bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymyxin B Induces Apoptosis in Kidney Proximal Tubular Cells
Authors: Azad Mohammad A. K. , Finnin Ben A. , Poudyal Anima , Davis Kathryn , Li Jinhua , Hill Prue A. , Nation Roger L. , Velkov Tony , Li Jian 
Published: June 2013

ABSTRACT

The nephrotoxicity of polymyxins is a major dose-limiting factor for treatment of infections caused by multidrug-resistant Gram-negative pathogens. The mechanism(s) of polymyxin-induced nephrotoxicity is not clear. This study aimed to investigate polymyxin B-induced apoptosis in kidney proximal tubular cells. Polymyxin B-induced apoptosis in NRK-52E cells was examined by caspase activation, DNA breakage, and translocation of membrane phosphatidylserine using Red-VAD-FMK [Val-Ala-Asp(O-Me) fluoromethyl ketone] staining, a terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and double staining with annexin V-propidium iodide (PI). The concentration dependence (50% effective concentration [EC
50
]) and time course for polymyxin B-induced apoptosis were measured in NRK-52E and HK-2 cells by fluorescence-activated cell sorting (FACS) with annexin V and PI. Polymyxin B-induced apoptosis in NRK-52E cells was confirmed by positive labeling from Red-VAD-FMK staining, TUNEL assay, and annexin V-PI double staining. The EC
50
(95% confidence interval [CI]) of polymyxin B for the NRK-52E cells was 1.05 (0.91 to 1.22) mM and was 0.35 (0.29 to 0.42) mM for HK-2 cells. At lower concentrations of polymyxin B, minimal apoptosis was observed, followed by a sharp rise in the apoptotic index at higher concentrations in both cell lines. After treatment of NRK-52E cells with 2.0 mM polymyxin B, the percentage of apoptotic cells (mean ± standard deviation [SD]) was 10.9% ± 4.69% at 6 h and reached plateau (>80%) at 24 h, whereas treatment with 0.5 mM polymyxin B for 24 h led to 93.6% ± 5.57% of HK-2 cells in apoptosis. Understanding the mechanism of polymyxin B-induced apoptosis will provide important information for discovering less nephrotoxic polymyxin-like lipopeptides.
The Trypanosoma brucei gambiense Secretome Impairs Lipopolysaccharide-Induced Maturation, Cytokine Production, and Allostimulatory Capacity of Dendritic Cells
Authors: Garzón Edwin , Holzmuller Philippe , Bras-Gonçalves Rachel , Vincendeau Philippe , Cuny Gérard , Lemesre Jean Loup , Geiger Anne 
Published: June 2013

ABSTRACTTrypanosoma brucei gambiense, a parasitic protozoan belonging to kinetoplastids, is the main etiological agent of human African trypanosomiasis (HAT), or sleeping sickness. One major characteristic of this disease is the dysregulation of the host immune system. The present study demonstrates that the secretome (excreted-secreted proteins) ofT. b. gambienseimpairs the lipopolysaccharide (LPS)-induced maturation of murine dendritic cells (DCs). The upregulation of major histocompatibility complex class II, CD40, CD80, and CD86 molecules, as well as the secretion of cytokines such as tumor necrosis factor alpha, interleukin-10 (IL-10), and IL-6, which are normally released at high levels by LPS-stimulated DCs, is significantly reduced when these cells are cultured in the presence of theT. b. gambiensesecretome. Moreover, the inhibition of DC maturation results in the loss of their allostimulatory capacity, leading to a dramatic decrease in Th1/Th2 cytokine production by cocultured lymphocytes. These results provide new insights into a novel efficient immunosuppressive mechanism directly involving the alteration of DC function which might be used byT. b. gambienseto interfere with the host immune responses in HAT and promote the infectious process.
Poison Domains Block Transit of Translocated Substrates via the Legionella pneumophila Icm/Dot System
Authors: Amyot Whitney M. , deJesus Dennise , Isberg Ralph R. 
Published: June 2013

ABSTRACT

Legionella pneumophila
uses the Icm/Dot type 4B secretion system (T4BSS) to deliver translocated protein substrates to the host cell, promoting replication vacuole formation. The conformational state of the translocated substrates within the bacterial cell is unknown, so we sought to determine if folded substrates could be translocated via this system. Fusions of
L. pneumophila
Icm/Dot-translocated substrates (IDTS) to dihydrofolate reductase (DHFR) or ubiquitin (Ub), small proteins known to fold rapidly, resulted in proteins with low translocation efficiencies. The folded moieties did not cause increased aggregation of the IDTS and did not impede interaction with the adaptor protein complex IcmS/IcmW, which is thought to form a soluble complex that promotes translocation. The translocation defect was alleviated with a Ub moiety harboring mutations known to destabilize its structure, indicating that unfolded proteins are preferred substrates. Real-time analysis of translocation, following movement during the first 30 min after bacterial contact with host cells, revealed that the folded moiety caused a kinetic defect in IDTS translocation. Expression of an IDTS fused to a folded moiety interfered with the translocation of other IDTS, consistent with it causing a blockage of the translocation channel. Furthermore, the folded protein fusions also interfered with intracellular growth, consistent with inefficient or impaired translocation of proteins critical for
L. pneumophila
intracellular growth. These studies indicate that substrates of the Icm/Dot T4SS are translocated to the host cytosol in an unfolded conformation and that folded proteins are stalled within the translocation channel, impairing the function of the secretion system.
Human and Mouse Macrophages Collaborate with Neutrophils To Kill Larval Strongyloides stercoralis
Authors: Bonne-Année Sandra , Kerepesi Laura A. , Hess Jessica A. , O'Connell Amy E. , Lok James B. , Nolan Thomas J. , Abraham David 
Published: June 2013

ABSTRACTMacrophages are multifunctional cells that are active in TH1- and TH2-mediated responses. In this study, we demonstrate that human and mouse macrophages collaborate with neutrophils and complement to kill the parasiteStrongyloides stercoralis in vitro. Infection of mice with worms resulted in the induction of alternatively activated macrophages (AAMϕ) within the peritoneal cavity. These cells killed the wormsin vivoand collaborated with neutrophils and complement during thein vitrokilling process. AAMϕ generatedin vitrokilled larvae more rapidly than naive macrophages, which killed larvae after a longer time period. In contrast, classically activated macrophages were unable to kill larvae eitherin vitroorin vivo. This study adds macrophages to the armamentarium of immune components that function in elimination of parasitic helminths and demonstrate a novel function by which AAMϕ control large extracellular parasites.
LacR Mutations Are Frequently Observed in Streptococcus intermedius and Are Responsible for Increased Intermedilysin Production and Virulence
Authors: Tomoyasu Toshifumi , Imaki Hidenori , Masuda Sachiko , Okamoto Ayumi , Kim Hyejin , Waite Richard D. , Whiley Robert A. , Kikuchi Ken , Hiramatsu Keiichi , Tabata Atsushi , Nagamune Hideaki 
Published: June 2013

ABSTRACT

Streptococcus intermedius
secretes a human-specific cytolysin, intermedilysin (ILY), which is considered to be the major virulence factor of this pathogen. We screened for a repressor of
ily
expression by using random gene disruption in a low-ILY-producing strain (PC574). Three independent high-ILY-producing colonies that had plasmid insertions within a gene that has high homology to
lacR
were isolated. Validation of these observations was achieved through disruption of
lacR
in strain PC574 with an erythromycin cassette, which also led to higher hemolytic activity, increased transcription of
ily
, and higher cytotoxicity against HepG2 cells, compared to the parental strain. The direct binding of LacR within the
ily
promoter region was shown by a biotinylated DNA probe pulldown assay, and the amount of ILY secreted into the culture supernatant by PC574 cells was increased by adding lactose or galactose to the medium as a carbon source. Furthermore, we examined
lacR
nucleotide sequences and the hemolytic activity of 50 strains isolated from clinical infections and 7 strains isolated from dental plaque. Of the 50 strains isolated from infections, 13 showed high ILY production, 11 of these 13 strains had one or more point mutations and/or an insertion mutation in LacR, and almost all mutations were associated with a marked decline in LacR function. These results strongly suggest that mutation in
lacR
is required for the overproduction of ILY, which is associated with an increase in pathogenicity of
S. intermedius
.
Detecting user dissatisfaction and understanding the underlying reasons
Authors: Arvidsson Ake , Zhang Ying 
Published: June 2013

Quantifying quality of experience for network applications is challenging as it is a subjective metric with multiple dimensions such as user expectation, satisfaction, and overall experience. Today, despite various techniques to support differentiated Quality of Service (QoS), the operators still lack of automated methods to translate QoS to QoE, especially for general web applications.
In this work, we take the approach of identifying unsatisfactory performance by searching for user initiated early terminations of web transactions from passive monitoring. However, user early abortions can be caused by other factors such as loss of interests. Therefore, naively using them to represent user dissatisfaction will result in large false positives. In this paper, we propose a systematic method for inferring user dissatisfaction from the set of early abortion behaviors observed from identifying the traffic traces. We conduct a comprehensive analysis on the user acceptance of throughput and response time, and compare them with the traditional MOS metric. Then we present the characteristics of early cancelation from dimensions like the types of URLs and objects. We evaluate our approach on four data sets collected in both wireline network and a wireless cellular network.
Lingering issues in distributed scheduling
Authors: Simatos Florian , Bouman Niek , Borst Sem 
Published: June 2013

Recent advances have resulted in queue-based algorithms for medium access control which operate in a distributed fashion, and yet achieve the optimal throughput performance of centralized scheduling algorithms. However, fundamental performance bounds reveal that the "cautious" activation rules involved in establishing throughput optimality tend to produce extremely large delays, typically growing exponentially in 1/(1-r), with r the load of the system, in contrast to the usual linear growth. Motivated by that issue, we explore to what extent more "aggressive" schemes can improve the delay performance. Our main finding is that aggressive activation rules induce a lingering effect, where individual nodes retain possession of a shared resource for excessive lengths of time even while a majority of other nodes idle. Using central limit theorem type arguments, we prove that the idleness induced by the lingering effect may cause the delays to grow with 1/(1-r) at a quadratic rate. To the best of our knowledge, these are the first mathematical results illuminating the lingering effect and quantifying the performance impact.
In addition extensive simulation experiments are conducted to illustrate and validate the various analytical results.
Aptamer Identification of Brain Tumor–Initiating Cells
Authors: Kim Youngmi , Wu Qiulian , Hamerlik Petra , Hitomi Masahiro , Sloan Andrew E. , Barnett Gene H. , Weil Robert J. , Leahy Patrick , Hjelmeland Anita B. , Rich Jeremy N. 
Published: June 2013

Abstract
Glioblastomas display cellular hierarchies with self-renewing tumor-initiating cells (TIC), also known as cancer stem cells, at the apex. Although the TIC hypothesis remains controversial and the functional assays to define the TIC phenotype are evolving, we and others have shown that TICs may contribute to therapeutic resistance, tumor spread, and angiogenesis. The identification of TICs has been informed by the use of markers characterized in normal stem cells, but this approach has an inherent limitation to selectively identify TICs. To develop reagents that enrich TICs but not matched non-TICs or tissue-specific stem cells, we adopted Cell-Systematic Evolution of Ligands by Exponential Enrichment (Cell-SELEX) to identify glioblastoma TIC-specific nucleic acid probes—aptamers—that specifically bind TICs. In this study, using Cell-SELEX with positive selection for TICs and negative selection for non-TICs and human neural progenitor cells, we identified TIC aptamers that specifically bind to TICs with excellent dissociation constants (Kd). These aptamers select and internalize into glioblastoma cells that self-renew, proliferate, and initiate tumors. As aptamers can be modified to deliver payloads, aptamers may represent novel agents that could selectively target or facilitate imaging of TICs. Cancer Res; 73(15); 4923–36. ©2013 AACR.
Drug-Eluting Balloon in Peripheral Intervention for Below the Knee Angioplasty Evaluation (DEBATE-BTK)
Authors: Liistro Francesco , Porto Italo , Angioli Paolo , Grotti Simone , Ricci Lucia , Ducci Kenneth , Falsini Giovanni , Ventoruzzo Giorgio , Turini Filippo , Bellandi Guido , Bolognese Leonardo 
Published: June 2013

Background—
The 1-year restenosis rate after balloon angioplasty of long lesions in below-the-knee arteries may be as high as 70%. Our aim was to investigate the efficacy of a paclitaxel drug-eluting balloons versus conventional percutaneous transluminal angioplasty (PTA) for the reduction of restenosis in diabetic patients with critical limb ischemia undergoing endovascular intervention of below-the-knee arteries.

Methods and Results—

The Drug-Eluting Balloon in Peripheral Intervention for Below the Knee Angioplasty Evaluation (DEBATE-BTK) is a randomized, open-label, single-center study comparing drug-eluting balloons and PTA. Inclusion criteria were diabetes mellitus, critical limb ischemia (Rutherford class 4 or higher), significant stenosis or occlusion >40 mm of at least 1 below-the-knee vessel with distal runoff, and life expectancy >1 year. Binary in-segment restenosis at a 1-year angiographic or ultrasonographic follow-up was the primary end point. Clinically driven target lesion revascularization, major amputation, and target vessel occlusion were the secondary end points. One hundred thirty-two patients with 158 infrapopliteal atherosclerotic lesions were enrolled. Mean length of the treated segments was 129±83 mm in the drug-eluting balloon group compared with 131±79 mm in the PTA group (
P
=0.7). Binary restenosis, assessed by angiography in >90% of patients, occurred in 20 of 74 lesions (27%) in the drug-eluting balloon group compared with 55 of 74 lesions (74%) in the PTA group (
P
<0.001); target lesion revascularization, in 12 (18%) versus 29 (43%;
P
=0.002); and target vessel occlusion, in 12 (17%) versus 41 (55%;
P
<0.001). Only 1 major amputation occurred, in the PTA group (
P
=0.9).

Conclusions—
Drug-eluting balloons compared with PTA strikingly reduce 1-year restenosis, target lesion revascularization, and target vessel occlusion in the treatment of below-the-knee lesions in diabetic patients with critical limb ischemia.

Clinical Trial Registration—

URL:
http://ClinicalTrials.gov
. Unique identifier: NCT01558505.
Costing the Earth: A Numbers Game or a Moral Imperative?
Authors: Roe Gerard 
Published: June 2013

Abstract
It is a simple truism that public policy must be guided by an objective analysis of the physical and economic consequences of climate change. It is equally true that policy making is an inherently value-laden endeavor. While these two threads are interconnected, the relative weight given to each depends on the certainty that the technical analyses can deliver. For climate change, the envelope of uncertainty is best understood at the global scale, and there are some well known and formidable challenges to reducing it. This uncertainty must in turn be compounded with much more poorly constrained uncertainties in regional climate, climate impacts, and future economic costs. The case can be made that technical analyses have reached the point of diminishing returns. Should meaningful action on climate change await greater analytical certainty? This paper argues that policy makers should give greater weight to moral arguments, in no small part because that is where the heart of the debate really lies.
Initial Clinical Findings of a Mathematical Model to Predict Survival of Head and Neck Cancer
Authors: Emerick Kevin S. , Leavitt Erica R. , Michaelson James S. , Diephuis Bradford , Clark John R. , Deschler Daniel G. 
Published: June 2013

Objectives(1) Identify clinical features that impact survival for head and neck cancer. (2) Determine the individual contribution to mortality of significant clinical features. (3) Develop a web‐based calculator to integrate clinical features and predict survival outcome for individual patients.Study DesignAnalysis of a national cancer database. We fit patient data to the binary‐biological model of cancer lethality, a mathematical model designed to predict cancer outcome. The model predicts the risk of cancer death, using information on tumor size, nodal status, and other prognostic factors.Subjects and MethodsAnalysis was carried out on a cohort of ~50,000 patients with head and neck cancer from the Survey, Epidemiology and End‐Results (SEER) 2009 data set and validated with a cohort of ~1300 patients from an institutional Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary database. We developed a web‐based calculator written in JavaScript, PHP, and HTML.ResultsThe risk of death due to head and neck cancer increases monotonically with tumor size. Each positive lymph node is associated with ~14% extra risk of death. Anatomical site, age, race, tumor extension, N stage, and extracapsular spread contribute to mortality. The lethal impact of these prognostics factors can be accurately estimated by the Size + Nodes + PrognosticMarkers (SNAP) method.ConclusionsThis predictive cancer model and web‐based calculator provide a basis for estimating the risk of death for head and neck cancer patients by assigning values to the lethal contributions of tumor size, number of positive nodes, anatomical site, tumor extension, N stage, extracapsular spread, age at diagnosis, and race.
Diagnosing early Barrett’s neoplasia and oesophageal squamous cell neoplasia by bioimpedance spectroscopy in human tissue
Authors: Knabe Mate , Kurz Christian , Knoll Thorsten , Velten Thomas , Vieth Michael , Manner Hendrik , Ell Christian , Pech Oliver 
Published: June 2013

BackgroundDetection of early oesophageal cancer in surrounding normal tissue can be challenging, but detection is essential to determine the subsequent treatment. Dysplastic tissue can be detected by using electrical impedance spectroscopy (EIS).ObjectiveThe aim of the present study was to evaluate the feasibility and value of EIS in the diagnosis of oesophageal neoplasia.MethodsThis prospective ex‐vivo study included 23 patients with early oesophageal cancer (17 with Barrett’s cancer and six with early squamous cell cancer). Immediately after endoscopic resection, the electrical properties of the resected specimens were investigated using a pencil probe (5 mm in diameter, frequency range from 100 Hz to 1 MHz). Punch biopsies were taken from the measured site in order to compare the results of EIS with histology.ResultsEIS was able to detect dysplastic oesophageal mucosa with a high rate of accuracy (82% in Barrett’s oesophagus and 100% in squamous oesophagus) A total of 54 different sites in 26 tumours were evaluated.ConclusionsEIS was able to differentiate reliably between non‐neoplastic and neoplastic oesophageal mucosa. Using EIS, it might be possible to use it for targeted biopsies and to avoid unnecessary biopsies during cancer surveillance in future.
The development of a patient-reported outcome measure for assessing nighttime symptoms of chronic obstructive pulmonary disease
Authors: Hareendran Asha , Palsgrove Andrew C , Mocarski Michelle , Schaefer Michael L , Setyawan Juliana , Carson Robyn , Make Barry 
Published: June 2013

Abstract

Background
The assessment of symptoms of chronic obstructive pulmonary disease (COPD) is important for monitoring and managing the disease and for evaluating outcomes of interventions. COPD patients experience symptoms during the day and night, and symptoms experienced at night often disturb sleep. The aim of this paper is to describe methods used to develop a patient-reported outcome (PRO) instrument for evaluating nighttime symptoms of COPD, and to document evidence for the content validity of the instrument.

Methods
Literature review and clinician interviews were conducted to inform discussion guides to explore patients’ nighttime COPD symptom experience. Data from focus groups with COPD patients was used to develop a conceptual framework and the content of a new PRO instrument. Patient understanding of the new instrument was assessed via cognitive interviews with COPD patients.

Results
The literature review confirmed that there is no instrument with evidence of content validity currently available to assess nighttime symptoms of COPD. Additionally, the literature review and clinician interviews suggested the need to understand patients’ experience of specific symptoms in order to evaluate nighttime symptoms of COPD. Analyses of patient focus group data (N = 27) supported saturation of concepts and aided in development of a conceptual framework. Items were generated using patients’ terminology to collect data on concepts in the framework including the occurrence and severity of COPD symptoms, use of rescue medication at night, and nocturnal awakening. Response options were chosen to reflect concepts that were salient to patients. Subsequent cognitive interviewing with ten COPD patients demonstrated that the items, response options, recall period, and instructions were understandable, relevant, and interpreted as intended.

Conclusions
A new PRO instrument, the Nighttime Symptoms of COPD Instrument (NiSCI), was developed with documented evidence of content validity. The NiSCI is ready for empirical testing, including item reduction and evaluation of psychometric properties.
Gold nanoarray deposited using alternating current for emission rate-manipulating nanoantenna
Authors: Xue Jiancai , Zhu Qiangzhong , Liu Jiaming , Li Yinyin , Zhou Zhang-Kai , Lin Zhaoyong , Yan Jiahao , Li Juntao , Wang Xue-Hua 
Published: June 2013

Abstract
We have proposed an easy and controllable method to prepare highly ordered Au nanoarray by pulse alternating current deposition in anodic aluminum oxide template. Using the ultraviolet–visible-near-infrared region spectrophotometer, finite difference time domain, and Green function method, we experimentally and theoretically investigated the surface plasmon resonance, electric field distribution, and local density of states enhancement of the uniform Au nanoarray system. The time-resolved photoluminescence spectra of quantum dots show that the emission rate increased from 0.0429 to 0.5 ns−1 (10.7 times larger) by the existence of the Au nanoarray. Our findings not only suggest a convenient method for ordered nanoarray growth but also prove the utilization of the Au nanoarray for light emission-manipulating antennas, which can help build various functional plasmonic nanodevices.

PACS

82.45.Yz, 78.47.jd, 62.23.Pq
Existence and exponential stability of periodic solutions for a class of Hamiltonian systems on time scales
Authors: Yang Li , Liao Yongzhi , Li Yongkun 
Published: June 2013

Abstract
In this paper, by using a fixed point theorem and the theory of calculus on time scales, we obtain some sufficient conditions for the existence and exponential stability of periodic solutions for a class of Hamiltonian systems on time scales. We also present numerical examples to show the feasibility of our results. The results of this paper are completely new and complementary to the previously known results even if the time scale

T
=
R

or ℤ.