Horizontal Deviation of a Spinning Projectile Penetrating into Granular Systems
Authors: Alshanti Waseem Ghazi
Published: June 2017

The absence of a general theory that describes the dynamical behavior of the particulate materials makes the numerical simulations the most current powerful tool that can grasp many mechanical problems relevant to the granular materials. In this paper, based on a two-dimensional soft particle discrete element method (DEM), a numerical approach is developed to investigate the consequence of the orthogonal impact into various granular beds of projectile rotating in both clockwise (CW) and counterclockwise (CCW) directions. Our results reveal that, depending on the rotation direction, there is a significant deviation of the x-coordinate of the final stopping point of a spinning projectile from that of its original impact point. For CW rotations, a deviation to the right occurs while a left deviation has been recorded for CCW rotation case.
Serum Glutamate Is a Predictor for the Diagnosis of Multiple Sclerosis
Authors: Al Gawwam Gheyath , Sharquie Inas K.
Published: June 2017

One neurotransmitter, glutamate, has been implicated in the autoimmune demyelination seen in multiple sclerosis (MS). Glutamate is present in many tissues in the body, so consideration should be given to whether the serum level of glutamate is likely well correlated with the activity of the disease. This research aimed to compare the serum glutamate levels from patients diagnosed with MS with those from an age-matched control population. A review of this data could shed light upon whether the serum testing of glutamate using Enzyme-Linked Immunosorbent Assay (ELISA) is a reliable indicator of MS activity. Serum samples were obtained from 55 patients with different patterns of MS and from 25 healthy adults as a control group. The ELISA technique was used to determine the glutamate levels in the serum samples. The mean serum glutamate level for patients with MS was1.318±0.543 nmol/ml and that of the controls was0.873±0.341 nmol/ml. The serum glutamate levels showed an area under the curve via the receiver operating characteristics (ROC) of 0.738, which was significant (pvalue = 0.001). The present study is the first to establish a strong connection between the serum glutamate levels and MS patients, where there was statistically significant elevation of serum glutamate in MS patients; hence this elevation might be used as a monitor to help in the diagnosis of MS patients.
Use of Brilliant Blue G in Descemet’s Membrane Endothelial Keratoplasty
Authors: Hayashi Takahiko , Yuda Kentaro , Oyakawa Itaru , Kato Naoko
Published: June 2017

Vital staining of the endothelial graft is essential during Descemet’s membrane endothelial keratoplasty (DMEK) to ensure surgical success. DMEK surgeons worldwide commonly use trypan blue (TB) to this end. However, TB may exert toxic effects on both the cornea and retina. Recently, Brilliant Blue G (BBG) has become recognized as an alternative stain for use during vitreoretinal surgery; BBG is associated with lower levels of toxicity. We retrospectively analyzed the utility of BBG staining during DMEK. We used 0.1% (w/v) BBG to stain the DMEK grafts of 12 patients. We evaluated the best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), and endothelial cell density (ECD) before and 3 and 6 months after surgery. BBG was effective in terms of graft visualization during DMEK. The BSCVA (log  MAR) improved from0.99±0.57to0.01±0.07(p<0.05). The CCT decreased from720.3±58.1 μm preoperatively to511.5±50.6 μm at 6 months postoperatively (p=0.0001). The ECD decreased from2,754±296 cells/mm2to1,708±426 cells/mm2at 6 months postoperatively (p<0.001). The ECD loss was37.9±16.3%. The outcomes using BBG were comparable to those of earlier reports that employed TB; thus, BBG may be a viable alternative to TB.
FOXM1 in Cancer: Interactions and Vulnerabilities
Authors: Gartel Andrei L.
Published: June 2017

FOXM1 is a transcription factor of the Forkhead family that is required for cell proliferation of normal cells. However, FOXM1 is repeatedly overexpressed in a variety of human cancers, and it has been implicated in all major hallmarks of cancer delineated by Hanahan and Weinberg. It has been postulated that the oncogenic potential of FOXM1 is determined by its capacity to transactivate target genes that are implicated in different phases of cancer development. However, FOXM1 may also play an oncogenic role by interacting with other proteins, such as β-catenin or SMAD3 to induce oncogenic WNT and TGFβ signaling pathways, respectively. In this review, I will discuss the protein–protein interactions of FOXM1 that are critical for cancer development and may represent novel targets for anticancer drugs. Cancer Res; 77(12); 3135–9. ©2017 AACR.
Human Subjects Protection and Cancer Surveillance Research: Revised Regulations, Expanded Opportunities
Authors: McLaughlin Robert H. , Gomez Scarlett Lin , Deapen Dennis , Induni Marta
Published: June 2017

On January 19, 2017, the United States federal government issued revisions to the Common Rule under which scientists who receive federal funding conduct research involving human subjects. The revised Common Rule expressly addresses public health surveillance in relation to scientific research and the protection of human subjects, and its impacts are anticipated to contribute to the efficiency of activities, including cancer registration and surveillance, and research that uses cancer registry data. Cancer Res; 77(12); 3140–3. ©2017 AACR.
The Landscape of Isoform Switches in Human Cancers
Authors: Vitting-Seerup Kristoffer , Sandelin Albin
Published: June 2017

Alternative usage of transcript isoforms from the same gene has been hypothesized as an important feature in cancers. However, differential usage of gene transcripts between conditions (isoform switching) has not been comprehensively characterized in and across cancer types. To this end, we developed methods for identification and visualization of isoform switches with predicted functional consequences. Using these methods, we characterized isoform switching in RNA-seq data from >5,500 cancer patients covering 12 solid cancer types. Isoform switches with potential functional consequences were common, affecting approximately 19% of multiple transcript genes. Among these, isoform switches leading to loss of DNA sequence encoding protein domains were more frequent than expected, particularly in pancancer switches. We identified several isoform switches as powerful biomarkers: 31 switches were highly predictive of patient survival independent of cancer types. Our data constitute an important resource for cancer researchers, available through interactive web tools. Moreover, our methods, available as an R package, enable systematic analysis of isoform switches from other RNA-seq datasets.

Implications: This study indicates that isoform switches with predicted functional consequences are common and important in dysfunctional cells, which in turn means that gene expression should be analyzed at the isoform level.

Visual Overview: http://mcr.aacrjournals.org/content/molcanres/15/9/1206/F1.large.jpg. Mol Cancer Res; 15(9); 1206–20. ©2017 AACR.
IKKβ-Mediated Resistance to Skin Cancer Development Is Ink4a/Arf-Dependent
Authors: Page Angustias , Bravo Ana , Suarez-Cabrera Cristian , Alameda Josefa P. , Casanova M. Llanos , Lorz Corina , Segrelles Carmen , Segovia José C. , Paramio Jesús M. , Navarro Manuel , Ramirez Angel
Published: June 2017

IKKβ (encoded by IKBKB) is a protein kinase that regulates the activity of numerous proteins important in several signaling pathways, such as the NF-κB pathway. IKKβ exerts a protumorigenic role in several animal models of lung, hepatic, intestinal, and oral cancer. In addition, genomic and proteomic studies of human tumors also indicate that IKBKB gene is amplified or overexpressed in multiple tumor types. Here, the relevance of IKKβ in skin cancer was determined by performing carcinogenesis studies in animal models overexpressing IKKβ in the basal skin layer. IKKβ overexpression resulted in a striking resistance to skin cancer development and an increased expression of several tumor suppressor proteins, such as p53, p16, and p19. Mechanistically, this skin tumor–protective role of IKKβ is independent of p53, but dependent on the activity of the Ink4a/Arf locus. Interestingly, in the absence of p16 and p19, IKKβ-increased expression favors the appearance of cutaneous spindle cell–like squamous cell carcinomas, which are highly aggressive tumors. These results reveal that IKKβ activity prevents skin tumor development, and shed light on the complex nature of IKKβ effects on cancer progression, as IKKβ can both promote and prevent carcinogenesis depending on the cell type or molecular context.

Implications: The ability of IKKβ to promote or prevent carcinogenesis suggests the need for further evaluation when targeting this protein. Mol Cancer Res; 15(9); 1255–64. ©2017 AACR.