bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Variants of the Native Class D β-Lactamase of Acinetobacter baumannii Pose an Emerging Threat through Increased Hydrolytic Activity against Carbapenems
Authors: Schroder Emma C. , Klamer Zachary L. , Saral Aysegul , Sugg Kyle A. , June Cynthia M. , Wymore Troy , Szarecka Agnieszka , Leonard David A.
Published: August 2016

The threat posed by the chromosomally encoded class D β-lactamase of
Acinetobacter baumannii
(OXA-51/66) has been unclear, in part because of its relatively low affinity and turnover rate for carbapenems. Several hundred clinical variants of OXA-51/66 have been reported, many with substitutions of active-site residues. We determined the kinetic properties of OXA-66 and five clinical variants with respect to a wide variety of β-lactam substrates. The five variants displayed enhanced activity against carbapenems and in some cases against penicillins, late-generation cephalosporins, and the monobactam aztreonam. Molecular dynamics simulations show that in OXA-66, P130 inhibits the side-chain rotation of I129 and thereby prevents doripenem binding because of steric clash. A single amino acid substitution at this position (P130Q) in the variant OXA-109 greatly enhances the mobility of both I129 and a key active-site tryptophan (W222), thereby facilitating carbapenem binding. This expansion of substrate specificity represents a very worrisome development for the efficacy of β-lactams against this troublesome pathogen.
Mutational Consequences of Ciprofloxacin in Escherichia coli
Authors: Song Lisa Yun , Goff Marisa , Davidian Christina , Mao Zhiyuan , London Marisa , Lam Karen , Yung Madeline , Miller Jeffrey H.
Published: August 2016

We examined the mutagenic specificity of the widely used antibiotic ciprofloxacin (CPR), which displays weak to moderate mutagenic activity in several bacteria and generates short in-frame deletions in
rpoB
in
Staphylococcus aureus
. To determine the spectrum of mutations in a system where any gene knockout would result in a recovered mutant, including frameshifts and both short and long deletions, we examined CPR-induced mutations in the thymidylate synthase-encoding
thyA
gene. Here, any mutation resulting in loss of thymidylate synthase activity generates trimethoprim (Trm) resistance. We found that deletions and insertions in all three reading frames predominated in the spectrum. They tend to be short deletions and cluster in two regions, one being a GC-rich region with potential extensive secondary structures. We also exploited the well-characterized
rpoB
-Rif
r
system in
Escherichia coli
to determine that cells grown in the presence of sublethal doses of CPR not only induced short in-frame deletions in
rpoB
, but also generated base substitution mutations resulting from induction of the SOS system. Some of the specific point mutations prominent in the spectrum of a strain that overproduces the
dinB
-encoded Pol IV were also present after growth in CPR. However, these mutations disappeared in CPR-treated
dinB
mutants, whereas the deletions remained. Moreover, CPR-induced deletions also occurred in a strain lacking all three SOS-induced polymerases. We discuss the implications of these findings for the consequences of overuse of CPR and other antibiotics.
Neuraminidase A-Exposed Galactose Promotes Streptococcus pneumoniae Biofilm Formation during Colonization
Authors: Blanchette Krystle A. , Shenoy Anukul T. , Milner Jeffrey , Gilley Ryan P. , McClure Erin , Hinojosa Cecilia A. , Kumar Nikhil , Daugherty Sean C. , Tallon Luke J. , Ott Sandra , King Samantha J. , Ferreira Daniela M. , Gordon Stephen B. , Tettelin Hervé , Orihuela Carlos J.
Published: August 2016

Streptococcus pneumoniae
is an opportunistic pathogen that colonizes the nasopharynx. Herein we show that carbon availability is distinct between the nasopharynx and bloodstream of adult humans: glucose is absent from the nasopharynx, whereas galactose is abundant. We demonstrate that pneumococcal neuraminidase A (NanA), which cleaves terminal sialic acid residues from host glycoproteins, exposed galactose on the surface of septal epithelial cells, thereby increasing its availability during colonization. We observed that
S. pneumoniae
mutants deficient in NanA and β-galactosidase A (BgaA) failed to form biofilms
in vivo
despite normal biofilm-forming abilities
in vitro
. Subsequently, we observed that glucose, sucrose, and fructose were inhibitory for biofilm formation, whereas galactose, lactose, and low concentrations of sialic acid were permissive. Together these findings suggested that the genes involved in biofilm formation were under some form of carbon catabolite repression (CCR), a regulatory network in which genes involved in the uptake and metabolism of less-preferred sugars are silenced during growth with preferred sugars. Supporting this notion, we observed that a mutant deficient in pyruvate oxidase, which converts pyruvate to acetyl-phosphate under non-CCR-inducing growth conditions, was unable to form biofilms. Subsequent comparative transcriptome sequencing (RNA-seq) analyses of planktonic and biofilm-grown pneumococci showed that metabolic pathways involving the conversion of pyruvate to acetyl-phosphate and subsequently leading to fatty acid biosynthesis were consistently upregulated during diverse biofilm growth conditions. We conclude that carbon availability in the nasopharynx impacts pneumococcal biofilm formation
in vivo
. Additionally, biofilm formation involves metabolic pathways not previously appreciated to play an important role.
Intestinal Enteroids Model Guanylate Cyclase C-Dependent Secretion Induced by Heat-Stable Enterotoxins
Authors: Pattison Amanda M. , Blomain Erik S. , Merlino Dante J. , Wang Fang , Crissey Mary Ann S. , Kraft Crystal L. , Rappaport Jeff A. , Snook Adam E. , Lynch John P. , Waldman Scott A.
Published: August 2016

Enterotoxigenic
Escherichia coli
(ETEC) causes ∼20% of the acute infectious diarrhea (AID) episodes worldwide, often by producing heat-stable enterotoxins (STs), which are peptides structurally homologous to paracrine hormones of the intestinal guanylate cyclase C (GUCY2C) receptor. While molecular mechanisms mediating ST-induced intestinal secretion have been defined, advancements in therapeutics have been hampered for decades by the paucity of disease models that integrate molecular and functional endpoints amenable to high-throughput screening. Here, we reveal that mouse and human intestinal enteroids in three-dimensional
ex vivo
cultures express the components of the GUCY2C secretory signaling axis. ST and its structural analog, linaclotide, an FDA-approved oral secretagog, induced fluid accumulation quantified simultaneously in scores of enteroid lumens, recapitulating ETEC-induced intestinal secretion. Enteroid secretion depended on canonical molecular signaling events responsible for ETEC-induced diarrhea, including cyclic GMP (cGMP) produced by GUCY2C, activation of cGMP-dependent protein kinase (PKG), and opening of the cystic fibrosis transmembrane conductance regulator (CFTR). Importantly, pharmacological inhibition of CFTR abrogated enteroid fluid secretion, providing proof of concept for the utility of this model to screen antidiarrheal agents. Intestinal enteroids offer a unique model, integrating the GUCY2C signaling axis and luminal fluid secretion, to explore the pathophysiology of, and develop platforms for, high-throughput drug screening to identify novel compounds to prevent and treat ETEC diarrheal disease.
Identification and Characterization of a Putative Manganese Export Protein in Vibrio cholerae
Authors: Fisher Carolyn R. , Wyckoff Elizabeth E. , Peng Eric D. , Payne Shelley M.
Published: August 2016

Manganese plays an important role in the cellular physiology and metabolism of bacterial species, including the human pathogen
Vibrio cholerae
. The intracellular level of manganese ions is controlled through coordinated regulation of the import and export of this element. We have identified a putative manganese exporter (VC0022), named
mneA
(
m
a
n
ganese
e
xporter
A
), which is highly conserved among
Vibrio
spp. An
mneA
mutant exhibited sensitivity to manganese but not to other cations. Under high-manganese conditions, the
mneA
mutant showed an almost 50-fold increase in intracellular manganese levels and reduced intracellular iron relative to those of its wild-type parent, suggesting that the mutant's manganese sensitivity is due to the accumulation of toxic levels of manganese and reduced iron. Expression of
mneA
suppressed the manganese-sensitive phenotype of an
Escherichia coli
strain carrying a mutation in the nonhomologous manganese export gene,
mntP
, further supporting a manganese export function for
V. cholerae
MneA. The level of
mneA
mRNA was induced approximately 2.5-fold after addition of manganese to the medium, indicating regulation of this gene by manganese. This study offers the first insights into understanding manganese homeostasis in this important pathogen.

IMPORTANCE
Bacterial cells control intracellular metal concentrations by coordinating acquisition in metal-limited environments with export in metal-excess environments. We identified a putative manganese export protein, MneA, in
Vibrio cholerae
. An
mneA
mutant was sensitive to manganese, and this effect was specific to manganese. The
mneA
mutant accumulated high levels of intracellular manganese with a concomitant decrease in intracellular iron levels when grown in manganese-supplemented medium. Expression of
mneA
in
trans
suppressed the manganese sensitivity of an
E. coli mntP
mutant. This study is the first to investigate manganese export in
V. cholerae
.
Comparative Subcellular Localization Analysis of Magnetosome Proteins Reveals a Unique Localization Behavior of Mms6 Protein onto Magnetite Crystals
Authors: Arakaki Atsushi , Kikuchi Daiki , Tanaka Masayoshi , Yamagishi Ayana , Yoda Takuto , Matsunaga Tadashi
Published: August 2016

The magnetosome is an organelle specialized for inorganic magnetite crystal synthesis in magnetotactic bacteria. The complex mechanism of magnetosome formation is regulated by magnetosome proteins in a stepwise manner. Protein localization is a key step for magnetosome development; however, a global study of magnetosome protein localization remains to be conducted. Here, we comparatively analyzed the subcellular localization of a series of green fluorescent protein (GFP)-tagged magnetosome proteins. The protein localizations were categorized into 5 groups (short-length linear, middle-length linear, long-length linear, cell membrane, and intracellular dispersing), which were related to the protein functions. Mms6, which regulates magnetite crystal growth, localized along magnetosome chain structures under magnetite-forming (microaerobic) conditions but was dispersed in the cell under nonforming (aerobic) conditions. Correlative fluorescence and electron microscopy analyses revealed that Mms6 preferentially localized to magnetosomes enclosing magnetite crystals. We suggest that a highly organized spatial regulation mechanism controls magnetosome protein localization during magnetosome formation in magnetotactic bacteria.

IMPORTANCE
Magnetotactic bacteria synthesize magnetite (Fe
3
O
4
) nanocrystals in a prokaryotic organelle called the magnetosome. This organelle is formed using various magnetosome proteins in multiple steps, including vesicle formation, magnetosome alignment, and magnetite crystal formation, to provide compartmentalized nanospaces for the regulation of iron concentrations and redox conditions, enabling the synthesis of a morphologically controlled magnetite crystal. Thus, to rationalize the complex organelle development, the localization of magnetosome proteins is considered to be highly regulated; however, the mechanisms remain largely unknown. Here, we performed comparative localization analysis of magnetosome proteins that revealed the presence of a spatial regulation mechanism within the linear structure of magnetosomes. This discovery provides evidence of a highly regulated protein localization mechanism for this bacterial organelle development.
Biogenic overgrowth on detrital pyrite in ca. 3.2 Ga Archean paleosols
Authors: Nabhan Sami , Wiedenbeck Michael , Milke Ralf , Heubeck Christoph
Published: August 2016

Regionally traceable paleosols in the lower Moodies Group of the Barberton greenstone belt (ca. 3.22 Ga, northeastern South Africa and Swaziland) contain locally abundant silicified nodules, originally composed of pedogenic carbonates and sulfates, interbedded with heavy-mineral laminae dominated by pyrite. Pyrite grains show rounded detrital cores and secondary idiomorphic rims with trace element concentrations and δ34S ratios clearly different from those of the cores. While cores have low Co and Ni concentrations and high Co/Ni ratios, rims show as much as 5.5 wt% of these elements and low Co/Ni ratios, reflecting the weathering of nearby ultramafic rocks. In-situ sulfur isotope analyses of pyrite cores show δ34SVCDT (Vienna Canyon Diablo troilite) values between +5‰ and −5‰, while the rims show δ34SVCDT values between −20‰ and −24.5‰, suggesting biogenic fractionation of sulfur. The close spatial association and microtextural evidence for nearly contemporaneous formation of the pedogenic sulfate nodules and the secondary pyrite rims suggests microbial processing of sulfur in the paleosols, which provided reduced and 34S-depleted sulfur for the growth of authigenic pyrite. This indicates that vadose-zone soil-forming processes in the Archean involved not only physical and chemical modification of moist, unconsolidated sediment in a terrestrial environment but also already included its microbiological modification.
Epidemiology of Zika virus, 1947–2007
Authors: Posen H Joshua , Keystone Jay S , Gubbay Jonathan B , Morris Shaun K
Published: August 2016

Introduction

Since 1947, Zika virus has been identified sporadically in humans in Africa and Asia; however, clinically consequential Zika virus disease had not been documented prior to the current outbreak in the Americas. Considering 6 decades have passed since the first identification of the virus, it is perhaps unexpected that Zika virus was recognised only recently as capable of causing disease epidemics. Substantial work on understanding the epidemiology of Zika virus has been conducted since the virus' first outbreak in 2007 in Micronesia; however, there has been little study of the earlier data on Zika virus.

Methods

A systematic literature search was conducted to identify evidence of Zika virus infection in humans from 1947 to 2007. Data extracted included seroprevalence of Zika virus infection, age distributions of positive test results and serologic test modalities used. Country-level and age-specific seroprevalence was calculated. Estimates of seroprevalence by different serologic test modalities were compared.

Results

12 026 citations were retrieved by the literature search, and 76 articles were included in this review. Evidence of Zika virus infection in humans was found in 29 countries in Africa, 8 countries in Asia and 1 country in Europe. Country-level seroprevalence of Zika virus infection ranged from 0.4% to 53.3%. Seroprevalence of Zika virus infection was found to increase across the lifespan; 15–40% of reproductive-age individuals may have been previously infected. No significant difference was found between estimates of seroprevalence by different serologic test modalities.

Discussion

Zika virus has likely been endemic for decades in certain regions of the world; however, the majority of reproductive-age individuals have likely not been infected. Historical evidence of Zika virus infection exists regardless of the serologic test modality used.
Are lower levels of red blood cell transfusion more cost-effective than liberal levels after cardiac surgery? Findings from the TITRe2 randomised controlled trial
Authors: Stokes E A , Wordsworth S , Bargo D , Pike K , Rogers C A , Brierley R C M , Angelini G D , Murphy G J , Reeves B C
Published: August 2016

Objective

To assess the incremental cost and cost-effectiveness of a restrictive versus a liberal red blood cell transfusion threshold after cardiac surgery.

Design

A within-trial cost-effectiveness analysis with a 3-month time horizon, based on a multicentre superiority randomised controlled trial from the perspective of the National Health Service (NHS) and personal social services in the UK.

Setting

17 specialist cardiac surgery centres in UK NHS hospitals.

Participants

2003 patients aged >16 years undergoing non-emergency cardiac surgery with a postoperative haemoglobin of <9 g/dL.

Interventions

Restrictive (transfuse if haemoglobin <7.5 g/dL) or liberal (transfuse if haemoglobin <9 g/dL) threshold during hospitalisation after surgery.

Main outcome measures

Health-related quality of life measured using the EQ-5D-3L to calculate quality-adjusted life years (QALYs).

Results

The total costs from surgery up to 3 months were £17 945 and £18 127 in the restrictive and liberal groups (mean difference is −£182, 95% CI −£1108 to £744). The cost difference was largely attributable to the difference in the cost of red blood cells. Mean QALYs to 3 months were 0.18 in both groups (restrictive minus liberal difference is 0.0004, 95% CI −0.0037 to 0.0045). The point estimate for the base-case cost-effectiveness analysis suggested that the restrictive group was slightly more effective and slightly less costly than the liberal group and, therefore, cost-effective. However, there is great uncertainty around these results partly due to the negligible differences in QALYs gained.

Conclusions

We conclude that there is no clear difference in the cost-effectiveness of restrictive and liberal thresholds for red blood cell transfusion after cardiac surgery.

Trial registration number

ISRCTN70923932; Results.
Predictors of patient satisfaction in an emergency care centre in central Saudi Arabia: a prospective study
Authors: Abolfotouh Mostafa A , Al-Assiri Mohammed H , Alshahrani Rabab T , Almutairi Zainab M , Hijazi Raid A , Alaskar Ahmed S
Published: August 2016

Aim

This study aimed to (i) assess the level of patient satisfaction and its association with different sociodemographic and healthcare characteristics in an emergency care centre (ECC) in Saudi Arabia and (ii) to identify the predictors of patients' satisfaction.

Methods

A prospective cohort study of 390 adult patients with Canadian triage category III and IV who visited ECC at King Abdulaziz Medical City, Riyadh, Saudi Arabia, between 1 July and end of September 2011 was conducted. All patients were followed up from the time of arrival at the front desk of ECC until being seen by a doctor, and were then interviewed. Patient satisfaction was measured using a previously validated interview-questionnaire, within two domains: clarity of medical information and relationship with staff. Patient perception of health status after as compared with before the visit, and overall life satisfaction were also measured. Data on patient characteristics and healthcare characteristics were collected. Multiple linear regression analysis was used, and significance was considered at p≤0.05.

Results

One-third (32.8%) of patients showed high level of overall satisfaction and 26.7% were unsatisfied, with percentage mean score of 70.36% (17.40), reflecting moderate satisfaction. After adjusting for all potential confounders, lower satisfaction with the ED visit was significantly associated with male gender (p<0.001), long waiting time (p=0.032) and low perceived health status compared with status at admission (p<0.001). Overall life satisfaction was not a significant predictor of patient satisfaction.

Conclusions

An appreciation of waiting time as the only significant modifiable risk factor of patient satisfaction is essential to improve the healthcare services, especially at emergency settings.
Systematic review and meta-analysis of the association between maternal smoking in pregnancy and childhood overweight and obesity
Authors: Rayfield Sarah , Plugge Emma
Published: August 2016

Background

By 2020, it is predicted that 60 million children worldwide will be overweight. Maternal smoking in pregnancy has been suggested as a contributing factor. Our objective was to systematically review studies on this, thereby expanding the evidence base for this association.

Methods

Systematic review with meta-analysis, Prospero Registration number CRD42012002859. We searched PubMed, Embase, Global Health, Web of Science and the Grey literature. We included prevalence, cohort and cross-sectional studies involving full-term, singleton pregnancies. Published and unpublished studies through to 1 January 2015 in all languages, demonstrating an objective overweight outcome up until 18 years of age and data presented as an OR, were included. Quality assessment was undertaken using an adaption of the Newcastle-Ottawa scale. Statistical analysis was performed using Review Manager V.5.3.

Findings

The meta-analysis included 39 studies of 236 687 children from Europe, Australia, North America and South America and Asia. Maternal smoking in pregnancy ranged from 5.5% to 38.7%, with the prevalence of overweight from 6.3% to 32.1% and obesity from 2.6% to 17%. Pooled adjusted ORs demonstrated an elevated odds of maternal smoking in pregnancy for childhood overweight (OR 1.37, 95% CI 1.28 to 1.46, I245%) and childhood obesity (OR 1.55, 95% CI 1.40 to 1.73, I224%).

Interpretation

Our results demonstrate an association between maternal prenatal smoking and childhood overweight. This contributes to the growing evidence for the aetiology of childhood overweight, providing important information for policymakers and health professionals alike in planning cessation programmes or antismoking interventions for pregnant female smokers.
First integrals of generalized Ermakov systems via the Hamiltonian formulation
Authors: Mahomed K. S. , Moitsheki R. J.
Published: August 2016

We obtain first integrals of the generalized two-dimensional Ermakov systems, in plane polar form, via the Hamiltonian approaches. There are two methods used for the construction of the first integrals, viz. the standard Hamiltonian and the partial Hamiltonian approaches. In the first approach, [Formula: see text] and [Formula: see text] in the Ermakov system are related as [Formula: see text]. In this case, we deduce four first integrals (three of which are functionally independent) which correspond to the Lie algebra sl[Formula: see text] in a direct constructive manner. We recover the results of earlier work that uses the relationship between symmetries and integrals. This results in the complete integrability of the Ermakov system. By use of the partial Hamiltonian method, we discover four new cases: [Formula: see text] with [Formula: see text], [Formula: see text], [Formula: see text]; [Formula: see text] with [Formula: see text], [Formula: see text], [Formula: see text]; [Formula: see text] with [Formula: see text], [Formula: see text], [Formula: see text] arbitrary and [Formula: see text] with [Formula: see text], [Formula: see text], [Formula: see text] arbitrary, where the [Formula: see text]s are constants in all cases. In the last two cases, we find that there are three operators each which give rise to three first integrals each. In both these cases, we have complete integrability of the Ermakov system. The first two cases each result in two first integrals each. For every case, both for the standard and partial Hamiltonian, the angular momentum type first integral arises and this is a consequence of the operator which depends on a momentum coordinate which is a generalized symmetry in the Lagrangian context.
Nuclear structure and decay properties of even–even nuclei in Z = 70−80 drip-line region
Authors: Mahapatro S. , Lahiri C. , Kumar Bharat , Mishra R. N. , Patra S. K.
Published: August 2016

We study nuclear structure properties for various isotopes of Ytterbium (Yb), Hafnium(Hf), Tungsten(W), Osmium(Os), Platinum(Pt) and Mercury(Hg) in [Formula: see text] = 70–80 drip-line region starting from [Formula: see text] to [Formula: see text] within the formalism of relativistic mean field (RMF) theory. The pairing correlation is taken care by using BCS approach. We compared our results with finite range droplet model(FRDM) and experimental data and found that the calculated results are in good agreement. Neutron shell closure is obtained at [Formula: see text] and [Formula: see text] in this region. We have also studied probable decay mechanisms of these elements.
Mixotrophy in the Marine Plankton
Authors: Stoecker Diane K. , Hansen Per Juel , Caron David A. , Mitra Aditee
Published: August 2016

Mixotrophs are important components of the bacterioplankton, phytoplankton, microzooplankton, and (sometimes) zooplankton in coastal and oceanic waters. Bacterivory among the phytoplankton may be important for alleviating inorganic nutrient stress and may increase primary production in oligotrophic waters. Mixotrophic phytoflagellates and dinoflagellates are often dominant components of the plankton during seasonal stratification. Many of the microzooplankton grazers, including ciliates and Rhizaria, are mixotrophic owing to their retention of functional algal organelles or maintenance of algal endosymbionts. Phototrophy among the microzooplankton may increase gross growth efficiency and carbon transfer through the microzooplankton to higher trophic levels. Characteristic assemblages of mixotrophs are associated with warm, temperate, and cold seas and with stratification, fronts, and upwelling zones. Modeling has indicated that mixotrophy has a profound impact on marine planktonic ecosystems and may enhance primary production, biomass transfer to higher trophic levels, and the functioning of the biological carbon pump.
Designing Policies to Make Cars Greener
Authors: Anderson Soren T. , Sallee James M.
Published: August 2016

We review what is known about the economic efficiency of fuel taxes relative to efficiency standards aimed at mitigating environmental externalities from cars. We present a simplified model of car choice that allows us to emphasize the relationships between fuel economy, other car attributes, and miles traveled. We focus on greenhouse gas emissions, although we note how other environmental externalities affect our conclusions. Our main conclusion—that standards are substantially less efficient than a fuel tax—is already familiar. Less familiar are points we make about the relative importance of the rebound effect, on the effects of attribute-based policies, and the implications of behavioral biases. We point to areas where we believe future research can have the greatest contribution, including work on uncertainty, heterogeneity, and empirical studies in low- and middle-income countries.
More than Meets the Eye: Hidden Structures in the Proteome
Authors: Wasserman Hal , Saphire Erica Ollmann
Published: August 2016

A central dogma of molecular biology is that the sequence of a protein dictates its particular fold and the fold dictates its function. Indeed, the sequence → structure → function hypothesis has been a guiding principle by which scientists approach molecular biology. Every student knows that the genome encodes information for the progression from primary sequence to secondary, tertiary, and ultimately quaternary structure. Yet with a growing number of proteins, a fifth level has been identified: rearrangement of existing structures into distinct forms. Recent observations indicate that replication of Ebola virus depends on this fifth level. We believe other viruses with compact genomes and rapid evolution under selective pressure will be a rich source of examples of polypeptides that rearrange to gain added functions. In this review, we describe mechanisms by which viral, prokaryotic, and eukaryotic polypeptides have adopted alternate structures to control or gain function.
Understanding Glaucomatous Optic Neuropathy: The Synergy Between Clinical Observation and Investigation
Authors: Quigley Harry A.
Published: August 2016

Glaucoma is a complex disorder of aging defined by the death of retinal ganglion cells and remodeling of connective tissues at the optic nerve head. Intraocular pressure-induced axonal injury at the optic nerve head leads to apoptosis. Loss of retinal ganglion cells follows a slowly progressive sequence. Clinical features of the disease have suggested and corroborated pathological events. The death of retinal ganglion cells causes secondary loss of neurons in the brain, but only as a by-product of injury to the retinal ganglion cells. Although therapy to lower intraocular pressure is moderately effective, new treatments are being developed to alter the remodeling of ocular connective tissue, to interrupt the injury signal from axon to soma, and to upregulate a variety of survival mechanisms.
Association between TLR4 and PTEN Involved in LPS-TLR4 Signaling Response
Authors: Yin Huahua , Tan Yan , Wu Xiaofeng , Yan Hong , Liu Feng , Yao Yuanzhang , Jiang Jianxin , Wan Qi , Li Lei
Published: August 2016

In this study, we explored the potential mechanisms of how PTEN regulating LPS induced TLR4 signaling pathway. The initial findings from ELISA demonstrate that PTEN influences TNF-αsecretion by its lipid phosphatase activity. Subsequently, western blot, immunoprecipitation assay, and immunofluorescence were performed to explore the activation process of PTEN by stimulation with LPS. As early as 20 minutes after LPS stimulation, reduced phosphorylation of PTEN was found obviously. Accordingly, the whole cell-scattered PTEN translocated towards the cell membrane 20 minutes after stimulating with LPS. Moreover, the weak physical association between PTEN and TLR4 in resting RAW264.7 cells increased gradually after the stimulation of LPS. Furthermore, our study showed PTEN decreased LPS-induced Akt activity and upregulated NF-κB-dependent gene transcription, identifying indirectly that the PTEN could regulate the activation of NF-κB by its downstream Akt kinase. In summary, our study illustrates the potential signal transduction process of PTEN while stimulated by LPS: by increasing the association of TLR4, PTEN recruits to its phosphoinositide substrate PI(3,4,5)P3 located on the cell membrane and exerts its dephosphorylated function and subsequently depresses the activity of downstream molecule Akt and results in activation of NF-κB, followed by the secretion of inflammatory mediators TNF-α.
Design of a Reliable Hybrid (PV/Diesel) Power System with Energy Storage in Batteries for Remote Residential Home
Authors: Ani Vincent Anayochukwu
Published: August 2016

This paper reports the experience acquired with a photovoltaic (PV) hybrid system simulated as an alternative to diesel system for a residential home located in Southern Nigeria. The hybrid system was designed to overcome the problem of climate change, to ensure a reliable supply without interruption, and to improve the overall system efficiency (by the integration of the battery bank). The system design philosophy was to maximize simplicity; hence, the system was sized using conventional simulation tool and representative insolation data. The system includes a 15 kW PV array, 21.6 kWh (3600 Ah) worth of battery storage, and a 5.4 kW (6.8 kVA) generator. The paper features a detailed analysis of the energy flows through the system and quantifies all losses caused by PV charge controller, battery storage round-trip, rectifier, and inverter conversions. In addition, simulation was run to compare PV/diesel/battery with diesel/battery and the results show that the capital cost of a PV/diesel hybrid solution with batteries is nearly three times higher than that of a generator and battery combination, but the net present cost, representing cost over the lifetime of the system, is less than one-half of the generator and battery combination.
Circulating Tumor DNA as an Early Indicator of Response to T-cell Transfer Immunotherapy in Metastatic Melanoma
Authors: Xi Liqiang , Pham Trinh Hoc-Tran , Payabyab Eden C. , Sherry Richard M. , Rosenberg Steven A. , Raffeld Mark
Published: August 2016

Purpose: Adoptive transfer of activated autologous tumor-infiltrating lymphocytes (TIL) can mediate complete, durable regressions in patients with metastatic melanoma. Responding patients generally do not have significant changes in noncutaneous RECIST targets before 30 to 60 days following TIL infusion, and complete responses are often not confirmed for 1 to 2 years. There is a critical need for a biomarker that can provide early information regarding the likelihood and duration of a response to enable rational decisions about altering therapy. We wished to evaluate the role of circulating tumor DNA (ctDNA) in separating responding from nonresponding patients.

Experimental Design: We studied BRAF V600E ctDNA levels by a sensitive allele-specific PCR assay in 388 serum samples from 48 patients who received TIL immunotherapy at the NCI and correlated differences in the dynamic patterns of their ctDNA measurements with response outcomes.

Results: A strong correlation was found between the presence or absence of an early serum peak of V600E ctDNA, and the likelihood of an objective response. Furthermore, patients that developed an early ctDNA peak and cleared their serum of V600E ctDNA were highly likely to achieve a complete response over the next 1 to 2 years. Patients that showed no peak of V600E ctDNA failed to achieve an objective response, with one exception.

Conclusions: We show that the dynamic changes occurring in BRAF V600E ctDNA levels within the first month following T-cell transfer immunotherapy in metastatic melanoma can be used to rapidly identify responding from nonresponding patients, potentially allowing clinicians to make critical treatment-related decisions in a more timely manner. These data also suggest that the majority of tumor killing by TIL occurs very early after the initiation of therapy. Clin Cancer Res; 22(22); 5480–6. ©2016 AACR.
Determinants of bone mineral density in post-menopause
Authors: Silva Cristiane F. F. , Amorim Paulo R. S. , Carvalho Cristiane J. , Sales Samuel S. , Lima Luciana M.
Published: August 2016

Post-menopause is the period of greatest bone loss and it is necessary to introduce preventative measures to mitigate its progression. Aim: compare the score of bone mineral density (BMD) and their risk factors and to determine those most influencing. Method: Cross-sectional, descriptive study of 62 postmenopausal women, healthy, average age 56.82 ± 4.02 years, evaluated for risk factors for osteoporosis and physical activity level. Absorption dual energy X-ray absorptiometry (DXA) evaluated lumbar spine and proximal femur. Groups, normal and reduced BMD were analyzed by Student’s t test, chisquare and correlations. Results: Women with lower body mass index (BMI), older age and longer duration of menopause had lower BMD at the femur. Black race and absence of family history correlated with higher BMD. Conclusion: BMI, age, weight, family history of osteoporosis, race, and time since menopause were the main determinants of BMD in postmenopausal women
Comparison of the effects of continuous and intermittent non invasive mechanical ventilation on cardiorespiratory parameters and autonomic modulation of healthy individuals
Authors: Pacagnelli Francis L. , Freire Ana Paula C. F. , Palma Mariana R. , Paes Laio L. , Cardoso Murylo V. , Vanderlei Luiz Carlos M.
Published: August 2016

Study design: Cross-sectional study. Objective: To evaluate the influence of continuous and intermittent noninvasive mechanical ventilation (NIV) on cardiac autonomic modulation and cardiorespiratory parameters in healthy women. Methods: Twenty subjects performed two types of NIV: continuous through CPAP and intermittent through Müller Reanimator. Initially they remained at rest for 20 minutes in spontaneous breathing. Then volunteers were subjected to 20 minutes of NIV application with the selected technique and finally remained at rest for 20 minutes in spontaneous breathing. Cardiorespiratory parameters and heart rate variability (HRV) were measured in all these moments. Results: There were no significant differences when comparing the two techniques. Differences were observed in HRV and cardiorespiratory parameters when analyzed individually. Lower values of heart rate and respiratory rate were observed in continuous ventilation when compared to values during ventilation with spontaneous breathing (p <0.005). In both techniques we observed significant increases in SpO2 during ventilation compared to spontaneous breathing. We observed an increase in parasympathetic modulation (RMSSD, HF ms2 and SD1) and overall variability (SDNN, RR triangular and SD2) in both techniques when compared ventilation to spontaneous breathing (p <0.005). Conclusion: There was no difference comparing the two types of NIV. However, when analyzed individually we observe different behavior of cardiorespiratory parameters and autonomic modulation
ANÁLISE DE ELEMENTOS DO RELEVO ATRAVÉS DO TOPOGRAPHIC POSITION INDEX (TPI) DA BACIA HIDROGRÁFICA DO ARROIO PUITÃ – OESTE DO RIO GRANDE DO SUL/BRASIL
Authors: Trentin Romario , Robaina Luis Eduardo De Souza , Baratto Débora Da Silva
Published: August 2016

O presente trabalho teve como objetivo a determinação de classes do Topographic Position Index (TPI) na bacia hidrográfica do arroio Puitã. O arroio Puitã localiza-se no sul do Brasil, oeste do estado do Rio Grande do Sul. A base altimétrica para a definição do Topographic Position Index, foram os dados de radar do “Shuttle Radar Topography Mission” (SRTM). O TPI é a base do sistema de classificação e, é simplesmente a diferença entre um valor de elevação de células e a altitude média da vizinhança em torno dessas células. Valores positivos significam que a célula é mais elevada do que os seus arredores, enquanto valores negativos significa que é mais baixa. A escala utilizada para a definição das classes de TPI, foi de 10 pixeis, ou seja, foi utilizado um raio de 10 pixeis para a análise da vizinhança que compõem a média de altitude e estabelece o valor de TPI do pixel central. As classes de TPI determinadas foram assim denominadas: vales; áreas planas; encostas suaves; encostas onduladas; encostas íngremes e topo das encostas. A área de encostas suaves predomina na bacia com 38,06% da área total. As áreas de encostas onduladas e áreas planas são as segunda e terceira, em área, com 27,15% e 27,11%, respectivamente. A área de topo das encostas é a que ocupa a menor área, com apenas 0,44% da área total. A aplicação da metodologia de determinação do relevo através Topographic Position Index apresentou um resultado que responde bem as feições de relevo observadas em campo, o que o potencializa para a aplicação em outras áreas.
EVOLUÇÃO DA PAISAGEM DO BAIRRO SANTA FELICIDADE (CURITIBA-PR), COM BASE NO CONCEITO DE HEMEROBIA
Authors: Nucci João Carlos , Belem Anderson Luiz Godinho , Kröker Rudolf
Published: August 2016

Foi utilizado o conceito de hemerobia (dependência de energia e de tecnologia para a manutenção da paisagem) para estudar a evolução da paisagem no bairro de Santa Felicidade (Curitiba-PR). Fotografias aéreas de 1957 e 1972 e imagens de satélite do software Google Earth de 2007 e 2009-12 foram interpretadas em ambiente SIG (Sistema de Informação Geográfica) permitindo a classificação e mapeamento da hemerobia das paisagens na escala 1:10.000. Sete classes de hemerobia foram identificadas: mínima, muito baixa, baixa, média, alta, muito alta e máxima. A hemerobia do bairro passou, em menos de 60 anos, das classes de baixa dependência energética e tecnológica (mínima até baixa), que ocupavam cerca de 90% da área, para o predomínio das classes mais elevadas (máxima, muito alta e alta) com mais de 60% da área total do bairro em 2009-12. As áreas restantes ainda com classes de hemerobia de mínima à baixa (30%), estão cada vez mais fragmentadas e com comprometimento de suas funções ecológicas. A análise diacrônica das cartas de hemerobia mostrou que a conservação das funções ecológicas da paisagem não foi prioridade do poder público no planejamento da ocupação do bairro.
AVANÇO E RETRAÇÃO DE ÁREA GLACIAL NO EXTREMO NORTE DA PENÍNSULA TRINITY, ANTÁRTICA, ENTRE 1988 E 2015
Authors: Sotille Maria Eliza , Bremer Ulisses Franz , Simões Jefferson Cardia
Published: August 2016

O extremo norte da Península Trinity, na Península Antártica, sofreu mudanças na sua área coberta de gelo e na temperatura do ar ao longo das últimas três décadas. Visando apontar os avanços e as retrações da massa de gelo ocorridas na área, realizamos um levantamento das variações da posição das frentes de 32 geleiras ao longo de 27 anos (1988–2015). O estudo usou 10 imagens Landsat para identificar as variações das frentes das geleiras e compará-las com as variações na temperatura média anual do ar. Nesse período, ocorreu o recuo de   aproximadamente 50 km² nas frentes de gelo da região e um avanço de ±10 km², resultando na perda de ±40 km² da área coberta por gelo no extremo norte da Península Trinity (em torno de ±2,7 % da área de estudo). No período 1988–2000 essa península perdeu ±25,1 km² de gelo somente em suas frentes, entre 2000 e 2006 a perda for de ±12,2 km² e entre 2006 e 2011 de 5,0 km². O período 2011–2015 foi o único a apresentar avanços maiores que retrações, com um aumento de ±2,5 km² (±0,16%) de área. Os dados da temperatura média do ar, provenientes da base antártica Esperanza (Argentina 63°23'S 56°59'O), obtidos no portal READER, mostram aumento na média durante o verão (dez-fev) ao longo dos últimos 30 anos (1985–2015), no período 1964–2014 esse aumento foi de 1,45°C.
Interactive Musical Display of Quantum Dot Emission Spectra
Authors: Janney Eathan , Muñoz-Matutano Guillermo
Published: August 2016

Quantum dots (QDs) are zero-dimensional semiconductor nanostructures composed of thousands of atoms. QDs are often referred to as artificial atoms because their small structure results in unique, atom-like behavior; like atoms, QDs have optical emission at discrete wavelengths. Here the authors describe a novel method to interactively learn about the spectral properties of QDs using musical intuitions. They transform spectral information from selected Indum Arsenide (InAs) QDs into musical information, including both pitch and rhythm. Thus, they generate a multisensory experience of spectral information allowing users to learn about the range of frequencies of QDs as well as their unique spectral properties resulting from coulombic interactions.
Understanding Some of the Key Factors Responsible for Transition within an Indian Cotton Weaving Tradition
Authors: Banerjee Abhradip
Published: August 2016

This article aims at providing insight into one of the most important questions that still lurks within the discourses of India’s industrialisation or de-industrialisation. By analysing the case of a particular cotton weaving tradition in India, this article tries to explore how the adoption of new technologies or inflow of capital has brought changes within the labour relationship, which has eventually led to the transition within many other Indian handloom weaving traditions. Other than mere descriptions of structural relationships between stakeholders belonging to different hierarchies of cloth production systems, this article, with its analytic ethnographical framework, focuses on the cultural nuances of the workplace and labour-capital relationships within this particular cotton-weaving tradition. It tries to illuminate how these people get involved, how they interact and engage in different sorts of contracts with one another. Therefore, this article may help in understanding how inequality in the distribution of technical skills and resources instigate the politics of labour relationships, and ultimately how such socio-political arrangements carve the future course of a cloth producing tradition.
Varieties of Fairness and Procedural Cultures: A Comparative Discussion
Authors: Husa Jaakko
Published: August 2016

Fairness is an important part of legal proceedings and fair trial. Procedural rules are an integral part of the legal cultural context that gives them meaning. This article discusses procedural cultures from the point view of legal language and legal culture. The multiplicity of law and legal cultures functions as a base for an analysis of criminal procedural law using plea bargaining as an example. The author highlights the differences between common law and civil law and shows that even though there has been convergence there are still significant legal cultural differences. This article reveals how there is a legal cultural variety in the ways in which fairness forms a part of the conception of fair trial as a European human right. The concluding section highlights the theoretical implications of the article as a whole by stressing the importance of sensitivity and the constant need to define the specific meaning.
Australian Trade Policy and the sme Backlash: Are Small and Medium Sized Enterprises (smes) Sufficiently Respected and Reflected in our Trade Agreements and Outcomes?
Authors: Zeller Bruno , Andersen Camilla Baasch
Published: August 2016

This paper discusses the importance of smes in the context of Australia’s trade policy. The question is asked; is sufficient attention given to smes in the drafting of ftas or is the trade policy directed to “the big end of town?” This paper highlights the difficulties of enterprises in navigating through the multitude of trade agreements. One of the issues is that the documentation accessing ftas is not uniform. This causes compliance problem specifically in relation to rules of origin. As a corollary to the different documentary requirements the associated transaction costs are examined with the conclusion that Australia does not exploit its growth potential, as smes are not maximizing their contribution to international trade.
Pension reform in the United Kingdom: an economic perspective
Authors: Disney Richard
Published: August 2016

This paper considers the evolution of the UK's pension programme in the light of various stated rationales for public intervention. It argues that the publicly-provided (tax-financed) pension programme has gone through four distinct stages since 1946. It examines some of the issues that have arisen in the context of private pension provision in the UK, both in the form of so-called ‘defined benefit’ and ‘defined contribution’ pension plans, as well as individual purchases of annuities.
Workplace pensions and remuneration in the public and private sectors in the UK
Authors: Cribb Jonathan , Emmerson Carl
Published: August 2016

We estimate the changing value of workplace pensions in the UK and incorporate their value into an estimate of the public sector pay differential. Falling pension membership in the private sector and growing value of public service pensions led to a significant increase in the estimated public sector pay differential from 1997 to 2009, even though headline pay grew faster in the private sector. From 2009 to 2012, although pay grew faster in the public sector, reforms to public service defined benefit pensions, particularly indexation to the CPI rather than RPI, significantly reduced the public pay differential.