bluuebunny/crossref_metadata_2025 huggingface dataset:
Micellar Enhanced Spectrofluorimetric Method for the Determination of Ponatinib in Human Plasma and Urine via Cremophor RH 40 as Sensing Agent
Authors: Darwish Hany W. , Bakheit Ahmed H. , Abdelhameed Ali Saber , AlKhairallah Amer S.
Published: December 2015

An impressively simple and precise spectrofluorimetric procedure was established and validated for ponatinib (PTB) quantitation in biological fluids such as human plasma and human urine. This method depends on examining the fluorescence characteristics of PTB in a micellar system of Cremophor RH 40 (Cr RH 40). Cr RH 40 enhanced the intrinsic fluorescence of PTB distinctly in aqueous water. The fluorescence spectra of PTB was recorded at 457 nm following its excitation at 305 nm. Maximum fluorescence intensity was attained by addition of 0.7 mL of Cr RH 40 and one mL of phosphate buffer to PTB aliquots and then dilution with distilled water. There is a linear relationship between the fluorescence intensity of PTB and its concentration over the range 5–120 ngmL−1, with limit of detection and limit of quantification equal to 0.905 ngmL−1and 2.742 ngmL−1, respectively. The accuracy and the precisions of the proposed method were checked and gave adequate results. The adopted method was applied with a great success for PTB quantitation in different biological matrices (spiked human plasma and urine) giving high recovery values.
Posterolateral Corner Reconstruction Alone Using a Fibular-Based Technique in a Patient with Persistent Unstable Revision Total Knee Arthroplasty
Authors: Cline Joseph T. , Alentorn-Geli Eduard , Choi J. H. James , Stuart Joseph J. , Kruger Terry , Moorman III Claude T.
Published: December 2015

Posterolateral rotatory instability is a relatively uncommon cause of unstable total knee arthroplasty (TKA). In most cases, surgical treatment requires revision TKA into a more constrained design or thicker polyethylene liner. We present a case of a patient with unstable TKA who remained unstable after increasing thickness of the polyethylene liner and undergoing more constrained TKA. After several revision surgeries, the patient was still unstable. Posterolateral corner reconstruction with a fibular-based technique using a tibialis anterior allograft was performed. At 1-year follow-up, the patient was stable and asymptomatic and with excellent function. A soft-tissue procedure only (fibular-based posterolateral corner reconstruction) can be effective at restoring posterolateral rotatory stability in a patient with persistent instability after revision TKA.
Rapid Accumulation of Total Lipid inRhizoclonium africanumKutzing as Biodiesel Feedstock under Nutrient Limitations and the Associated Changes at Cellular Level
Authors: Satpati Gour Gopal , Kanjilal Sanjit , Narayana Prasad Rachapudi Badari , Pal Ruma
Published: December 2015

Increase of total lipid and the proportion of the favorable fatty acids in marine green filamentous macroalgaRhizoclonium africanum(Chlorophyceae) was studied under nitrate and phosphate limitations. These stresses were given by both eliminating and doubling the required amounts of nitrate and phosphate salts in the growth media. A significant twofold increase in total lipid (193.03 mg/g) was achieved in cells in absence of nitrate in the culture medium, followed by phosphate limitation (142.65 mg/g). The intracellular accumulation of neutral lipids was observed by fluorescence microscopy. The scanning electron microscopic study showed the major structural changes under nutrient starvation. Fourier transform infrared spectroscopy (FTIR) revealed the presence of ester (C-O-C stretching), ketone (C-C stretching), carboxylic acid (O-H bending), phosphine (P-H stretching), aromatic (C-H stretching and bending), and alcohol (O-H stretching and bending) groups in the treated cells indicating the high accumulation of lipid hydrocarbons in the treated cells. Elevated levels of fatty acids favorable for biodiesel production, that is, C16:0, C16:1, C18:1, and C20:1, were identified under nitrate- and phosphate-deficient conditions. This study shows that the manipulation of cultural conditions could affect the biosynthetic pathways leading to increased lipid production while increasing the proportion of fatty acids suitable for biodiesel production.
Regression Model to Predict Global Solar Irradiance in Malaysia
Authors: Ahmed Kutty Hairuniza , Masral Muhammad Hazim , Rajendran Parvathy
Published: December 2015

A novel regression model is developed to estimate the monthly global solar irradiance in Malaysia. The model is developed based on different available meteorological parameters, including temperature, cloud cover, rain precipitate, relative humidity, wind speed, pressure, and gust speed, by implementing regression analysis. This paper reports on the details of the analysis of the effect of each prediction parameter to identify the parameters that are relevant to estimating global solar irradiance. In addition, the proposed model is compared in terms of the root mean square error (RMSE), mean bias error (MBE), and the coefficient of determination (R2) with other models available from literature studies. Seven models based on single parameters (PM1 to PM7) and five multiple-parameter models (PM7 to PM12) are proposed. The new models perform well, with RMSE ranging from 0.429% to 1.774%,R2ranging from 0.942 to 0.992, and MBE ranging from −0.1571% to 0.6025%. In general, cloud cover significantly affects the estimation of global solar irradiance. However, cloud cover in Malaysia lacks sufficient influence when included into multiple-parameter models although it performs fairly well in single-parameter prediction models.
Global Stability of a Variation Epidemic Spreading Model on Complex Networks
Authors: Xu De-gang , Xu Xi-yang , Yang Chun-hua , Gui Wei-hua
Published: December 2015

Epidemic spreading on networks becomes a hot issue of nonlinear systems, which has attracted many researchers’ attention in recent years. A novel epidemic spreading model with variant factors in complex networks is proposed and investigated in this paper. One main feature of this model is that virus variation is investigated in the process of epidemic dynamical spreading. The global dynamics of this model involving an endemic equilibrium and a disease-free equilibrium are, respectively, discussed. Some sufficient conditions are given for the existence of the endemic equilibrium. In addition, the global asymptotic stability problems of the disease-free equilibrium and the endemic equilibrium are also investigated by the Routh-Hurwitz stability criterion and Lyapunov stability criterion. And the uniform persistence condition of the new system is studied. Finally, numerical simulations are provided to illustrate obtained theoretical results.
Original Reaction Sequence of Pb(Yb1/2Nb1/2)O3-PbTiO3: Consequences on Dielectric Properties and Chemical Order
Authors: Cochard Charlotte , Karolak Fabienne , Bogicevic Christine , Guedes Orland , Janolin Pierre-Eymeric
Published: December 2015

The solid solution [Pb(Yb1/2Nb1/2)O3]1−x-[PbTiO3]xwas synthesized withx≤60%, using several high-temperature techniques as well as room-temperature mechanosynthesis. The high-temperature synthesis reveals a reaction path involving the synthesis first of the end-members before the solid solution. The density and dielectric constant measured on the ceramics prepared from these powders indicate the crucial role of the synthesis technique in the subsequent properties. Mechanosynthesis results in ceramics with higher density and dielectric constant. Identical optimized sintering conditions were then applied to all investigated compositions and the resulting dielectric properties and chemical orders were compared. All polar orders (antiferroelectricity, ferroelectricity, and relaxor behavior) were evidenced. The 1 : 1 chemical order on the B-site of Pb(Yb1/2Nb1/2)O3results in the formation of a double perovskite Pb2YbNbO6, and the superstructures in the X-ray diagrams signing the existence of this order persist up to 30% PbTiO3. The underlying mechanism for substitution of Yb or Nb by Ti is presented.
Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis
Authors: Kelleni Mina Thabet , Amin Entesar Farghaly , Abdelrahman Aly Mohamed
Published: December 2015

Doxorubicin (DOX) is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. The aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in DW p.o. for seven days) and sitagliptin (10 mg/kg dissolved in DW p.o. for seven days) in a model of DOX-induced (single dose 15 mg/kg i.p. at the fifth day) cardiotoxicity in rats. Results of our study revealed that pretreatment with metformin or sitagliptin produced significant (P<0.05) cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group. These results may suggest using metformin and/or sitagliptin as preferable drugs for diabetic patients suffering from cancer and receiving DOX in their chemotherapy regimen.
Characterization of Fatty Acids in Crenarchaeota by GC-MS and NMR
Authors: Hamerly Timothy , Tripet Brian , Wurch Louie , Hettich Robert L. , Podar Mircea , Bothner Brian , Copié Valérie
Published: December 2015

Lipids composed of condensed isoprenyl units connected to glycerol backbones by ether linkages are a distinguishing feature of Archaea. Data suggesting that fatty acids with linear hydrocarbon chains are present in some Archaea have been available for decades. However, lack of genomic and biochemical evidence for the metabolic machinery required to synthesize and degrade fatty acids has left the field unclear on this potentially significant biochemical aspect. Because lipids are energy currency and cell signaling molecules, their presence in Archaea is significant for understanding archaeal biology. A recent large-scale bioinformatics analysis reignited the debate as to the importance of fatty acids in Archaea by presenting genetic evidence for the presence of enzymes required for anabolic and catabolic fatty acid metabolism across the archaeal domain. Here, we present direct biochemical evidence from gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy for the presence of fatty acids in two members of the Crenarchaeota,Sulfolobus solfataricusandIgnicoccus hospitalis. This is the first report providing biochemical data for the existence of fatty acids in these Crenarchaeota, opening new discussions on energy balance and the potential for the discovery of new thermostable enzymes for industry.
Projection-Based Adaptive Backstepping Control of a Transport Aircraft for Heavyweight Airdrop
Authors: Liu Ri , Sun Xiuxia , Dong Wenhan , Xu Guangzhi
Published: December 2015

An autopilot inner loop that combines backstepping control with adaptive function approximation is developed for airdrop operations. The complex nonlinear uncertainty of the aircraft-cargo model is factorized into a known matrix and an uncertainty function, and a projection-based adaptive approach is proposed to estimate this function. Using projection in the adaptation law bounds the estimated function and guarantees the robustness of the controller against time-varying external disturbances and uncertainties. The convergence properties and robustness of the control method are proved via Lyapunov theory. Simulations are conducted under the condition that one transport aircraft performs a maximum load airdrop task at a height of 82 ft, using single row single platform mode. The results show good performance and robust operation of the controller, and the airdrop mission performance indexes are satisfied, even in the presence of ±15% uncertainty in the aerodynamic coefficients, ±0.01 rad/s pitch rate disturbance, and 20% actuators faults.
Effects of “Danzhi Decoction” on Chronic Pelvic Pain, Hemodynamics, and Proinflammatory Factors in the Murine Model of Sequelae of Pelvic Inflammatory Disease
Authors: Bu Xiaoling , Liu Yanxia , Lu Qiudan , Jin Zhe
Published: December 2015

Objective.To evaluate the effect of Danzhi decoction (DZD) on chronic pelvic pain (CPP), hemodynamics, and proinflammatory factors of sequelae of pelvic inflammatory diseases (SPID) in murine model.Methods.SPID mice were randomly treated with high-dose DZD, mid-dose DZD, low-dose DZD, aspirin, and vehicle for 3 estrous circles. The Mouse Grimace Scale (MGS) was performed to evaluate CPP; blood flows of the upper genital tract, pelvic wall, and mesentery were used to assess hemodynamics in SPID mice; expressions of vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), and osteopontin (OPN) were measured by Western blot and immunochemistry.Results.Treatment with dose-dependent DZD significantly decreased the MGS scores, accelerated blood flows of the pelvis, and reduced expressions of VEGF, Ang-2, and OPN in the upper genital tract.Conclusions and Discussions.DZD was effective in relieving CPP and improving hemodynamics of the pelvic blood-stasis microenvironment in SPID mice. There was a relationship between CPP and the pelvic blood-stasis microenvironment. Furthermore, DZD might play a positive role in the anti-inflammatory process.
Assessment of Random Error in Phantom Dosimetry with the Use of Error Simulation in Statistical Software
Authors: Hoogeveen R. C. , Martens E. P. , van der Stelt P. F. , Berkhout W. E. R.
Published: December 2015

Objective. To investigate if software simulation is practical for quantifying random error (RE) in phantom dosimetry.Materials and Methods.We applied software error simulation to an existing dosimetry study. The specifications and the measurement values of this study were brought into the software (R version 3.0.2) together with the algorithm of the calculation of the effective dose (E). Four sources of RE were specified: (1) the calibration factor; (2) the background radiation correction; (3) the read-out process of the dosimeters; and (4) the fluctuation of the X-ray generator.Results.The amount of RE introduced by these sources was calculated on the basis of the experimental values and the mathematical rules of error propagation. The software repeated the calculations ofEmultiple times (n=10,000) while attributing the applicable RE to the experimental values. A distribution ofEemerged as a confidence interval around an expected value.Conclusions.Credible confidence intervals aroundEin phantom dose studies can be calculated by using software modelling of the experiment. With credible confidence intervals, the statistical significance of differences between protocols can be substantiated or rejected. This modelling software can also be used for a power analysis when planning phantom dose experiments.
Stereochemical Investigations of DiastereomericN-[2-(Aryl)-5-methyl-4-oxo-1,3-thiazolidine-3-yl]-pyridine-3-carboxamides by Nuclear Magnetic Resonance Spectroscopy (1D and 2D)
Authors: Demir-Ordu Öznur , Demir-Dündar Hale , Ozkirimli Sumru
Published: December 2015

Some newN-[2-(aryl)-5-methyl-4-oxo-1,3-thiazolidine-3-yl]-pyridine-3-carboxamides were synthesized and their structures were investigated by IR, NMR (1H,13C, and 2D), and mass spectra. The presence of C-2 and C-5 stereogenic centers on the thiazolidinone ring resulted in diastereoisomeric pairs. The configurations of two stereogenic centers were assigned based upon1H NMR analysis of coupling constants and 2D nuclear overhauser enhancement spectroscopy (NOESY) experiment. Resolution of the diastereoisomers was performed by high performance liquid chromatography (HPLC) using a chiral stationary phase.
Contrast-Enhanced Ultrasonography Features of Breast Malignancies with Different Sizes: Correlation with Prognostic Factors
Authors: Zhao Li-Xia , Liu Hui , Wei Qing , Xu Guang , Wu Jian , Xu Hui-Xiong , Wu Rong , Pu Huan
Published: December 2015

This study was to investigate the correlation between contrast-enhanced ultrasonography (CEUS) characteristics with prognostic factors in breast cancers with different sizes. A retrospective analysis of CEUS characteristics of 104 pathologically proven malignant lesions from 104 women was conducted. Lesions were divided into two groups according to their size measured by US (Group 1: maximum diameter ≤20 mm; Group 2: maximum diameter >20 mm). Features including enhancement degree, order and pattern, enlargement of the enhancement area, and penetrating vessels on CEUS were evaluated. Pathologic prognostic factors, including estrogen and progesterone receptor status, and the expression of c-erb-B2, p53, Ki-67, and VEGF were assessed. Comparison of enhancement pattern parameters between Group 1 and Group 2 showed statistically significant differences (P<0.0001). A significant correlation was found between enlargement of the enhancement area and ER positivity in Group 1 (P=0.032). In Group 2 the absence of penetrating vessels was significantly associated with VEGF negativity (P=0.022) and ER negativity (P=0.022). Centripetal enhancement reflected VEGF negativity (P=0.033) in lesions with diameter >20 mm. Thus, breast cancers with different sizes show different CEUS features; small breast cancers show homogeneous enhancement pattern while cancers with diameter >20 mm show homogeneous enhancement pattern. Some CEUS characteristics of differently sized breast cancers could be correlated with prognostic factors, which may be useful in prognosis assessment.
Role of the RAGE Axis during the Immune Response after Severe Trauma: A Prospective Pilot Study
Authors: Uhle Florian , Lichtenstern Christoph , Brenner Thorsten , Fleming Thomas , Koch Christian , Hecker Andreas , Heiss Christian , Nawroth Peter Paul , Hofer Stefan , Weigand Markus Alexander , Weismüller Katja
Published: December 2015

Background. Severe traumatization induces a complex pathophysiology, driven by the patient’s own immune system. The initial activation is a result of damage‐associated molecular patterns, which are released from disrupted and dying cells and recognized by immune receptors, for example, RAGE. In this study we aimed to evaluate the contribution of the RAGE axis to early and late immune responses. Methods. We enrolled 16 patients with severe trauma together with 10 patients after major abdominal surgery and 10 healthy volunteers. Blood samples were taken on admission and every 48 h for a total of 8 days. Plasma concentrations of various RAGE ligands as well as RAGE isoforms and IL‐6 were measured by ELISA. Monocyte surface expression of RAGE and HLA‐DR was assessed by flow cytometry. Results. High and transient levels of IL‐6 and methylglyoxal characterize the early immune response after trauma, whereas samples from later time points provide evidence for a secondary release of RAGE ligands. Conclusion. Our results provide evidence for a persisting activation of the RAGE axis while classical mediators like IL‐6 disappear early. Considering the immunocompromised phenotype of the monocytes, the RAGE ligands might be substantial contributors to the well‐known secondary stage of impaired immune responsiveness in trauma patients.
MyD88Polymorphisms and Association with Susceptibility to Salmonella Pullorum
Authors: Liu Xian-Qing , Wang Fei , Jin Jie , Zhou Yu-Guang , Ran Jin-Shan , Feng Ze-Qing , Wang Yan , Liu Yi-Ping
Published: December 2015

Myeloid differentiation primary response gene 88 (MYD88), a universal adapter protein, plays an important role in activating the nuclear factor-κB (NF-κB) and regulating the expression of proinflammatory genes like tumor necrosis factor (TNF) and interleukin-1 (IL-1), which were highly involved in Salmonella Pullorum infection. To detect the relationship between polymorphisms of theMyD88gene and Salmonella Pullorum disease, we screened the coding region (CDS) of theMYD88gene by DNA pool construction and sequencing based on case-control study. Eight single nucleotide polymorphisms (SNPs) in the sequenced fragment (5 exons), 7 known loci and one novel mutation named G4810372T (SNP8), were found in the fifth exon. In addition, we found 7 nonsynonymous substitutions. The allele frequency of only one SNP, g.4810191C > T (SNP1), was significantly different (P<0.05) between case and control groups. The genotype frequencies of SNP1 (g.4810191C > T) and SNP3 (g.4810257G > T) were of significant difference between the case and the control groups (P<0.05). Collectively, SNPs of theMyD88gene were significantly associated with susceptibility to Salmonella Pullorum infection, which can be used as a disease-resistant marker in chicken. These results provided a theoretical basis for future research on chicken breeding by marker-assisted selection.
Ex VivoAntioxidant Activity of Selected Medicinal Plants against Fenton Reaction-Mediated Oxidation of Biological Lipid Substrates
Authors: Pai Kotebagilu Namratha , Reddy Palvai Vanitha , Urooj Asna
Published: December 2015

Free radical-mediated oxidation is often linked to various degenerative diseases. Biological substrates with lipids as major components are susceptible to oxygen-derived lipid peroxidation due to their composition. Lipid peroxide products act as biomarkers in evaluating the antioxidant potential of various plants and functional foods. The study focused on evaluation of the antioxidant potential of two extracts (methanol and 80% methanol) of four medicinal plants,Andrographis paniculata,Costus speciosus, Canthium parviflorum, andAbrus precatorius, against Fenton reaction-mediated oxidation of three biological lipid substrates; cholesterol, low-density lipoprotein, and brain homogenate. The antioxidant activity of the extracts was measured by thiobarbituric acid reactive substances method. Also, the correlation between the polyphenol, flavonoid content, and the antioxidant activity in biological substrates was analyzed. Results indicated highest antioxidant potential by 80% methanol extract ofCanthium parviflorum(97.55%), methanol extract ofAndrographis paniculata(72.15%), and methanol extract ofCanthium parviflorum(49.55%) in cholesterol, low-density lipoprotein, and brain, respectively. The polyphenol and flavonoid contents of methanol extract ofAndrographis paniculatain cholesterol (r=0.816) and low-density lipoprotein (r=0.948) andCostus speciosusin brain (r=0.977, polyphenols, andr=0.949, flavonoids) correlated well with the antioxidant activity. The findings prove the antioxidant potential of the selected medicinal plants against Fenton reaction in biological lipid substrates.
Case with a Nonreassuring Fetal Status Induced by Massive Hematemesis due to Mallory-Weiss Tear That Required Emergency Cesarean Section at 38 Weeks’ Gestation
Authors: Suzuki Takashi , Wagata Maiko , Konno Hiroko , Ito Takahiro , Torii Yuichi , Murakoshi Takeshi
Published: December 2015

We describe a rare case of Mallory-Weiss tear with massive hematemesis at 38 weeks’ gestation. A 35-year-old woman presented with epigastralgia followed by massive hematemesis. An emergency endoscopy indicated active pulsatile bleeding at the esophagocardial junction. Although an emergency endoscopic hemostasis was successful, late decelerations without acceleration on cardiotocogram were observed. Therefore, the patient underwent emergency cesarean section, along with blood transfusion, following the endoscopic hemostasis. The hemoglobin level just before the operation was 5.1 g/dL. We suspected that massive hematemesis induced maternal acute anemia and hypovolemia, which resulted in a nonreassuring fetal status. Hence, urgent endoscopic hemostasis, adequate blood transfusion, and emergency cesarean section were needed. Mallory-Weiss tear during the third trimester may have a possibility of massive hematemesis and urgent blood transfusion, emergency endoscopic hemostasis, and emergency cesarean section may be needed.
Computational Analysis of the Binding Specificities of PH Domains
Authors: Jiang Zhi , Liang Zhongjie , Shen Bairong , Hu Guang
Published: December 2015

Pleckstrin homology (PH) domains share low sequence identities but extremely conserved structures. They have been found in many proteins for cellular signal-dependent membrane targeting by binding inositol phosphates to perform different physiological functions. In order to understand the sequence-structure relationship and binding specificities of PH domains, quantum mechanical (QM) calculations and sequence-based combined with structure-based binding analysis were employed in our research. In the structural aspect, the binding specificities were shown to correlate with the hydropathy characteristics of PH domains and electrostatic properties of the bound inositol phosphates. By comparing these structure properties with sequence-based profiles of physicochemical properties, PH domains can be classified into four functional subgroups according to their binding specificities and affinities to inositol phosphates. The method not only provides a simple and practical paradigm to predict binding specificities for functional genomic research but also gives new insight into the understanding of the basis of diseases with respect to PH domain structures.
On a Degenerate Evolution System Associated with the Bean Critical-State for Type II Superconductors
Authors: Aramaki Junichi
Published: December 2015

We study a degenerate evolution system containing thep-curl system in a bounded domain with initial and boundary conditions for the magnetic fieldHunder the influence of a system forceF. This is concerned with an approximation of Bean’s critical-state model for type II superconductors. We will show the existence, uniqueness, and regularity of solutions. Moreover we will get the properties of the limit solution asp→∞.
Auditory Cortical Maturation in a Child with Cochlear Implant: Analysis of Electrophysiological and Behavioral Measures
Authors: Silva Liliane Aparecida Fagundes , Couto Maria Inês Vieira , Tsuji Robinson Koji , Bento Ricardo Ferreira , Carvalho Ana Claudia Martinho de , Matas Carla Gentile
Published: December 2015

The purpose of this study was to longitudinally assess the behavioral and electrophysiological hearing changes of a girl inserted in a CI program, who had bilateral profound sensorineural hearing loss and underwent surgery of cochlear implantation with electrode activation at 21 months of age. She was evaluated using the P1 component of Long Latency Auditory Evoked Potential (LLAEP); speech perception tests of the Glendonald Auditory Screening Procedure (GASP); Infant Toddler Meaningful Auditory Integration Scale (IT-MAIS); and Meaningful Use of Speech Scales (MUSS). The study was conducted prior to activation and after three, nine, and 18 months of cochlear implant activation. The results of the LLAEP were compared with data from a hearing child matched by gender and chronological age. The results of the LLAEP of the child with cochlear implant showed gradual decrease in latency of the P1 component after auditory stimulation (172 ms–134 ms). In the GASP, IT-MAIS, and MUSS, gradual development of listening skills and oral language was observed. The values of the LLAEP of the hearing child were expected for chronological age (132 ms–128 ms). The use of different clinical instruments allow a better understanding of the auditory habilitation and rehabilitation process via CI.
Optical Image Encryption Using Devil’s Vortex Toroidal Lens in the Fresnel Transform Domain
Authors: Singh Hukum , Yadav A. K. , Vashisth Sunanda , Singh Kehar
Published: December 2015

We have carried out a study of optical image encryption in the Fresnel transform (FrT) domain, using a random phase mask (RPM) in the input plane and a phase mask based on devil’s vortex toroidal lens (DVTL) in the frequency plane. The original images are recovered from their corresponding encrypted images by using the correct parameters of theFrTand the parameters of DVTL. The use of a DVTL-based structured mask enhances security by increasing the key space for encryption and also aids in overcoming the problem of axis alignment associated with an optical setup. The proposed encryption scheme is a lensless optical system and its digital implementation has been performed using MATLAB 7.6.0 (R2008a). The scheme has been validated for a grayscale and a binary image. The efficacy of the proposed scheme is verified by computing mean-squared-error (MSE) between the recovered and the original images. We have also investigated the scheme’s sensitivity to the encryption parameters and examined its robustness against occlusion and noise attacks.
Endotoxin-Induced Tryptophan Degradation along the Kynurenine Pathway: The Role of Indolamine 2,3-Dioxygenase and Aryl Hydrocarbon Receptor-Mediated Immunosuppressive Effects in Endotoxin Tolerance and Cancer and Its Implications for Immunoparalysis
Authors: Wirthgen Elisa , Hoeflich Andreas
Published: December 2015

The degradation of tryptophan (TRP) along the kynurenine pathway plays a crucial role as a neuro- and immunomodulatory mechanism in response to inflammatory stimuli, such as lipopolysaccharides (LPS). In endotoxemia or sepsis, an enhanced activation of the rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO) is associated with a higher mortality risk. It is assumed that IDO induced immunosuppressive effects provoke the development of a protracted compensatory hypoinflammatory phase up to a complete paralysis of the immune system, which is characterized by an endotoxin tolerance. However, the role of IDO activation in the development of life-threatening immunoparalysis is still poorly understood. Recent reports described the impact of inflammatory IDO activation and aryl hydrocarbon receptor- (AhR-) mediated pathways on the development of LPS tolerance and immune escape of cancer cells. These immunosuppressive mechanisms offer new insights for a better understanding of the development of cellular dysfunctions in immunoparalysis. This review provides a comprehensive update of significant biological functions of TRP metabolites along the kynurenine pathway and the complex regulation of LPS-induced IDO activation. In addition, the review focuses on the role of IDO-AhR-mediated immunosuppressive pathways in endotoxin tolerance and carcinogenesis revealing the significance of enhanced IDO activity for the establishment of life-threatening immunoparalysis in sepsis.
Incretin-Based Therapy for Prevention of Diabetic Vascular Complications
Authors: Mima Akira
Published: December 2015

Diabetic vascular complications are the most common cause of mortality and morbidity worldwide, with numbers of affected individuals steadily increasing. Diabetic vascular complications can be divided into two categories: macrovascular and　microvascular complications. Macrovascular complications include coronary artery disease　and cerebrovascular disease, while microvascular complications include retinopathy and chronic kidney disease. These complications result from metabolic abnormalities, including hyperglycemia, elevated levels of free fatty acids, and insulin resistance. Multiple mechanisms have been proposed to mediate the adverse effects of these metabolic disorders on vascular tissues, including stimulation of protein kinase C signaling and activation of the polyol pathway by oxidative stress and inflammation. Additionally, the loss of tissue-specific insulin signaling induced by hyperglycemia and toxic metabolites can induce cellular dysfunction and both macro- and microvascular complications characteristic of diabetes. Despite these insights, few therapeutic methods are available for the management of diabetic complications. Recently, incretin-based therapeutic agents, such as glucagon-like peptide-1 and dipeptidyl peptidase-4 inhibitors, have been reported to elicit vasotropic actions, suggesting a potential for effecting an actual reduction in diabetic vascular complications. The present review will summarize the relationship between multiple adverse biological mechanisms in diabetes and putative incretin-based therapeutic interventions intended to prevent diabetic vascular complications.
Optimal Bowel Preparation for Video Capsule Endoscopy
Authors: Song Hyun Joo , Moon Jeong Seop , Shim Ki-Nam
Published: December 2015

During video capsule endoscopy (VCE), several factors, such as air bubbles, food material in the small bowel, and delayed gastric and small bowel transit time, influence diagnostic yield, small bowel visualization quality, and cecal completion rate. Therefore, bowel preparation before VCE is as essential as bowel preparation before colonoscopy. To date, there have been many comparative studies, consensus, and guidelines regarding different kinds of bowel cleansing agents in bowel preparation for small bowel VCE. Presently, polyethylene glycol- (PEG-) based regimens are given primary recommendation. Sodium picosulphate-based regimens are secondarily recommended, as their cleansing efficacy is less than that of PEG-based regimens. Sodium phosphate as well as complementary simethicone and prokinetics use are considered. In this paper, we reviewed previous studies regarding bowel preparation for small bowel VCE and suggested optimal bowel preparation of VCE.
Combined Antitumor Therapy with Metronomic Topotecan and Hypoxia-Activated Prodrug, Evofosfamide, in Neuroblastoma and Rhabdomyosarcoma Preclinical Models
Authors: Zhang Libo , Marrano Paula , Wu Bing , Kumar Sushil , Thorner Paul , Baruchel Sylvain
Published: December 2015

Purpose: Tumor cells residing in tumor hypoxic zones are a major cause of drug resistance and tumor relapse. In this study, we investigated the efficacy of evofosfamide, a hypoxia-activated prodrug, and its combination with topotecan in neuroblastoma and rhabdomyosarcoma preclinical models.

Experimental Design: Neuroblastoma and rhabdomyosarcoma cells were tested in vitro to assess the effect of evofosfamide on cell proliferation, both as a single agent and in combination with topotecan. In vivo antitumor activity was evaluated in different xenograft models. Animal survival was studied with the neuroblastoma metastatic tumor model.

Results: All tested cell lines showed response to evofosfamide under normoxic conditions, but when exposed to hypoxia overnight, a 2- to 65-fold decrease of IC50 was observed. Adding topotecan to the evofosfamide treatment significantly increased cytotoxicity in vitro. In neuroblastoma xenograft models, single-agent evofosfamide treatment delayed tumor growth. Complete tumor regression was observed in the combined topotecan/evofosfamide treatment group after 2-week treatment. Combined treatment also improved survival in a neuroblastoma metastatic model, compared to single-agent treatments. In rhabdomyosarcoma xenograft models, combined treatment was more effective than single agents. We also showed that evofosfamide mostly targeted tumor cells within hypoxic regions while topotecan was more effective to tumor cells in normoxic regions. Combined treatment induced tumor cell apoptosis in both normoxic and hypoxic regions.

Conclusions: Evofosfamide shows antitumor effects in neuroblastoma and rhabdomyosarcoma xenografts. Compared with single-agent, evofosfamide/topotecan, combined therapy improves tumor response, delays tumor relapse, and enhances animal survival in preclinical tumor models. Clin Cancer Res; 22(11); 2697–708. ©2015 AACR.
Translation Inhibition by Rocaglates Is Independent of eIF4E Phosphorylation Status
Authors: Chu Jennifer , Cencic Regina , Wang Wenyu , Porco John A. , Pelletier Jerry
Published: December 2015

Rocaglates are natural products that inhibit protein synthesis in eukaryotes and exhibit antineoplastic activity. In vitro biochemical assays, affinity chromatography experiments coupled with mass spectrometry analysis, and in vivo genetic screens have identified eukaryotic initiation factor (eIF) 4A as a direct molecular target of rocaglates. eIF4A is the RNA helicase subunit of eIF4F, a complex that mediates cap-dependent ribosome recruitment to mRNA templates. The eIF4F complex has been implicated in tumor initiation and maintenance through elevated levels or increased phosphorylation status of its cap-binding subunit, eIF4E, thus furthering the interest toward developing rocaglates as antineoplastic agents. Recent experiments have indicated that rocaglates also interact with prohibitins 1 and 2, proteins implicated in c-Raf-MEK-ERK signaling. Because increased ERK signaling stimulates eIF4E phosphorylation status, rocaglates are also expected to inhibit eIF4E phosphorylation status, a point that has not been thoroughly investigated. It is currently unknown whether the effects on translation observed with rocaglates are solely through eIF4A inhibition or also a feature of blocking eIF4E phosphorylation. Here, we show that rocaglates inhibit translation through an eIF4E phosphorylation–independent mechanism. Mol Cancer Ther; 15(1); 136–41. ©2015 AACR.
Human Leukocyte Antigen–Presented Macrophage Migration Inhibitory Factor Is a Surface Biomarker and Potential Therapeutic Target for Ovarian Cancer
Authors: Patterson Andrea M. , Kaabinejadian Saghar , McMurtrey Curtis P. , Bardet Wilfried , Jackson Ken W. , Zuna Rosemary E. , Husain Sanam , Adams Gregory P. , MacDonald Glen , Dillon Rachelle L. , Ames Harold , Buchli Rico , Hawkins Oriana E. , Weidanz Jon A. , Hildebrand William H.
Published: December 2015

T cells recognize cancer cells via HLA/peptide complexes, and when disease overtakes these immune mechanisms, immunotherapy can exogenously target these same HLA/peptide surface markers. We previously identified an HLA-A2–presented peptide derived from macrophage migration inhibitory factor (MIF) and generated antibody RL21A against this HLA-A2/MIF complex. The objective of the current study was to assess the potential for targeting the HLA-A2/MIF complex in ovarian cancer. First, MIF peptide FLSELTQQL was eluted from the HLA-A2 of the human cancerous ovarian cell lines SKOV3, A2780, OV90, and FHIOSE118hi and detected by mass spectrometry. By flow cytometry, RL21A was shown to specifically stain these four cell lines in the context of HLA-A2. Next, partially matched HLA-A*02:01+ ovarian cancer (n = 27) and normal fallopian tube (n = 24) tissues were stained with RL21A by immunohistochemistry to assess differential HLA-A2/MIF complex expression. Ovarian tumor tissues revealed significantly increased RL21A staining compared with normal fallopian tube epithelium (P < 0.0001), with minimal staining of normal stroma and blood vessels (P < 0.0001 and P < 0.001 compared with tumor cells) suggesting a therapeutic window. We then demonstrated the anticancer activity of toxin-bound RL21A via the dose-dependent killing of ovarian cancer cells. In summary, MIF-derived peptide FLSELTQQL is HLA-A2–presented and recognized by RL21A on ovarian cancer cell lines and patient tumor tissues, and targeting of this HLA-A2/MIF complex with toxin-bound RL21A can induce ovarian cancer cell death. These results suggest that the HLA-A2/MIF complex should be further explored as a cell-surface target for ovarian cancer immunotherapy. Mol Cancer Ther; 15(2); 313–22. ©2015 AACR.
A Cyclin-Dependent Kinase Inhibitor, Dinaciclib, Impairs Homologous Recombination and Sensitizes Multiple Myeloma Cells to PARP Inhibition
Authors: Alagpulinsa David A. , Ayyadevara Srinivas , Yaccoby Shmuel , Shmookler Reis Robert J.
Published: December 2015

PARP1/2 are required for single-strand break repair, and their inhibition causes DNA replication fork collapse and double-strand break (DSB) formation. These DSBs are primarily repaired via homologous recombination (HR), a high-fidelity repair pathway. Should HR be deficient, DSBs may be repaired via error-prone nonhomologous end-joining mechanisms, or may persist, ultimately resulting in cell death. The combined disruption of PARP and HR activities thus produces synthetic lethality. Multiple myeloma cells are characterized by chromosomal instability and pervasive DNA damage, implicating aberrant DNA repair. Cyclin-dependent kinases (CDK), upstream modulators of HR, are dysregulated in multiple myeloma. Here, we show that a CDK inhibitor, dinaciclib, impairs HR repair and sensitizes multiple myeloma cells to the PARP1/2 inhibitor ABT-888. Dinaciclib abolishes ABT-888–induced BRCA1 and RAD51 foci and potentiates DNA damage, indicated by increased γH2AX foci. Dinaciclib treatment reduces expression of HR repair genes, including Rad51, and blocks BRCA1 phosphorylation, a modification required for HR repair, thus inhibiting HR repair of chromosome DSBs. Cotreatment with dinaciclib and ABT-888 in vitro resulted in synthetic lethality of multiple myeloma cells, but not normal CD19+ B cells, and slowed growth of multiple myeloma xenografts in SCID mice almost two-fold. These findings support combining dinaciclib with PARP inhibitors for multiple myeloma therapy. Mol Cancer Ther; 15(2); 241–50. ©2015 AACR.
Telomere Length as a Prognostic Factor for Overall Survival in Colorectal Cancer Patients
Authors: Jia Houjun , Wang Ziwei
Published: January 2016

Background/Aims: The stabilization of telomere length has important roles in the carcinogenesis of colorectal cancer. A systemic review and meta-analysis of published studies was performed to assess the prognostic role of telomere length in colorectal cancer. Methods: Pubmed and Embase were searched for eligible studies on the association between telomere length and overall survival in colorectal cancer patients. The pooled hazard ratio (HR) and corresponding 95% confidence intervals (95%CI) was calculated using fixed-effects or random-effects model according to the magnitude of between-study heterogeneity. Results: Seven individual studies with a total of 956 colorectal cancer patients were included. Long telomere length in cancer tissues was marginally associated with poorer overall survival (Random-effects HR = 1.85, 95% 0.90 to 3.83, P = 0.09). When using studies with adjusted estimates, long telomere length in cancer tissues was independently and significantly associated with poorer overall survival (Fixed-effects HR = 2.70, 95% 1.51 to 4.84, P = 0.001). However, short telomere length in peripheral blood leukocytes was independently and significantly associated with poorer overall survival (Fixed-effects HR = 2.01, 95% 1.46 to 2.77, P < 0.001). Conclusions: There is some evidence for telomere length as a prognostic factor for overall survival in colorectal cancer patients. More studies with large number of participants are needed to further assess the prognostic significance of telomere length in colorectal cancer patients.
Phylogeographic relationships and shallow mitochondrial divergence of Algerian populations of Salamandra algira
Authors: Merabet Khaled , Sanchez Eugenia , Dahmana Abdelhak , Bogaerts Sergé , Donaire David , Steinfartz Sebastian , Joger Ulrich , Vences Miguel , Karar Mokrane , Moali Aissa
Published: December 2015

The North African fire salamander, Salamandra algira, is distributed in Algeria, Morocco and Ceuta (Spanish territory located on the north coast of Africa), but until now rather limited information has been available on the populations across the Algerian part of its range. We here provide a first analysis of the phylogeography of this species in Algeria, based on 44 samples from populations distributed across 15 localities in Central Algeria. We sequenced three segments of mitochondrial DNA, covering 12S rRNA, cytochrome b (Cytb) and the D-loop. The mtDNA sequences of the Algerian samples were strongly different from the Moroccan populations occurring west of the Moulouya River (corresponding to the subspecies S. a. tingitana and S. a. splendens) but sister to the genetically rather similar population from the Beni Snassen Massif in eastern Morocco (subspecies S. algira spelaea). Among the Algerian specimens studied, those from the westernmost site, Chrea Massif, were the sister clade to the remaining populations, and the overall genetic divergence was low, with a maximum of five mutational steps in a 295 bp fragment of cytochrome b.
Estimating Daytime Planetary Boundary Layer Heights over a Valley from Rawinsonde Observations at a Nearby Airport: An Application to the Page Valley in Virginia, United States
Authors: Lee Temple R. , De Wekker Stephan F. J.
Published: December 2015

The planetary boundary layer (PBL) height is an essential parameter required for many applications, including weather forecasting and dispersion modeling for air quality. Estimates of PBL height are not easily available and often come from twice-daily rawinsonde observations at airports, typically at 0000 and 1200 UTC. Questions often arise regarding the applicability of PBL heights retrieved from these twice-daily observations to surrounding locations. Obtaining this information requires knowledge of the spatial variability of PBL heights. This knowledge is particularly limited in regions with mountainous terrain. The goal of this study is to develop a method for estimating daytime PBL heights in the Page Valley, located in the Blue Ridge Mountains of Virginia. The approach includes using 1) rawinsonde observations from the nearest sounding station [Dulles Airport (IAD)], which is located 90 km northeast of the Page Valley, 2) North American Regional Reanalysis (NARR) output, and 3) simulations with the Weather Research and Forecasting (WRF) Model. When selecting days on which PBL heights from NARR compare well to PBL heights determined from the IAD soundings, it is found that PBL heights are higher (on the order of 200–400 m) over the Page Valley than at IAD and that these differences are typically larger in summer than in winter. WRF simulations indicate that larger sensible heat fluxes and terrain-following characteristics of PBL height both contribute to PBL heights being higher over the Page Valley than at IAD.
Dynamics of the ITCZ Boundary Layer
Authors: Gonzalez Alex O. , Slocum Christopher J. , Taft Richard K. , Schubert Wayne H.
Published: December 2015

This paper presents high-resolution numerical solutions of a nonlinear zonally symmetric slab model of the intertropical convergence zone (ITCZ) boundary layer. The boundary layer zonal and meridional flows are forced by a specified pressure field, which can also be interpreted as a specified geostrophically balanced zonal wind field ug(y). One narrow on-equatorial peak in boundary layer pumping is produced when the forcing is easterly geostrophic flow along the equator and two narrow peaks in boundary layer pumping are produced on opposite sides of the equator (a double ITCZ) when the forcing is westerly geostrophic flow along the equator. In the case when easterlies are surrounding a westerly wind burst, once again a double ITCZ is produced, but the ITCZs have significantly more intense boundary layer pumping than the case of only westerly geostrophic flow. A comparison of the numerical solutions to those of classical Ekman theory suggests that the meridional advection term υ(∂υ/∂y) plays a vital role in strengthening and narrowing boundary layer pumping regions while weakening and broadening boundary layer suction regions.