bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiospectral denoising framework for multispectral optoacoustic imaging based on sparse signal representation
Authors: Tzoumas Stratis , Rosenthal Amir , Lutzweiler Christian , Razansky Daniel , Ntziachristos Vasilis
Published: October 2014

Purpose:

One of the major challenges in dynamic multispectral optoacoustic imaging is its relatively low signal‐to‐noise ratio which often requires repetitive signal acquisition and averaging, thus limiting imaging rate. The development of denoising methods which prevent the need for signal averaging in time presents an important goal for advancing the dynamic capabilities of the technology.

Methods:

In this paper, a denoising method is developed for multispectral optoacoustic imaging which exploits the implicit sparsity of multispectral optoacoustic signals both in space and in spectrum. Noise suppression is achieved by applying thresholding on a combined wavelet‐Karhunen–Loève representation in which multispectral optoacoustic signals appear particularly sparse. The method is based on inherent characteristics of multispectral optoacoustic signals of tissues, offering promise for general application in different incarnations of multispectral optoacoustic systems.

Results:

The performance of the proposed method is demonstrated on mouse images acquired in vivo for two common additive noise sources: time‐varying parasitic signals and white noise. In both cases, the proposed method shows considerable improvement in image quality in comparison to previously published denoising strategies that do not consider multispectral information.

Conclusions:

The suggested denoising methodology can achieve noise suppression with minimal signal loss and considerably outperforms previously proposed denoising strategies, holding promise for advancing the dynamic capabilities of multispectral optoacoustic imaging while retaining image quality.
Breast tumor segmentation in high resolution x‐ray phase contrast analyzer based computed tomography
Authors: Brun E. , Grandl S. , Sztrókay‐Gaul A. , Barbone G. , Mittone A. , Gasilov S. , Bravin A. , Coan P.
Published: October 2014

Purpose:

Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human‐guided breast tumor segmentation. This method has been applied to high‐resolution images of excised human organs, each of several gigabytes.

Methods:

The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure's possible applications.

Results:

A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists.

Conclusions:

The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high‐resolution x‐ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.
Sidewinding with minimal slip: Snake and robot ascent of sandy slopes
Authors: Marvi Hamidreza , Gong Chaohui , Gravish Nick , Astley Henry , Travers Matthew , Hatton Ross L. , Mendelson Joseph R. , Choset Howie , Hu David L. , Goldman Daniel I.
Published: October 2014

Limbless organisms such as snakes can navigate nearly all terrain. In particular, desert-dwelling sidewinder rattlesnakes (
Crotalus cerastes
) operate effectively on inclined granular media (such as sand dunes) that induce failure in field-tested limbless robots through slipping and pitching. Our laboratory experiments reveal that as granular incline angle increases, sidewinder rattlesnakes increase the length of their body in contact with the sand. Implementing this strategy in a physical robot model of the snake enables the device to ascend sandy slopes close to the angle of maximum slope stability. Plate drag experiments demonstrate that granular yield stresses decrease with increasing incline angle. Together, these three approaches demonstrate how sidewinding with contact-length control mitigates failure on granular media.
Response to Comment on “Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring”
Authors: Eftekhari Sanaz , Shahrokhi Amene , Tsintsadze Vera , Nardou Romain , Brouchoud Corinne , Conesa Magali , Burnashev Nail , Ferrari Diana C. , Ben-Ari Yehezkel
Published: October 2014

Bambini-Junior
et al
. questioned whether our treatment in two rodent models of autism has a long-lasting effect into adulthood. In response, we show that bumetanide treatment around delivery attenuates autistic behavioral features in adult offspring. Therefore, the polarity of γ-aminobutyric acid (GABA) actions during delivery exerts long-lasting priming actions after birth.
Halting harmful helminths
Authors: Hoffmann Karl F. , Brindley Paul J. , Berriman Matthew
Published: October 2014

Vaccines and new drugs are needed to combat parasitic worm infections
Stem cell recipe offers diabetes hope
Authors: Vogel Gretchen
Published: October 2014

Researchers coax stem cells into becoming long-sought insulin-producing β cells.
Evaluation of the Xpert
vanA
/
vanB
Assay Using Enriched Inoculated Broths for Direct Detection of
vanB
Vancomycin-Resistant Enterococci
Authors: Zhou X. , Arends J. P. , Kampinga G. A. , Ahmad H. M. , Dijkhuizen B. , van Barneveld P. , Rossen J. W. A. , Friedrich A. W.
Published: October 2014

Rapid and accurate detection of VRE (vancomycin-resistant enterococci) is required for adequate antimicrobial treatment and infection prevention measures. Previous studies using PCR for the detection of VRE, including Cepheid's Xpert
vanA
/
vanB
assay, reported accurate detection of
vanA
VRE; however, many false-positive results were found for
vanB
VRE. This is mainly due to nonenterococcal
vanB
genes, which can be found in the gut flora. Our goal was to optimize the rapid and accurate detection of
vanB
VRE and to improve the positive predictive value (PPV) by limiting false-positive results. We evaluated the use of the Xpert
vanA
/
vanB
assay on rectal swabs and on enriched inoculated broths for the detection of
vanB
VRE. By adjusting the cycle threshold (

C
T

) cutoff value to ≤25 for positivity by PCR on enriched broths, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 96.9%, 100%, 100%, and 99.5% for
vanB
VRE, respectively. As shown in this study,

C
T

values of ≤25 acquired from enriched broths can be considered true positive. For broths with

C
T

values between 25 and 30, we recommend confirming the results by culture.

C
T

values of >30 appeared to be true negative. In conclusion, this study shows that the Cepheid's Xpert
vanA
/
vanB
assay performed on enriched inoculated broths with an adjusted cutoff

C
T

value is a useful and rapid tool for the detection of
vanB
VRE.
Matrix-Assisted Laser Desorption Ionization–Time of Flight (MALDI-TOF) Mass Spectrometry Using the Vitek MS System for Rapid and Accurate Identification of Dermatophytes on Solid Cultures
Authors: De Respinis Sophie , Monnin Valérie , Girard Victoria , Welker Martin , Arsac Maud , Cellière Béatrice , Durand Géraldine , Bosshard Philipp P. , Farina Claudio , Passera Marco , Van Belkum Alex , Petrini Orlando , Tonolla Mauro
Published: October 2014

The objective of this research was to extend the Vitek MS fungal knowledge base version 2.0.0 to allow the robust identification of clinically relevant dermatophytes, using a variety of strains, incubation times, and growth conditions. First, we established a quick and reliable method for sample preparation to obtain a reliable and reproducible identification independently of the growth conditions. The Vitek MS V2.0.0 fungal knowledge base was then expanded using 134 well-characterized strains belonging to 17 species in the genera
Epidermophyton
,
Microsporum
, and
Trichophyton
. Cluster analysis based on mass spectrum similarity indicated good species discrimination independently of the culture conditions. We achieved a good separation of the subpopulations of the
Trichophyton
anamorph of
Arthroderma benhamiae
and of anthropophilic and zoophilic strains of
Trichophyton interdigitale
. Overall, the 1,130 mass spectra obtained for dermatophytes gave an estimated identification performance of 98.4%. The expanded fungal knowledge base was then validated using 131 clinical isolates of dermatophytes belonging to 13 taxa. For 8 taxa all strains were correctly identified, and for 3 the rate of successful identification was >90%; 75% (6/8) of the
M. gypseum
strains were correctly identified, whereas only 47% (18/38) of the African
T. rubrum
population (also called
T. soudanense
) were recognized accurately, with a large quantity of strains misidentified as
T. violaceum
, demonstrating the close relationship of these two taxa. The method of sample preparation was fast and efficient and the expanded Vitek MS fungal knowledge base reliable and robust, allowing reproducible dermatophyte identifications in the routine laboratory.
A Highly Sensitive Europium Nanoparticle-Based Immunoassay for Detection of Influenza A/B Virus Antigen in Clinical Specimens
Authors: Zhang Panhe , Vemula Sai Vikram , Zhao Jiangqin , Du Bingchen , Mohan Haleyurgirisetty , Liu Jikun , El Mubarak Haja Sittana , Landry Marie L. , Hewlett Indira
Published: October 2014

We report the development of a novel europium nanoparticle-based immunoassay (ENIA) for rapid detection of influenza A and influenza B viruses. The ENIA demonstrated sensitivities of 90.7% (147/162) for influenza A viruses and 81.80% (9/11) for influenza B viruses compared to those for an in-house reverse transcription (RT)-PCR assay in testing of influenza-positive clinical samples.
Unabated Adenovirus Replication following Activation of the cGAS/STING-Dependent Antiviral Response in Human Cells
Authors: Lam Eric , Falck-Pedersen Erik
Published: October 2014

The cGAS/STING DNA sensing complex has recently been established as a predominant pathogen recognition receptor (PRR) for DNA-directed type I interferon (IFN) innate immune activation. Using replication-defective adenovirus vectors and replication-competent wild-type adenovirus, we have modeled the influence of the cGAS/STING cascade in permissive human cell lines (A549, HeLa, ARPE19, and THP1). Wild-type adenovirus induced efficient early activation of the cGAS/STING cascade in a cell-specific manner. In all responsive cell lines, cGAS/STING short hairpin RNA (shRNA) knockdown resulted in a loss of TBK1 and interferon response factor 3 (IRF3) activation, a lack of beta interferon transcript induction, loss of interferon-dependent STAT1 activation, and diminished induction of interferon-stimulated genes (ISGs). Adenoviruses that infect through the coxsackievirus-adenovirus receptor (CAR) (Ad2 and Ad5) and the CD46 (Ad35) and desmoglein-2 (Ad7) viral receptors all induce the cGAS/STING/TBK1/IRF3 cascade. The magnitude of the IRF3/IFN/ISG antiviral response was strongly influenced by serotype, with Ad35>Ad7>Ad2. For each serotype, no enhancement of viral DNA replication or virus production occurred in cGAS or STING shRNA-targeted cell line pools. We found no replication advantage in permissive cell lines that do not trigger the cGAS/STING cascade following infection. The cGAS/STING/TBK1/IRF3 cascade was not a direct target of viral antihost strategies, and we found no evidence that Ad stimulation of the cGAS/STING DNA response had an impact on viral replication efficiency.

IMPORTANCEThis study shows for the first time that the cGAS DNA sensor directs a dominant IRF3/IFN/ISG antiviral response to adenovirus in human cell lines. Activation of cGAS occurs with viruses that infect through different high-affinity receptors (CAR, CD46, and desmoglein-2), and the magnitude of the cGAS/STING DNA response cascade is influenced by serotype-specific functions. Furthermore, activation of the cGAS cascade occurred in a cell-specific manner. Activation of the cGAS/STING response did not impact viral replication, and viral immune evasion strategies did not target the cGAS/STING/TBK1/IRF3 cascade. These studies provide novel insight into the early innate recognition response to adenovirus.
Subepicardial haematoma, a rare and potentially lethal complication of CTO-PCI: case of an exceptional recovery after conservative management
Authors: de Vos Annemiek M J , van der Schaaf Rene J
Published: October 2014

We present the case of an 82-year-old woman undergoing high-risk chronic total occlusion percutaneous coronary intervention (CTO-PCI) of the right coronary artery. Hours after the procedure, a subepicardial haematoma was diagnosed as a result of coronary perforation during the procedure. This rare and potentially lethal complication evolved exceptionally benignly after conservative management; our patient fully recovered. Increasingly complex procedures in high-risk patient categories warrant awareness of procedural complications, especially those that are subtle and appear relatively late, and are therefore most hazardous. Recognition of this rare complication and choosing the optimal strategy is of the utmost importance when dealing with patients who undergo PCI. We here describe the rare case of a potential lethal complication in high-risk CTO-PCI, which evolved relatively benignly.
Cherubism with multiple dental abnormalities: a rare presentation
Authors: Misra Satya Ranjan , Mishra Lora , Mohanty Neeta , Mohanty Susant
Published: October 2014

Cherubism is a progressive, hereditary fibro-osseous lesion exclusively affecting the jaw bones. It is caused by the abnormal functioning of osteoblasts and osteoclasts, leading to replacement of normal bone by cellular fibrous tissue and immature bone, which produces painless progressive growth of the jaw, with a round facial appearance. It was first described in 1933 by Jones as ‘familial multilocular cystic disease of the jaws’. The term ‘cherubism’ was later coined to describe the rounded facial appearance resulting from jaw hypertrophy that was reminiscent of cherubs depicted throughout Renaissance art. The bony lesions generally occur at an early age, affect one or both jaws symmetrically, and grow progressively until puberty. Spontaneous regression is seen in most cases, although surgical re-contouring may be required for others for aesthetic reasons.
Framework for improving workflow stability: deployment of optimized capacity buffers in a synchronized construction production
Authors: Arashpour Mehrdad , Wakefield Ron , Blismas Nick , Lee E.W.M.
Published: October 2014

Construction sites are dynamic environments due to the influence of variables such as changes in design and processes, unsteady demand, and unavailability of trades. These variables adversely affect productivity and can cause an unstable workflow in the network of trade contractors. Previous research on workflow stability in the construction and manufacturing domains has shown the effectiveness of ‘pull’ production or ‘rate driven’ construction. Pull systems authorize the start of construction when a job is completed and leaves the trade contractor network. However, the problem with pull systems is that completion dates are not explicitly considered and therefore additional mechanisms are required to ensure the due date integrity. On this basis, the aim of this investigation is to improve the coordination between output and demand using optimal-sized capacity buffers. Towards this aim, production data of two Australian construction companies were collected and analyzed. Capacity and cost optimizations were conducted to find the optimum buffer that strikes the balance between late completion costs and lost revenue opportunity. Following this, simulation experiments were designed and run to analyze different ‘what-if’ production scenarios. The findings show that capacity buffers enable builders to ensure a desired service level. Size of the capacity buffer is more sensitive to the level of variability in contractor processes than other production variables. This work contributes to the body-of-knowledge by improving production control in construction and deployment of capacity buffers to achieve a stable workflow. In addition, construction companies can use the easy-to-use framework tested in this study to compute the optimal size for capacity buffers that maximizes profit and prevents late completions.
Low-dose prazosin in combination with 5-HT6 antagonist PRX-07034 has antipsychotic effects
Authors: Abraham Renny , Nirogi Ramakrishna , Shinde Anil , Irupannanavar Shantaveer
Published: October 2014

An extensive amount of research has focused on the development of new pharmacological agents to treat schizophrenia. Varying from person to person, schizophrenia is a heterogeneous disease with symptoms of positive, negative, and cognitive deficits. PRX-07034, a 5-hydroxytryptamine6 (5-HT6) receptor antagonist has been evaluated for its potential in treating obesity and cognitive deficits. This study evaluated PRX-07034 (0.1, 0.3, and 1.0 mg/kg body mass, by intraperitoneal (i.p.) injection), in combination with a low dose of prazosin (0.3 mg/kg, i.p.), for its antipsychotic potential. The research utilized a stereotypy assay, an open field test, an object recognition task, and prepulse inhibition. Dizocilpine, a non-competitive N-methyl-d-aspartate (NMDA) antagonist, was also administered in the above-mentioned assays as a psychomimetic. The combination of PRX-07034 and prazosin alleviated stereotypy and hyperlocomotor activity while enhancing memory in an object recognition task, and reversed sensory-gating deficits induced by dizocilpine. Examination of the medial prefrontal cortex revealed that a combination of PRX-07034 and prazosin reduced the dizocilpine-mediated increase of 5-HT. These results suggest that the combination of a 5-HT6 antagonist with low doses of prazosin could have therapeutic potential in the treatment of schizophrenia.
INTELLIGENT MULTIAGENT COORDINATION BASED ON REINFORCEMENT HIERARCHICAL NEURO-FUZZY MODELS
Authors: MENDOZA LEONARDO FORERO , VELLASCO MARLEY , FIGUEIREDO KARLA
Published: October 2014

This paper presents the research and development of two hybrid neuro-fuzzy models for the hierarchical coordination of multiple intelligent agents. The main objective of the models is to have multiple agents interact intelligently with each other in complex systems. We developed two new models of coordination for intelligent multiagent systems, which integrates the Reinforcement Learning Hierarchical Neuro-Fuzzy model with two proposed coordination mechanisms: the MultiAgent Reinforcement Learning Hierarchical Neuro-Fuzzy with a market-driven coordination mechanism (MA-RL-HNFP-MD) and the MultiAgent Reinforcement Learning Hierarchical Neuro-Fuzzy with graph coordination (MA-RL-HNFP-CG). In order to evaluate the proposed models and verify the contribution of the proposed coordination mechanisms, two multiagent benchmark applications were developed: the pursuit game and the robot soccer simulation. The results obtained demonstrated that the proposed coordination mechanisms greatly improve the performance of the multiagent system when compared with other strategies.
A possible explanation of pressure dependence of critical temperature Tc of alkali doped C60 superconductors
Authors: Pandey Rajiv Kumar
Published: October 2014

The pressure dependent changes in transition temperature (Tc) of alkali doped C 60 superconductor has been studied theoretically considering the combination of phonon mediated mechanism and high energy electronic interaction mechanism. The latter mechanism involves bond polarization in interaction with conduction electrons. The expression for Tc, isotope effect coefficient (α) and (dTc/dP)P has been obtained to explain the observed experimental results of alkali doped C 60. A good agreement has been found in experimental (Tc) and (dTc/dP)P = 0 values and calculated values.
Synthesis, characterization and photodynamic therapy properties of an octa-4-tert-butylphenoxy-substituted phosphorus(V) triazatetrabenzcorrole
Authors: Shi Maohu , Tian Jiangwei , Mkhize Colin , Kubheka Gugu , Zhou Jinfeng , Mack John , Nyokong Tebello , Shen Zhen
Published: October 2014

A novel octa-4-tert-butylphenoxy-substituted phosphorus(V) triazatetrabenzcorrole (PVTBC), has been synthesized and characterized by MALDI-TOF MS and NMR, FT-IR and MCD spectroscopy. The fluorescence emission spectrum was used to determine the fluorescence quantum yield and the quantum yield for singlet oxygen generation was calculated by using 1,3-diphenylisobenzofuran as a scavenger. The photocytoxicity against U87MG cells was measured. The results indicated that PVTBC is potentially useful as an NIR region photosensitizer for photodynamic therapy (PDT).
Redox properties of nitrophenylporphyrins and electrosynthesis of nitrophenyl-linked Zn porphyrin dimers or arrays
Authors: Fang Yuanyuan , Jiang Xiaoqin , Ou Zhongping , Michelin Clément , Desbois Nicolas , Gros Claude P. , Kadish Karl M.
Published: October 2014

Five nitrophenylporphyrins were investigated as to their electrochemical properties in CH 2 Cl 2 containing 0.1 M TBAP. The investigated compounds are represented as ( NO 2 Ph )x Ph 4-x PorM , where Por represents the dianion of the porphyrin macrocycle, Ph is a phenyl group on meso-position of the macrocycle, NO 2 Ph is a meso-substituted nitrophenyl group, M = 2 H , Pd II or Zn II and x = 1 or 2. Each porphyrin undergoes an initial one electron reduction at E1/2 = -1.07 to -1.12 V where the added negative charge is almost totally localized on the meso-nitrophenyl group of the compound. This reversible reduction is then followed by one or more irreversible reductions of the nitrophenyl anion at more negative potentials which overlap with reduction of the conjugated porphyrin macrocycle. The initial one electron addition was monitored by thin-layer UV-vis spectroelectrochemistry which confirmed formation of a reduced nitrophenyl group in each case but also gave spectral evidence for a linkage of the one-electron reduction products in the case of the Zn derivatives, giving Zn porphyrin dimers or arrays which are characterized by a 14–15 nm red-shifted Soret band and two well-defined Q-bands, consistent with conversion from an unreduced four coordinate Zn II nitrophenylporphyrin to a five-coordinate Zn II complex with an unreduced porphyrin macrocycle.
On the spectral distribution of large weighted random regular graphs
Authors: Goldmakher Leo , Khoury Cap , Miller Steven J. , Ninsuwan Kesinee
Published: October 2014

McKay proved the limiting spectral measures of the ensembles of d-regular graphs with N vertices converge to Kesten's measure as N → ∞. Given a large d-regular graph we assign random weights, drawn from some distribution [Formula: see text], to its edges. We study the relationship between [Formula: see text] and the associated limiting spectral distribution obtained by averaging over the weighted graphs. We establish the existence of a unique "eigendistribution" (a weight distribution [Formula: see text] such that the associated limiting spectral distribution is a rescaling of [Formula: see text]). Initial investigations suggested that the eigendistribution was the semi-circle distribution, which by Wigner's Law is the limiting spectral measure for real symmetric matrices. We prove this is not the case, though the deviation between the eigendistribution and the semi-circular density is small (the first seven moments agree, and the difference in each higher moment is O(1/d2)). Our analysis uses combinatorial results about closed acyclic walks in large trees, which may be of independent interest.
Tracing the source of ‘Metals in Soil Gas’ with Pb isotope ratios at the Jiaolongzhang base metal deposit, north-western China
Authors: Yang Xu , Mingqi Wang , Yuyan Gao , He Zhang
Published: October 2014

The ‘Metals in Soil Gas’ (MSG) survey has proven to be a useful tool for mineral exploration under exotic overburden. Tracing the source of these metals with Pb isotopes is helpful to understand the formation of MSG. Lead isotope ratios in MSG samples were determined by ICP-MS (Model HP4500); the Pb isotope ratios in loess, red soil, wall rocks and ores were measured following decomposition and separation using a VG-354 thermal ionization mass spectrometer (TIMS) for comparison. The results of the study of samples collected over the Jiaolongzhang base metal deposit show that the Pb isotope ratios of MSG background samples are markedly distinct from those ratios of any medium (loess, red soil layer, wall-rocks and ores) in the vicinity of the deposit. The Pb isotope ratios in the MSG anomalous samples (
206
Pb/
204
Pb = 18.34–18.56,
207
Pb/
204
Pb = 15.622–15.809 and
208
Pb/
204
Pb = 38.184–38.691) are totally different from those in the samples of background areas (
206
Pb/
204
Pb = 16.46–17.68,
207
Pb/
204
Pb = 13.985–14.945 and
208
Pb/
204
Pb = 34.199–36.884). The Pb isotope ratios of MSG anomalous samples scatter near the ratios of the mineralized wall-rocks (
206
Pb/
204
Pb = 18.554–18.874,
207
Pb/
204
Pb = 15.618–15.755 and
208
Pb/
204
Pb = 38.629–39.126) and sulphides (
206
Pb/
204
Pb = 18.130–18.251,
207
Pb/
204
Pb = 15.671–15.767 and
208
Pb/
204
Pb = 38.350–38.582). It can be concluded that some of the Pb in MSG anomalous samples originates from deep sulphide mineralization and Pb isotope ratios of MSG anomalous samples indicate that an MSG survey can detect the deeply concealed mineral deposits under exotic cover.
Na+-independent phosphate transport in Caco2BBE cells
Authors: Candeal Eduardo , Caldas Yupanqui A. , Guillén Natalia , Levi Moshe , Sorribas Víctor
Published: October 2014

Pi transport in epithelia has both Na+-dependent and Na+-independent components, but so far only Na+-dependent transporters have been characterized in detail and molecularly identified. Consequently, in the present study, we initiated the characterization and analysis of intestinal Na+-independent Pi transport using an in vitro model, Caco2BBE cells. Only Na+-independent Pi uptake was observed in these cells, and Pi uptake was dramatically increased when cells were incubated in high-Pi DMEM (4 mM) from 1 day to several days. No response to low-Pi medium was observed. The increased Pi transport was mainly caused by Vmax changes, and it was prevented by actinomycin D and cycloheximide. Pi transport in cells grown in 1 mM Pi (basal DMEM) decreased at pH > 7.5, and it was inhibited with proton ionophores. Pi transport in cells incubated with 4 mM Pi increased with alkaline pH, suggesting a preference for divalent phosphate. Pi uptake in cells in 1 mM Pi was completely inhibited only by Pi and partially inhibited by phosphonoformate, oxalate, DIDS, SITS, SO42−, HCO3−, and arsenate. This inhibition pattern suggests that more than one Pi transporter is active in cells maintained with 1 mM Pi. Phosphate transport from cells maintained at 4 mM Pi was only partially inhibited by phosphonoformate, oxalate, and arsenate. Attempts to identify the responsible transporters showed that multifunctional anion exchangers of the Slc26 family as well as members of Slc17, Slc20, and Slc37 and the Pi exporter xenotropic and polytropic retrovirus receptor 1 are not involved.
Local pH domains regulate NHE3-mediated Na+reabsorption in the renal proximal tubule
Authors: Brasen Jens Christian , Burford James L. , McDonough Alicia A. , Holstein-Rathlou Niels-Henrik , Peti-Peterdi Janos
Published: October 2014

The proximal tubule Na+/H+exchanger 3 (NHE3), located in the apical dense microvilli (brush border), plays a major role in the reabsorption of NaCl and water in the renal proximal tubule. In response to a rise in blood pressure NHE3 redistributes in the plane of the plasma membrane to the base of the brush border, where NHE3 activity is reduced. This NHE3 redistribution is assumed to provoke pressure natriuresis; however, it is unclear how NHE3 redistribution per se reduces NHE3 activity. To investigate if the distribution of NHE3 in the brush border can change the reabsorption rate, we constructed a spatiotemporal mathematical model of NHE3-mediated Na+reabsorption across a proximal tubule cell and compared the model results with in vivo experiments in rats. The model predicts that when NHE3 is localized exclusively at the base of the brush border, it creates local pH microdomains that reduce NHE3 activity by >30%. We tested the model's prediction experimentally: the rat kidney cortex was loaded with the pH-sensitive fluorescent dye BCECF, and cells of the proximal tubule were imaged in vivo using confocal fluorescence microscopy before and after an increase of blood pressure by ∼50 mmHg. The experimental results supported the model by demonstrating that a rise of blood pressure induces the development of pH microdomains near the bottom of the brush border. These local changes in pH reduce NHE3 activity, which may explain the pressure natriuresis response to NHE3 redistribution.
Hierarchical effects of task engagement on amplitude modulation encoding in auditory cortex
Authors: Niwa Mamiko , O'Connor Kevin N. , Engall Elizabeth , Johnson Jeffrey S. , Sutter M. L.
Published: October 2014

We recorded from middle lateral belt (ML) and primary (A1) auditory cortical neurons while animals discriminated amplitude-modulated (AM) sounds and also while they sat passively. Engagement in AM discrimination improved ML and A1 neurons' ability to discriminate AM with both firing rate and phase-locking; however, task engagement affected neural AM discrimination differently in the two fields. The results suggest that these two areas utilize different AM coding schemes: a “single mode” in A1 that relies on increased activity for AM relative to unmodulated sounds and a “dual-polar mode” in ML that uses both increases and decreases in neural activity to encode modulation. In the dual-polar ML code, nonsynchronized responses might play a special role. The results are consistent with findings in the primary and secondary somatosensory cortices during discrimination of vibrotactile modulation frequency, implicating a common scheme in the hierarchical processing of temporal information among different modalities. The time course of activity differences between behaving and passive conditions was also distinct in A1 and ML and may have implications for auditory attention. At modulation depths ≥ 16% (approximately behavioral threshold), A1 neurons' improvement in distinguishing AM from unmodulated noise is relatively constant or improves slightly with increasing modulation depth. In ML, improvement during engagement is most pronounced near threshold and disappears at highly suprathreshold depths. This ML effect is evident later in the stimulus, and mainly in nonsynchronized responses. This suggests that attention-related increases in activity are stronger or longer-lasting for more difficult stimuli in ML.
The Signature Sequence Region of the Human Drug Transporter Organic Anion Transporting Polypeptide 1B1 Is Important for Protein Surface Expression
Authors: Taylor-Wells Jennina , Meredith David
Published: October 2014

The organic anion transporting polypeptides (OATPs) encompass a family of membrane transport proteins responsible for the uptake of xenobiotic compounds. Human organic anion transporting polypeptide 1B1 (OATP1B1) mediates the uptake of clinically relevant compounds such as statins and chemotherapeutic agents into hepatocytes, playing an important role in drug delivery and detoxification.
The OATPs have a putative 12-transmembrane domain topology and a highly conserved signature sequence (human OATP1B1: DSRWVGAWWLNFL), spanning the extracellular loop 3/TM6 boundary. The presence of three conserved tryptophan residues at the TM interface suggests a structural role for the sequence. This was investigated by site-directed mutagenesis of selected amino acids within the sequence D251E, W254F, W258/259F, and N261A. Transport was measured using the substrate estrone-3-sulfate and surface expression detected by luminometry and confocal microscopy, facilitated by an extracellular FLAG epitope. Uptake of estrone-3-sulfate and the surface expression of D251E, W254F, and W258/259F were both significantly reduced from the wild type OATP1B1-FLAG in transfected HEK293T cells. Confocal microscopy revealed that protein was produced but was retained intracellularly. The uptake and expression of N261A were not significantly different. The reduction in surface expression and intracellular protein retention indicates a structural and/or membrane localization role for these signature sequence residues in the human drug transporter OATP1B1.
2-Layered Architecture of Vague Logic Based Multilevel Queue Scheduler
Authors: Raheja Supriya , Dadhich Reena , Rajpal Smita
Published: October 2014

In operating system the decisions which CPU scheduler makes regarding the sequence and length of time the task may run are not easy ones, as the scheduler has only a limited amount of information about the tasks. A good scheduler should be fair, maximizes throughput, and minimizes response time of system. A scheduler with multilevel queue scheduling partitions the ready queue into multiple queues. While assigning priorities, higher level queues always get more priorities over lower level queues. Unfortunately, sometimes lower priority tasks get starved, as the scheduler assures that the lower priority tasks may be scheduled only after the higher priority tasks. While making decisions scheduler is concerned only with one factor, that is, priority, but ignores other factors which may affect the performance of the system. With this concern, we propose a 2-layered architecture of multilevel queue scheduler based on vague set theory (VMLQ). The VMLQ scheduler handles the impreciseness of data as well as improving the starvation problem of lower priority tasks. This work also optimizes the performance metrics and improves the response time of system. The performance is evaluated through simulation using MatLab. Simulation results prove that the VMLQ scheduler performs better than the classical multilevel queue scheduler and fuzzy based multilevel queue scheduler.
Differential Effect of Isooctane Doses on HaCaT and HeLa: A Multimodal Analysis
Authors: Das Lopamudra , Basu Sanmitra , Sengupta Sanghamitra , Das Soumen , Chatterjee Jyotirmoy
Published: October 2014

A multimodal approach is effective in analyzing biological problems critically and thus also useful in assessing cytotoxicity under chemicals assaults. In this study effects of isooctane, an organic solvent and component of gasoline produced in petroleum industries, have been explored on normal (HaCaT) and cancerous (HeLa) epithelial cells. Besides morphological alterations, impacts on viability, prime molecular expressions, and bioelectrical properties on exposure to different doses of isooctane were noted. Scanning electron microscopy and viability assay demonstrated remarkable structural alterations and cell death, respectively, in HaCaT but not in HeLa. Transcriptomic and immunocytochemical studies on E-cadherin expression also elucidated pronounced toxic effects on HaCaT. Remarkable changes on the bioelectrical properties (e.g., impedance and phase angle) of the HaCaT, in contrast to HeLa, at different temporal points on isooctane exposure also indicated cytotoxic effects in the former. Hence this study illustrated cytotoxicity of isooctane on HaCaT multidimensionally which was evaded by HeLa.
Sex-Related Differences in the Effects of the Mediterranean Diet on Glucose and Insulin Homeostasis
Authors: Bédard Alexandra , Corneau Louise , Lamarche Benoît , Dodin Sylvie , Lemieux Simone
Published: October 2014

Objective. To document sex differences in the impact of the Mediterranean diet (MedDiet) on glucose/insulin homeostasis and to verify whether these sex-related effects were associated with changes in nonesterified fatty acids (NEFA).Methods. All foods were provided to 38 men and 32 premenopausal women (24–53 y) during 4 weeks. Variables were measured during a 180 min OGTT before and after the MedDiet.Results. A sex-by-time interaction for plasma insulin iAUC was found (men: −17.8%,P=0.02; women: +9.4%,P=0.63;Pfor sex-by-time interaction = 0.005). A sex-by-time interaction was also observed for insulin sensitivity (Cederholm index,P=0.03), for which only men experienced improvements (men: +8.1%,P=0.047; women: −5.9%,P=0.94). No sex difference was observed for glucose and C-peptide responses. Trends toward a decrease in NEFA AUC (P=0.06) and an increase in NEFA suppression rate (P=0.06) were noted, with no sex difference. Changes in NEFA were not associated with change in insulin sensitivity.Conclusions. Results suggest that the more favorable changes in glucose/insulin homeostasis observed in men compared to women in response to the MedDiet are not explained by sex differences in NEFA response. This clinical trial is registered with clinicaltrials.govNCT01293344.
Venous Thromboembolism following Elective Aesthetic Plastic Surgery: A Longitudinal Prospective Study in 1254 Patients
Authors: Valente Denis Souto , Carvalho Lauro Aita , Zanella Rafaela Koehler , Valente Sibelie
Published: October 2014

Background. Venous thromboembolism (VTE) is a disorder with short-term mortality and long-term morbidity. Healthy patients submitted to elective aesthetic plastic surgeries (EAPS) have risk factors to develop VTE not well established yet. The objective of this study was to examine the incidence and risk factors for VTE in these patients. Methods. Longitudinal, prospective (minimum follow-up of 3 months), observational study. Comprehensive information on patient characteristics and surgeries performed was obtained. Preoperative, intraoperative, and postoperative risk factors were analyzed for their association with VTE. Results. A total of 1254 patients were included in the study. Postoperative VTE occurred in 17 (1,35%) of patients. VTE was more frequent in patients more than 40 years old (82.3%). Smoking, patients with 2 or 3 pregnancies, and hormone replacement therapy, and oral contraceptives use presents higher levels of VTE. In this study we have not found any correlation between liposuction, augmentation mammoplasty, mastopexy, and rhinoplasty as an isolated risk factor for VTE. Conclusions. The incidence of VTE in patients undergoing EAPS was 1.35%. Patients with more than 40 years of age, tobacco users, patients with 2 or more pregnancies, and hormone replacement therapy or oral contraceptives use presents higher levels of VTE.
Immunological Testing Reveals Exposure to Malaria in the Hypoendemic Region of Iran
Authors: Obeidi Narges , Rajasekariah G-Halli , Nabipour Iraj , Amirinejad Roya , Dogcio Diane , Emami Habib
Published: October 2014

Background. South eastern parts of Iran remain endemic for malaria infection. There is some concern that malaria infection may spread into Bushehr, which is located in the south western part bordering the Persian Gulf and at the periphery of the declared endemic region Hormozgan province due to frequency of visitors from eastern endemic areas and from neighboring malaria endemic countries. We investigated malaria prevalence in Bushehr. Methods and Results. Attempts were made to identify malaria active infection in blood smears and malaria specific antibody and antigens in serum samples. Traditional blood smears prepared from 1955 blood specimens yielded no definitive malaria positive case by microscopic technique. A total of 270 (13.8%) serum samples were positive for malaria antibodies. Using specific ELISA kits, presence of histidine rich proteins and lactate dehydrogenase antigens were investigated in serum samples. No histidine rich proteins specific for P. falciparum were detected amongst 270 antibody positive samples. However, six samples representing 0.3% of total population, were found to be positive for plasmodium pan specific lactate dehydrogenase antigens. This suggested the possibility of low level exposure to malaria in Bushehr community. Conclusions. Out of a total of 1955 samples tested, 270 (13.8%) were positive for malaria antibodies and six (0.3%) of these were positive for plasmodium-specific lactate dehydrogenase antigen suggesting a low level exposure to malaria in a hypoendemic region based on immunological testing. Since none of the 270 antibody samples were positive for histidine rich protein antigens, there is scope for further testing of blood samples by molecular methods such as polymerase chain reactions to confirm the plasmodium species and provide information valuable for future investigations. Our testing strategy for hypoemdemic malaria can be used as a template for investing malaria in 32 eliminating countries for testing ongoing transmission. This approach may be useful as a method in epidemiological studies.
ϕ-Prime and ϕ-Primary Elements in Multiplicative Lattices
Authors: Manjarekar C. S. , Bingi A. V.
Published: October 2014

We investigate ϕ-prime and ϕ-primary elements in a compactly generated multiplicative lattice L. By a counterexample, it is shown that a ϕ-primary element in L need not be primary. Some characterizations of ϕ-primary and ϕ-prime elements in L are obtained. Finally, some results for almost prime and almost primary elements in L with characterizations are obtained.
MHC-Restricted Phosphopeptides from Insulin Receptor Substrate-2 and CDC25b Offer Broad-Based Immunotherapeutic Agents for Cancer
Authors: Zarling Angela L. , Obeng Rebecca C. , Desch A. Nicole , Pinczewski Joel , Cummings Kara L. , Deacon Donna H. , Conaway Mark , Slingluff Craig L. , Engelhard Victor H.
Published: October 2014

Cancer cells display novel phosphopeptides in association with MHC class I and II molecules. In this study, we evaluated two HLA-A2–restricted phosphopeptides derived from the insulin receptor substrate (IRS)-2 and the cell-cycle regulator CDC25b. These proteins are both broadly expressed in multiple malignancies and linked to cancer cell survival. Two phosphopeptides, termed pIRS-21097–1105 and pCDC25b38–46, served as targets of strong and specific CD8 T-cell memory responses in normal human donors. We cloned T-cell receptor (TCR) cDNAs from murine CD8 T-cell lines specific for either pIRS-21097–1105 or pCDC25b38–46. Expression of these TCRs in human CD8 T cells imparted high-avidity phosphopeptide-specific recognition and cytotoxic and cytokine-secreting effector activities. Using these cells, we found that endogenously processed pIRS-21097–1105 was presented on HLA-A2+ melanomas and breast, ovarian, and colorectal carcinomas. Presentation was correlated with the level of the Ser1100-phosphorylated IRS-2 protein in metastatic melanoma tissues. The highest expression of this protein was evident on dividing malignant cells. Presentation of endogenously processed pCDC25b38–46 was narrower, but still evident on HLA-A2+ melanoma, breast carcinoma, and lymphoblastoid cells. Notably, pIRS-21097–1105–specific and pCDC25b38–46–specific TCR-expressing human CD8 T cells markedly slowed tumor outgrowth in vivo. Our results define two new antigens that may be developed as immunotherapeutic agents for a broad range of HLA-A2+ cancers. Cancer Res; 74(23); 6784–95. ©2014 AACR.
Inhibition of Adaptive Immunity by IL9 Can Be Disrupted to Achieve Rapid T-cell Sensitization and Rejection of Progressive Tumor Challenges
Authors: Hoelzinger Dominique B. , Dominguez Ana Lucia , Cohen Peter A. , Gendler Sandra J.
Published: October 2014

The tolerogenic cytokine IL9 promotes T regulatory cell function and allergic airway inflammation, but it has not been extensively studied in cancer. In this report, we used IL9-deficient mice to investigate the effects of IL9 in multiple models of breast and colon cancer development. Eliminating endogenous IL9 enabled sensitization of host T cells to tumors, leading to their early rejection without the requirement of vaccines or immunomodulatory therapies. Notably, IL9-deficient mice acquired immunologic memory, which actively protected from residual disease and tumor rechallenge, an effect linked to activation of CD8+ T cells. Depletion of either CD8+ or CD4+ T cells abolished the benefits of IL9 loss to tumor control. Adoptive transfer experiments showed that T cells from tumor-rejecting IL9-deficient mice retained their effector competency in wild-type animals. Moreover, neutralizing IL9 antibody phenocopied the effects of IL9 gene deletion by slowing tumor progression in wild-type animals. Our results show the ability of IL9 to function as an inhibitor of adaptive immunity that prevents the formation of immunologic memory to a growing tumor, highlighting the potential for IL9 neutralization as a unique tool for cancer immunotherapy. Cancer Res; 74(23); 6845–55. ©2014 AACR.
HSP90 Supports Tumor Growth and Angiogenesis through PRKD2 Protein Stabilization
Authors: Azoitei Ninel , Diepold Kristina , Brunner Cornelia , Rouhi Arefeh , Genze Felicitas , Becher Alexander , Kestler Hans , van Lint Johan , Chiosis Gabriela , Koren John , Fröhling Stefan , Scholl Claudia , Seufferlein Thomas
Published: October 2014

The kinase PRKD2 (protein kinase D) is a crucial regulator of tumor cell-endothelial cell communication in gastrointestinal tumors and glioblastomas, but its mechanistic contributions to malignant development are not understood. Here, we report that the oncogenic chaperone HSP90 binds to and stabilizes PRKD2 in human cancer cells. Pharmacologic inhibition of HSP90 with structurally divergent small molecules currently in clinical development triggered proteasome-dependent degradation of PRKD2, augmenting apoptosis in human cancer cells of various tissue origins. Conversely, ectopic expression of PRKD2 protected cancer cells from the apoptotic effects of HSP90 abrogation, restoring blood vessel formation in two preclinical models of solid tumors. Mechanistic studies revealed that PRKD2 is essential for hypoxia-induced accumulation of hypoxia-inducible factor-1α (HIF1α) and activation of NF-κB in tumor cells. Notably, ectopic expression of PRKD2 was able to partially restore HIF1α and secreted VEGF-A levels in hypoxic cancer cells treated with HSP90 inhibitors. Taken together, our findings indicate that signals from hypoxia and HSP90 pathways are interconnected and funneled by PRKD2 into the NF-κB/VEGF-A signaling axis to promote tumor angiogenesis and tumor growth. Cancer Res; 74(23); 7125–36. ©2014 AACR.
Hedgehog Signaling Drives Radioresistance and Stroma-Driven Tumor Repopulation in Head and Neck Squamous Cancers
Authors: Gan Gregory N. , Eagles Justin , Keysar Stephen B. , Wang Guoliang , Glogowska Magdalena J. , Altunbas Cem , Anderson Ryan T. , Le Phuong N. , Morton J. Jason , Frederick Barbara , Raben David , Wang Xiao-Jing , Jimeno Antonio
Published: October 2014

Local control and overall survival in patients with advanced head and neck squamous cell cancer (HNSCC) remains dismal. Signaling through the Hedgehog (Hh) pathway is associated with epithelial-to-mesenchymal transition, and activation of the Hh effector transcription factor Gli1 is a poor prognostic factor in this disease setting. Here, we report that increased GLI1 expression in the leading edge of HNSCC tumors is further increased by irradiation, where it contributes to therapeutic inhibition. Hh pathway blockade with cyclopamine suppressed GLI1 activation and enhanced tumor sensitivity to radiotherapy. Furthermore, radiotherapy-induced GLI1 expression was mediated in part by the mTOR/S6K1 pathway. Stroma exposed to radiotherapy promoted rapid tumor repopulation, and this effect was suppressed by Hh inhibition. Our results demonstrate that Gli1 that is upregulated at the tumor–stroma intersection in HNSCC is elevated by radiotherapy, where it contributes to stromal-mediated resistance, and that Hh inhibitors offer a rational strategy to reverse this process to sensitize HNSCC to radiotherapy. Cancer Res; 74(23); 7024–36. ©2014 AACR.