bluuebunny/crossref_metadata_2025 huggingface dataset:
The Activity of Glycopeptide Antibiotics against Resistant Bacteria Correlates with Their Ability To Induce the Resistance System
Authors: Kwun Min Jung , Hong Hee-Jeon
Published: August 2014

Glycopeptide antibiotics containing a hydrophobic substituent display the best activity against vancomycin-resistant enterococci, and they have been assumed to be poor inducers of the resistance system. Using a panel of 26 glycopeptide derivatives and the model resistance system in
Streptomyces coelicolor
, we confirmed this hypothesis at the level of transcription. Identification of the structural glycopeptide features associated with inducing the expression of resistance genes has important implications in the search for more effective antibiotic structures.
Thorax Injury Lowers Resistance to Infection in Drosophila melanogaster
Authors: Chambers Moria C. , Jacobson Eliana , Khalil Sarah , Lazzaro Brian P.
Published: August 2014

The route of infection can profoundly affect both the progression and outcome of disease. We investigated differences in
Drosophila melanogaster
defense against infection after bacterial inoculation into two sites—the abdomen and the thorax. Thorax inoculation results in increased bacterial proliferation and causes high mortality within the first few days of infection. In contrast, abdomen inoculation results in minimal mortality and lower bacterial loads than thorax inoculation. Inoculation into either site causes systemic infection. Differences in mortality and bacterial load are due to injury of the thorax and can be recapitulated by abdominal inoculation coupled with aseptic wounding of the thorax. This altered resistance appears to be independent of classical immune pathways and opens new avenues of research on the role of injury during defense against infection.
Probing the Structure of the S105 Hole
Authors: To Kam H. , Young Ry
Published: August 2014

For most phages, holins control the timing of host lysis. During the morphogenesis period of the infection cycle, canonical holins accumulate harmlessly in the cytoplasmic membrane until they suddenly trigger to form lethal lesions called holes. The holes can be visualized by cryo-electron microscopy and tomography as micrometer-scale interruptions in the membrane. To explore the fine structure of the holes formed by the lambda holin, S105, a cysteine-scanning accessibility study was performed. A collection of
S105
alleles encoding holins with a single Cys residue in different positions was developed and characterized for lytic function. Based on the ability of 4-acetamido-4′-((iodoacetyl) amino) stilbene-2,2′-disulfonic acid, disodium salt (IASD), to modify these Cys residues, one face of transmembrane domain 1 (TMD1) and TMD3 was judged to face the lumen of the S105 hole. In both cases, the lumen-accessible face was found to correspond to the more hydrophilic face of the two TMDs. Judging by the efficiency of IASD modification, it was concluded that the bulk of the S105 protein molecules were involved in facing the lumen. These results are consistent with a model in which the perimeters of the S105 holes are lined by the holin molecules present at the time of lysis. Moreover, the findings that TMD1 and TMD3 face the lumen, coupled with previous results showing TMD2-TMD2 contacts in the S105 dimer, support a model in which membrane depolarization drives the transition of S105 from homotypic to heterotypic oligomeric interactions.
Maturation of the Human Papillomavirus 16 Capsid
Authors: Cardone Giovanni , Moyer Adam L. , Cheng Naiqian , Thompson Cynthia D. , Dvoretzky Israel , Lowy Douglas R. , Schiller John T. , Steven Alasdair C. , Buck Christopher B. , Trus Benes L.
Published: August 2014

Papillomaviruses are a family of nonenveloped DNA viruses that infect the skin or mucosa of their vertebrate hosts. The viral life cycle is closely tied to the differentiation of infected keratinocytes. Papillomavirus virions are released into the environment through a process known as desquamation, in which keratinocytes lose structural integrity prior to being shed from the surface of the skin. During this process, virions are exposed to an increasingly oxidative environment, leading to their stabilization through the formation of disulfide cross-links between neighboring molecules of the major capsid protein, L1. We used time-lapse cryo-electron microscopy and image analysis to study the maturation of HPV16 capsids assembled in mammalian cells and exposed to an oxidizing environment after cell lysis. Initially, the virion is a loosely connected procapsid that, under
in vitro
conditions, condenses over several hours into the more familiar 60-nm-diameter papillomavirus capsid. In this process, the procapsid shrinks by ~5% in diameter, its pentameric capsomers change in structure (most markedly in the axial region), and the interaction surfaces between adjacent capsomers are consolidated. A C175S mutant that cannot achieve normal inter-L1 disulfide cross-links shows maturation-related shrinkage but does not achieve the fully condensed 60-nm form. Pseudoatomic modeling based on a 9-Å resolution reconstruction of fully mature capsids revealed C-terminal disulfide-stabilized “suspended bridges” that form intercapsomeric cross-links. The data suggest a model in which procapsids exist in a range of dynamic intermediates that can be locked into increasingly mature configurations by disulfide cross-linking, possibly through a Brownian ratchet mechanism.

IMPORTANCE
Human papillomaviruses (HPVs) cause nearly all cases of cervical cancer, a major fraction of cancers of the penis, vagina/vulva, anus, and tonsils, and genital and nongenital warts. HPV types associated with a high risk of cancer, such as HPV16, are generally transmitted via sexual contact. The nonenveloped virion of HPVs shows a high degree of stability, allowing the virus to persist in an infectious form in environmental fomites. In this study, we used cryo-electron microscopy to elucidate the structure of the HPV16 capsid at different stages of maturation. The fully mature capsid adopts a rigid, highly regular structure stabilized by intermolecular disulfide bonds. The availability of a pseudoatomic model of the fully mature HPV16 virion should help guide understanding of antibody responses elicited by HPV capsid-based vaccines.
The effects of pre-exhaustion, exercise order, and rest intervals in a full-body resistance training intervention
Authors: Fisher James Peter , Carlson Luke , Steele James , Smith Dave
Published: August 2014

Pre-exhaustion (PreEx) training is advocated on the principle that immediately preceding a compound exercise with an isolation exercise can target stronger muscles to pre-exhaust them to obtain greater adaptations in strength and size. However, research considering PreEx training method is limited. The present study looked to examine the effects of a PreEx training programme. Thirty-nine trained participants (male = 9, female = 30) completed 12 weeks of resistance training in 1 of 3 groups: a group that performed PreEx training (n = 14), a group that performed the same exercise order with a rest interval between exercises (n = 17), and a control group (n = 8) that performed the same exercises in a different order (compound exercises prior to isolation). No significant between-group effects were found for strength in chest press, leg press, or pull-down exercises, or for body composition changes. Magnitude of change was examined for outcomes also using effect size (ES). ESs for strength changes were considered large for each group for every exercise (ranging 1.15 to 1.62). In conclusion, PreEx training offers no greater benefit to performing the same exercises with rest between them compared with exercises performed in an order that prioritises compound movements.
One-Dimensional Nanostructured TiO2for Photocatalytic Degradation of Organic Pollutants in Wastewater
Authors: Feng Ting , Feng Gen Sheng , Yan Lei , Pan Jia Hong
Published: August 2014

The present paper reviews the progress in the synthesis of one-dimensional (1D) TiO2nanostructures and their environmental applications in the removal of organic pollutants. According to the shape, 1D TiO2nanostructures can be divided into nanorods, nanotubes, nanowires/nanofibers, and nanobelts. Each of them can be synthesized via different technologies, such as sol-gel template method, chemical vapor deposition, and hydrothermal method. These methods are discussed in this paper, and the recent development of the synthesis technologies is also presented. Furthermore, the organic pollutants, degradation using the synthesized 1D TiO2nanostructures is studied as an important application of photocatalytic oxidation (PCO). The 1D nanostructured TiO2exhibited excellent photocatalytic activity in a PCO process, and the mechanism of photocatalytic degradation of organic pollutants is also discussed. Moreover, the modification of 1D TiO2nanostructures using metal ions, metal oxide, or inorganic element can further enhance the photocatalytic activity of the photocatalyst. This phenomenon can be explained by the suppression of e−-h+pairs recombination rate, increased specific surface area, and reduction of band gap. In addition, 1D nanostructured TiO2can be further constructed as a film or membrane, which may extend its practical applications.
Neurologic Complications Associated with Sjögren’s Disease: Case Reports and Modern Pathogenic Dilemma
Authors: Colaci Michele , Cassone Giulia , Manfredi Andreina , Sebastiani Marco , Giuggioli Dilia , Ferri Clodoveo
Published: August 2014

Objectives. Sjögren’s syndrome (SS) may be complicated by some neurological manifestations, generally sensory polyneuropathy. Furthermore, involvement of cranial nerves was described as rare complications of SS.Methods. We reported 2 cases: the first one was a 40-year-old woman who developed neuritis of the left optic nerve as presenting symptom few years before the diagnosis of SS; the second was a 54-year-old woman who presented a paralysis of the right phrenic nerve 7 years after the SS onset. An exhaustive review of the literature on patients with cranial or phrenic nerve involvements was also carried out.Results. To the best of our knowledge, our second case represents the first observation of SS-associated phrenic nerve mononeuritis, while optic neuritis represents the most frequent cranial nerve involvement detectable in this connective tissue disease. Trigeminal neuropathy is also frequently reported, whereas neuritis involving the other cranial nerves is quite rare.Conclusions. Cranial nerve injury is a harmful complication of SS, even if less commonly recorded compared to peripheral neuropathy. Neurological manifestations may precede the clinical onset of SS; therefore, in patients with apparently isolated cranial nerve involvement, a correct diagnosis of the underlying SS is often delayed or overlooked entirely; in these instances, standard clinicoserological assessment is recommendable.
Existence of Solutions for Two-Point Boundary Value Problem of Fractional Differential Equations at Resonance
Authors: Hu Lei , Zhang Shuqin , Shi Ailing
Published: August 2014

We establish the existence results for two-point boundary value problem of fractional differential equations at resonance by means of the coincidence degree theory. Furthermore, a result on the uniqueness of solution is obtained. We give an example to demonstrate our results.
Multiple Mini-Interviews (MMI) and Semistructured Interviews for the Selection of Family Medicine Residents: A Comparative Analysis
Authors: Andrades Marie , Bhanji Seema , Kausar Samreen , Majeed Fouad , Pinjani Sheilla
Published: August 2014

Background. Family Medicine Residency Program at the Aga Khan University has applicants for the residency position in excess of the positions offered resulting in formulation of certain selection criteria. The objective of this study was to compare MMI versus semistructured interviews for assessing noncognitive domains in the selection of residents. The secondary objectives were to determine perceptions of the interviewers and candidates for the acceptability and feasibility of MMI as a selection tool. Methods. The candidates underwent semistructured interviews along with MMI and identical attributes were tested in both. The attributes tested were safe doctor, communication skills, professionalism, problem solving, team approach, ethical issues, reasons for selecting family medicine, and commitment to the program. Descriptive statistics were calculated and comparison between ratings for MMI and interview was performed by Wilcoxon sign rank test. Results. Total number of candidates was 14. On comparison between interview and MMI, the scores were not statistically different for all attributes except ethics (mean interview scores: 3.04, mean MMI scores: 2.5, and P value 0.046). Conclusion. The study showed no difference between MMI and semistructured interviews. However, it needs to be replicated in order to determine the predictive validity and feasibility of MMI over time.
An Evaluation of SMR Economic Attractiveness
Authors: Boarin Sara , Ricotti Marco E.
Published: August 2014

The nuclear “renaissance” that is taking place worldwide concerns the new build of GW size reactor plants, but smaller GenIII+ NPP (Small Modular Reactors, SMR) are on the verge to be commercially available and are raising increasing public interest. These reactor concepts rely on the pressurized water technology, capitalizing on thousands of reactor-years operations and enhancing the passive safety features, thanks to the smaller plant and equipment size. On the other hand, smaller plant size pays a loss of economy of scale, which might have a relevant impact on the generation costs of electricity, given the capital-intensive nature of nuclear power technology. The paper explores the economic advantages/disadvantages of multiple SMR compared to alternative large plants of the same technology and equivalent total power installed. The metrics used in the evaluation is twofold, as appropriate for liberalized markets of capital and electricity: investment profitability and investment risk are assessed, from the point of view of the plant owner. Results show that multiple SMR deployed on the same site may prove competitive with investment returns of larger plants, while offering, in addition, unique features that mitigate the investment risk.
The Spectral Analysis of Dynamic Laser Speckle Patterns Generated by Brownian Particle Suspensions: A Stroboscopic Effect Based Filtering Technique
Authors: Wang Dake , Ranger James , Moyer Adam
Published: August 2014

The power spectrum of the time-varying intensity in the dynamic laser speckle patterns is determined by passing the shifted power spectrum through a low-pass filter which is implemented via the signal integration. The light intensity is modulated sinusoidally to induce the stroboscopic effect which shifts the resonant frequency component of the spectrum to 0 Hz. The homodyne dynamic laser speckles generated by the quasi-inelastic scattering of the Brownian motions in colloidal suspensions are investigated. Within the frequency range from 10 Hz to 10 kHz used in this work, the bandwidth of the Lorenztian power spectrums is shown to be inversely proportional to the particle size, which is in agreement with the prediction of the dynamic light scattering theory of diffusing particle. The spatial variation observed in the full-field power spectrum maps is caused by the nonuniform distribution of average speckle intensity and varies with the modulation frequency. However, the bandwidths measured at different locations are found to be intensity independent.
Numerical Study on Improved Baffle in Compact Test Separator
Authors: Wei Yanhai , Wang Xinran , He Limin , Jiao Shenghua , Zhang Guoqiang , Cheng Hao , Li Yujiang , Li Tao
Published: August 2014

The aim of this paper is to design two improved baffles to solve the injection problem caused by traditional baffle in compact test separatorand use FLUENT software to study their effects on separator pressure loss and separation efficiency. The result shows: that anti-injection baffle can make compact test separator with a high separation efficiency with a relatively low pressure loss. Also, the diameter of anti-injection plate which makes the compact test separator at its highest separation efficiency is slightly smaller than that which makes the lowest pressure loss.
The Possible Role of Medial Prefrontal Cortex Beta-1-Adrenoceptors in Morphine-Induced Amnesia
Authors: Torkaman-Boutorabi Anahita , Hashemi-Hezaveh Seyed-Milad , Sheidadoust Hadi , Zarrindast Mohammad-Reza
Published: August 2014

The prelimbic region of the medial prefrontal cortex (mPFC) in the brain is crucial for memory. Norepinephrine elicits an important influence on mPFC functions. The stimulation of β-adrenoceptors (β-ARs) may play a critical role in the consolidation of long-term memory. The present study examines the possible role of β1-ARs located in the mPFC on morphine-induced amnesia in rats. The animals were bilaterally implanted with chronic cannulas in the mPFC, trained in a step-through-type passive avoidance task and tested 24 h after training to measure step-through latency. Our present results indicated that posttraining intraperitoneal administration of morphine (2.5, 5 and 7.5 mg/kg) dose-dependently reduced the step-through latency. Different doses of xamoterol (0.01, 0.1 and 1 µg/rat) have shown no significant change in the step-through latency, but posttraining intra-mPFC microinjection of atenolol (0.2 and 0.4 µg/rat) had an amnesic effect. Moreover, atenolol-caused amnesia was reversed by an ineffective dose of xamoterol (0.1 µg/rat). On the other hand, coadministration of an ineffective dose of atenolol (0.1 µg/rat) with an ineffective dose of morphine (2.5 mg/kg) induced an amnesic effect. Meanwhile, xamoterol had no effect on morphine-induced amnesia. These results suggest that β1-ARs of the prelimbic region in the mPFC may play an important role in morphine-induced amnesia.
Prognostic Implications of Left Ventricular Dyssynchrony for Major Adverse Cardiovascular Events in Asymptomatic Women and Men: The Multi‐Ethnic Study of Atherosclerosis
Authors: Sharma Ravi K. , Volpe Gustavo , Rosen Boaz D. , Ambale‐Venkatesh Bharat , Donekal Sirisha , Fernandes Veronica , Wu Colin O. , Carr Jeffrey , Bluemke David A. , Lima João A. C.
Published: August 2014

Background

Left ventricular (
LV
) dyssynchrony is related to adverse outcomes in systolic heart failure, but its prognostic importance in asymptomatic population is not known. Our objective was to assess the prognostic implications of
LV
mechanical dyssynchrony in a large multiethnic population before the occurrence of global
LV
dysfunction.

Methods and Results

A total of 1392 participants in the Multi‐Ethnic Study of Atherosclerosis (
MESA
; mean age: 64.7 years; 46% were women) with cardiac magnetic resonance imaging at baseline were followed for a median duration of 8.3 years.
Harmonic phase imaging
analysis was used to derive systolic circumferential strain. Greater standard deviation of time to peak systolic strain (
SD
‐
TPS
) indicates greater dyssynchrony. With
SD
‐
TPS
as a continuous variable, Cox proportional hazards analysis was used to assess hazards ratio after adjusting for demographics, cardiovascular risk factors,
LV
mass‐to‐volume ratio, and ejection fraction. Using the 75th percentile of
SD
‐
TPS
as a cutoff, Kaplan–Meier analysis was performed between 2 categorical groups for each gender. Higher values of dyssynchrony in women predicted major adverse cardiovascular events, defined as myocardial infarction, heart failure, stroke, and death (hazard ratio
:
1.01 per 1‐ms increment in
SD
‐
TPS
,
P
=0.015), hard coronary events (
hazard ratio:
1.05 per 1‐ms increment in
SD
‐
TPS
,
P
=0.026), and cerebrovascular events (
hazard ratio:
1.03 per 1‐ms increment in
SD
‐
TPS
,
P
=0.013). In contrast, dyssynchrony in men was not predictive of events. Kaplan–Meier analyses in women revealed increased event occurrence in the higher dyssynchrony group, but this was not the case in men.

Conclusions

In an asymptomatic cohort, greater
LV
dyssynchrony determined by
cardiac magnetic resonance imaging
predicts adverse cardiovascular outcome in women but not in men.

Clinical Trial Registration

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00005487.
A phylogenetic analysis of the southern African gecko genus Afroedura Loveridge (Squamata: Gekkonidae), with the description of nine new species from Limpopo and Mpumalanga provinces of South Africa
Authors: JACOBSEN NIELS H. G. , KUHN ARIANNA L. , KUHN ARIANNA L. , JACKMAN TODD R. , BAUER AARON M.
Published: August 2014

A molecular phylogeny of the largely rupicolous geckos of the gekkonid genus Afroedura is presented based on a combination of mitochondrial and nuclear gene sequence data. Previously recognized species groups are only partly recovered, with A. pondolia retrieved as very distantly related to the congeners to which it was previously considered allied. Afroedura hawequensis forms a monotypic group that is sister to all other species, which are allocated to the A. nivaria, A. transvaalica, A. africana, A. multiporis, A. marleyi, and A. langi groups. The taxonomic status of species occurring in the former Transvaal province of South Africa (now Limpopo and Mpumalanga provinces) is reviewed based on morphological and molecular evidence. Afroedura rupestris sp. nov. is described in the A. multiporis group, A. maripi sp. nov., A. pongola sp. nov., and A. rondavelica sp. nov., are described in the A. marleyi group, and A. broadleyi sp. nov., A. granitica sp. nov., A. leoloensis sp. nov., A. pienaari sp. nov., and A. waterbergensis sp. nov. are described in the A. langi group. In addition, A. haackei, A. namaquensis, and A. tirasensis, are all raised to specific status. The description of nine new species highlights Limpopo and Mpumalanga provinces as previously unrecognized centers of diversity for the genus Afroedura. A key to the species of Afroedura is provided.
Source-Destination Cultural Differences, Immigrants’ Skill Levels, and Immigrant Stocks: Evidence from Six OECD Member Countries
Authors: White Roger , Yamasaki Nicole
Published: August 2014

Examining data for 79 immigrant source countries and six OECD member destination countries during the years 1975–2000, we find that source-destination cultural differences inhibit international migration. We also report that existing immigrant stocks act to offset, at least in part, the migration-inhibiting effects of cultural differences. Employing educational attainment as a proxy for skill, we find variation across low-, medium-, and high-skilled immigrant cohorts both with respect to the cultural distance-migration relationship and in terms of the extent to which existing immigrant stocks offset the influence of cultural differences. Our results appear robust to econometric techniques, sample composition, and endogeneity issues.
Ototoxic Effect of Ultrastop Antifog Solution Applied to the Guinea Pig Middle Ear
Authors: Nomura Kazuhiro , Oshima Hidetoshi , Yamauchi Daisuke , Hidaka Hiroshi , Kawase Tetsuaki , Katori Yukio
Published: August 2014

Objectives

Recent advances in endoscopic technology have allowed its application to middle ear surgery. An antifog agent is necessary for endoscopy because moisture and blood may obscure visibility. Ultrastop is one of the most commonly used antifog agents. The current study examined the ototoxic effect of topical application of Ultrastop in the guinea pig ear.

Study Design

A preliminary experimental animal study.

Setting

University hospital.

Subjects and Methods

Eighteen male Hartley guinea pigs (weight, 480‐620 g) were divided into 3 groups to be treated with Ultrastop, gentamicin (50 mg/mL, positive control), or saline solution (negative control). After auditory brainstem responses were measured, topical solutions of 0.2 mL were applied through a small hole made at the tympanic bulla. Posttreatment auditory brainstem responses were obtained 14 days after the treatment. The extent of middle ear damage was investigated and scored.

Results

The saline‐treated group showed no deterioration in auditory brainstem response threshold. The Ultrastop‐treated and gentamicin‐treated groups showed severe deterioration in auditory brainstem response threshold. Middle ear examination revealed extensive changes in the Ultrastop‐treated group and medium changes in the gentamicin‐treated group.

Conclusion

Ultrastop applied topically to the guinea pig middle ear caused significant middle ear inflammation and hearing impairment.
Evaluation of the photobiomodulation in L929 cell culture
Authors: Marques Juliana Mangolin , Pacheco-Soares Cristina , Silva Newton Soares Da
Published: August 2014

Low-level laser therapy has become an important tool for bio-modulation process. It can induce stimulatory or inhibitory effects according to cell behavior at specific irradiation. Our objective was to determine L929 cell line response to irradiation at λ 685 and 830 nm, concentrations of 5 and 10% fetal bovine serum and different energy densities of 0.1, 0.5, 1, 2, 3, 5, 7, 10, 20, and 30 J/cm2. Thus, cells were plated at 1 × 105 cells/mL and irradiated with semiconductor laser As-Ga-Al. Twenty-four hours after irradiation, cells were subjected to MTT, neutral red, crystal violet tests, and cell staining was performed using the kit Alexa Fluor 488 Annexin V-FITC and propidium iodide. Our results showed that low-level laser therapy stimulates effect when the energy density is 5 to 3030 J/cm2 and inhibits effects on energy density 0.1 to 3 J/cm2. This inhibitory effect was evidenced by the absence of dead cells labeled, decreased cell density, and by the absorption of neutral red in intact cells. The study also demonstrated that fetal bovine serum, at different concentrations, did not affect response of the cells after irradiation.
Additional stories of microRNAs
Authors: Lee Heon-Jin
Published: August 2014

MicroRNAs (miRNAs) have been shown to be major regulators of eukaryotic gene expression. Traditionally, miRNAs were thought to control highly complex signal transduction and other biological pathways by targeting coding transcripts, accounting for their important role in cellular events. Traditional miRNA biogenesis and function focused on several key enzymes that functioned in miRNA maturation and miRNA inhibitory function upon binding to 3′-untranslated region of target transcripts. However, recent studies have revealed that miRNA biosynthesis and function is complicated, with many exceptions to conventional miRNA mechanisms. In addition to those noncanonical miRNA functions, this review introduces newly discovered biogenesis and regulatory mechanisms, as well as a new class of miRNA-sized small RNA and miRNA methylation. miRNA inhibition and intercellular miRNA signaling are also discussed. Taken together, these insights extend current understanding of miRNAs.
Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury
Authors: Chen Qi Xing , Song Sheng Wen , Chen Qing Hua , Zeng Cong Li , Zheng Xia , Wang Jun Lu , Fang Xiang Ming
Published: August 2014

Introduction

The production of antimicrobial peptides by airway epithelial cells is an important component of the innate immune response to pulmonary infection and inflammation. Hepcidin is a β-defensin-like antimicrobial peptide and acts as a principal iron regulatory hormone. Hepcidin is mostly produced by hepatocytes, but is also expressed by other cells, such as airway epithelial cells. However, nothing is known about its function in lung infections and inflammatory diseases. We therefore sought to investigate the role of airway epithelial cell-derived hepcidin in sepsis-induced acute lung injury.

Methods

Acute lung injury was induced by polymicrobial sepsis via cecal ligation and puncture (CLP) surgery. Adenovirus-mediated short hairpin RNA specific for the mouse hepcidin gene hepc1 and control adenovirus were intratracheally injected into mice. The adenovirus-mediated knockdown of hepcidin in airway epithelial cells was evaluated in vivo. Lung injury and the seven-day survival rate were assessed. The levels of hepcidin-related iron export protein ferroportin were measured, and the iron content and function of alveolar macrophages were evaluated.

Results

The hepcidin level in airway epithelial cells was upregulated during polymicrobial sepsis. The knockdown of airway epithelial cell-derived hepcidin aggravated the polymicrobial sepsis-induced lung injury and pulmonary bacterial infection and increased mortality (53.33% in Ad-shHepc1-treated mice versus 12.5% in Ad-shNeg-treated mice, P <0.05). The knockdown of hepcidin in airway epithelial cells also led to reduced ferroportin degradation and a low intracellular iron content in alveolar macrophages. Moreover, alveolar macrophages form the airway epithelial cell-derived hepcidin knockdown mice showed impaired phagocytic ability than those from the control mice.

Conclusions

Airway epithelial cell-derived hepcidin plays an important role in CLP-induced acute lung injury. The severe lung injury in the airway epithelial cell-derived hepcidin knockdown mice is at least partially related to the altered intracellular iron level and function of alveolar macrophages.
Foundation News
Authors: Smith Sara E.
Published: August 2014

For the best results, how do you teach modern methods of geophysical exploration? A hands-on approach is the answer. Get into the field, put your hands on the equipment, wrestle with the data, and learn new things about geophysics.
Geophysical tutorial
Authors: Niccoli Matteo
Published: August 2014

This is the first of a two-part tutorial on color maps. My goal is to share the methods I developed ( Niccoli, 2012 ; Niccoli and Lynch, 2012 ; Niccoli, 2013 ) to evaluate default color maps and choose more perceptual alternatives (Part 1) and to make your own map based on perceptual principles (Part 2). For both parts, there will be an accompanying IPython Notebook with extended examples and analyses and open data. You can find the notebooks and code at github.com/seg/tutorials .
Somatic Mutations Predict Poor Outcome in Patients With Myelodysplastic Syndrome After Hematopoietic Stem-Cell Transplantation
Authors: Bejar Rafael , Stevenson Kristen E. , Caughey Bennett , Lindsley R. Coleman , Mar Brenton G. , Stojanov Petar , Getz Gad , Steensma David P. , Ritz Jerome , Soiffer Robert , Antin Joseph H. , Alyea Edwin , Armand Philippe , Ho Vincent , Koreth John , Neuberg Donna , Cutler Corey S. , Ebert Benjamin L.
Published: August 2014

Purpose

Recurrently mutated genes in myelodysplastic syndrome (MDS) are pathogenic drivers and powerfully associated with clinical phenotype and prognosis. Whether these types of mutations predict outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with MDS is not known.

Patients and Methods

We used massively parallel sequencing to examine tumor samples collected from 87 patients with MDS before HSCT for coding mutations in 40 recurrently mutated MDS genes.

Results

Mutations were identified in 92% of patients, most frequently in the ASXL1 (29%), TP53 (21%), DNMT3A (18%), and RUNX1 (16%) genes. In univariable analyses, only TP53 mutations were associated with shorter overall (OS; hazard ratio [HR], 3.74; P < .001) and progression-free survival (HR, 3.97; P < .001). After adjustment for clinical variables associated with these end points, mutations in TP53 (HR, 2.30; P = .027), TET2 (HR, 2.40; P = .033), and DNMT3A (HR, 2.08; P = .049) were associated with decreased OS. In multivariable analysis including clinical variables, complex karyotype status, and candidate genes, mutations in TP53 (HR, 4.22; P ≤ .001) and TET2 (HR, 1.68; P = .037) were each independently associated with shorter OS. Nearly one half of patients (46%) carried a mutation in TP53, DNMT3A, or TET2 and accounted for 64% of deaths. Three-year OS in patients without these mutations was 59% (95% CI, 43% to 72%), versus 19% (95% CI, 9% to 33%) in patients with these mutations.

Conclusion

Mutations in TP53, TET2, or DNMT3A identify patients with MDS with shorter OS after HSCT.
Uncarboxylated Osteocalcin Stimulates 25-Hydroxy Vitamin D Production in Leydig Cell Line Through a GPRC6a-Dependent Pathway
Authors: De Toni Luca , De Filippis Vincenzo , Tescari Simone , Ferigo Marco , Ferlin Alberto , Scattolini Valentina , Avogaro Angelo , Vettor Roberto , Foresta Carlo
Published: August 2014

Recent studies disclosed a cross talk between testis and bone. By the action of LH, Leydig cells are able to modulate bone metabolism through testosterone and insulin-like factor 3. Moreover, LH modulates the Leydig expression of CYP2R1, the key enzyme involved in vitamin D (Vit D) 25-hydroxylation. However, pathways regulating CYP2R1 expression have been poorly investigated. The cross talk from the bone to the testis of the vitamin D 25-hydroxylase CYP2R1 involves osteocalcin (OC), which is produced by the osteoblasts and stimulates the production of testosterone by the Leydig cells through its putative receptor GPRC6A, a cation-sensing G-protein-coupled receptor. The aim of this study was to investigate the possible action of OC on CYP2R1 expression and 25-hydroxy Vit D (25-OH Vit D) production in a mouse Leydig cell line (MA-10). After confirmation of the expression of GPRC6A by MA-10, we found that stimulation with either human chorionic gonadotropin or uncarboxylated-OC (ucOC) increases CYP2R1 protein expression in a dose-dependent manner and, in turn, increases the release of 25-OH Vit D in culture medium. This effect was abolished by receptor blockade with, respectively, anti-LH receptor and anti-GPRC6A antibodies. Moreover, both agonists converged to phosphorylation of Erk1/2 by a likely differential action on second messengers. Human chorionic gonadotropin induced slow “tonic” increase of intercellular calcium and accumulation of cAMP, whereas ucOC mainly induced phasic increase of cell calcium. Supporting these findings, we found that serum ucOC positively correlated with 25-OH Vit D levels in 40 overweight male patients and 21 controls. Altogether, our results suggest that OC contributes with LH to 25-OH Vit D production by Leydig cells.
Time-Delay Interferometry
Authors: Tinto Massimo , Dhurandhar Sanjeev V.
Published: August 2014

Equal-arm detectors of gravitational radiation allow phase measurements many orders of magnitude below the intrinsic phase stability of the laser injecting light into their arms. This is because the noise in the laser light is common to both arms, experiencing exactly the same delay, and thus cancels when it is differenced at the photo detector. In this situation, much lower level secondary noises then set the overall performance. If, however, the two arms have different lengths (as will necessarily be the case with space-borne interferometers), the laser noise experiences different delays in the two arms and will hence not directly cancel at the detector. In order to solve this problem, a technique involving heterodyne interferometry with unequal arm lengths and independent phase-difference readouts has been proposed. It relies on properly time-shifting and linearly combining independent Doppler measurements, and for this reason it has been called time-delay interferometry (TDI).

This article provides an overview of the theory, mathematical foundations, and experimental aspects associated with the implementation of TDI. Although emphasis on the application of TDI to the Laser Interferometer Space Antenna (LISA) mission appears throughout this article, TDI can be incorporated into the design of any future space-based mission aiming to search for gravitational waves via interferometric measurements. We have purposely left out all theoretical aspects that data analysts will need to account for when analyzing the TDI data combinations.
Evaluation and model of rehabilitation for primary malignant bone sarcoma patients after limb salvage
Authors: Hudson Suzy , Bamdad Katayoon , Briggs Tim
Published: August 2014

Background and aims

It has long been suspected that the rehabilitation available to patients with primary malignant bone sarcoma (PMBS) is not always adequate and appropriate to their needs. The National Specialised Commissioning Group (NSCG) commissioned the 2012–2013 Quality Improvement Development and Innovation Scheme (QIDIS) project (rehabilitation programme) to review the current rehabilitation services available to the PMBS patient groups at all five bone sarcoma specialist centres in England.

Methods

The 220 participating PMBS patients were provided with questionnaires, and clinicians at the participating centres were interviewed face-to-face. Patients were analysed in groups: upper limb and lower limb, and in the subgroups major and minor surgery. The groups were compared according to their preferences for rehabilitation interventions, the additional rehabilitation post-surgery that they felt was or would have been beneficial, and by their Toronto Extremity Salvage Scores (TESS).

Results

Out of the 220 questionnaires provided, 136 questionnaires were returned (a 62% response rate). This study identified the lack of the following factors to be associated with PMBS patients' rehabilitation and functional outcomes: equitable access to rehabilitation treatments; suitable rehabilitation admission; allied health professional (AHP) clinical progress reviews; a reliable and equitable referral system with robust referral criteria; a rehabilitation case coordinator; a nationally accepted functional outcome measure; and patients' involvement in the management of their rehabilitation to achieve the best possible outcome.

Conclusions

This study identified gaps in the current rehabilitation services for PMBS patients and makes several recommendations. The authors designed a postoperative model of rehabilitation, which identifies a number of target areas that may improve current rehabilitation services and enable rehabilitation professionals to assess a PMBS patient's needs to identify the most suitable rehabilitation programme for them.
A case study of knowledge brokerage in occupational therapy
Authors: Hitch Danielle , Rowan Susan , Nicola-Richmond Kelli
Published: August 2014

Background/aims

Knowledge brokerage is a relatively new method for promoting knowledge translation in health-care services; it promotes knowledge translation through an intermediary person known as a knowledge broker. Knowledge brokerage was introduced in response to the recognised challenges to evidence-based practice as existing methods are found to have a variable impact on practice.

Methods

This study was conducted using a single workplace, phenomenological, case study design. Seven participants, who are in academic, managerial, clinical and knowledge broker positions, were asked to reflect on their experience of participating in a pilot knowledge brokerage project within a regional health service. The Gibbs Model of Reflective Practice was used as a basis for both eliciting and analysing participants' reflections, and the data were analysed thematically.

Findings

Themes that were identified across both time points and/or by both participants and the knowledge broker are reported here. These themes were classified into four categories: doing research; lived experience; building, cementing and maintaining relationships; and enacting knowledge brokerage.

Conclusions

A number of positive outcomes for the health service and university were identified, and knowledge brokerage will become a sustained feature of the relationship between these two organisations. This study has expanded the current evidence base for knowledge brokerage in healthcare services, and provides information that may be useful to those considering implementation of knowledge broker roles for supporting evidence-based practice.
Supporting Primary Care Practices in Building Capacity to Use Health Information
Data
Authors: Fernald Douglas , Wearner Robyn , Dickinson W. Perry
Published: August 2014

Introduction: Our objective was to describe essential support resources and
strategies in order to advance the pace and scope of the use of health information
technology (HIT) data.Background and Context: Primary data were collected between
January 2011 and October 2012. The primary study population comprised 51 primary care
practices enrolled in the Colorado Beacon Consortium in western Colorado.Methods: We
used qualitative methods embedded in a mixed-method evaluation: monthly narrative
reports from practices; interviews with providers and staff; and focused, group
discussions with quality improvement (QI) advisors and staff from the Health Information
Technology Regional Extension Center.Findings: Practices valued effective support
strategies to assist with using HIT, including the following: translating rules and
regulations into individual practice settings; facilitating peer-to-peer connections;
providing processes and tools for practice improvement; maintaining accountability and
momentum; and providing local electronic health record (EHR) technical expertise.
Benefits of support included improved quality measures, operational improvements,
increased provider and staff engagement, and deeper understanding of EHR
data.Discussion: The findings affirm the utility of practice facilitation for
HIT-focused aims with personalized attention and cross-fertilization among practices for
improvements. Facilitation to sustain ongoing improvements and prepare for future
HIT-intensive improvement activities was highly valued. In addition to the general
practice facilitator, an EHR technical expert was critical to improving practice
capacity to use electronic clinical data. Collaborative learning expands the pool of
mentors and teachers, who can further translate their own lessons into practical advice
for their peers, yielding the emergence of a stronger sense of community among the
practices.Conclusions: Using HIT more effectively in primary care will require
sustained, focused efforts by practices as regulations, incentives and HIT evolve.
Ongoing support for community-based practice facilitators; collaborative learning; and
local, personalized EHR advisors will help practices care for patients while more
effectively deploying HIT to improve care.
Isolation and structural elucidation of norlignan polymers from the heartwood of Cryptomeria japonica
Authors: Yanase Yu , Sakamoto Kazuyuki , Imai Takanori
Published: August 2014

The norlignan (NorL) is a class of secondary metabolites, which occurs in the heartwood (hW) of certain softwood species. Although the NorL is often assumed to be secondarily altered (e.g., oxidized and/or polymerized in the hW over time), the formation and the chemical structure of oxidized/polymerized products remained unclear. In this study, we focused on the question whether an NorL oligomer/polymer exists in the hW of Cryptomeria japonica. First, NorL model polymers were prepared by horseradish peroxidase-catalyzed oxidation and their chemical structures were investigated by size exclusion chromatography-high-performance liquid chromatography (SEC-HPLC), nuclear magnetic resonance (NMR), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Second, methanol (MeOH) extracted from the hW of C. japonica was fractionated, and one of the fractions contained NorL polymers as demonstrated by its chromatographic and spectrometric data in comparison with those of model polymers. Third, five kinds of agatharesinol (AGA) model dimers were synthesized and their chemical structures were determined. 13C-NMR signals corresponding to the model dimer structures were observed in the NMR spectrum of the natural polymer fraction. In summary, an NorL polymer was found in the hW of C. japonica, and its preliminary chemical structure was proposed for the first time.
Perceptions of a university subject on leadership and intrapersonal development: reflections of the scholarship recipients
Authors: Shek Daniel T.L. , Wu Florence K.Y. , Law Moon Y.M.
Published: August 2014

Under the new 4-year undergraduate curriculum, students admitted to The Hong Kong Polytechnic University have to take a course on “Leadership and Intra-personal Development”. A subject entitled “Tomorrow’s Leaders” was developed to help students satisfy this requirement. In the second piloting exercise, five outstanding students taking this subject were invited to write reflective journals. Several common themes from these reflections are highlighted from the analyses. First, students believed there was a need for this subject. Second, the students liked the course, and they identified many positive attributes in the subject and its implementation. Third, the instructors were appreciated by the students. Fourth, the subject was seen by the students to be beneficial to their development. Finally, some suggestions for improvement were noted. When the present findings are integrated with other evaluation findings, it can be concluded that the subject is able to promote psychosocial competencies in university students taking this subject.
Is there a stepwise increase in neonatal morbidities according to histological stage (or grade) of acute chorioamnionitis and funisitis?: effect of gestational age at delivery
Authors: Lee Yeri , Kim Hyun-Joo , Choi Suk-Joo , Oh Soo-young , Kim Jung-Sun , Roh Cheong-Rae , Kim Jong-Hwa
Published: August 2014

Aims: To test if there is a stepwise difference in neonatal outcomes according to the stage (or grade) of histological inflammatory response in the chorioamniotic membranes and umbilical cords of preterm premature rupture of membranes (PPROM).

Method: This retrospective study included singleton pregnancies diagnosed as PPROM and delivered prior to 34 weeks of gestation (n=339). Acute histological chorioamnionitis and funisitis were subdivided into stages (or grade) as defined by Redline et al. Neonatal composite morbidities and mortality were also monitored. Univariate and multivariate analyses were conducted.

Results: Increasing stage (or grade) of acute histological chorioamnionitis and funisitis was significantly associated with an earlier gestational age at membrane rupture and delivery. Among neonatal outcomes, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, retinopathy of prematurity, and composite morbidity showed incremental incidence according to increased stage (or grade) of acute chorioamnionitis, while periventricular leukomalacia and necrotizing enterocolitis did not. Only RDS, BPD, and composite morbidity showed similar incremental incidences associated with severity of funisitis stage. However, the incremental trends of each neonatal outcome were found to be nonsignificant by multivariate analysis adjusting confounding variables including gestational age at delivery.

Conclusion: Higher incidences of neonatal morbidity according to increased stage (or grade) of either acute histological chorioamnionitis or funisitis were due to an earlier gestational age at delivery.
Oligomers with structural elements of imidazolidinetrione obtained from oxamic acid and oxamide: polyurethane foams modified by structural elements of imidazolidinetrione
Authors: Zarzyka Iwona
Published: August 2014

Hydroxyalkyl derivatives containing oxamidoester and oxamide fragments have been separately obtained using oxamic acid, oxamide and alkylene carbonates. It has been proven that the presence of oxamidoester and oxamide structural fragments in oligomer structures is responsible for the thermal stability of these products. Rigid, thermally stable polyurethane foams were obtained with the use of oligomers with oxamidoestercarbamidoimide, carbamide, oxamidoester and oxamide groups as polyols components. The properties of these foamed materials were compared with each other and with the properties of reference foams. It was found that the polyurethane foams characterized by the best properties were obtained from hydroxypropyl derivatives of oxamide.