bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarkers of Brain Damage: S100B and NSE Concentrations in Cerebrospinal Fluid—A Normative Study
Authors: Hajduková Lenka , Sobek Ondřej , Prchalová Darina , Bílková Zuzana , Koudelková Martina , Lukášková Jiřina , Matuchová Inka
Published: September 2015

NSE and S100B belong among the so-called structural proteins of the central nervous system (CNS). Lately, this group of structural proteins has been profusely used as specific biomarkers of CNS tissue damage. So far, the majority of the research papers have focused predominantly on the concentrations of these proteins in blood in relation to CNS damage of various origins. Considering the close anatomic and functional relationship between the brain or spinal cord and cerebrospinal fluid (CSF), in case of a CNS injury, a rapid and pronounced increase of the concentrations of structural proteins specifically in CSF takes place. This study inquires into the physiological concentrations of NSE and S100B proteins in CSF, carried out on a sufficiently large group of 601 patients. The detected values can be used for determination of a normal reference range in CSF in a clinical laboratory diagnostics.
Immobilization Techniques and Integrated Signal Enhancement for POC Nanocolor Microfluidic Devices
Authors: Schlauf Marlies , Assadollahi Saied , Palkovits Roland , Pointl Peter , Schalkhammer Thomas Gerhard Maria
Published: September 2015

Resonance enhanced absorption (REA) nanocolor microfluidic devices are new promising bioassay platforms, which employ nanoparticle‐ (NP‐) protein conjugates for the immunodetection of medically relevant markers in biologic samples such as blood, urine, and saliva. The core component of a REA test device is a PET chip coated with aluminum and SiO2 thin layers, onto which biorecognitive molecules are immobilized. Upon addition of a sample containing the analyte of interest, a NP‐protein‐analyte complex is formed in the test device that is captured on the REA chip, for example, via streptavidin‐biotin interaction. Thereby, a colored symbol is generated, which allows optical readout. Silver enhancement of the bound nanoparticles may be used to increase the sensitivity of the assay. Herein, we demonstrate that adsorptive immobilization via a cationic polymeric interlayer is a competitive and fast technique for the binding of the capture protein streptavidin onto planar SiO2 surfaces such as REA biochips. Moreover, we report the development of a silver enhancement technology that operates even in the presence of high chloride concentrations as may be encountered in biologic samples. The silver enhancement reagents may be integrated into the microfluidic assay platform to be released upon sample addition. Hereby, a highly sensitive one‐step assay can be realized.
The Relationship between Focal Surfaces and Surfaces at a Constant Distance from the Edge of Regression on a Surface
Authors: Yurttancikmaz Semra , Tarakci Omer
Published: September 2015

We investigate the relationship between focal surfaces and surfaces at a constant distance from the edge of regression on a surface. We show that focal surfacesF1andF2of the surfaceMcan be obtained by means of some special surfaces at a constant distance from the edge of regression on the surfaceM.
Robust Control for Lateral and Longitudinal Channels of Small-Scale Unmanned Helicopters
Authors: Feng Bao
Published: September 2015

Lateral and longitudinal channels are two closely related channels whose control stability influences flight performance of small-scale unmanned helicopters directly. This paper presents a robust control approach for lateral and longitudinal channels in the presence of parameter uncertainties and exogenous disturbances. The proposed control approach is performed by two steps. First, by performing system identification in frequency domain, system model of lateral and longitudinal channels can be accurately identified. Then, a robustH∞state feedback controller is designed to stabilize the helicopter in lateral and longitudinal channels simultaneously under extraneous disturbances situation. The proposed approach takes advantages that it reduces order of the controller by preestimating some parameters (like flapping angles) without sacrificing control accuracy. Numerical results show the reliability and effectiveness of the proposed method.
BF3·Et2O Catalysed 4-Aryl-3-phenyl-benzopyrones, Pro-SERMs, and Their Characterization
Authors: Srivastava Ambika , Singh Pooja , Kumar Rajesh
Published: September 2015

We have synthesized the novel 4-(4-hydroxy-benzyl)-3-phenyl-chromen-2-one which is a precursor of SERMs with a smaller number of steps and good yield. Two methodologies for the synthesis have been worked out. Anhydrous BF3·Et2O catalyzed reaction was found to be selective for product formation while anhydrous AlCl3, FeCl3, and SnCl4catalyzed ones were nonselective.
Numerical Investigation on Vortex Shedding from a Hydrofoil with a Beveled Trailing Edge
Authors: Lee Seung-Jae , Lee Jun-Hyeok , Suh Jung-Chun
Published: September 2015

To better understand the vortex shedding mechanism and to assess the capability of our numerical methodology, we conducted numerical investigations of vortex shedding from truncated and oblique trailing edges of a modified NACA 0009 hydrofoil. The hybrid particle-mesh method and the vorticity-based subgrid scale model were employed to simulate these turbulent wake flows. The hybrid particle-mesh method combines the vortex-in-cell and the penalization methods. We have implemented numerical schemes to more efficiently use available computational resources. In this study, we numerically investigated vortex shedding from various beveled trailing edges at a Reynolds number of 106. We then compared the numerical results with the experimental data, which show good agreement. We also conducted numerical simulations of wakes behind the hydrofoil at rest in periodically varying flows. Results reveal that vortex shedding is affected by the periodicity of a free-stream flow, as well as the trailing-edge shape.
Shifting and Variational Properties for Fourier-Feynman Transform and Convolution
Authors: Kim Byoung Soo
Published: September 2015

Shifting, scaling, modulation, and variational properties for Fourier-Feynman transform of functionals in a Banach algebraSare given. Cameron and Storvick's translation theorem can be obtained as a corollary of our result. We also study shifting, scaling, and modulation properties for the convolution product of functionals inS.
Sea Buckthorn Leaf Extract Protects Jejunum and Bone Marrow of60Cobalt-Gamma-Irradiated Mice by Regulating Apoptosis and Tissue Regeneration
Authors: Bala Madhu , Gupta Manish , Saini Manu , Abdin M. Z. , Prasad Jagdish
Published: September 2015

A single dose (30 mg/kg body weight) of standardized sea buckthorn leaf extract (SBL-1), administered 30 min before whole body60Co-gamma-irradiation (lethal dose, 10 Gy), protected >90% of mice population. The purpose of this study was to investigate the mechanism of action of SBL-1 on jejunum and bone marrow, quantify key bioactive compounds, and analyze chemical composition of SBL-1. Study with 9-week-old inbred male Swiss albino Strain ‘A’ mice demonstrated that SBL-1 treatment before60Co-gamma-irradiation (10 Gy) significantly (p<0.05) countered radiation induced decreases in jejunum crypts (1.27-fold), villi number (1.41-fold), villus height (1.25-fold), villus cellularity (2.27-fold), cryptal Paneth cells (1.89-fold), and Bcl2 level (1.54-fold). It countered radiation induced increases in cryptal apoptotic cells (1.64-fold) and Bax levels (1.88-fold). It also countered radiation (2 Gy and 3 Gy) induced bone marrow apoptosis (1.59-fold and 1.85-fold) and micronuclei frequency (1.72-fold and 2.6-fold). SBL-1 rendered radiation protection by promoting cryptal stem cells proliferation, by regulating apoptosis, and by countering radiation induced chromosomal damage. Quercetin, Ellagic acid, Gallic acid, high contents polyphenols, tannins, and thiols detected in SBL-1 may have contributed to radiation protection by neutralization of radiation induced oxidative species, supporting stem cell proliferation and tissue regeneration.
Overcome Cancer Cell Drug Resistance Using Natural Products
Authors: Wang Pu , Yang Hua Li , Yang Ying Juan , Wang Lan , Lee Shao Chin
Published: September 2015

Chemotherapy is one of the major treatment methods for cancer. However, failure in chemotherapy is not uncommon, mainly due to dose-limiting toxicity associated with drug resistance. Management of drug resistance is important towards successful chemotherapy. There are many reports in the Chinese literature that natural products can overcome cancer cell drug resistance, which deserve sharing with scientific and industrial communities. We summarized the reports into four categories: (1)in vitrostudies using cell line models; (2) serum pharmacology; (3)in vivostudies using animal models; and (4) clinical studies. Fourteen single compounds were reported to have antidrug resistance activity for the first time.In vitro, compounds were able to overcome drug resistance at nontoxic or subtoxic concentrations, in a dose-dependent manner, by inhibiting drug transporters, cell detoxification capacity, or cell apoptosis sensitivity. Studiesin vivoshowed that single compounds, herbal extract, and formulas had potent antidrug resistance activities. Importantly, many single compounds, herbal extracts, and formulas have been used clinically to treat various diseases including cancer. The review provides comprehensive data on use of natural compounds to overcome cancer cell drug resistance in China, which may facilitate the therapeutic development of natural products for clinical management of cancer drug resistance.
Mucinous Bladder Adenocarcinoma: Case Report and Literature Review
Authors: Santos Bruno Mello R. , de Souza Julia Duarte , Lima Rachel Silviano Brandão Correa , de Lima Enaldo Melo
Published: September 2015

Primary mucinous adenocarcinoma is an extremely rare type of bladder cancer, with aggressive behavior and poor response to chemotherapy and radiotherapy. The symptoms are similar to those of other bladder tumors. Surgery is the main treatment and remains the only curative option. There may be a progression from mucinous metaplasia to mucinous adenoma and then mucinous adenocarcinoma. We present the case of a 40-year-old woman with recurrent lower urinary tract infections, submitted to imaging tests, which showed a bladder tumor. After transurethral resection, pathology showed intestinal mucinous carcinoma. Metastatic work-up was negative. New surgical procedure showed metaplasia but no recurrence of the carcinoma. The patient is now using antibiotic prophylaxis and will undergo a cystoscopy every 3 months and computed tomography in one year.
Econometric Modelling of the Variations of Norway’s Export Trade across Continents and over Time: The Two-Stage Non-Full Rank Hierarchical Linear Econometric Model Approach
Authors: Tesfay Yohannes Yebabe , Solibakke Per Bjarte
Published: September 2015

This paper applies the two-stage hierarchical non-full rank linear econometric model to make a deep analysis based on revenue generated from key Norwegian export items over the world’s continents. The model’s ability to analyse the variation of Norway’s export trade gives us the following interesting details: (1) for each continent intra- and intervariation of export items, (2) access to deep knowledge about the characteristics of the Norway’s export items revenue, (3) quantifying the economic importance and sustainability of export items within continents; and finally (4) comparing a given export item economic importance across continents. The results suggest the following important policy implications for Norway. First, Europe is the most important trade partner for Norway. In fact, 81.5% of Norwegian export items are transported to Europe. Second, there is a structural shift in Norwegian exports from North and Central America to Asia and Oceania. Third, the new importance of Asia and Oceania is also emphasized by the 85% increase in export revenues over the period 1988–2012. The trade pattern has changed and trade policy must change accordingly. The analysis has shown that in 2012 there are two important export continents for Norway: Europe and Asia and Oceania.
Weyl-Euler-Lagrange Equations of Motion on Flat Manifold
Authors: Kasap Zeki
Published: September 2015

This paper deals with Weyl-Euler-Lagrange equations of motion on flat manifold. It is well known that a Riemannian manifold is said to be flat if its curvature is everywhere zero. Furthermore, a flat manifold is one Euclidean space in terms of distances. Weyl introduced a metric with a conformal transformation for unified theory in 1918. Classical mechanics is one of the major subfields of mechanics. Also, one way of solving problems in classical mechanics occurs with the help of the Euler-Lagrange equations. In this study, partial differential equations have been obtained for movement of objects in space and solutions of these equations have been generated by using the symbolic Algebra software. Additionally, the improvements, obtained in this study, will be presented.
Usefulness of Nonenhanced Computed Tomography for Diagnosing Urolithiasis without Pyuria in the Emergency Department
Authors: Lee Dong Hoon , Chang In Ho , Kim Jin Wook , Chi Byung Hoon , Park Sung Bin
Published: September 2015

We compared the clinical utility of nonenhanced computed tomography (NECT) and intravenous urography (IVU) in patients with classic symptoms of renal colic without evidence of a urine infection. This was a retrospective analysis of IVU and NECT performed in adult patients with suspected renal colic at an emergency department between January 2005 and December 2013. The records of all patients in NECT and IVU groups were reviewed, and the patients were categorized according to the cause of their symptoms. A total of 2218 patients were enrolled. Of these patients, 1525 (68.8%) underwent IVU and 693 (31.2%) underwent NECT. The patients in NECT group were older (45.48 ± 14.96 versus 42.37 ± 13.68 years,p< 0.001), had less gross hematuria (7.6 versus 2.9%,p< 0.001), and were admitted more often (18.6 versus 12.0%,p< 0.001) than the patients in IVU group. Urinary stones were detected in 1413 (63.7%) patients. NECT had a higher detection rate of urolithiasis than IVP (74.0 versus 59.0%,p< 0.001). No significant difference was observed in the incidence of urinary stones greater than 4mm between groups from the radiologic findings (p= 0.79) or the full medical record review (p= 0.87).
Preference for Efficiency or Confusion? A Note on a Boundedly Rational Equilibrium Approach to Individual Contributions in a Public Good Game
Authors: Corazzini Luca , Tyszler Marcelo
Published: September 2015

By using data from a voluntary contribution mechanism experiment with heterogeneous endowments and asymmetric information, we estimate a quantal response equilibrium (QRE) model to assess the relative importance of efficiency concerns versus noise in accounting for subjects overcontribution in public good games. In the benchmark specification, homogeneous agents, overcontribution is mainly explained by error and noise in behavior. Results change when we consider a more general QRE specification with cross-subject heterogeneity in concerns for (group) efficiency. In this case, we find that the majority of the subjects make contributions that are compatible with the hypothesis of preference for (group) efficiency. A likelihood-ratio test confirms the superiority of the more general specification of the QRE model over alternative specifications.
Investigation of the Validity of the Universal Scaling Law on Linear Chains of Silver Nanoparticles
Authors: Alsawafta Mohammed , Wahbeh Mamoun , Truong Vo-Van
Published: September 2015

Due to the wide range of variation in the plasmonic characteristics of the metallic nanoparticles arranged in linear arrays, the optical spectra of these arrays provide a powerful platform for spectroscopic studies and biosensing applications. Due to the coupling effect between the interacting nanoparticles, the excited resonance mode is shifted with the interparticle separation. The change in the resonance energy of the coupled mode is expressed by the fractional plasmon shift which would normally follow a universal scaling behavior. Such a universal law has been successfully applied on a system of dimers under parallel polarization. It has been found that the plasmon shift decays exponentially over interparticle spacing. The decay length is independent of both the nanoparticle and dielectric properties of the surrounding medium. In this paper, the discrete dipole approximation (DDA) is used to examine the validity of extending the universal scaling law to linear chains of several interacting nanoparticles embedded in various host media for both parallel and perpendicular polarizations. Our calculations reveal that the decay length of both the coupled longitudinal mode (LM) and transverse modes (TM) is strongly dependent on the refractive index of the surrounding medium (nm). The decay constant of the LM is linearly proportional to nm while the corresponding constant of the TM decays exponentially with nm. Upon changing the nanoparticle size, the change in the peak position of the LM decreases exponentially with the interparticle separation and hence, it obeys the universal law. The sensitivity of coupled LM to the nanoparticle size is more pronounced at both smaller nanoparticle sizes and separations. The sensitivity of the coupled TM to the nanoparticle size on the other hand changes linearly with the separation and therefore, the universal law does not apply in the case of the excited TM.
Pancreatic Cancer Cell Migration and Metastasis Is Regulated by Chemokine-Biased Agonism and Bioenergetic Signaling
Authors: Roy Ishan , McAllister Donna M. , Gorse Egal , Dixon Kate , Piper Clinton T. , Zimmerman Noah P. , Getschman Anthony E. , Tsai Susan , Engle Dannielle D. , Evans Douglas B. , Volkman Brian F. , Kalyanaraman Balaraman , Dwinell Michael B.
Published: September 2015

Patients with pancreatic ductal adenocarcinoma (PDAC) invariably succumb to metastatic disease, but the underlying mechanisms that regulate PDAC cell movement and metastasis remain little understood. In this study, we investigated the effects of the chemokine gene CXCL12, which is silenced in PDAC tumors, yet is sufficient to suppress growth and metastasis when re-expressed. Chemokines like CXCL12 regulate cell movement in a biphasic pattern, with peak migration typically in the low nanomolar concentration range. Herein, we tested the hypothesis that the biphasic cell migration pattern induced by CXCL12 reflected a biased agonist bioenergetic signaling that might be exploited to interfere with PDAC metastasis. In human and murine PDAC cell models, we observed that nonmigratory doses of CXCL12 were sufficient to decrease oxidative phosphorylation and glycolytic capacity and to increase levels of phosphorylated forms of the master metabolic kinase AMPK. Those same doses of CXCL12 locked myosin light chain into a phosphorylated state, thereby decreasing F-actin polymerization and preventing cell migration in a manner dependent upon AMPK and the calcium-dependent kinase CAMKII. Notably, at elevated concentrations of CXCL12 that were insufficient to trigger chemotaxis of PDAC cells, AMPK blockade resulted in increased cell movement. In two preclinical mouse models of PDAC, administration of CXCL12 decreased tumor dissemination, supporting our hypothesis that chemokine-biased agonist signaling may offer a useful therapeutic strategy. Our results offer a mechanistic rationale for further investigation of CXCL12 as a potential therapy to prevent or treat PDAC metastasis. Cancer Res; 75(17); 3529–42. ©2015 AACR.
Tuning Sensitivity of CAR to EGFR Density Limits Recognition of Normal Tissue While Maintaining Potent Antitumor Activity
Authors: Caruso Hillary G. , Hurton Lenka V. , Najjar Amer , Rushworth David , Ang Sonny , Olivares Simon , Mi Tiejuan , Switzer Kirsten , Singh Harjeet , Huls Helen , Lee Dean A. , Heimberger Amy B. , Champlin Richard E. , Cooper Laurence J.N.
Published: September 2015

Many tumors overexpress tumor-associated antigens relative to normal tissue, such as EGFR. This limits targeting by human T cells modified to express chimeric antigen receptors (CAR) due to potential for deleterious recognition of normal cells. We sought to generate CAR+ T cells capable of distinguishing malignant from normal cells based on the disparate density of EGFR expression by generating two CARs from monoclonal antibodies that differ in affinity. T cells with low-affinity nimotuzumab-CAR selectively targeted cells overexpressing EGFR, but exhibited diminished effector function as the density of EGFR decreased. In contrast, the activation of T cells bearing high-affinity cetuximab-CAR was not affected by the density of EGFR. In summary, we describe the generation of CARs able to tune T-cell activity to the level of EGFR expression in which a CAR with reduced affinity enabled T cells to distinguish malignant from nonmalignant cells. Cancer Res; 75(17); 3505–18. ©2015 AACR.
Childhood Determination of Hodgkin Lymphoma among U.S. Servicemen
Authors: Mack Thomas M. , Norman James E. , Rappaport Edward , Cozen Wendy
Published: September 2015

Background: Hodgkin lymphoma in young adults is inexplicably linked to economic development.

Methods: We conducted a nested case–control study of the 656 servicemen with Hodgkin lymphoma diagnosed between ages 17 to 32 while on active duty in the U.S. military during 1950–68. Controls, chosen randomly from the servicemen on duty at the time, were matched on service, birth year, and induction date. Information came from preinduction records and military records for the period ending at onset or the equivalent date.

Results: Risk was independently increased with small sib-ship size [OR, 2.3; confidence interval (CI), 1.6–3.5], low birth order (OR, 1.9; CI, 1.4–2.6), and an interval of at least 5 years between birth and that of a previous or subsequent sibling (OR, 2.1; CI, 1.5–3.1). Other factors independently and significantly associated with elevated risk of Hodgkin lymphoma were: tallness, high body mass index, more education (but not higher income) in the county of birth, BB or AB blood type, and past infectious mononucleosis (but a deficit of other childhood viral infections). Early fatherhood conveyed high risk (OR, 2.6; CI, 1.4–4.8), especially if with a high-risk sibling configuration. Factors unrelated to risk included personal education, preinduction or military occupation, induction test score, and rank. Findings were similar for nodular sclerosis and mixed cell histologic subtypes.

Conclusions: Protection from the environment in childhood, but not in adulthood, increases the likelihood of young adult Hodgkin lymphoma, which may result from nonspecific isolation from early infections and/or exposure to late infection by a specific but unidentified ubiquitous childhood virus.

Impact: Events in childhood protect against later Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev; 24(11); 1707–15. ©2015 AACR.
New Strategies in Human Papillomavirus–Related Oropharynx Cancer: Effecting Advances in Treatment for a Growing Epidemic
Authors: Massarelli Erminia , Ferrarotto Renata , Glisson Bonnie S.
Published: September 2015

The past two decades have been witness to a steadily increasing incidence of oropharynx cancer, specifically related to human papillomavirus (HPV), primarily affecting middle-aged Caucasian men, in North America and Europe. The ever-increasing incidence, now clearly an epidemic, of this unique clinicopathologic entity demands new perspectives in diagnosis and staging and presents unique challenges in clinical research, given the excellent prognosis afforded by chemoradiation for the majority of these patients. To reduce the morbidity of late toxicity in survivors without compromising the high rates of survival currently enjoyed, and simultaneously address the poor prognosis of those with recurrence, it is critical to capitalize on the viral etiology and translate discoveries in genomics, target/drug discovery, viral oncogenesis, and immunbiology to improved outcomes for patients. Herein, we review ongoing and planned clinical research for HPV-related oropharynx cancer, the basis for which is constituted by prior clinical observations, knowledge of the genomic alterations and altered biology associated with HPV-related oncogenesis, and hope that molecularly targeted and immunomodulatory therapies can be harnessed. Clin Cancer Res; 21(17); 3821–8. ©2015 AACR.
Blockade of Programmed Death 1 Augments the Ability of Human T Cells Engineered to Target NY-ESO-1 to Control Tumor Growth after Adoptive Transfer
Authors: Moon Edmund K. , Ranganathan Raghuveer , Eruslanov Evgeniy , Kim Soyeon , Newick Kheng , O'Brien Shaun , Lo Albert , Liu Xiaojun , Zhao Yangbing , Albelda Steven M.
Published: September 2015

Purpose: Tumor-infiltrating lymphocytes (TILs) become hypofunctional, although the mechanisms are not clear. Our goal was to generate a model of human tumor-induced TIL hypofunction to study mechanisms and to test anti-human therapeutics.

Experimental Design: We transduced human T cells with a published, optimized T-cell receptor (TCR) that is directed to a peptide within the cancer testis antigen, NY-ESO-1. After demonstrating antigen-specific in vitro activity, these cells were used to target a human lung cancer line that expressed NY-ESO-1 in the appropriate HLA context growing in immunodeficient mice. The ability of anti-PD1 antibody to augment efficacy was tested.

Results: Injection of transgenic T cells had some antitumor activity, but did not eliminate the tumors. The injected T cells became profoundly hypofunctional accompanied by upregulation of PD1, Tim3, and Lag3 with coexpression of multiple inhibitory receptors in a high percentage of cells. This model allowed us to test reagents targeted specifically to human T cells. We found that injections of an anti-PD1 antibody in combination with T cells led to decreased TIL hypofunction and augmented the efficacy of the adoptively transferred T cells.

Conclusions: This model offers a platform for preclinical testing of adjuvant immunotherapeutics targeted to human T cells prior to transition to the bedside. Because the model employs engineering of human T cells with a TCR clone instead of a CAR, it allows for study of the biology of tumor-reactive TILs that signal through an endogenous TCR. The lessons learned from TCR-engineered TILs can thus be applied to tumor-reactive TILs. Clin Cancer Res; 22(2); 436–47. ©2015 AACR.

See related commentary by Yang, p. 275
Pharmacological Inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis in Mice Cardiac Fibroblast and Post-Myocardial-Infarction Models
Authors: Fan Guang-Pu , Wang Wei , Zhao Hui , Cai Lin , Zhang Pei-De , Yang Zi-He , Zhang Jing , Wang Xu
Published: September 2015

Background: To investigate the role of focal adhesion kinase (FAK)-mediated signaling in hypoxia-induced cardiac fibroblasts (CFs) differentiation and cardiac fibrosis post-myocardial infarction (MI) on a mice model. Methods: CFs of neonatal C57BL/6 mice were treated under normoxic, hypoxic, or hypoxic+PP2 (known as a Src kinase family inhibitor) conditions. Gene expressions of FAK, alpha-smooth muscle actin (α-SMA) and collagen type I alpha 1 (Col1α1), or α-SMA and vimentin levels were performed by RT-PCR and immunofluorescence staining, respectively. Thirty mice were surgically treated into Sham (n=7) and MI (n=23) groups; and FAK inhibitor PF-562271 was given to six survivor MI mice (as PF group, from 15 survivors). Heart function and collagenous tissues were examined by echocardiography, as well as by Masson‘s trichrome and Sirius red staining, respectively. Type I collagen, FAK protein, mTOR, ERK1/2, AKT, P70S6K and phospho-FAK levels were also analyzed. Results: FAK inhibition with PP2 significantly decreased CFs differentiation and collagen synthesis under hypoxia treatment. In vivo, PF-562271 treatment resulted in fibrosis attenuation; however, deteriorated heart function of MI mice could not be significantly improved. PF-562271 may affect phospho-mTOR (p<0.05), phospho-ERK1/2 (p<0.01), phospho-AKT (p<0.001) and phospho-P70S6K (p<0.05) to exert its benefits. FAK can be activated either under hypoxia in CFs or MI in a mouse model to promote fibrosis. However, pharmacological inhibition of FAK can attenuate fibrosis response. Conclusion: This study provides novel evidence that FAK inhibition may become a promising pharmaceutical strategy to attenuate fibrosis post-MI.
Coupled Plasma Filtration Adsorption in Patients with a History of Kidney Transplantation: Report of Two Cases
Authors: Lai Quirino , Di Pietro Verdiana , Iesari Samuele , Amabili Sofia , De Luca Linda , Clemente Katia , Famulari Antonio , Pisani Francesco
Published: September 2015

Coupled plasma filtration adsorption (CPFA) is an extracorporeal treatment based on plasma filtration associated with an adsorbent cartridge and hemofiltration. CPFA is able to remove inflammatory mediators and it has been used to treat severe sepsis, septic shock and multiple organ dysfunction syndrome. Limited experience exists on the use of CPFA after solid organ transplantation. We report our experience with CPFA in 2 kidney transplant recipients with post-nephrolithotomy septic shock and severe unexplained rhabdomyolysis. In both the cases, excellent results were observed. In selected cases, CPFA can be safely and effectively used in patients with a solid organ transplant. However, additional studies are needed in this particular setting, to further investigate the potential role of CPFA for the treatment of other conditions associated with excessive inflammation, such as in rheumatologic disorders and delayed graft function.
Immune Reactivity of Synthetic Peptides Originated from Hypervariable Region 1 of Hepatitis C Synthetic Consensuses with Egyptian Sera Infected with Hepatitis C Virus Type 4
Authors: Abdel-Fattah Mohamed , Charmy Ragia , Tawfik Abdel-Rahman
Published: September 2015

We have studied the immune reactivity of hypervariable region 1 (HVR1) of hepatitis C virus (HCV) against HCV immune positive and negative sera. Two published HVR1 consensus nucleotide sequences (Italian and Chinese) were synthesized, and with both of them, a splicing by overlap extension polymerase chain reaction, cloning and sequencing were performed. From the corresponding amino acid sequences, 3 Italian and 1 Chinese HVR1 peptides were selected for synthesis. The 4 peptides (MB1-MB4; GenBank No.: HQ846888-HQ846891) were used to screen 47 and 31 HCV (type 4) immune positive and negative sera, respectively, by enzyme-linked immunosorbent assay (ELISA). The 3 Italian HVR1 peptides (MB1, MB2, MB3) showed reactivities of 83, 68 and 76.6%, respectively, while the Chinese HVR1 peptide (MB4) showed a reactivity of 80.8%. Our results supported that the HVR1 is an attractive target for a peptide-based vaccine as it contains neutralizing epitopes, and all of the HCV patients' sera used in this study have anti-HVR1 antibodies. Interestingly, the amino acid sequence of peptide MB1 has a close sequence similarity with the published mimotope R9, and it shows a high ELISA reactivity. So, MB1 could be tested in combination with other HCV-related peptides as a supplemental assay for HCV diagnosis.
Cardiorenal Syndrome Type 1: Activation of Dual Apoptotic Pathways
Authors: Pastori Silvia , Virzì Grazia Maria , Brocca Alessandra , de Cal Massimo , Cantaluppi Vincenzo , Castellani Chiara , Fedrigo Marny , Thiene Gaetano , Valente Maria Luisa , Angelini Annalisa , Vescovo Giorgio , Ronco Claudio
Published: September 2015

Cardiorenal syndrome type 1 (CRS1) pathophysiology is complex, and immune-mediated damage, including alterations in the immune response with monocyte apoptosis and cytokine release, has been reported as a potential mechanism. In this study, we examined the putative role of renal tubular epithelial cell (RTC) apoptosis as a pathogenic mechanism in CRS1. In particular, we investigated the caspase pathways involved in induced apoptosis. We enrolled 29 patients with acute heart failure (AHF), 11 patients with CRS1, and 15 controls (CTR) without AHF or acute kidney injury (AKI). Patients who had AKI prior to the episode of AHF or who had any other potential causes of AKI were excluded. Plasma from different groups was incubated with RTCs for 24 h. Subsequently, cell apoptosis, DNA fragmentation, and caspase-3, -8, and -9 activities were investigated in RTCs incubated with AHF, CRS1, and CTR plasma. A p value <0.5 was considered statistically significant. A quantitative analysis of apoptosis showed significantly higher apoptosis rates in CRS1 patients compared to AHF patients and CTR (p < 0.01). This increase in apoptosis was strongly confirmed by caspase-3 levels (ρ = 0.73). Caspase-8 and -9 were significantly higher in CRS1 patients compared to AHF patients and CTR (p < 0.01). Furthermore, caspase-3 levels showed a significantly positive correlation with caspase-8 (ρ = 0.57) and -9 (ρ = 0.47; p < 0.001). This study demonstrated the significantly heightened presence of dual apoptotic disequilibrium in CRS1. Our findings indicated that apoptosis may have a central role in the mechanism of CRS1, and it could be a potential therapeutic target in this syndrome.
Arterial Stiffness Gradient
Authors: Fortier Catherine , Agharazii Mohsen
Published: September 2015

Background: Aortic stiffness is a strong predictor of cardiovascular mortality in various clinical conditions. The aim of this review is to focus on the arterial stiffness gradient, to discuss the integrated role of medium-sized muscular conduit arteries in the regulation of pulsatile pressure and organ perfusion and to provide a rationale for integrating their mechanical properties into risk prediction. Summary: The physiological arterial stiffness gradient results from a higher degree of vascular stiffness as the distance from the heart increases, creating multiple reflective sites and attenuating the pulsatile nature of the forward pressure wave along the arterial tree down to the microcirculation. The stiffness gradient hypothesis simultaneously explains its physiological beneficial effects from both cardiac and peripheral microcirculatory points of view. The loss or reversal of stiffness gradient leads to the transmission of a highly pulsatile pressure wave into the microcirculation. This suggests that a higher degree of stiffness of medium-sized conduit arteries may play a role in protecting the microcirculation from a highly pulsatile forward pressure wave. Using the ratio of carotid-femoral pulse wave velocity (PWV) to carotid-radial PWV, referred to as PWV ratio, a recent study in a dialysis cohort has shown that the PWV ratio is a better predictor of mortality than the classical carotid-femoral PWV. Key Messages: Theoretically, the use of the PWV ratio seems more logical for risk determination than aortic stiffness as it provides a better estimation of the loss of stiffness gradient, which is the unifying hypothesis that explains the impact of aortic stiffness both on the myocardium and on peripheral organs.
Choice of Reference Serum Creatinine in Defining Acute Kidney Injury
Authors: Siew Edward D. , Matheny Michael E.
Published: September 2015

Background/Aims: The study of acute kidney injury (AKI) has expanded with the increasing availability of electronic health records and the use of standardized definitions. Understanding the impact of AKI between settings is limited by heterogeneity in the selection of reference creatinine to anchor the definition of AKI. In this mini-review, we discuss different approaches used to select reference creatinine and their relative merits and limitations. Methods: We reviewed the literature to obtain representative examples of published baseline creatinine definitions when pre-hospital data were not available, as well as literature evaluating the estimation of baseline renal function, using PubMed and reference back-tracing within known works. Results: (1) Pre-hospital creatinine values are useful in determining reference creatinine, and in high-risk populations, the mean outpatient serum creatinine value 7-365 days before hospitalization closely approximates nephrology adjudication, (2) in patients without pre-hospital data, the eGFR 75 approach does not reliably estimate true AKI incidence in most at-risk populations, (3) using the lowest inpatient serum creatinine may be reasonable, especially in those with preserved kidney function, but may generously estimate AKI incidence and severity and miss community-acquired AKI that does not fully resolve, (4) using more specific definitions of AKI (e.g., KIDGO stages 2 and 3) may help to reduce the effects of misclassification when using surrogate values and (5) leveraging available clinical data may help refine the estimate of reference creatinine. Conclusions: Choosing reference creatinine for AKI calculation is important for AKI classification and study interpretation. We recommend obtaining data on pre-hospital kidney function, wherever possible. In studies where surrogate estimates are used, transparency in how they are applied and discussion that informs the reader of potential biases should be provided. Further work to refine the estimation of reference creatinine is needed.
Incidence of Major Cardiovascular Events in Immigrants to Ontario, Canada
Authors: Tu Jack V. , Chu Anna , Rezai Mohammad R. , Guo Helen , Maclagan Laura C. , Austin Peter C. , Booth Gillian L. , Manuel Douglas G. , Chiu Maria , Ko Dennis T. , Lee Douglas S. , Shah Baiju R. , Donovan Linda R. , Sohail Qazi Zain , Alter David A.
Published: September 2015

Background—

Immigrants from ethnic minority groups represent an increasing proportion of the population in many high-income countries, but little is known about the causes and amount of variation between various immigrant groups in the incidence of major cardiovascular events.

Methods and Results—

We conducted the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) Immigrant Study, a big data initiative, linking information from Citizenship and Immigration Canada’s Permanent Resident database to 9 population-based health databases. A cohort of 824 662 first-generation immigrants aged 30 to 74 as of January 2002 from 8 major ethnic groups and 201 countries of birth who immigrated to Ontario, Canada between 1985 and 2000 were compared with a reference group of 5.2 million long-term residents. The overall 10-year age-standardized incidence of major cardiovascular events was 30% lower among immigrants than among long-term residents. East Asian immigrants (predominantly ethnic Chinese) had the lowest incidence overall (2.4 in males, 1.1 in females per 1000 person-years), but this increased with greater duration of stay in Canada. South Asian immigrants, including those born in Guyana, had the highest event rates (8.9 in males, 3.6 in females per 1000 person-years), along with immigrants born in Iraq and Afghanistan. Adjustment for traditional risk factors reduced but did not eliminate the differences in cardiovascular risk between various ethnic groups and long-term residents.

Conclusions—

Striking differences in the incidence of cardiovascular events exist among immigrants to Canada from different ethnic backgrounds. Traditional risk factors explain a part but not all of these differences.
Haplodeficiency of
Klotho
Gene Causes Arterial Stiffening via Upregulation of Scleraxis Expression and Induction of Autophagy
Authors: Chen Kai , Zhou Xiaoli , Sun Zhongjie
Published: September 2015

The prevalence of arterial stiffness increases with age, whereas the level of the aging-suppressor protein klotho decreases with age. The objective of this study is to assess whether haplodeficiency of
klotho
gene causes arterial stiffness and to investigate the underlying mechanism. Pulse wave velocity, a direct measure of arterial stiffness, was increased significantly in klotho heterozygous (

klotho
+/−

) mice versus their age-matched wild-type (WT) littermates, suggesting that haplodeficiency of
klotho
causes arterial stiffening. Notably, plasma aldosterone levels were elevated significantly in

klotho
+/−

mice. Treatment with eplerenone (6 mg/kg per day IP), an aldosterone receptor blocker, abolished klotho deficiency–induced arterial stiffening in

klotho
+/−

mice. Klotho deficiency was associated with increased collagen and decreased elastin contents in the media of aortas. In addition, arterial matrix metalloproteinase-2, matrix metalloproteinase-9, and transforming growth factor-β1 expression and myofibroblast differentiation were increased in

klotho
+/−

mice. These klotho deficiency–related changes can be blocked by eplerenone. Protein expression of scleraxis, a transcription factor for collagen synthesis, and LC3-II/LC3-I, an index of autophagy, were upregulated in aortas of

klotho
+/−

mice, which can be abolished by eplerenone. In cultured mouse aortic smooth muscle cells, aldosterone increased collagen-1 expression that can be completely eliminated by small interfering RNA knockdown of scleraxis. Interestingly, aldosterone decreased elastin levels in smooth muscle cells, which can be abolished by small interfering RNA knockdown of Beclin-1, an autophagy-related gene. In conclusion, this study demonstrated for the first time that klotho deficiency–induced arterial stiffening may involve aldosterone-mediated upregulation of scleraxis and induction of autophagy, which led to increased collagen-1 expression and decreased elastin levels, respectively.
An Effective Evolutionary Hybrid for Solving the Permutation Flowshop Scheduling Problem
Authors: Amirghasemi Mehrdad , Zamani Reza
Published: September 2015

This paper presents an effective evolutionary hybrid for solving the permutation flowshop scheduling problem. Based on a memetic algorithm, the procedure uses a construction component that generates initial solutions through the use of a novel reblocking mechanism operating according to a biased random sampling technique. This component is aimed at forcing the operations having smaller processing times to appear on the critical path. The goal of the construction component is to fill an initial pool with high-quality solutions for a memetic algorithm that looks for even higher-quality solutions. In the memetic algorithm, whenever a crossover operator and possibly a mutation are performed, the offspring genome is fine-tuned by a combination of 2-exchange swap and insertion local searches. The same with the employed construction method; in these local searches, the critical path notion has been used to exploit the structure of the problem. The results of computational experiments on the benchmark instances indicate that these components have strong synergy, and their integration has created a robust and effective procedure that outperforms several state-of-the-art procedures on a number of the benchmark instances. By deactivating different components enhancing the evolutionary module of the procedure, the effects of these components have also been examined.
The Korea Syndrome: An Examination of War-Weariness Theory
Authors: Ian Stapleton Bradford
Published: September 2015

In recent years, numerous commentators have maintained that an Iraq syndrome (or Afghanistan syndrome, or both) will inhibit U.S. foreign policy and reduce the leeway U.S. presidents have to use force overseas. To assess the plausibility of those predictions—and the validity and scope of war-weariness theory—this article provides a thorough examination of how the Korean War influenced subsequent U.S. decisions regarding the use of military force during the Dien Bien Phu crisis in 1954 and the first offshore islands confrontation with the People's Republic of China in 1955. The analysis suggests that military quagmires (such as Korea) are likely to exert only minor influence on great powers’ subsequent decisions on whether to use military force but are much more likely to influence how great powers do so.
Shall We Ask Al-Azhar? Maybe Not
Authors: Parolin Gianluca P.
Published: September 2015

This article analyzes the constitutional crisis precipitated by the approval of legislation on sharia-compliant state bonds under the brief enforcement of the 2012 Constitution in Egypt. The crisis confirms the centrality of constitutional design choices for the operation of sharia provisions. In particular, projecting a religious institution with conspicuous political capital in the deliberative process upended the previous arrangement of (almost) complete state control over sharia matters. This stands in sharp contrast to how drafters trivialized these design considerations and focused on the wording of the sharia provisions themselves. Moreover, the poor drafting of these sharia provisions—art. 219 in particular—did not provide for the proper constraints on the institutions involved, as shown in the recommendations on the Ṣukūk Bill put forward by the Body of Senior Scholars of al-Azhar.
Constitutional Reform and Emergency Powers in Egypt and Tunisia
Authors: Zwitter Andrej
Published: September 2015

Legal mechanisms governing the state of emergency can play an important role in authoritarian rule and post-revolutionary transition periods. Egypt has experienced the terror of a regime empowered by emergency law. In Tunisia, emergency law was not so much an issue before but rather after the Jasmine revolution. Given the importance of emergency regulations in both cases, this article provides brief process-oriented accounts of the constitutional reforms triggered by the Arab Spring. It furthermore takes a critical look at how Egypt and Tunisia have redesigned these norms in the latest constitutions of early 2014. On the basis of criteria regarding the rule of law and mechanisms of crisis governance in modern democracies, this article then analyses and evaluates the key elements regarding checks and balances pertaining to emergency regulations in the 2014 constitutions.
The Notions of Citizenship and the Civil State in the Egyptian Transition Process
Authors: Steuer Clément , Blouët Alexis
Published: September 2015

This article deals with two notions that have become central in the Egyptian political and constitutional transition process since 2011 – citizenship and the “Civil State” – and presents the struggle to define them that took place during the 2012 writing of the Constitution. Even though the principle of citizenship is not seriously contested by any of the important political players, its scope and relationship with Islamic normativity (subordination, preeminence, or independence) have both been fiercely debated. As for the notion of the Civil State, it is characterized by an important semantic haziness, which results in a political tension around the issue of its definition, although there is relative consensus in Egypt regarding the term itself. The political and legal struggles around the writing and the adoption of the 2012 Constitution reveal how the tension related to these two notions has been embodied in the discussions surrounding several constitutional articles.
New bryophyte taxon records for tropical countries II
Authors: Eggers Jens , Frahm Jan-Peter , Pursell Ronald A.
Published: September 2015

taxon records for tropical countries II
Revision der Gattung Oncophorus (Musci, Dicranaceae)

Authors: Frahm Jan-Peter , Buchbender Volker , Lachmann Sven , Reifenrath Kerstin , Werner Florian
Published: September 2015

The 12 species so far comprised in the genus Oncophorus are reduced to 6. Oncophorus fauriei Card. ex Ihs. and O. muratae Broth. ex Ihs. are synonymous with C. crispifolius, O. decumbens (Thwait. & Mitt.) Broth. is a species of Dicranum, O. gracilentus Zeng is a species of Dicranella, O. gracillimus Dix. is a synonym of O. wahlenbergii, O. sardous Herz. a synonym of O. virens.
Sobre el género Streptopogon (Pottiaceae, Musci) en Argentina subtropical

Authors: Matteri Celina M. , Schiavone María M.
Published: September 2015

Four species of Streptopogon are new to Argentina. The Bolivian S. heterophyllus, the only species previously registered is excluded from the Argentinian flora, and a major range extension of the Mexican S. matudianus is presented. Treatment of all four taxa includes descriptions, illustrations and SEM micrographs of sporophytic characters.