bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of purinergic receptors (P2) in the renal medulla promotes endothelin-dependent natriuresis in male rats
Authors: Gohar Eman Y. , Speed Joshua S. , Kasztan Malgorzata , Jin Chunhua , Pollock David M.
Published: May 2016

Renal endothelin-1 (ET-1) and purinergic signaling systems regulate Na+reabsorption in the renal medulla. A link between the renal ET-1 and purinergic systems was demonstrated in vitro, however, the in vivo interaction between these systems has not been defined. To test whether renal medullary activation of purinergic (P2) receptors promotes ET-dependent natriuresis, we determined the effect of increased medullary NaCl loading on Na+excretion and inner medullary ET-1 mRNA expression in anesthetized adult male Sprague-Dawley rats in the presence and absence of purinergic receptor antagonism. Isosmotic saline (NaCl; 284 mosmol/kgH2O) was infused into the medullary interstitium (500 μl/h) during a 30-min baseline urine collection period, followed by isosmotic or hyperosmotic saline (1,800 mosmol/kgH2O) for two further 30-min urine collection periods. Na+excretion was significantly increased during intramedullary infusion of hyperosmotic saline. Compared with isosmotic saline, hyperosmotic saline infused into the renal medulla caused significant increases in inner medullary ET-1 mRNA expression. Renal intramedullary infusion of the P2 receptor antagonist suramin inhibited the increase in Na+excretion and inner medullary ET-1 mRNA expression induced by NaCl loading in the renal medulla. Activation of medullary P2Y2/4receptors by infusion of UTP increased urinary Na+excretion. Combined ETAand ETBreceptor blockade abolished the natriuretic response to intramedullary infusion of UTP. These data demonstrate that activation of medullary P2 receptors promotes ET-dependent natriuresis in male rats, suggesting that the renal ET-1 and purinergic signaling systems interact to efficiently facilitate excretion of a NaCl load.
The role of Nedd4-1 WW domains in binding and regulating human organic anion transporter 1
Authors: Xu Da , Wang Haoxun , Gardner Carol , Pan Zui , Zhang Ping L. , Zhang Jinghui , You Guofeng
Published: May 2016

Human organic anion transporter 1 (hOAT1), expressed at the basolateral membrane of kidney proximal tubule cells, mediates the active renal secretion of a diverse array of clinically important drugs, including anti-human immunodeficiency virus therapeutics, antitumor drugs, antibiotics, antihypertensives, and anti-inflammatories. We have previously demonstrated that posttranslational modification of hOAT1 by ubiquitination is an important mechanism for the regulation of this transporter. The present study aimed at identifying the ubiquitin ligase for hOAT1 and its mechanism of action. We showed that overexpression of neural precursor cell expressed, developmentally downregulated (Nedd)4-1, an E3 ubiquitin ligase, enhanced hOAT1 ubiquitination, decreased hOAT1 expression at the cell surface, and inhibited hOAT1 transport activity. In contrast, overexpression of the ubiquitin ligase-dead mutant Nedd4-1/C867S was without effects on hOAT1. Furthermore, knockdown of endogenously expressed Nedd4-1 by Nedd4-1-specific small interfering RNA reduced hOAT1 ubiquitination. Immunoprecipitation experiments in cultured cells and rat kidney slices and immunofluorescence experiments in rat kidney slices showed that there was a physical interaction between OAT1 and Nedd4-1. Nedd4-1 contains four protein-protein interacting WW domains. When these WW domains were inactivated by mutating two amino acid residues in each of the four WW domains (Mut-WW1: V210W/H212G, Mut-WW2: V367W/H369G, Mut-WW3: I440W/H442G, and Mut-WW4: I492W/H494G, respectively), only Mut-WW2 and Mut-WW3 significantly lost their ability to bind and to ubiquitinate hOAT1. As a result, Mut-WW2 and Mut-WW3 were unable to suppress hOAT1-mediated transport as effectively as wild-type Nedd4-1. In conclusion, this is the first demonstration that Nedd4-1 regulates hOAT1 ubiquitination, expression, and transport activity through its WW2 and WW3 domains.
Heat pulse excitability of vestibular hair cells and afferent neurons
Authors: Rabbitt Richard D. , Brichta Alan M. , Tabatabaee Hessam , Boutros Peter J. , Ahn JoongHo , Della Santina Charles C. , Poppi Lauren A. , Lim Rebecca
Published: May 2016

In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (Δ T ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (d T/d t) and an inward conduction current driven by Δ T. An iberiotoxin-sensitive inhibitory conduction current was also evoked by Δ T, rising in <3 ms and decaying with a time constant of ∼24 ms. The inhibitory component dominated whole cell currents in 50% of hair cells at −68 mV and in 67% of hair cells at −60 mV. Responses were quantified and described on the basis of first principles of thermodynamics. Results identify key molecular targets underlying heat pulse excitability in vestibular sensory organs and provide quantitative methods for rational application of optical heat pulses to examine protein biophysics and manipulate cellular excitability.
Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor Cells
Authors: Young Fraser I. , Telezhkin Vsevolod , Youde Sarah J. , Langley Martin S. , Stack Maria , Kemp Paul J. , Waddington Rachel J. , Sloan Alastair J. , Song Bing
Published: May 2016

Cellular heterogeneity presents an important challenge to the development of cell‐based therapies where there is a fundamental requirement for predictable and reproducible outcomes. Transplanted Dental Pulp Stem/Progenitor Cells (DPSCs) have demonstrated early promise in experimental models of spinal cord injury and stroke, despite limited evidence of neuronal and glial‐like differentiation after transplantation. Here, we report, for the first time, on the ability of single cell‐derived clonal cultures of murine DPSCs to differentiate in vitro into immature neuronal‐like and oligodendrocyte‐like cells. Importantly, only DPSC clones with high nestin mRNA expression levels were found to successfully differentiate into Map2 and NF‐positive neuronal‐like cells. Neuronally differentiated DPSCs possessed a membrane capacitance comparable with primary cultured striatal neurons and small inward voltage‐activated K+ but not outward Na+ currents were recorded suggesting a functionally immature phenotype. Similarly, only high nestin‐expressing clones demonstrated the ability to adopt Olig1, Olig2, and MBP‐positive immature oligodendrocyte‐like phenotype. Together, these results demonstrate that appropriate markers may be used to provide an early indication of the suitability of a cell population for purposes where differentiation into a specific lineage may be beneficial and highlight that further understanding of heterogeneity within mixed cellular populations is required.
Development and Validation of an UHPLC-QqQ-MS Technique for Simultaneous Determination of Ten Bioactive Components in Fangji Huangqi Tang
Authors: Wang Xiaoli , Liu Xiao , Zhu Tingting , Cai Baochang
Published: May 2016

The aim of this study is to develop an ultrahigh performance liquid chromatography method coupled with triple quadrupole mass spectrometry for simultaneous determination of tetrandrine, fangchinoline, atractylenolide I, atractylenolide III, calycosin-7-O-β-D-glucoside, glycyrrhizin, liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin in Fangji Huangqi Tang (FHT). The chromatographic separation was performed on a reversed-C18column, eluted with a mixture of 0.1% acetic acid and acetonitrile at 0.4 mL/min. The separation of these ten compounds was achieved by linear gradient elution. The method was strictly validated with respect to specificity, precision, accuracy, and repeatability. All the compounds showed good linearities (r≥0.999). The LOQs of the ten components were 0.36, 0.18, 0.09, 0.43, 0.02, 1.89, 0.26, 0.18, 0.61, and 0.48 ng/mL for tetrandrine, fangchinoline, atractylenolide I, atractylenolide III, calycosin-7-O-β-D-glucoside, glycyrrhizin, liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin, respectively. The LODs of the ten components were 0.11, 0.05, 0.03, 0.13, 0.01, 0.57, 0.08, 0.05, 0.18, and 0.14 ng/mL for tetrandrine, fangchinoline, atractylenolide I, atractylenolide III, calycosin-7-O-β-D-glucoside, glycyrrhizin, liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin, respectively. The method was proven to be specific and reliable, which would provide a meaningful basis for the quality control and evaluation of FHT during its clinical application.
A New Approach to Fuzzy Metric Spaces and Their Similarity-Based Construction
Authors: Soylu Gültekin , Güloğlu Mutlu
Published: May 2016

We introduce a space of functions which can be interpreted as a similarity-based approach to fuzzy metric spaces. The triangle inequality we propose is defined by means of a fuzzy ordering. We compare the introduced space with fuzzy metric spaces in the sense of Seikkala and Kaleva. Finally we complete the work discovering the corresponding classical as well as fuzzy topologies.
Development of a Rapid Point-of-Use DNA Test for the Screening of Genuity® Roundup Ready 2 Yield® Soybean in Seed Samples
Authors: Chandu Dilip , Paul Sudakshina , Parker Mathew , Dudin Yelena , King-Sitzes Jennifer , Perez Tim , Mittanck Don W. , Shah Manali , Glenn Kevin C. , Piepenburg Olaf
Published: May 2016

Testing for the presence of genetically modified material in seed samples is of critical importance for all stakeholders in the agricultural industry, including growers, seed manufacturers, and regulatory bodies. While rapid antibody-based testing for the transgenic protein has fulfilled this need in the past, the introduction of new variants of a given transgene demands new diagnostic regimen that allows distinguishing different traits at the nucleic acid level. Although such molecular tests can be performed by PCR in the laboratory, their requirement for expensive equipment and sophisticated operation have prevented its uptake in point-of-use applications. A recently developed isothermal DNA amplification technique, recombinase polymerase amplification (RPA), combines simple sample preparation and amplification work-flow procedures with the use of minimal detection equipment in real time. Here, we report the development of a highly sensitive and specific RPA-based detection system for Genuity Roundup Ready 2 Yield (RR2Y) material in soybean (Glycine max) seed samples and present the results of studies applying the method in both laboratory and field-type settings.
Effect of Acetate Group Content in Ethylene-Vinyl Acetate Copolymer on Properties of Composite Based on Low Density Polyethylene and Polyamide-6
Authors: Bui Nhi Dinh , Vu Ngo Dinh , Minh Thao Thi , Dam Huong Thi Thanh , Spiridonova Regina Romanovna , Sirotkin Semenovich Alexandr
Published: May 2016

The effect of the content of vinyl acetate groups in ethylene-vinyl acetate copolymer on the properties of polymer composite based on low density polyethylene and polyamide-6 was studied. Ethylene-vinyl acetate copolymer containing less vinyl acetate groups (10–14 wt.%) has a positive compatibility effect on polymer composite than ethylene-vinyl acetate copolymer containing 21–30 wt.% vinyl acetate groups. The polymer composites of LDPE, PA-6, and EVA containing 10–14 wt.% vinyl acetate groups possess the ability of biodegradation. The physical-mechanical properties of sample and molecular mass reduce after 28 days of incubation.
Effects ofLycium barbarumPolysaccharides on Apoptosis, Cellular Adhesion, and Oxidative Damage in Bone Marrow Mononuclear Cells of Mice Exposed to Ionizing Radiation Injury
Authors: Zhou Jing , Pang Hua , Li Wenbo , Liu Qiong , Xu Lu , Liu Qian , Liu Ying
Published: May 2016

Lycium barbarumhas been used for more than 2500 years as a traditional herb and food in China. We investigated the effects ofLycium barbarumpolysaccharides (LBP) on apoptosis, oxidative damage, and expression of adhesion molecules in bone marrow mononuclear cells (BMNC) of mice injured by ionizing radiation. Kunming mice were exposed to X-rays; then mice in the LBP groups were continuously injected with various concentrations of LBP intraperitoneally for 14 days. Mice in the control group were continuously injected with normal saline (NS) by the same route for 14 days. A normal group was set up. After 1, 7, and 14 days of treatment, mice were killed and BMNC were extracted. Cell cycle, apoptosis, and the expression of adhesion molecules CD44 and CD49d were detected by flow cytometry. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were identified by colorimetric analyses. LBP significantly decreased the percentage of G0/G1phase, apoptosis, MDA level, and expression of CD44 and CD49d and distinctly increased the activity of SOD. LBP showed a protective effect on BMNC against ionizing radiation-induced apoptosis and oxidative damage and altered the expression of adhesion molecule.
Molecular Identification of Sex inPhoenix dactyliferaUsing Inter Simple Sequence Repeat Markers
Authors: Al-Ameri Abdulhafed A. , Al-Qurainy Fahad , Gaafar Abdel-Rhman Z. , Khan Salim , Nadeem M.
Published: May 2016

Early sex identification of Date Palm (Phoenix dactyliferaL.) at seedling stage is an economically desirable objective, which will significantly increase the profits of seed based cultivation. The utilization of molecular markers at this stage for early and rapid identification of sex is important due to the lack of morphological markers. In this study, a total of two hundred Inter Simple Sequence Repeat (ISSR) primers were screened among male and female Date palm plants to identify putative sex-specific marker, out of which only two primers (IS_A02 and IS_A71) were found to be associated with sex. The primer IS_A02 produced a unique band of size 390 bp and was found clearly in all female plants, while it was absent in all male plants. Contrary to this, the primer IS_A71 produced a unique band of size 380 bp and was clearly found in all male plants, whereas it was absent in all the female plants. Subsequently, these specific fragments were excised, purified, and sequenced for the development of sequence specific markers further in future for the implementation on dioecious Date Palm for sex determination. These markers are efficient, highly reliable, and reproducible for sex identification at the early stage of seedling.
Therapeutic Efficacy of Topically Applied Antioxidant Medicinal Plant Extracts in a Mouse Model of Experimental Dry Eye
Authors: Choi Won , Lee Jee Bum , Cui Lian , Li Ying , Li Zhengri , Choi Ji Suk , Lee Hyo Seok , Yoon Kyung Chul
Published: May 2016

Purpose. To investigate the therapeutic effects of topical administration of antioxidant medicinal plant extracts in a mouse model of experimental dry eye (EDE). Methods. Eye drops containing balanced salt solution (BSS) or 0.001%, 0.01%, and 0.1% extracts were applied for the treatment of EDE. Tear volume, tear film break‐up time (BUT), and corneal fluorescein staining scores were measured 10 days after desiccating stress. In addition, we evaluated the levels of interleukin‐ (IL‐) 1β, tumor necrosis factor‐ (TNF‐) α, IL‐6, interferon‐ (IFN‐) γ, and IFN‐γ associated chemokines, percentage of CD4+C‐X‐C chemokine receptor type 3 positive (CXCR3+) T cells, goblet cell density, number of 4‐hydroxy‐2‐nonenal (4‐HNE) positive cells, and extracellular reactive oxygen species (ROS) production. Results. Compared to the EDE and BSS control groups, the mice treated with topical application of the 0.1% extract showed significant improvements in all clinical parameters, IL‐1β, IL‐6, TNF‐α, and IFN‐γ levels, percentage of CD4+CXCR3+ T cells, goblet cell density, number of 4‐HNE‐positive cells, and extracellular ROS production (P < 0.05). Conclusions. Topical application of 0.1% medicinal plant extracts improved clinical signs, decreased inflammation, and ameliorated oxidative stress marker and ROS production on the ocular surface of the EDE model mice.
Effect of Particle Size on the Wear Property of Magnetorheological Fluid
Authors: Zhang Qiuxiang , Liu Xinhua , Ren Yankun , Wang Lifeng , Hu Yuan
Published: May 2016

Aiming to study the effect of particle size on the wear property of magnetorheological fluid (MRF), experiment materials, preparation process, and test methods are elaborated, and three different MRF samples consisting of particles of different size are prepared. Test experiments are carried out and the effect of particle size on the wear property of MRF is discussed. Moreover, the microstructures of particles extracted from MRF obtained before and after the wear experiments are observed by scanning electron microscope (SEM). Experimental results show that the particle size has a significant effect on wear property of MRF. Furthermore, the MRF with particles of 1.5–2.8 μm diameter on average is good for the requirement of engineering applications.
HIV Infection and Osteoarticular Tuberculosis: Strange Bedfellows
Authors: Hodkinson B. , Osman N. , Botha-Scheepers S.
Published: May 2016

We report the case of a 47-year-old female patient with rheumatoid arthritis and HIV infection presenting with a 3-week history of a painful swollen knee, increased serum inflammatory markers, and a low CD4 lymphocyte count. The diagnosis of TB arthritis was made by synovial fluid culture, GeneXpert/PCR, and confirmed by histopathology of a synovial biopsy. A mini literature review suggests that although HIV infection is associated with extrapulmonary TB, osteoarticular TB is a relatively unusual presentation in an HIV positive patient. The diagnostic utility of the GeneXpert test is explored. We also describe the patient’s good response to an intra-articular corticosteroid injection in combination with standard anti-TB therapy.
Hematopoietic Effects of Paeoniflorin and Albiflorin on Radiotherapy‐Induced Myelosuppression Mice
Authors: Zhu Yingli , Wang Linyuan , Yang Zhihui , Wang Jingxia , Li Wei , Zhou Jianyu , Zhang Jianjun
Published: May 2016

Paeonia lactiflora root (baishao in Chinese) is a commonly used herb in traditional Chinese medicine (TCM). Paeoniflorin (PF) and albiflorin (AF) are two major active constituents of P. lactiflora. In this paper, we aimed to investigate the hematopoietic effects of PF and AF on myelosuppression mice induced by radiotherapy and to explore the underlying mechanism. The finding indicated that PF and AF significantly increased the numbers of white blood cells (WBC) and reversed the atrophy of thymus. Furthermore, PF and AF increased the levels of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and interleukin‐3 (IL‐3) and reduced the levels of tumor necrosis factor‐α (TNF‐α) in serum and increased the level of colony‐stimulating factor (G‐CSF) in plasma. Lastly, PF and AF not only enhanced the mRNA levels of GM‐CSF and G‐CSF in the spleens, but also increased the protein levels of G‐CSF and GM‐CSF in bone marrow. Our results suggest that PF and AF may promote the recovery of bone marrow hemopoietic function in a myelosuppressed mouse model.
Sclerostin Antibody Therapy for the Treatment of Osteoporosis: Clinical Prospects and Challenges
Authors: MacNabb Claire , Patton D. , Hayes J. S.
Published: May 2016

It is estimated that over 200 million adults worldwide have osteoporosis, a disease that has increasing socioeconomic impact reflected by unsustainable costs associated with disability, fracture management, hospital stays, and treatment. Existing therapeutic treatments for osteoporosis are associated with a variety of issues relating to use, clinical predictability, and health risks. Consequently, additional novel therapeutic targets are increasingly sought. A promising therapeutic candidate is sclerostin, a Wnt pathway antagonist and, as such, a negative regulator of bone formation. Sclerostin antibody treatment has demonstrated efficacy and superiority compared to other anabolic treatments for increasing bone formation in both preclinical and clinical settings. Accordingly, it has been suggested that sclerostin antibody treatment is set to achieve market approval by 2017 and aggressively compete as the gold standard for osteoporotic treatment by 2021. In anticipation of phase III trial results which may potentially signify a significant step in achieving market approval here, we review the preclinical and clinical emergence of sclerostin antibody therapies for both osteoporosis and alternative applications. Potential clinical challenges are also explored as well as ongoing developments that may impact on the eventual clinical application of sclerostin antibodies as an effective treatment of osteoporosis.
A Novel Compact Dual-Polarized Antenna
Authors: Cheng Yong , Li Yadan , Lu Wenjun
Published: May 2016

A novel compact dual-polarized antenna is proposed. The antenna has a 1.43% impedance bandwidth which is from 1801 MHz to 1827 MHz for return loss larger than 10 dB. The isolation between the two ports is above 28 dB in the bandwidth, and the gain is 6.6 dBi. The proposed antenna not only consists of a full-planar structure, but also is easy to be fabricated for its simple structure. Additionally, a section of slots and slits is cut on the radiation patch to reduce the area of it to 54% compared with the conventional square patch.
The Influence of Salt Solution on Morphological Changes in a Geosynthetic Clay Liner
Authors: Budihardjo Mochamad Arief
Published: May 2016

Morphological variations of geosynthetic clay liner (GCL) samples, hydrated with two different permeates, distilled water and NaCl solution (100 mM concentration), were observed in detail using microscopic analysis. After the GCL samples were hydrated with the NaCl solution, they were observed with an optical microscope. While the surface of the treated GCL samples was similar to the surface of the untreated GCL, a crystal deposit was found on the surface of the treated samples. Using a scanning electron microscope (SEM), a more solid appearance was observed for the bentonite particles contained in the GCL after the sample was hydrated with distilled water in comparison to the GCL sample that was hydrated with the NaCl solution. It appears that salt solution hydration results in less swelling of the bentonite particles. Furthermore, the energy-dispersive X-ray spectrometer (EDS) results showed that distilled water hydration had no effect on the distribution of the elements contained in the GCL samples. However, bound chlorine was observed, which demonstrated that the bentonite particles had absorbed the NaCl solution. In addition, changes in the hydraulic conductivity of the hydrated GCL samples were also observed.
Superspace Unitary Operator in Superfield Approach to Non-Abelian Gauge Theory with Dirac Fields
Authors: Bhanja T. , Shukla D. , Malik R. P.
Published: May 2016

Within the framework of augmented version of the superfield approach to Becchi-Rouet-Stora-Tyutin (BRST) formalism, we derive the superspace unitary operator (and its Hermitian conjugate) in the context of four (3 + 1)-dimensional (4D) interacting non-Abelian 1-form gauge theory with Dirac fields. The ordinary 4D non-Abelian theory, defined on the flat 4D Minkowski spacetime manifold, is generalized onto a (4, 2)-dimensional supermanifold which is parameterized by the spacetime bosonic coordinatesxμ(withμ=0,1,2,3) and a pair of Grassmannian variables (θ,θ-) which satisfy the standard relationships:θ2=θ-2=0and  θθ-+θ-θ=0. Various consequences of the application of the above superspace (SUSP) unitary operator (and its Hermitian conjugate) are discussed. In particular, we obtain the results of the application of horizontality condition (HC) and gauge-invariant restriction (GIR) in the language of the above SUSP operators. One of the novel results of our present investigation is the derivation of explicit expressions for the SUSP unitary operator (and its Hermitian conjugate) without imposing any Hermitian conjugation condition fromoutsideon the parameters and (super)fields of the supersymmetric version of our 4D interacting non-Abelian 1-form theory with Dirac fields.
Fibrinolytic Treatment after Transient Ischaemic Attack Caused by Prosthetic Mitral Valve Thrombosis
Authors: Koban Cornel , Neuß Michael , Tambor Grit , Hölschermann Frank , Butter Christian
Published: May 2016

Prosthetic valve thrombosis is one of the most severe complications after surgical valve replacement. There are many possible presentations: from asymptomatic to life-threatening complications. We report on a 61-year-old female patient with prosthetic replacement of the aortic and mitral valve in the in-house department of cardiac surgery 3 months ago. The patient was suffering from aphasia during 5 minutes in domesticity. After her presentation in the emergency room, the echocardiographic examination revealed a thrombotic formation of the prosthetic mitral valve. At presentation, the anticoagulation was outside the effective range (INR: 1.7). A successful thrombolytic therapy with the plasminogen activator urokinase was begun with complete resolution of the thrombus.
Hopf Bifurcation Control in a FAST TCP and RED Model via Multiple Control Schemes
Authors: Ding Dawei , Wang Chun , Ding Lianghui , Wang Nian , Liang Dong
Published: May 2016

We focus on the Hopf bifurcation control problem of a FAST TCP model with RED gateway. The system gain parameter is chosen as the bifurcation parameter, and the stable region and stability condition of the congestion control model are given by use of the linear stability analysis. When the system gain passes through a critical value, the system loses the stability and Hopf bifurcation occurs. Considering the negative influence caused by Hopf bifurcation, we apply state feedback controller, hybrid controller, and time-delay feedback controller to postpone the onset of undesirable Hopf bifurcation. Numerical simulations show that the hybrid controller is the most sensitive method to delay the Hopf bifurcation with identical parameter conditions. However, nonlinear state feedback control and time-delay feedback control schemes have larger control parameter range in the Internet congestion control system with FAST TCP and RED gateway. Therefore, we can choose proper control method based on practical situation including unknown conditions or parameter requirements. This paper plays an important role in setting guiding system parameters for controlling the FAST TCP and RED model.
Maternal Embryonic Leucine Zipper Kinase (MELK) as a Novel Mediator and Biomarker of Radioresistance in Human Breast Cancer
Authors: Speers Corey , Zhao Shuang G. , Kothari Vishal , Santola Alyssa , Liu Meilan , Wilder-Romans Kari , Evans Joseph , Batra Nidhi , Bartelink Harry , Hayes Daniel F. , Lawrence Theodore S. , Brown Powel H. , Pierce Lori J. , Feng Felix Y.
Published: May 2016

Purpose: While effective targeted therapies exist for estrogen receptor–positive and HER2-positive breast cancer, no such effective therapies exist for triple-negative breast cancer (TNBC); thus, it is clear that additional targets for radiosensitization and treatment are critically needed.

Experimental Design: Expression microarrays, qRT-PCR, and Western blotting were used to assess MELK RNA and protein expression levels. Clonogenic survival assays were used to quantitate the radiosensitivity of cell lines at baseline and after MELK inhibition. The effect of MELK knockdown on DNA damage repair kinetics was determined using γH2AX staining. The in vivo effect of MELK knockdown on radiosensitivity was performed using mouse xenograft models. Kaplan–Meier analysis was used to estimate local control and survival information, and a Cox proportional hazards model was constructed to identify potential factors impacting local recurrence-free survival.

Results: MELK expression is significantly elevated in breast cancer tissues compared with normal tissue as well as in TNBC compared with non-TNBC. MELK RNA and protein expression is significantly correlated with radioresistance in breast cancer cell lines. Inhibition of MELK (genetically and pharmacologically) induces radiation sensitivity in vitro and significantly delayed tumor growth in vivo in multiple models. Kaplan–Meier survival and multivariable analyses identify increasing MELK expression as being the strongest predictor of radioresistance and increased local recurrence in multiple independent datasets.

Conclusions: Here, we identify MELK as a potential biomarker of radioresistance and target for radiosensitization in TNBC. Our results support the rationale for developing clinical strategies to inhibit MELK as a novel target in TNBC. Clin Cancer Res; 22(23); 5864–75. ©2016 AACR.
Macrophage-Mediated Trogocytosis Leads to Death of Antibody-Opsonized Tumor Cells
Authors: Velmurugan Ramraj , Challa Dilip K. , Ram Sripad , Ober Raimund J. , Ward E. Sally
Published: May 2016

Understanding the complex behavior of effector cells such as monocytes or macrophages in regulating cancerous growth is of central importance for cancer immunotherapy. Earlier studies using CD20-specific antibodies have demonstrated that the Fcγ receptor (FcγR)–mediated transfer of the targeted receptors from tumor cells to these effector cells through trogocytosis can enable escape from antibody therapy, leading to the viewpoint that this process is protumorigenic. In the current study, we demonstrate that persistent trogocytic attack results in the killing of HER2-overexpressing breast cancer cells. Further, antibody engineering to increase FcγR interactions enhances this tumoricidal activity. These studies extend the complex repertoire of activities of macrophages to trogocytic-mediated cell death of HER2-overexpressing target cells and have implications for the development of effective antibody-based therapies. Mol Cancer Ther; 15(8); 1879–89. ©2016 AACR.
Unintentional Long-Term Esophageal Stenting due to a Complete Response in a Patient with Stage UICC IV Adenocarcinoma of the Gastroesophageal Junction
Authors: Paeschke Anna , Bojarski Christian , Küpferling Susanne , Hucklenbroich Thomas , Siegmund Britta , Daum Severin
Published: May 2016

Endoscopic stent implantation is a common short-treatment option in palliative settings in patients with esophageal cancer. Advanced disease is associated with low survival rates; therefore, data on the long-term outcome are limited. So far, cases of long-term remission or even cure of metastasized adenocarcinoma of the gastroesophageal junction or stomach (AGS) have only been reported from Asia. A 51-year-old male patient primarily diagnosed with metastasized adenocarcinoma of the gastroesophageal junction (GEJ) [type I, cT3cN+cM1 (hep), CEA positive, UICC stage IV] received palliative esophageal stenting with a self-expandable metal stent. As disease progressed after four cycles with epirubicin, oxaliplatin, and capecitabin, treatment was changed to 5-FU and Irinotecan. The patient did not return after 5 cycles of FOLFIRI, but presented 4 years later with mild dysphagia. Endoscopy surprisingly revealed no relevant stenosis or stent migration. Repeated histological analyses of a residual mass at the GEJ did not detect malignancy. Since the initially diagnosed hepatic metastases were no longer detectable by computed tomography, cure from esophageal cancer was assumed. Dysphagia was ascribed to esophageal motility disorder by a narrowed esophageal lumen after long-term stenting. Thus, endoscopic stent implantation is an important method in palliative treatment of dysphagia related to AGS. New systemic treatment strategies like trastuzumab in Her2neu positive cases or new VEGF-inhibitors like ramucirumab will lead to more long-time survivors with AGS. In conclusion, future endoscopic treatment strategies in AGS represent a challenge for the development of new stent techniques in either extraction or programmed complete dissolution.
Cognitive Behavioral Therapy for Patients with Social Anxiety Disorder Who Remain Symptomatic following Antidepressant Treatment: A Randomized, Assessor-Blinded, Controlled Trial
Authors: Yoshinaga Naoki , Matsuki Satoshi , Niitsu Tomihisa , Sato Yasunori , Tanaka Mari , Ibuki Hanae , Takanashi Rieko , Ohshiro Keiko , Ohshima Fumiyo , Asano Kenichi , Kobori Osamu , Yoshimura Kensuke , Hirano Yoshiyuki , Sawaguchi Kyoko , Koshizaka Masaya , Hanaoka Hideki , Nakagawa Akiko , Nakazato Michiko , Iyo Masaomi , Shimizu Eiji
Published: May 2016

Background: Although antidepressants are still a commonly used treatment for social anxiety disorder (SAD), a significant proportion of patients fail to remit following antidepressants. However, no standard approach has been established for managing such patients. This study aimed to examine the effectiveness of cognitive behavioral therapy (CBT) as an adjunct to usual care (UC) compared with UC alone in SAD patients who remain symptomatic following antidepressant treatment. Methods: This was a prospective randomized open-blinded end-point study with two parallel groups (CBT + UC, and UC alone, both for 16 weeks) conducted from June 2012 to March 2014. SAD patients who remain symptomatic following antidepressant treatment were recruited, and a total sample size of 42 was set based on pilot results. Results: Patients were randomly allocated to CBT + UC (n = 21) or UC alone (n = 21). After 16 weeks, adjusted mean reduction in the Liebowitz Social Anxiety Scale from baseline for CBT + UC and UC alone was −40.87 and 0.68, respectively; the between-group difference was −41.55 (−53.68 to −29.42, p < 0.0001). Response rates were 85.7 and 10.0% for CBT + UC and UC alone, respectively (p < 0.0001). The corresponding remission rates were 47.6 and 0.0%, respectively (p = 0.0005). Significant differences were also found in favor of CBT + UC for social anxiety symptoms, depressive symptoms, and functional impairment. Conclusions: Our results suggest that in SAD patients who have been ineffectively treated with antidepressants, CBT is an effective treatment adjunct to UC over 16 weeks in reducing social anxiety and related symptoms.
Effects of a Psychological Internet Intervention in the Treatment of Mild to Moderate Depressive Symptoms: Results of the EVIDENT Study, a Randomized Controlled Trial
Authors: Klein Jan Philipp , Berger Thomas , Schröder Johanna , Späth Christina , Meyer Björn , Caspar Franz , Lutz Wolfgang , Arndt Alice , Greiner Wolfgang , Gräfe Viola , Hautzinger Martin , Fuhr Kristina , Rose Matthias , Nolte Sandra , Löwe Bernd , Andersson Gerhard , Vettorazzi Eik , Moritz Steffen , Hohagen Fritz
Published: May 2016

Background: Mild to moderate depressive symptoms are common but often remain unrecognized and treated inadequately. We hypothesized that an Internet intervention in addition to usual care is superior to care as usual alone (CAU) in the treatment of mild to moderate depressive symptoms in adults. Methods: This trial was controlled, randomized and assessor-blinded. Participants with mild to moderate depressive symptoms (Patient Health Questionnaire, PHQ-9, score 5-14) were recruited from clinical and non-clinical settings and randomized to either CAU or a 12-week Internet intervention (Deprexis) adjunctive to usual care. Outcomes were assessed at baseline, 3 months (post-assessment) and 6 months (follow-up). The primary outcome measure was self-rated depression severity (PHQ-9). The main analysis was based on the intention-to-treat principle and used linear mixed models. Results: A total of 1,013 participants were randomized. Changes in PHQ-9 from baseline differed signiﬁcantly between groups (t825 = 6.12, p < 0.001 for the main effect of group). The post-assessment between-group effect size in favour of the intervention was d = 0.39 (95% CI: 0.13-0.64). It was stable at follow-up, with d = 0.32 (95% CI: 0.06-0.69). The rate of participants experiencing at least minimally clinically important PHQ-9 change at the post-assessment was higher in the intervention group (35.6 vs. 20.2%) with a number needed to treat of 7 (95% CI: 5-10). Conclusions: The Internet intervention examined in this trial was superior to CAU alone in reducing mild to moderate depressive symptoms. The magnitude of the effect is clinically important and has public health implications.
Hyperpigmented Torpedo Maculopathy with Pseudo-Lacuna: A 5-Year Follow-Up
Authors: Rohl Austin , Vance Sushma
Published: May 2016

Purpose: The aim of the study was to describe a case of globally hyperpigmented torpedo maculopathy that also contained a novel central lesion resembling a ‘pseudo-lacuna’. We compare the morphology of the lesion after 5 years of follow-up. Case Presentation: An asymptomatic 10-year-old Caucasian male was referred by his optometrist after having found a hyperpigmented lesion on routine dilated examination in 2010. Color fundus photography OS from October 2015 showed a 1.74 × 0.67 mm hyperpigmented oval-shaped lesion temporal to the macula. Since June 2010, the hyperpigmented torpedo lesion appeared to have assumed a more ovoid shape and increased in size in the vertical axis. Centrally, there was a small pearlescent-colored pseudo-lacuna lesion that seemed to also have significantly increased in size since June 2010. Enhanced depth imaging optical coherence tomography of this pseudo-lacuna showed retinal pigment epithelium clumping and migration. Fundus autofluorescence revealed reduced autofluorescence of the torpedo lesion and marked hyperautofluorescence of the pseudo-lacuna. Fluorescein angiography shows no neovascular disease or leakage. Conclusion: Torpedo maculopathy has been described previously as a hypopigmented, nonprogressive lesion of unknown etiology. The findings of global hyperpigmentation, pseudo-lacuna formation, and morphologic changes over time in this lesion challenge these classically held descriptions, and necessitate long-term follow-up with multimodal imaging.
Notes on the occurrence of Chitoria sordida sordida (Moore, 1866) (Nymphalidae: Apaturinae) in Tsirang District, Bhutan
Authors: Irungbam Jatishwor Singh , Chib Mennakshi Singh , Fric Zdenek Faltynek
Published: May 2016

Observations on the distribution of Nymphalid butterfly, Sordid Emperor (Chitoria sordida sordida (Moore, 1866) in southern Bhutan are presented in this paper.  The confirmation is based on four years of observation of species in the warm broadleaf forest of Tsirang during July to October.  The species is legally protected under Schedule II of the Indian (Wildlife) Protection Act, 1997.
A badger in Bannerghatta: an opportunistic record of the Ratel Mellivora capensis (Schreber, 1776) (Mammalia: Carnivora: Mustelidae) from Karnataka, India
Authors: Krishnan Avinash , Panwar Sunil , Gayathri Aaranya , Phalke Sagarika , Abani Venkateshaiah Dilip
Published: May 2016

A single observation of a Ratel Mellivora capensis has been photo-documented in Bannerghatta National Park on 2 November 2015. This record being the first contemporary evidence of badgers in this region of Karnataka, India, the paper also presents a case study of badgers being close to a highly human-dominated landscape which could be due to some ecological factors that may be conducive as a habitat within the Park. Though a resident population and distribution within the BNP could not be ascertained, it can be proposed that the region may be an extension of range of its most recently documented distribution in the Eastern Ghats landscape.
Reporting the occurrence of the Variegated Plushblue Flos adriana (Lepidoptera: Lycaenidae: Theclinae) from Garhwal, Uttarakhand extending its known range
Authors: Venkatesh Vidya
Published: May 2016

The butterfly, Variegated Plushblue Flos adriana is reported from Lansdowne, Pauri Garhwal, Uttarakhand, India extending its known range westwards.
New distribution record of Sarcopyramis napalensis Wall. (Melastomataceae) from Garhwal Himalaya, Uttarakhand, India
Authors: Tiwari J. K. , Tiwari P. , Rawat Dinesh Singh , Ballabha Radha , Rana C. S.
Published: May 2016

Sarcopyramis napalensis Wall. is reported for the first time from the Garhwal Himalaya, Uttarakhand. A detailed description, phenology, distribution and figures are provided here.
The conservation status of Derris scandens (Roxb.) Benth. var. saharanpurensis (Thoth.) Thoth. (Fabaceae), a climber endemic to Saharanpur, Uttar Pradesh, India
Authors: Malik Vijai
Published: May 2016

This paper presents observations on the population size and conservation status of Derris scandens var. saharanpurensis (Fabaceae), a woody climber endemic to Saharanpur, Uttar Pradesh, India.  The surveys were made in Saharanpur forest division, which forms the type locality of this variety.  On the basis of field observations this taxon is recommended for IUCN criteria of Critically Endangered [CR B1ab(iii,v)+2ab(iii,v)+2c(iv); C2a(i); D].
Treatment of Obesity
Authors: Wolfe Bruce M. , Kvach Elizaveta , Eckel Robert H.
Published: May 2016

This review focuses on the mechanisms underlying, and indications for, bariatric surgery in the reduction of cardiovascular disease (CVD), as well as other expected benefits of this intervention. The fundamental basis for bariatric surgery for the purpose of accomplishing weight loss is the determination that severe obesity is a disease associated with multiple adverse effects on health, which can be reversed or improved by successful weight loss in patients who have been unable to sustain weight loss by nonsurgical means. An explanation of possible indications for weight loss surgery as well as specific bariatric surgical procedures is presented, along with review of the safety literature of such procedures. Procedures that are less invasive or those that involve less gastrointestinal rearrangement accomplish considerably less weight loss but have substantially lower perioperative and longer-term risk. The ultimate benefit of weight reduction relates to the reduction of the comorbidities, quality of life, and all-cause mortality. With weight loss being the underlying justification for bariatric surgery in ameliorating CVD risk, current evidence-based research is discussed concerning body fat distribution, dyslipidemia, hypertension, diabetes mellitus, inflammation, obstructive sleep apnea, and others. The rationale for bariatric surgery reducing CVD events is discussed and juxtaposed with impacts on all-cause mortalities. Given the improvement of established obesity-related CVD risk factors after weight loss, it is reasonable to expect a reduction of CVD events and related mortality after weight loss in populations with obesity. The quality of the current evidence is reviewed, and future research opportunities and summaries are stated.
Popau, Pop, or an “American Way of Living”? An
Introduction to Aracy Amaral's “From the Stamps to the
Bubble”
Authors: Gotti Sofia
Published: May 2016

The introductory text foregrounds the article “From the Stamps to the Bubble” (1968) by Brazilian historian and curator Aracy A. Amaral. It seeks to locate the primary document within a broader historiography of Brazilian art in the second half of the 1960s, and examine the ways in which the military dictatorship, along with certain cultural exchanges facilitated by Brazil's economic development in this period affected artistic production. Placing particular attention on the multiple terminologies that were in use when the article was written, the introduction focuses on the contiguities of Pop Art in the Brazilian cultural milieu. It argues that Pop was present inasmuch as it inspired artists to initiate a process of radical experimentation, which empowered them to depart from an avant-garde tradition founded on geometric abstraction.
Interactive Spatial Sonification of Multidimensional Data for Composition and Auditory Display
Authors: Barrett Natasha
Published: May 2016

This article presents a new approach to interactive spatial sonification of multidimensional data as a tool for spatial sound synthesis, for composing temporal–spatial musical materials, and as an auditory display for scientists to analyze multidimensional data sets in time and space. The approach applies parameter-mapping sonification and is currently implemented in an application called Cheddar, which was programmed in Max/MSP. Cheddar sonifies data in real time, where the user can modify a wide variety of temporal, spatial, and sonic parameters during the listening process, and thus more easily uncover patterns and processes in the data than when applying non-real-time, noninteractive techniques. The design draws on existing literature concerning perception and acoustics, and it applies the author's practical experience in acousmatic composition, spectromorphology, and sound semantics, while addressing accuracy, flexibility, and ease of use. Although previous sonification applications have addressed some degree of real-time control and spatialization, this approach integrates space and sound in an interactive framework. Spatial information is sonified in high-order 3-D ambisonics, where the user can interactively move the virtual listening position to reveal details easily missed from fixed or noninteractive spatial views. Sounds used as input to the sonification take advantage of the rich spectra and extramusical attributes of acoustic sources, which, although previously theorized, are investigated here in a practical context thoroughly tested alongside acoustic and psychoacoustic considerations. Furthermore, when using Cheddar, no specialized knowledge of programming, acoustics, or psychoacoustics is required. These approaches position Cheddar at the junction between science and art. With one application serving both disciplines, the patterns and processes of science are more fluently appropriated into music or sound art, and vice versa for scientific research, science public outreach, and education.
Horizonal Extensions of Attention: A Phenomenological Study of the Contextuality and Habituality of Experience
Authors: Wehrle Maren , Breyer Thiemo
Published: May 2016

Attention is a complex process that modulates perception in various ways. Phenomenological philosophy provides an array of concepts for describing the rich structures of attention, thereby avoiding reductions to singular aspects of an experiential spectrum. By suggesting various modes and levels of attentional experience, we intend to do some justice to its complexity, taking into account sub-personal and personal factors on the side of subjective (noetic) horizons and feature-oriented as well as context-oriented aspects on the side of objective (noematic) horizons.
Colloquium 1 Commentary on Politis
Authors: McPartland Keith
Published: May 2016

This paper examines the interpretation of erôs in Plato’s Symposium developed by Vasilis Politis in his paper, “The Volatility of Erôs.” The paper first argues that some of the central claims made by Politis are untenable. It then suggests that there is, nevertheless, an important distinction that Politis points to between the way in which erôs is directed specifically at beauty and the way in which desires for the good are directed specifically at goodness. An attempt is made to put this distinction on a new footing incorporating some recent work on Plato’s moral psychology.