bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of an NKX3.1-G9a-UTY transcriptional regulatory network that controls prostate differentiation
Authors: Dutta Aditya , Le Magnen Clémentine , Mitrofanova Antonina , Ouyang Xuesong , Califano Andrea , Abate-Shen Cory
Published: June 2016

Clues to cancer from an identity change

The prostate and seminal vesicle have closely related developmental histories and both are regulated by the same androgenic hormones. A better understanding of the molecular mechanisms controlling the development of the two tissues could help solve why cancer arises frequently in the prostate but only rarely in seminal vesicles. Working with cell and mouse models, Dutta
et al.
show that forced expression of a single gene, the homeobox gene
NKX3.1
, causes seminal vesicle epithelium to differentiate into prostate.
NKX3.1
regulates the expression of a gene program associated with prostate differentiation by interacting with the G9a histone methyltransferase. Disruption of this regulatory network probably contributes to prostate cancer development.

Science
, this issue p.
1576
Corals' microbial sentinels
Authors: Ainsworth Tracy D. , Gates Ruth D.
Published: June 2016

The coral microbiome will be key to future reef health
Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain
Authors: Lake Blue B. , Ai Rizi , Kaeser Gwendolyn E. , Salathia Neeraj S. , Yung Yun C. , Liu Rui , Wildberg Andre , Gao Derek , Fung Ho-Lim , Chen Song , Vijayaraghavan Raakhee , Wong Julian , Chen Allison , Sheng Xiaoyan , Kaper Fiona , Shen Richard , Ronaghi Mostafa , Fan Jian-Bing , Wang Wei , Chun Jerold , Zhang Kun
Published: June 2016

Single-nucleus gene expression

Identifying the genes expressed at the level of a single cell nucleus can better help us understand the human brain. Blue
et al.
developed a single-nuclei sequencing technique, which they applied to cells in classically defined Brodmann areas from a postmortem brain. Clustering of gene expression showed concordance with the area of origin and defining 16 neuronal subtypes. Both excitatory and inhibitory neuronal subtypes show regional variations that define distinct cortical areas and exhibit how gene expression clusters may distinguish between distinct cortical areas. This method opens the door to widespread sampling of the genes expressed in a diseased brain and other tissues of interest.

Science
, this issue p.
1586
Single-qubit gates based on targeted phase shifts in a 3D neutral atom array
Authors: Wang Yang , Kumar Aishwarya , Wu Tsung-Yao , Weiss David S.
Published: June 2016

How to single out the right atoms

For a quantum computer to be useful, its qubits have to be able to change their state in response to external stimuli. But when a large number of qubits are packed in a three-dimensional (3D) structure to optimize the use of space, altering one qubit can unintentionally change the state of others. Wang
et al.
devised a clever way to perform high-fidelity quantum gates only on intended qubits in a 3D array of Cs atoms. Although the operation initially changed the state of some of the other atoms, additional manipulation recovered their original state. The technique may be applicable to other quantum computing implementations.

Science
, this issue p.
1562
The social dilemma of autonomous vehicles
Authors: Bonnefon Jean-François , Shariff Azim , Rahwan Iyad
Published: June 2016

Codes of conduct in autonomous vehicles

When it becomes possible to program decision-making based on moral principles into machines, will self-interest or the public good predominate? In a series of surveys, Bonnefon
et al.
found that even though participants approve of autonomous vehicles that might sacrifice passengers to save others, respondents would prefer not to ride in such vehicles (see the Perspective by Greene). Respondents would also not approve regulations mandating self-sacrifice, and such regulations would make them less willing to buy an autonomous vehicle.

Science
, this issue p.
1573
; see also p.
1514
Polyelemental nanoparticle libraries
Authors: Chen Peng-Cheng , Liu Xiaolong , Hedrick James L. , Xie Zhuang , Wang Shunzhi , Lin Qing-Yuan , Hersam Mark C. , Dravid Vinayak P. , Mirkin Chad A.
Published: June 2016

Multimetal nanoparticle synthesis

Multicomponent nanoparticles can be difficult to synthesize. Rather than mixing in one type of particle, the compounds often separate and form distinct particles. Using dip-pen lithography, Chen
et al.
show how adding reactants to very small volumes forces the reactants to form single particles containing various combinations of five different transition metal ions. Scanning transmission electron microscopy and energy-dispersive x-ray spectroscopy revealed the shapes of the nanoparticles and how metallic composition varied within them. For example, the quinary particle containing gold, silver, cobalt, copper, and nickel consisted of three domains of binary alloys.

Science
, this issue p.
1565
Making babies
GMO Sapiens The Life-Changing Science of Designer Babies
Paul Knoepfler
World Scientific, 2016. 282 pp.
The End of Sex and the Future of Human Reproduction
Henry T. Greely
Harvard University Press, 2016. 391 pp.
Authors: Greenbaum Dov
Published: June 2016

Advances in genetics introduce new promise and perils into the business of being born
Exploring the many-body localization transition in two dimensions
Authors: Choi Jae-yoon , Hild Sebastian , Zeiher Johannes , Schauß Peter , Rubio-Abadal Antonio , Yefsah Tarik , Khemani Vedika , Huse David A. , Bloch Immanuel , Gross Christian
Published: June 2016

Bosons refusing to thermalize in 2D

Messy, interacting quantum-mechanical systems are difficult to analyze theoretically. In a single spatial dimension, the calculations are still tractable, and experiments have recently confirmed the prediction that sufficiently strong disorder can disrupt the transport of interacting particles. In two dimensions, however, the theoretical blueprint is missing. Choi
et al.
used single-site imaging of cold
87
Rb atoms in an optical lattice to show that similar localization occurs in two-dimensional (2D) systems. The study highlights the power of quantum simulation to solve problems that are currently inaccessible to classical computing techniques.

Science
, this issue p.
1547
Avoid the kinks when measuring mobility
Authors: McCulloch Iain , Salleo Alberto , Chabinyc Michael
Published: June 2016

Transistor measurements can overstate organic semiconductor charge carrier mobility
Our driverless dilemma
Authors: Greene Joshua D.
Published: June 2016

When should your car be willing to kill you?
Converting to adapt
Authors: Colonna Marco , Cervantes-Barragan Luisa
Published: June 2016

Gut microbiota affect T cell plasticity in the intestinal lining
Sequence Analysis of Fluoroquinolone Resistance-Associated Genes
gyrA
and
gyrB
in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India
Authors: Singhal Ritu , Reynolds Paul R. , Marola Jamie L. , Epperson L. Elaine , Arora Jyoti , Sarin Rohit , Myneedu Vithal Prasad , Strong Michael , Salfinger Max
Published: June 2016

Fluoroquinolones (FQs) are broad-spectrum antibiotics recommended for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients. FQ resistance, caused by mutations in the
gyrA
and
gyrB
genes of
Mycobacterium tuberculosis
, is increasingly reported worldwide; however, information on mutations occurring in strains from the Indian subcontinent is scarce. Hence, in this study, we aimed to characterize mutations in the
gyrA
and
gyrB
genes of acid-fast bacillus (AFB) smear-positive sediments or of
M. tuberculosis
isolates from AFB smear-negative samples from patients in India suspected of having MDR-TB. A total of 152 samples from patients suspected of having MDR-TB were included in the study. One hundred forty-six strains detected in these samples were characterized by sequencing of the
gyrA
and
gyrB
genes. The extracted DNA was subjected to successive amplifications using a nested PCR protocol, followed by sequencing. A total of 27 mutations were observed in the
gyrA
genes of 25 strains, while no mutations were observed in the
gyrB
genes. The most common mutations occurred at amino acid position 94 (13/27 [48.1%]); of these, the D94G mutation was the most prevalent. The
gyrA
mutations were significantly associated with patients with rifampin (RIF)-resistant TB. Heterozygosity was seen in 4/27 (14.8%) mutations, suggesting the occurrence of mixed populations with different antimicrobial susceptibilities. A high rate of FQ-resistant mutations (17.1%) was obtained among the isolates of TB patients suspected of having MDR-TB. These observations emphasize the need for accurate and rapid molecular tests for the detection of FQ-resistant mutations at the time of MDR-TB diagnosis.
Verification of an Automated, Digital Dispensing Platform for At-Will Broth Microdilution-Based Antimicrobial Susceptibility Testing
Authors: Smith Kenneth P. , Kirby James E.
Published: June 2016

With rapid emergence of multidrug-resistant bacteria, there is often a need to perform susceptibility testing for less commonly used or newer antimicrobial agents. Such testing can often be performed only by using labor-intensive, manual dilution methods and lies outside the capacity of most clinical labs, necessitating reference laboratory testing and thereby delaying the availability of susceptibility data. To address the compelling clinical need for microbiology laboratories to perform such testing in-house, we explored a novel, automated, at-will broth microdilution-based susceptibility testing platform. Specifically, we used the modified inkjet printer technology in the HP D300 digital dispensing system to dispense, directly from stock solutions into a 384-well plate, the 2-fold serial dilution series required for broth microdilution testing. This technology was combined with automated absorbance readings and data analysis to determine MICs. Performance was verified by testing members of the
Enterobacteriaceae
for susceptibility to ampicillin, cefazolin, ciprofloxacin, colistin, gentamicin, meropenem, and tetracycline in comparison to the results obtained with a broth microdilution reference standard. In precision studies, essential and categorical agreement levels were 96.8% and 98.3%, respectively. Furthermore, significantly fewer D300-based measurements were outside ±1 dilution from the modal MIC, suggesting enhanced reproducibility. In accuracy studies performed using a panel of 80 curated clinical isolates, rates of essential and categorical agreement and very major, major, and minor errors were 94%, 96.6%, 0%, 0%, and 3.4%, respectively. Based on these promising initial results, it is anticipated that the D300-based methodology will enable hospital-based clinical microbiology laboratories to perform at-will broth microdilution testing of antimicrobials and to address a critical testing gap.
CD4-Induced Antibodies Promote Association of the HIV-1 Envelope Glycoprotein with CD4-Binding Site Antibodies
Authors: Gardner Matthew R. , Fellinger Christoph H. , Prasad Neha R. , Zhou Amber S. , Kondur Hema R. , Joshi Vinita R. , Quinlan Brian D. , Farzan Michael
Published: June 2016

The HIV-1 envelope glycoprotein (Env) is a trimer of gp120/gp41 heterodimers that mediates viral entry. Env binds cellular CD4, an association which stabilizes a conformation favorable to its subsequent association with a coreceptor, typically CCR5 or CXCR4. The CD4- and coreceptor-binding sites serve as epitopes for two classes of HIV-1-neutralizing antibodies: CD4-binding site (CD4bs) and CD4-induced (CD4i) antibodies, respectively. Here we observed that, at a fixed total concentration, mixtures of the CD4i antibodies (E51 or 412d) and the CD4bs antibody VRC01 neutralized the HIV-1 isolates 89.6, ADA, SG3, and SA32 more efficiently than either antibody alone. We found that E51, and to a lesser extent 412d and 17b, promoted association of four CD4bs antibodies to the Env trimer but not to monomeric gp120. We further demonstrated that the binding of the sulfotyrosine-binding pocket by CCR5mim2-Ig was sufficient for promoting CD4bs antibody binding to Env. Interestingly, the relationship is not reciprocal: CD4bs antibodies were not as efficient as CD4-Ig at promoting E51 or 412d binding to Env trimer. Consistent with these observations, CD4-Ig, but none of the CD4bs antibodies tested, substantially increased HIV-1 infection of a CD4-negative, CCR5-positive cell line. We conclude that the ability of CD4i antibodies to promote VRC01 association with Env trimers accounts for the increase potency of VRC01 and CD4i antibody mixtures. Our data further suggest that potent CD4bs antibodies avoid inducing Env conformations that bind CD4i antibodies or CCR5.

IMPORTANCE
Potent HIV-1-neutralizing antibodies can prevent viral transmission and suppress an ongoing infection. Here we show that CD4-induced (CD4i) antibodies, which recognize the conserved coreceptor-binding site of the HIV-1 envelope glycoprotein (Env), can increase the association of Env with potent broadly neutralizing antibodies that recognize the CD4-binding site (CD4bs antibodies). We further show that, unlike soluble forms of CD4, CD4bs antibodies poorly induce envelope glycoprotein conformations that efficiently bind CCR5. This study provides insight into the properties of potent CD4bs antibodies and suggests that, under some conditions, CD4i antibodies can improve their potency. These observations may be helpful to the development of vaccines designed to elicit specific antibody classes.
Opposing Roles of Double-Stranded RNA Effector Pathways and Viral Defense Proteins Revealed with CRISPR-Cas9 Knockout Cell Lines and Vaccinia Virus Mutants
Authors: Liu Ruikang , Moss Bernard
Published: June 2016

Vaccinia virus (VACV) decapping enzymes and cellular exoribonuclease Xrn1 catalyze successive steps in mRNA degradation and prevent double-stranded RNA (dsRNA) accumulation, whereas the viral E3 protein can bind dsRNA. We showed that dsRNA and E3 colocalized within cytoplasmic viral factories in cells infected with a decapping enzyme mutant as well as with wild-type VACV and that they coprecipitated with antibody. An E3 deletion mutant induced protein kinase R (PKR) and eukaryotic translation initiation factor alpha (eIF2α) phosphorylation earlier and more strongly than a decapping enzyme mutant even though less dsRNA was made, leading to more profound effects on viral gene expression. Human HAP1 and A549 cells were genetically modified by clustered regularly interspaced short palindromic repeat-Cas9 (CRISPR-Cas9) to determine whether the same pathways restrict E3 and decapping mutants. The E3 mutant replicated in PKR knockout (KO) HAP1 cells in which RNase L is intrinsically inactive but only with a double knockout (DKO) of PKR and RNase L in A549 cells, indicating that both pathways decreased replication equivalently and that no additional dsRNA pathway was crucial. In contrast, replication of the decapping enzyme mutant increased significantly (though less than that of wild-type virus) in DKO A549 cells but not in DKO HAP1 cells where a smaller increase in viral protein synthesis occurred. Xrn1 KO A549 cells were viable but nonpermissive for VACV; however, wild-type and mutant viruses replicated in triple-KO cells in which RNase L and PKR were also inactivated. Since KO of PKR and RNase L was sufficient to enable VACV replication in the absence of E3 or Xrn1, the poor replication of the decapping mutant, particularly in HAP1 DKO, cells indicated additional translational defects.

IMPORTANCE
Viruses have evolved ways of preventing or counteracting the cascade of antiviral responses that double-stranded RNA (dsRNA) triggers in host cells. We showed that the dsRNA produced in excess in cells infected with a vaccinia virus (VACV) decapping enzyme mutant and by wild-type virus colocalized with the viral E3 protein in cytoplasmic viral factories. Novel human cell lines defective in either or both protein kinase R and RNase L dsRNA effector pathways and/or the cellular 5′ exonuclease Xrn1 were prepared by CRISPR-Cas9 gene editing. Inactivation of both pathways was necessary and sufficient to allow full replication of the E3 mutant and reverse the defect cause by inactivation of Xrn1, whereas the decapping enzyme mutant still exhibited defects in gene expression. The study provided new insights into functions of the VACV proteins, and the well-characterized panel of CRISPR-Cas9-modified human cell lines should have broad applicability for studying innate dsRNA pathways.
Results of a nationally implemented de novo cardiac screening programme in elite rugby players in England
Authors: Ghani Saqib , Papadakis Michael , Kemp Simon , Zaidi Abbas , Sheikh Nabeel , Gati Sabiha , Raju Hariharan , Smith Andy , Palmer Corin , Somauroo John , Sharma Sanjay
Published: June 2016

Background/aim

Screening of young competitive athletes remains a contentious issue. In 2010, a nationwide cardiac screening for all elite rugby players was introduced in England. This provided a unique opportunity to prospectively assess the feasibility and cost-effectiveness of a de novo, ECG-based cardiac screening programme.

Methods

Between 2010 and 2012, 1191 rugby players aged ≥14 years underwent cardiac screening with a health questionnaire, 12-lead ECG and a consultation with a cardiologist. The players with concerning findings on initial evaluation were offered on-site transthoracic echocardiogram (TTE). Athletes were referred for further investigations as deemed necessary. The overall cost of the screening programme was estimated.

Results

After initial evaluation, 9.7% of athletes underwent on-site TTE; 8.2% underwent on-site TTE due to ECG anomalies and 1.4% underwent on-site TTE due to concerns on the questionnaire. After TTE, only 2.9% of the total cohort was referred for further evaluation. Two players were diagnosed with potentially serious conditions; one with Wolff-Parkinson-White, who resumed competition after catheter ablation, and one with hypertrophic cardiomyopathy, who withdrew from competition. During a mean follow-up of 52.8±5.5 months, none of the players who were reassured experienced any adverse cardiac events. The total cost of the screening programme was £59 875, which averaged to a cost of £50 per player or £29 938 per condition identified. Application of refined ECG criteria would reduce the ECG false-positive rate to 4.9%.

Conclusions

Preparticipation cardiac screening with 12-lead ECG is feasible. Refinement of the ECG criteria, the use of on-site TTE and expert setting can minimise the burden of unnecessary investigations and reduce costs.
Clinical reasoning of junior doctors in emergency medicine: a grounded theory study
Authors: Adams E , Goyder C , Heneghan C , Brand L , Ajjawi R
Published: June 2016

Introduction

Emergency medicine (EM) has a high case turnover and acuity making it a demanding clinical reasoning domain especially for junior doctors who lack experience. We aimed to better understand their clinical reasoning using dual cognition as a guiding theory.

Methods

EM junior doctors were recruited from six hospitals in the south of England to participate in semi-structured interviews (n=20) and focus groups (n=17) based on recall of two recent cases. Transcripts were analysed using a grounded theory approach to identify themes and to develop a model of junior doctors' clinical reasoning in EM.

Results

Within cases, clinical reasoning occurred in three phases. In phase 1 (case framing), initial case cues and first impressions were predominantly intuitive, but checked by analytical thought and determined the urgency of clinical assessment. In phase 2 (evolving reasoning), non-analytical single cue and pattern recognitions were common which were subsequently validated by specific analytical strategies such as use of red flags. In phase 3 (ongoing uncertainty) analytical self-monitoring and reassurance strategies were used to precipitate a decision regarding discharge.

Conclusion

We found a constant dialectic between intuitive and analytical cognition throughout the reasoning process. Our model of clinical reasoning by EM junior doctors illustrates the specific contextual manifestations of the dual cognition theory. Distinct diagnostic strategies are identified and together these give EM learners and educators a framework and vocabulary for discussion and learning about clinical reasoning.
Safety in numbers for cyclists beyond national-level and city-level data: a study on the non-linearity of risk within the city of Hong Kong
Authors: Yao Shenjun , Loo Becky P Y
Published: June 2016

Objective

This paper examines the relationship between bicycle collisions and the amount of cycling at the local level. Most previous research has focused on national and city comparisons, little is known about differences within a city (the mesoscale).

Methods

This study mainly used three types of data sets relating to bicycle collisions, use of bicycles and local neighbourhood characteristics in Hong Kong. In particular, bicycle usage, measured as bicycle-kilometres travelled, was estimated from travel surveys following the activity-based approach. Negative binomial regression models were established to model the relationship between the amount of cycling and the occurrence of bicycle collisions at the spatial scale of the Tertiary Planning Unit, which is the smallest planning unit of the city.

Results

The numbers of bicycle collisions went up with the increasing use of bicycles, but the increase in the number of collisions in a given community was less than a linear proportion of the bicycle flow. When other local neighbourhood variables are controlled, the amount of cycling is a statistically significant variable in accounting for the number of collisions.

Conclusions

Even in a highly motorised city where bicycles are a minor transport mode, cyclists are less likely to be involved in road collisions in communities with higher cycling volume. Since cycling activities are likely to vary within a city, a more local-based approach in promoting cycling is needed. In particular, the higher safety risks in neighbourhoods of low bicycle usage, especially at an initial stage of promoting cycling, need to be addressed properly.
Laundry pod and non-pod detergent related emergency department visits occurring in children in the USA
Authors: Swain Thomas A , McGwin Gerald , Griffin Russell
Published: June 2016

Objective

Previous studies have reported that children are at risk of severe injuries from exposure to laundry detergent pods. For the first time, this study sought to compare demographic and exposure characteristics and risk among children exposed to pod and non-pod laundry detergents presenting to emergency departments (EDs).

Methods

Data from the National Electronic Injury Surveillance System (NEISS) from 2012–2014 were used. All observations with injuries involving laundry detergent (NEISS code 0949) were included in this study. The χ2test was used for bivariate analysis and logistic regression was used to determine the OR and 95% CI of hospitalisation for pod related versus non-pod laundry detergent exposures.

Results

From 2012–2014, there were an estimated 26 062 non-pod and 9814 pod laundry detergent related exposures among those aged 18 years and younger. For pod detergent, children aged 0–5 years had the most injuries. Poisoning (71.3%) was the most common diagnosis for pod detergent while contact dermatitis (72.2%) was most common for non-pod detergent. Hospitalisation occurred in 12.5% of pod detergent cases and just 3.0% of non-pod cases. Compared with non-pod detergent, those exposed to pod detergent were 4 times as likely to be hospitalised (OR 4.02; 95% CI 1.96 to 8.24).

Conclusions

A greater effort should be made to appropriately educate the public about the dangers of laundry detergents, specifically pods, so a safe home environment can be established. While new regulations such as childproof containers, opaque packaging, and less appealing and colourful pods could reduce the number of pod related ED visits for children, caregivers should store detergents, along with other chemicals, in a secure location where children cannot easily access them.
Tandem aldol condensation-Diels–Alder-aromatization sequence of reactions: a new pathway for the synthesis of 2-tetralone derivatives
Authors: Abaee M. Saeed , Doustkhah Esmail , Mohammadi Mohaddeseh , Mojtahedi Mohammad M. , Harms Klaus
Published: June 2016

A series of new polysubstituted derivatives of 2-tetralones possessing two ester groups were synthesized via a tandem aldol condensation-Diels–Alder-aromatization sequence of reactions. All the three steps took place in one pot and in the presence of aminofunctionalized silica coated Fe3O4 nanoparticles as the catalyst. In situ formed dienes reacted with diethyl acetylenedicarboxylate at room temperature and the process was followed by spontaneous aromatization of the cycloadducts to produce high yields of the final tetralone products. Further studies suggest that the process goes through an initial aldol condensation-cycloaddition sequence followed by oxidation and rearrangement steps. After completion of the reactions, the catalyst could be recycled and reused efficiently in subsequent reactions.
The cardioprotection of dihydrotanshinone I against myocardial ischemia–reperfusion injury via inhibition of arachidonic acid ω-hydroxylase
Authors: Wei Yidan , Xu Meijuan , Ren Yi , Lu Guo , Xu Yangmei , Song Yangyang , Ji Hui
Published: June 2016

Arachidonic acid (AA) is a precursor that is metabolized by several enzymes to many biological eicosanoids. Accumulating data indicate that the ω-hydroxylation metabolite of AA, 20-hydroxyeicosatetraenoic acid (20-HETE), is considered to be involved in the myocardial ischemia–reperfusion injury (MIRI). The inhibitors of AA ω-hydroxylase, however, are demonstrated to exhibit protective effects on MIRI. Dihydrotanshinone I (DI), a bioactive constituent of danshen, is proven to be a potent inhibitor of AA ω-hydroxylase by our preliminary study in vitro. The purpose of the present study was to investigate the cardioprotection of DI against MIRI and its effects on the concentrations of 20-HETE in vivo. Rats subjected to 30 min of ischemia followed by 24 h of reperfusion were assigned to intravenously receive vehicle (sham and ischemia–reperfusion), low (1 mg/kg), middle (2 mg/kg), or high (4 mg/kg) doses of DI before reperfusion. The results demonstrated that DI treatment could improve cardiac function, reduce infarct size, ameliorate the variations in myocardial zymogram and histopathological disorders, decrease 20-HETE generation, and regulate apoptosis-related protein in myocardial ischemia–reperfusion rats. These findings suggested DI could exert considerable cardioprotective action on MIRI by the attenuation of 20-HETE generation, subsequent myocardial injury, and apoptosis through inhibition on AA ω-hydroxylase.
Phosphate rock: origin, importance, environmental impacts, and future roles
Authors: Fayiga Abioye O. , Nwoke O.C.
Published: June 2016

Phosphate rock (PR) is an important mineral resource with numerous uses and applications in agriculture and the environment. PR is used in the manufacture of detergents, animal feed, and phosphate (PO43–) fertilizers. Leaching or runoff losses from PR products like PO43– fertilizers, animal feeds, and detergents could cause eutrophication of surface waters enriched in PO43– by these losses. Although direct application of PR reduces pollution by acting as a slow-release fertilizer, its effectiveness is limited by several factors. The major limitation of PR in direct application is its low solubility, which reduces its availability for soil reactions or plant uptake. Strategies used to increase the effectiveness of directly applied PR are based on increasing acidity, as this increases PR solubility. The application of PR in agriculture may have adverse effects because it contains hazardous elements that could be transferred to the soil through the application of fertilizers, especially after long term use. Chemical analysis of PR obtained from top PR-producing countries, however, shows that hazardous elements contained therein are below tolerable limits for PO43– fertilizers. Studies have also reported that the radionuclides in PR do not pose any radiological risk. The presence of these elements in PR can be put to positive use if they are extracted before they are applied to farmlands. This makes PR a source of rare earth metals and radionuclides that could be used in technological development and as a future energy source. The affinity of PR for metals makes it a useful adsorbent for the removal of metals from aqueous solutions and an excellent material for metal immobilization in contaminated soils. PR is a very important finite resource but its applications have adverse environmental implications.
Frequency dependence and fuel effect on optical properties of nano TiO2-based structures
Authors: Ghasemifard Mahdi , Ghamari Misagh , Iziy Meysam
Published: June 2016

TiO2-(Ti[Formula: see text]Si[Formula: see text]O2 nanopowders (TS-NPs) with average particle size around 90 nm were successfully synthesized by controlled auto-combustion method by using citric acid/nitric acid (AC:NA) and urea/metal cation (U:MC). The structure of powders was studied based on their X-ray diffraction (XRD) patterns. The XRD of TS-NPs shows that rutile and anatase are the main phases of TS-NPs for AC:NA and U:MC, respectively. Particle size and histogram of nanopowders were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Optical properties of TS-NPs were calculated by Fourier transform infrared spectroscopy (FTIR) and Kramers–Kroning (KK) relation. Plasma frequencies of TS-NPs obtained from energy loss functions depend on fuels as a result of changes in crystal structure, particle size distribution, and morphology.
New insights into quantum gravity from gauge/gravity duality
Authors: Engelhardt Netta , Horowitz Gary T.
Published: June 2016

Using gauge/gravity duality, we deduce several nontrivial consequences of quantum gravity from simple properties of the dual field theory. These include: (1) a version of cosmic censorship, (2) restrictions on evolution through black hole singularities, and (3) the exclusion of certain cosmological bounces. In the classical limit, the latter implies a new singularity theorem.
Modelling Infinite Length Panels Using the Finite Element Method
Authors: Fenner Patrick , Watson Andrew , Featherston Carol
Published: June 2016

This paper compares three finite element models for determining the buckling and post-buckling performance of infinite length thin walled composite and metal stiffened panels — such as for modeling theoretical aircraft upper wing skin panels — namely single bay, double half-bay and quad half-bay models. The quad half-bay model is shown to be the ideal model as all wavelengths of buckling are permitted. This model gives an accurate estimate of postbuckling behavior that can include advanced behavior such as mode jumping or collapse while the single bay and double half-bay models are more restrictive and do not allow for accurate mode jumping to take place. Sample panels are analyzed for buckling performance using the computer program VICONOPT, which assumes an infinite length structure based on exact strip theory. This analysis is then compared to results from the quad half-bay FEM model, using the Abaqus solver, where the two models are in good agreement for the initial buckling performance for both the metal and composite panels. Buckling prediction for the quad half-bay model is within [Formula: see text] for the critical buckling mode, and within [Formula: see text] of all compared modes; and postbuckling performance compares well with the results of previous investigation of the same sample panel geometry.
Estimation of Dispersion in an Open Channel from an Elevated Source Using an Upwind Local Meshless Method
Authors: Siraj-ul-Islam  , Singh Vikendra , Kumar Sushil
Published: June 2016

Numerical solution of steady state partial differential equation (PDE) model is proposed using a stabilized local meshless method (SLMM). The PDE model under consideration is used to approximate longitudinal dispersion of suspended particles of turbulent flow moving with both zero and nonzero settling velocities. In the proposed technique, a shape parameter based SLMM is used to calculate effects of mean velocity and variable eddy diffusivity accurately. In the case of zero settling velocity, when particles are injected from a line source located at some height, numerical results confirm the experimental results. Numerical results of the SLMM also confirm numerical results produced by finite difference method (FDM) as well.
An Extended Cell-Based Smoothed Three-Node Mindlin Plate Element (XCS-MIN3) for Free Vibration Analysis of Cracked FGM Plates
Authors: Nguyen-Thoi T. , Rabczuk T. , Ho-Huu V. , Le-Anh L. , Dang-Trung H. , Vo-Duy T.
Published: June 2016

A cell-based smoothed three-node Mindlin plate element (CS-MIN3) was recently proposed and proven to be robust for static and free vibration analyses of Mindlin plates. The method improves significantly the accuracy of the solution due to softening effect of the cell-based strain smoothing technique. In addition, it is very flexible to apply for arbitrary complicated geometric domains due to using only three-node triangular elements which can be easily generated automatically. However so far, the CS-MIN3 has been only developed for isotropic material and for analyzing intact structures without possessing internal cracks. The paper hence tries to extend the CS-MIN3 by integrating itself with functionally graded material (FGM) and enriched functions of the extended finite element method (XFEM) to give a so-called extended cell-based smoothed three-node Mindlin plate (XCS-MIN3) for free vibration analysis of cracked FGM plates. Three numerical examples with different conditions are solved and compared with previous published results to illustrate the accuracy and reliability of the XCS-MIN3 for free vibration analysis of cracked FGM plates.
Light enhanced resistive switching in BaTiO3/CoFeB/BaTiO3 structure
Authors: Li Hongwei , Sun Bai , Wei Lujun , Wu Jianhong , Jia Xiangjiang , Zhao Wenxi , Chen Peng
Published: June 2016

Obvious resistive switching is observed under light irradiation in BaTiO3/CoFeB/BaTiO3 trilayer prepared by magnetron sputtering system while the same sample shows extremely small resistive switching effect in the dark. Under the irradiation of 31.4[Formula: see text]mW/cm2, the ratio of high resistance to low resistance (OFF/ON ratio) of the sample annealed at 600[Formula: see text]C can keep about 80 in more than 70 test cycles without obvious decay. The current conduction mechanism is PF emission in LRS and space charge limited conduction (SCLC) in HRS. The origin of the resistive switching behavior can be explained by considering the trapping and detrapping of charges.
Ursodeoxycholic acid inhibits TNFα-induced IL-8 release from monocytes
Authors: O'Dwyer Aoife M. , Lajczak Natalia K. , Keyes Jennifer A. , Ward Joseph B. , Greene Catherine M. , Keely Stephen J.
Published: June 2016

Monocytes are critical to the pathogenesis of inflammatory bowel disease (IBD) as they infiltrate the mucosa and release cytokines that drive the inflammatory response. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid with anti-inflammatory actions, has been proposed as a potential new therapy for IBD. However, its effects on monocyte function are not yet known. Primary monocytes from healthy volunteers or cultured U937 monocytes were treated with either the proinflammatory cytokine, TNFα (5 ng/ml) or the bacterial endotoxin, lipopolysaccharide (LPS; 1 μg/ml) for 24 h, in the absence or presence of UDCA (25–100 μM). IL-8 release into the supernatant was measured by ELISA. mRNA levels were quantified by qPCR and changes in cell signaling proteins were determined by Western blotting. Toxicity was assessed by measuring lactate dehydrogenase (LDH) release. UDCA treatment significantly attenuated TNFα-, but not LPS-driven, release of IL-8 from both primary and cultured monocytes. UDCA inhibition of TNFα-driven responses was associated with reduced IL-8 mRNA expression. Both TNFα and LPS stimulated NFκB activation in monocytes, while IL-8 release in response to both cytokines was attenuated by an NFκB inhibitor, BMS-345541. Interestingly, UDCA inhibited TNFα-, but not LPS-stimulated, NFκB activation. Finally, TNFα, but not LPS, induced phosphorylation of TNF receptor associated factor (TRAF2), while UDCA cotreatment attenuated this response. We conclude that UDCA specifically inhibits TNFα-induced IL-8 release from monocytes by inhibiting TRAF2 activation. Since such actions would serve to dampen mucosal immune responses in vivo, our data support the therapeutic potential of UDCA for IBD.
Antiapoptotic effect of exercise training on ovariectomized rat hearts
Authors: Huang Chih-Yang , Lin Yi-Yuan , Hsu Chih-Chao , Cheng Shiu-Min , Shyu Woei-Cherng , Ting Hua , Yang Ai-Lun , Ho Tsung-Jung , Lee Shin-Da
Published: June 2016

The purpose of this study was to evaluate the effects of exercise training on cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways in ovariectomized rats. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from three groups of Sprague-Dawley rats, which were divided into a sham-operated group, a bilaterally ovariectomized group (OVX), and a bilaterally ovariectomized group that underwent treadmill running exercise for 60 min/day, 5 sessions/wk, for 10 wk (OVX-EX). The abnormal myocardial architecture, cardiac trichome-stained fibrosis and cardiac TUNEL-positive apoptotic cells in ovariectomized rats improved after exercise training. The protein levels of tumor necrosis factor-α, tumor necrosis factor receptor 1, Fas ligand, Fas receptors, Fas-associated death domain, activated caspase-8 and activated caspase-3 (Fas receptor-dependent apoptotic pathways), as well as t-Bid, Bad, Bak, Bax, cytosolic cytochrome c, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) were decreased in the OVX-EX group compared with the OVX group. Exercise training suppressed ovariectomy-induced cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways in ovariectomized rat models. These findings might indicate a new therapeutic effect for exercise training to prevent cardiac apoptosis in menopausal or bilaterally oophorectomized women.
Mechanisms of spreading depolarization in vertebrate and insect central nervous systems
Authors: Spong Kristin E. , Andrew R. David , Robertson R. Meldrum
Published: June 2016

Spreading depolarization (SD) is generated in the central nervous systems of both vertebrates and invertebrates. SD manifests as a propagating wave of electrical depression caused by a massive redistribution of ions. Mammalian SD underlies a continuum of human pathologies from migraine to stroke damage, whereas insect SD is associated with environmental stress-induced neural shutdown. The general cellular mechanisms underlying SD seem to be evolutionarily conserved throughout the animal kingdom. In particular, SD in the central nervous system of Locusta migratoria and Drosophila melanogaster has all the hallmarks of mammalian SD. Locust SD is easily induced and monitored within the metathoracic ganglion (MTG) and can be modulated both pharmacologically and by preconditioning treatments. The finding that the fly brain supports repetitive waves of SD is relatively recent but noteworthy, since it provides a genetically tractable model system. Due to the human suffering caused by SD manifestations, elucidating control mechanisms that could ultimately attenuate brain susceptibility is essential. Here we review mechanisms of SD focusing on the similarities between mammalian and insect systems. Additionally we discuss advantages of using invertebrate model systems and propose insect SD as a valuable model for providing new insights to mammalian SD.
Effect of coordinate frame compatibility on the transfer of implicit and explicit learning across limbs
Authors: Poh Eugene , Carroll Timothy J. , Taylor Jordan A.
Published: June 2016

Insights into the neural representation of motor learning can be obtained by investigating how learning transfers to novel task conditions. We recently demonstrated that visuomotor rotation learning transferred strongly between left and right limbs when the task was performed in a sagittal workspace, which afforded a consistent remapping for the two limbs in both extrinsic and joint-based coordinates. In contrast, transfer was absent when performed in horizontal workspace, where the extrinsically defined perturbation required conflicting joint-based remapping for the left and right limbs. Because visuomotor learning is thought to be supported by both implicit and explicit forms of learning, however, it is unclear to what extent these distinct forms of learning contribute to interlimb transfer. In this study, we assessed the degree to which interlimb transfer, following visuomotor rotation training, reflects explicit vs. implicit learning by obtaining verbal reports of participants' aiming direction before each movement. We also determined the extent to which these distinct components of learning are constrained by the compatibility of coordinate systems by comparing transfer between groups of participants who reached to targets arranged in the horizontal and sagittal planes. Both sagittal and horizontal conditions displayed complete transfer of explicit learning to the untrained limb. In contrast, transfer of implicit learning was incomplete, but the sagittal condition showed greater transfer than the horizontal condition. These findings suggest that explicit strategies developed with one limb can be fully implemented in the opposite limb, whereas implicit transfer depends on the degree to which new sensorimotor maps are spatially compatible for the two limbs.
Decreased cerebellar-cerebral connectivity contributes to complex task performance
Authors: Katz Curren , Knops André
Published: June 2016

The cerebellum's role in nonmotor processes is now well accepted, but cerebellar interaction with cerebral targets is not well understood. Complex cognitive tasks activate cerebellar, parietal, and frontal regions, but the effective connectivity between these regions has never been tested. To this end, we used psycho-physiological interactions (PPI) analysis to test connectivity changes of cerebellar and parietal seed regions in complex (2-digit by 1-digit multiplication, e.g., 12 × 3) vs. simple (1-digit by 1-digit multiplication, e.g., 4 × 3) task conditions (“complex − simple”). For cerebellar seed regions (lobule VI, hemisphere and vermis), we found significantly decreased cerebellar-parietal, cerebellar-cingulate, and cerebellar-frontal connectivity in complex multiplication. For parietal seed regions (PFcm, PFop, PFm) we found significantly increased parietal-parietal and parietal-frontal connectivity in complex multiplication. These results suggest that decreased cerebellar-cerebral connectivity contributes to complex task performance. Interestingly, BOLD activity contrasts revealed partially overlapping parietal areas of increased BOLD activity but decreased cerebellar-parietal PPI connectivity.
“Real-time” imaging of cortical and subcortical sites of cardiovascular control: concurrent recordings of sympathetic nerve activity and fMRI in awake subjects
Authors: Macefield Vaughan G. , Henderson Luke A.
Published: June 2016

We review our approach to functionally identifying cortical and subcortical areas involved in the generation of spontaneous fluctuations in sympathetic outflow to muscle or skin. We record muscle sympathetic nerve activity (MSNA) or skin sympathetic nerve activity (SSNA), via a tungsten microelectrode inserted percutaneously into the common peroneal nerve, at the same time as performing functional magnetic resonance imaging (fMRI) of the brain. By taking advantage of the neurovascular coupling delay associated with BOLD (blood oxygen level dependent) fMRI, and the delay associated with conduction of a burst of sympathetic impulses to the peripheral recording site, we can identify structures in which BOLD signal intensity covaries with MSNA or SSNA. Using this approach, we found MSNA-coupled increases in BOLD signal intensity in the mid-insula and dorsomedial hypothalamus on the left side, and in dorsolateral prefrontal cortex, posterior cingulate cortex, precuneus, ventromedial hypothalamus and rostral ventrolateral medulla on both sides. Conversely, spontaneous bursts of SSNA were positively correlated with BOLD signal intensity in the ventromedial thalamus and posterior insula on the left side, and in the anterior insula, orbitofrontal cortex and frontal cortex on the right side, and in the mid-cingulate cortex and precuneus on both sides. Inverse relationships were observed between MSNA and BOLD signal intensity in the right ventral insula, nucleus tractus solitarius and caudal ventrolateral medulla, and between SSNA and signal intensity in the left orbitofrontal cortex. These results emphasize the contributions of cortical regions of the brain to sympathetic outflow in awake human subjects, and the extensive interactions between cortical and subcortical regions in the ongoing regulation of sympathetic nerve activity to muscle and skin in awake human subjects.
Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation
Authors: Davenport Gregory C. , Hittner James B. , Otieno Vincent , Karim Zachary , Mukundan Harshini , Fenimore Paul W. , Hengartner Nicolas W. , McMahon Benjamin H. , Kempaiah Prakasha , Ong’echa John M. , Perkins Douglas J.
Published: June 2016

Bacteremia and malaria coinfection is a common and life-threatening condition in children residing in sub-Saharan Africa. We previously showed that coinfection with Gram negative (G[−]) enteric Bacilli andPlasmodium falciparum(Pf[+]) was associated with reduced high-density parasitemia (HDP, >10,000 parasites/μL), enhanced respiratory distress, and severe anemia. Since inflammatory mediators are largely unexplored in such coinfections, circulating cytokines were determined in four groups of children (n=206, aged <3 yrs): healthy;Pf[+] alone; G[−] coinfected; and G[+] coinfected.Staphylococcus aureusand non-TyphiSalmonellawere the most frequently isolated G[+] and G[−] organisms, respectively. Coinfected children, particularly those with G[−] pathogens, had lower parasite burden (peripheral and geometric mean parasitemia and HDP). In addition, both coinfected groups had increased IL-4, IL-5, IL-7, IL-12, IL-15, IL-17, IFN-γ, and IFN-αand decreased TNF-αrelative to malaria alone. Children with G[−] coinfection had higher IL-1βand IL-1Ra and lower IL-10 than thePf[+] group and higher IFN-γthan the G[+] group. To determine how the immune response to malaria regulates parasitemia, cytokine production was investigated with a multiple mediation model. Cytokines with the greatest mediational impact on parasitemia were IL-4, IL-10, IL-12, and IFN-γ. Results here suggest that enhanced immune activation, especially in G[−] coinfected children, acts to reduce malaria parasite burden.