bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Contextual Information Recommendation Model and Its Application in e-Commerce Customer Satisfaction Management
Authors: Guo Feipeng , Lu Qibei
Published: April 2015

In the current supply chain environment, distributed cognition theory tells us that various types of context information in which a recommendation is provided are important for e-commerce customer satisfaction management. However, traditional recommendation model does not consider the distributed and differentiated impact of different contexts on user needs, and it also lacks adaptive capacity of contextual recommendation service. Thus, a contextual information recommendation model based on distributed cognition theory is proposed. Firstly, the model analyzes the differential impact of various sensitive contexts and specific examples on user interest and designs a user interest extraction algorithm based on distributed cognition theory. Then, the sensitive contexts extracted from user are introduced into the process of collaborative filtering recommendation. The model calculates similarity among user interests. Finally, a novel collaborative filtering algorithm integrating with context and user similarity is designed. The experimental results in e-commerce and benchmark dataset show that this model has a good ability to extract user interest and has higher recommendation accuracy compared with other methods.
3D Self-Deployment Algorithm in Mobile Wireless Sensor Networks
Authors: Miao Chunyu , Dai Guoyong , Zhao Xiaomin , Tang Zhongze , Chen Qingzhang
Published: April 2015

The sensor deployment problem of wireless sensor networks (WSNs) is a key issue in the researches and the applications of WSNs. Fewer works focus on the 3D autonomous deployment. Aimed at the problem of sensor deployment in three-dimensional spaces, the 3D self-deployment (3DSD) algorithm in mobile sensor networks is proposed. A 3D virtual force model is utilized in the 3DSD method. A negotiation tactic is introduced to ensure network connectivity, and a density control strategy is used to balance the node distribution. The proposed algorithm can fulfill the nodes autonomous deployment in 3D space with obstacles. Simulation results indicate that the deployment process of 3DSD is relatively rapid and the nodes are well distributed. Furthermore, the coverage ratio of 3DSD approximates the theoretical maximum value.
Dynamic Analysis of Three-Layer Sandwich Beams with Thick Viscoelastic Damping Core for Finite Element Applications
Authors: Cortés Fernando , Sarría Imanol
Published: April 2015

This paper presents an analysis of the dynamic behaviour of constrained layer damping (CLD) beams with thick viscoelastic layer. A homogenised model for the flexural stiffness is formulated using Reddy-Bickford’s quadratic shear in each layer, and it is compared with Ross-Kerwin-Ungar (RKU) classical model, which considers a uniform shear deformation for the viscoelastic core. In order to analyse the efficiency of both models, a numerical application is accomplished and the provided results are compared with those of a 2D model using finite elements, which considers extensional and shear stress and longitudinal, transverse, and rotational inertias. The intermediate viscoelastic material is characterised by a fractional derivative model, with a frequency dependent complex modulus. Eigenvalues and eigenvectors are obtained from an iterative method avoiding the computational problems derived from the frequency dependence of the stiffness matrices. Also, frequency response functions are calculated. The results show that the new model provides better accuracy than the RKU one as the thickness of the core layer increases. In conclusion, a new model has been developed, being able to reproduce the mechanical behaviour of thick CLD beams, reducing storage needs and computational time compared with a 2D model, and improving the results from the RKU model.
Prevalence ofHelicobacter pylori vacA,cagA, andiceAGenotypes in Cuban Patients with Upper Gastrointestinal Diseases
Authors: Feliciano Onelkis , Gutierrez Oderay , Valdés Lidunka , Fragoso Trini , Calderin Ana Maria , Valdes Antonio Eduardo , Llanes Rafael
Published: April 2015

Virulence factors ofHelicobacter pylorican predict the development of different gastroduodenal diseases. There are scarce reports in Cuba aboutH. pyloriisolates genotyping. The aim of the present investigation was to identify allelic variation of the virulence genesvacA,cagA, andiceAin sixty-eight patients diagnosed asH. pyloripositive by culture. In seven out of 68 patients, strains from both gastric regions were obtained and considered independent. DNA was extracted from all theH. pyloristrains and evaluated by PCR-genotyping. ThevacAs1 allele,cagAgene, andiceA2allele were the most prevalent (72.0%, 56.0%, and 57.3%, respectively). Alleles from m-region showed a similar frequency as s1a and s1b subtypes. The presence of multipleH. pylorigenotypes in a single biopsy and two gastric region specimens were found. Significant statistical association was observed betweeniceA2allele and patients with non-peptic ulcer dyspepsia (NUD) (P=0.037) as well as virulence genotypes (s1,s1m2) and patients over 40 years old (P<0.05). In conclusion, the results demonstrated a high prevalence ofH. pylorivirulent genotypes in Cuban patients over 40 years old whileiceA2alleles demonstrated a good specificity in patients with NUD.
PMC-12, a Prescription of Traditional Korean Medicine, Improves Amyloidβ-Induced Cognitive Deficits through Modulation of Neuroinflammation
Authors: Park Min Young , Jung Yeon Suk , Park Jung Hwa , Choi Young Whan , Lee Jaewon , Kim Cheol Min , Baek Jin Ung , Choi Byung Tae , Shin Hwa Kyoung
Published: April 2015

PMC-12 is a prescription used in traditional Korean medicine that consists of a mixture of four herbal medicines,Polygonum multiflorum,Rehmannia glutinosa,Polygala tenuifolia, andAcorus gramineus, which have been reported to have various pharmacological effects on age-related neurological diseases. In the present study, we investigated whether PMC-12 improves cognitive deficits associated with decreased neuroinflammation in an amyloid-β-(Aβ-) induced mouse model and exerts the antineuroinflammatory effects in lipopolysaccharide-(LPS-) stimulated murine BV2 microglia. Intracerebroventricular injection ofAβ25-35in mice resulted in impairment in learning and spatial memory, whereas this was reversed by oral administration of PMC-12 (100 and 500 mg/kg/day) in dose-dependent manners. Moreover, PMC-12 reduced the increase of Aβexpression and activation of microglia and astrocytes in theAβ25-35-injected brain. Furthermore, quantitative PCR data showed that inflammatory mediators were significantly decreased by administration of PMC-12 in Aβ-injected brains. Consistent with thein vivodata, PMC-12 significantly reduced the inflammatory mediators in LPS-stimulated BV2 cells without cell toxicity. Moreover, PMC-12 exhibited anti-inflammatory properties via downregulation of ERK, JNK, and p38 MAPK pathways. These findings suggest that the protective effects of PMC-12 may be mediated by its antineuroinflammatory activities, resulting in the attenuation of memory impairment; accordingly, PMC-12 may be useful in the prevention and treatment of AD.
A New Sensitive Sensor for Simultaneous Differential Pulse Voltammetric Determination of Codeine and Acetaminophen Using a Hydroquinone Derivative and Multiwall Carbon Nanotubes Carbon Paste Electrode
Authors: Garazhian Elahe , Shishehbore M. Reza
Published: April 2015

A new sensitive sensor was fabricated for simultaneous determination of codeine and acetaminophen based on 4-hydroxy-2-(triphenylphosphonio)phenolate (HTP) and multiwall carbon nanotubes paste electrode at trace levels. The sensitivity of codeine determination was deeply affected by spiking multiwall carbon nanotubes and a modifier in carbon paste. Electron transfer coefficient,α, catalytic electron rate constant,k, and the exchange current density,j0, for oxidation of codeine at the HTP-MWCNT-CPE were calculated using cyclic voltammetry. The calibration curve was linear over the range 0.2–844.7 μM with two linear segments, and the detection limit of 0.063 μM of codeine was obtained using differential pulse voltammetry. The modified electrode was separated codeine and acetaminophen signals by differential pulse voltammetry. The modified electrode was applied for the determination of codeine and acetaminophen in biological and pharmaceutical samples with satisfactory results.
Metabolic Engineering ofEscherichia colifor Poly(3-hydroxybutyrate) Production under Microaerobic Condition
Authors: Wei Xiao-Xing , Zheng Wei-Tao , Hou Xue , Liang Jian , Li Zheng-Jun
Published: April 2015

The alcohol dehydrogenase promoterPadhEand mixed acid fermentation pathway deficient mutants ofEscherichia coliwere employed to produce poly(3-hydroxybutyrate) (P3HB) under microaerobic condition. TheE. colimutant withackA-pta, poxB, ldhA, andadhEdeletions accumulated 0.67 g/L P3HB, up to 78.84% of cell dry weight in tube cultivation. The deletion of pyruvate formate-lyase genepflBdrastically decreased P3HB production and P3HB content to 0.09 g/L and 24.44%, respectively. OverexpressingpflBvia the plasmid in its knocked out mutant restored cell growth and P3HB accumulation, indicating the importance of the pyruvate formate-lyase in microaerobic carbon metabolism. The engineeredE. coliBWapld (pWYC09) produced 5.00 g/L P3HB from 16.50 g/L glucose in 24 h batch fermentation, and P3HB production yield from glucose was 0.30 g/g, which reached up to 63% of maximal theoretical yield.
Gastric Carcinogenesis and Underlying Molecular Mechanisms:Helicobacter pyloriand Novel Targeted Therapy
Authors: Nishizawa Toshihiro , Suzuki Hidekazu
Published: April 2015

The oxygen-derived free radicals that are released from activated neutrophils are one of the cytotoxic factors ofHelicobacter pylori-induced gastric mucosal injury. Increased cytidine deaminase activity inH. pylori-infected gastric tissues promotes the accumulation of various mutations and might promote gastric carcinogenesis. Cytotoxin-associated gene A (CagA) is delivered into gastric epithelial cells via bacterial type IV secretion system, and it causes inflammation and activation of oncogenic pathways.H. pyloriinfection induces epigenetic transformations, such as aberrant promoter methylation in tumor-suppressor genes. Aberrant expression of microRNAs is also reportedly linked to gastric tumorogenesis. Moreover, recent advances in molecular targeting therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2 (HER-2) therapies. This updated review article highlights possible mechanisms of gastric carcinogenesis includingH. pylori-associated factors.
An Estimate of the Probability Density Function of the Sum of a Random Number N of Independent Random Variables
Authors: Gifuni Angelo , Sorrentino Antonio , Ferrara Giuseppe , Migliaccio Maurizio
Published: April 2015

A new estimate of the probability density function (PDF) of the sum of a random number of independent and identically distributed (IID) random variables Xi (i=1, 2, …, N) is shown. The sum PDF is represented as a sum of normal PDFs weighted according to the N PDF. The analytical model is verified by numerical simulations. The comparison is made by the Chi-Square Goodness-of-Fit test.
Parametric Study of Time-Dependent Corrosion Product Activity due to56Mn,58Co, and60Co in the Primary Coolant Circuit of a Typical Pressurized Water Reactor
Authors: Rafique Muhammad , Mirza Nasir M. , Mirza Sikander M. , Kearfott Kimberlee J. , Abbasi Shahab A. , Naeem Syed F.
Published: April 2015

Results of a detailed study, based on the parametric analysis of activated corrosion products, in primary coolant of a typical pressurized water reactor (PWR) are presented. The parameters influencing time dependent buildup of corrosion product activity (CPA) in primary coolant loop of PWR were identified. The computer program CPAIR was used to accommodate for time dependent corrosion rates. The behaviors of56Mn,58Co, and60Co were studied over the reactor operational time. During the course of normal operation of reactor, the CPA is dominated by56Mn, while58Co and60Co are the predominant radionuclides after reactor shutdown. Parametric study suggests that the total CPA is most sensitive to ion-exchanger removal rates. For a removal rate of 300 cm3-s−1, the specific activity due to56Mn has the maximum value of 3.552 × 104 Bq-m−3after 1,000 hours of reactor operation. This value decreases drastically to 8.325 × 103 Bq-m−3at removal rate of 900 cm3-s−1. Additionally, CPA due to56Mn,58Co, and60Co shows strong dependence on removal rates from the core material surfaces. Variations in the values of radionuclide removal rates from piping surface and radionuclide removal rate from deposition on pipes showed only very small effects on CPA buildup.
A Cascade-Based Emergency Model for Water Distribution Network
Authors: Shuang Qing , Yuan Yongbo , Zhang Mingyuan , Liu Yisheng
Published: April 2015

Water distribution network is important in the critical physical infrastructure systems. The paper studies the emergency resource strategies on water distribution network with the approach of complex network and cascading failures. The model of cascade-based emergency for water distribution network is built. The cascade-based model considers the network topology analysis and hydraulic analysis to provide a more realistic result. A load redistribution function with emergency recovery mechanisms is established. From the aspects of uniform distribution, node betweenness, and node pressure, six recovery strategies are given to reflect the network topology and the failure information, respectively. The recovery strategies are evaluated with the complex network indicators to describe the failure scale and failure velocity. The proposed method is applied by an illustrative example. The results showed that the recovery strategy considering the node pressure can enhance the network robustness effectively. Besides, this strategy can reduce the failure nodes and generate the least failure nodes per time.
Esophagojejunal Anastomosis Fistula, Distal Esophageal Stenosis, and Metalic Stent Migration after Total Gastrectomy
Authors: Al Hajjar Nadim , Popa Calin , Al-Momani Tareg , Margarit Simona , Graur Florin , Tantau Marcel
Published: April 2015

Esophagojejunal anastomosis fistula is the main complication after a total gastrectomy. To avoid a complex procedure on friable inflamed perianastomotic tissues, a coated self-expandable stent is mounted at the site of the anastomotic leak. A complication of stenting procedure is that it might lead to distal esophageal stenosis. However, another frequently encountered complication of stenting is stent migration, which is treated nonsurgically. When the migrated stent creates life threatening complications, surgical removal is indicated. We present a case of a 67-year-old male patient who was treated at our facility for a gastric adenocarcinoma which developed, postoperatively, an esophagojejunostomy fistula, a distal esophageal stenosis, and a metallic coated self-expandable stent migration. To our knowledge, this is the first reported case of an esophagojejunostomy fistula combined with a distal esophageal stenosis as well as with a metallic coated self-expandable stent migration.
Epigenetic Regulations of Inflammatory Cyclooxygenase‐Derived Prostanoids: Molecular Basis and Pathophysiological Consequences
Authors: Harizi Hedi
Published: April 2015

The potential relevance of prostanoid signaling in immunity and immunological disorders, or disease susceptibility and individual variations in drug responses, is an important area for investigation. The deregulation of Cyclooxygenase‐ (COX‐) derived prostanoids has been reported in several immunoinflammatory disorders such as asthma, rheumatoid arthritis, cancer, and autoimmune diseases. In addition to the environmental factors and the genetic background to diseases, epigenetic mechanisms involved in the fine regulation of prostanoid biosynthesis and/or receptor signaling appeared to be an additional level of complexity in the understanding of prostanoid biology and crucial in controlling the different components of the COX pathways. Epigenetic alterations targeting inflammatory components of prostanoid biosynthesis and signaling pathways may be important in the process of neoplasia, depending on the tissue microenvironment and target genes. Here, we focused on the epigenetic modifications of inflammatory prostanoids in physiological immune response and immunological disorders. We described how major prostanoids and their receptors can be functionally regulated epigenetically and consequently the impact of these processes in the pathogenesis inflammatory diseases and the development of therapeutic approaches that may have important clinical applications.
Chronic Treatment with a Water-Soluble Extract from the Culture Medium ofGanoderma lucidumMycelia Prevents Apoptosis and Necroptosis in Hypoxia/Ischemia-Induced Injury of Type 2 Diabetic Mouse Brain
Authors: Xuan Meiyan , Okazaki Mari , Iwata Naohiro , Asano Satoshi , Kamiuchi Shinya , Matsuzaki Hirokazu , Sakamoto Takeshi , Miyano Yoshiyuki , Iizuka Hiroshi , Hibino Yasuhide
Published: April 2015

Type 2 diabetes mellitus has been known to increase systemic oxidative stress by chronic hyperglycemia and visceral obesity and aggravate cerebral ischemic injury. On the basis of our previous study regarding a water-soluble extract from the culture medium ofGanoderma lucidummycelia (designed as MAK), which exerts antioxidative and neuroprotective effects, the present study was conducted to evaluate the preventive effects of MAK on apoptosis and necroptosis (a programmed necrosis) induced by hypoxia/ischemia (H/I) in type 2 diabetic KKAy mice. H/I was induced by a combination of unilateral common carotid artery ligation with hypoxia (8% O2for 20 min) and subsequent reoxygenation. Pretreatment with MAK (1 g/kg, p.o.) for a week significantly reduced H/I-induced neurological deficits and brain infarction volume assessed at 24 h of reoxygenation. Histochemical analysis showed that MAK significantly suppressed superoxide production, neuronal cell death, and vacuolation in the ischemic penumbra, which was accompanied by a decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells. Furthermore, MAK decreased the expression of receptor-interacting protein kinase 3 mRNA and protein, a key molecule for necroptosis. These results suggest that MAK confers resistance to apoptotic and necroptotic cell death and relieves H/I-induced cerebral ischemic injury in type 2 diabetic mice.
Co-UWSN: Cooperative Energy-Efficient Protocol for Underwater WSNs
Authors: Ahmed S. , Javaid N. , Khan F. A. , Durrani M. Y. , Ali A. , Shaukat A. , Sandhu M. M. , Khan Z. A. , Qasim U.
Published: April 2015

Sensor networks feature low-cost sensor devices with wireless network capability, limited transmit power, resource constraints, and limited battery energy. Cooperative routing exploits the broadcast nature of wireless medium and transmits cooperatively using nearby sensor nodes as relays. It is a promising technique that utilizes cooperative communication to improve the communication quality of single-antenna sensor nodes. In this paper, we propose a cooperative transmission scheme for underwater sensor networks (UWSNs) to enhance the network performance. Cooperative diversity has been introduced to combat fading. Cooperative UWSN (Co-UWSN) is proposed, which is a reliable, energy-efficient, and high throughput routing protocol for UWSN. Destination and potential relays are selected that utilize distance and signal-to-noise ratio computation of the channel conditions as cost functions. This contributes to sufficient decrease in path losses occurring in the links and transferring of data with much reduced path loss. Simulation results show that Co-UWSN protocol performs better in terms of end-to-end delay, energy consumption, and network lifetime. Selected protocols for comparison are energy-efficient depth-based routing (EEDBR), improved adaptive mobility of courier nodes in threshold-optimized depth-based routing (iAMCTD), cooperative routing protocol for UWSN, and cooperative partner node selection criteria for cooperative routing Coop (Re and dth).
Functions Like Convex Functions
Authors: Pavić Zlatko
Published: April 2015

The paper deals with convex sets, functions satisfying the global convexity property, and positive linear functionals. Jensen's type inequalities can be obtained by using convex combinations with the common center. Following the idea of the common center, the functional forms of Jensen's inequality are considered in this paper.
Identifying Highly Penetrant Disease Causal Mutations Using Next Generation Sequencing: Guide to Whole Process
Authors: Erzurumluoglu A. Mesut , Rodriguez Santiago , Shihab Hashem A. , Baird Denis , Richardson Tom G. , Day Ian N. M. , Gaunt Tom R.
Published: April 2015

Recent technological advances have created challenges for geneticists and a need to adapt to a wide range of new bioinformatics tools and an expanding wealth of publicly available data (e.g., mutation databases, and software). This wide range of methods and a diversity of file formats used in sequence analysis is a significant issue, with a considerable amount of time spent before anyone can even attempt to analyse the genetic basis of human disorders. Another point to consider that is although many possess “just enough” knowledge to analyse their data, they do not make full use of the tools and databases that are available and also do not fully understand how their data was created. The primary aim of this review is to document some of the key approaches and provide an analysis schema to make the analysis process more efficient and reliable in the context of discovering highly penetrant causal mutations/genes. This review will also compare the methods used to identify highly penetrant variants when data is obtained from consanguineous individuals as opposed to nonconsanguineous; and when Mendelian disorders are analysed as opposed to common-complex disorders.
Encoding Sequential Information in Semantic Space Models: Comparing Holographic Reduced Representation and Random Permutation
Authors: Recchia Gabriel , Sahlgren Magnus , Kanerva Pentti , Jones Michael N.
Published: April 2015

Circular convolution and random permutation have each been proposed as neurally plausible binding operators capable of encoding sequential information in semantic memory. We perform several controlled comparisons of circular convolution and random permutation as means of encoding paired associates as well as encoding sequential information. Random permutations outperformed convolution with respect to the number of paired associates that can be reliably stored in a single memory trace. Performance was equal on semantic tasks when using a small corpus, but random permutations were ultimately capable of achieving superior performance due to their higher scalability to large corpora. Finally, “noisy” permutations in which units are mapped to other units arbitrarily (no one-to-one mapping) perform nearly as well as true permutations. These findings increase the neurological plausibility of random permutations and highlight their utility in vector space models of semantics.
Phase I Hepatic Immunotherapy for Metastases Study of Intra-Arterial Chimeric Antigen Receptor–Modified T-cell Therapy for CEA+ Liver Metastases
Authors: Katz Steven C. , Burga Rachel A. , McCormack Elise , Wang Li Juan , Mooring Wesley , Point Gary R. , Khare Pranay D. , Thorn Mitchell , Ma Qiangzhong , Stainken Brian F. , Assanah Earle O. , Davies Robin , Espat N. Joseph , Junghans Richard P.
Published: April 2015

Purpose: Chimeric antigen receptor–modified T cells (CAR-T) have demonstrated encouraging results in early-phase clinical trials. Successful adaptation of CAR-T technology for CEA-expressing adenocarcinoma liver metastases, a major cause of death in patients with gastrointestinal cancers, has yet to be achieved. We sought to test intrahepatic delivery of anti-CEA CAR-T through percutaneous hepatic artery infusions (HAIs).

Experimental Design: We conducted a phase I trial to test HAI of CAR-T in patients with CEA+ liver metastases. Six patients completed the protocol, and 3 received anti-CEA CAR-T HAIs alone in dose-escalation fashion (108, 109, and 1010 cells). We treated an additional 3 patients with the maximum planned CAR-T HAI dose (1010 cells × 3) along with systemic IL2 support.

Results: Four patients had more than 10 liver metastases, and patients received a mean of 2.5 lines of conventional systemic therapy before enrollment. No patient suffered a grade 3 or 4 adverse event related to the CAR-T HAIs. One patient remains alive with stable disease at 23 months following CAR-T HAI, and 5 patients died of progressive disease. Among the patients in the cohort that received systemic IL2 support, CEA levels decreased 37% (range, 19%–48%) from baseline. Biopsies demonstrated an increase in liver metastasis necrosis or fibrosis in 4 of 6 patients. Elevated serum IFNγ levels correlated with IL2 administration and CEA decreases.

Conclusions: We have demonstrated the safety of anti-CEA CAR-T HAIs with encouraging signals of clinical activity in a heavily pretreated population with large tumor burdens. Further clinical testing of CAR-T HAIs for liver metastases is warranted. Clin Cancer Res; 21(14); 3149–59. ©2015 AACR.
CDKN2A/p16 Loss Implicates CDK4 as a Therapeutic Target in Imatinib-Resistant Dermatofibrosarcoma Protuberans
Authors: Eilers Grant , Czaplinski Jeffrey T. , Mayeda Mark , Bahri Nacef , Tao Derrick , Zhu Meijun , Hornick Jason L. , Lindeman Neal I. , Sicinska Ewa , Wagner Andrew J. , Fletcher Jonathan A. , Mariño-Enriquez Adrian
Published: April 2015

Dermatofibrosarcoma protuberans (DFSP) is an aggressive PDGFB-dependent cutaneous sarcoma characterized by infiltrative growth and frequent local recurrences. Some DFSP progress to a higher-grade fibrosarcomatous form, with rapid growth and increased risk of metastasis. Imatinib provides clinical benefit in approximately 50% of patients with unresectable or metastatic DFSP. However, efficacious medical therapies have not been developed for imatinib-resistant DFSP. We established a model of imatinib-resistant DFSP and evaluated CDK4/6 inhibition as a genomically credentialed targeted therapy. DFSP105, an imatinib-resistant human cell line, was established from a fibrosarcomatous DFSP (FS-DFSP), and was studied by SNP arrays and sequencing to identify targetable genomic alterations. Findings were validated in vitro and in vivo, and confirmed in a series including 12 DFSP and 6 FS-DFSP. SNP analysis of DFSP105 revealed a homozygous deletion encompassing CDKN2A and CDKN2B. The resultant p16 loss implicated CDK4/6 as a potential therapeutic target in DFSP. We further demonstrated CDKN2A homozygous deletion in 1 of 12 conventional DFSP and 2 of 6 FS-DFSP, whereas p16 expression was lost in 4 of 18 DFSP. In vitro treatment of DFSP105 with two structurally distinct selective CDK4/6 inhibitors, PD-0332991 and LEE011, led to inhibition of RB1 phosphorylation and inhibition of proliferation (GI50 160 nmol/L and 276 nmol/L, respectively). In vivo treatment of DFSP105 with PD-0332991 (150 mg/kg) inhibited xenograft growth in mice, in comparison with imatinib-treated or -untreated tumors. In conclusion, CDKN2A deletion can contribute to DFSP progression. CDK4/6 inhibition is a preclinically effective treatment against p16-negative, imatinib-resistant FS-DFSP, and should be evaluated as a therapeutic strategy in patients with unresectable or metastatic imatinib-resistant DFSP. Mol Cancer Ther; 14(6); 1346–53. ©2015 AACR.
Effective Targeting of Estrogen Receptor–Negative Breast Cancers with the Protein Kinase D Inhibitor CRT0066101
Authors: Borges Sahra , Perez Edith A. , Thompson E. Aubrey , Radisky Derek C. , Geiger Xochiquetzal J. , Storz Peter
Published: April 2015

Invasive ductal carcinomas (IDC) of the breast are associated with altered expression of hormone receptors (HR), amplification or overexpression of HER2, or a triple-negative phenotype. The most aggressive cases of IDC are characterized by a high proliferation rate, a great propensity to metastasize, and their ability to resist to standard chemotherapy, hormone therapy, or HER2-targeted therapy. Using progression tissue microarrays, we here demonstrate that the serine/threonine kinase protein kinase D3 (PKD3) is highly upregulated in estrogen receptor (ER)–negative (ER−) tumors. We identify direct binding of the ER to the PRKD3 gene promoter as a mechanism of inhibition of PKD3 expression. Loss of ER results in upregulation of PKD3, leading to all hallmarks of aggressive IDC, including increased cell proliferation, migration, and invasion. This identifies ER− breast cancers as ideal for treatment with the PKD inhibitor CRT0066101. We show that similar to a knockdown of PKD3, treatment with this inhibitor targets all tumorigenic processes in vitro and decreases growth of primary tumors and metastasis in vivo. Our data strongly support the development of PKD inhibitors for clinical use for ER− breast cancers, including the triple-negative phenotype. Mol Cancer Ther; 14(6); 1306–16. ©2015 AACR.
Selective Delivery of PEGylated Compounds to Tumor Cells by Anti-PEG Hybrid Antibodies
Authors: Tung Hsin-Yi , Su Yu-Cheng , Chen Bing-Mae , Burnouf Pierre-Alain , Huang Wei-Chiao , Chuang Kuo-Hsiang , Yan Yu-Ting , Cheng Tian-Lu , Roffler Steve R.
Published: April 2015

Polyethylene glycol (PEG) is attached to many peptides, proteins, liposomes, and nanoparticles to reduce their immunogenicity and improve their pharmacokinetic and therapeutic properties. Here, we describe hybrid antibodies that can selectively deliver PEGylated medicines, imaging agents, or nanomedicines to target cells. Human IgG1 hybrid antibodies αPEG:αHER2 and αPEG:αCD19 were shown by ELISA, FACS, and plasmon resonance to bind to both PEG and HER2 receptors on SK-BR-3 breast adenocarcinoma and BT-474 breast ductal carcinoma cells or CD19 receptors on Ramos and Raji Burkitt's lymphoma cells. In addition, αPEG:αHER2 specifically targeted PEGylated proteins, liposomes, and nanoparticles to SK-BR-3 cells that overexpressed HER2, but not to HER2-negative MCF-7 breast adenocarcinoma cells. Endocytosis of PEGylated nanoparticles into SK-BR-3 cells was induced specifically by the αPEG:αHER2 hybrid antibody, as observed by confocal imaging of the accumulation of Qdots inside SK-BR-3 cells. Treatment of HER2+ SK-BR-3 and BT-474 cancer cells with αPEG:αHER2 and the clinically used chemotherapeutic agent PEGylated liposomal doxorubicin for 3 hours enhanced the in vitro effectiveness of PEGylated liposomal doxorubicin by over two orders of magnitude. Hybrid anti-PEG antibodies offer a versatile and simple method to deliver PEGylated compounds to cellular locations and can potentially enhance the therapeutic efficacy of PEGylated medicines. Mol Cancer Ther; 14(6); 1317–26. ©2015 AACR.
Animal Eye Models for Uveal Melanoma
Authors: Cao Jinfeng , Jager Martine J.
Published: April 2015

Animal models play an important role in understanding tumor growth and may be used to develop novel therapies against human malignancies. The significance of the results from animal experiments depends on the selection of the proper model. Many attempts have been made to create appropriate animal models for uveal melanoma and its characteristic metastatic behavior. One approach is to use transgenic animal models or to implant tumor cells. A variety of tumor types have been used for this purpose: tumor cells, such as Greene melanoma, murine B16 melanoma, and human uveal melanoma cells, may be implanted in the eyes of hamsters, rats, rabbits, and mice, among others. Various inoculation routes, including into the anterior chamber and posterior compartment, and retro-orbitally, have been applied to obtain tumor growth mimicking ocular uveal melanoma. However, when we choose animal models, we must be conscious of many disadvantages, such as variable tumor growth, or the need for immunosuppression in xenogeneic grafts. In this paper, we will discuss the various eye models.
Transgenic Models in Retinoblastoma Research
Authors: Nair Rohini M. , Vemuganti Geeta K.
Published: April 2015

Understanding the mechanism of retinoblastoma (Rb) tumor initiation, development, progression and metastasis in vivo mandates the use of animal models that mimic this intraocular tumor in its genetic, anatomic, histologic and ultrastructural features. An early setback for developing mouse Rb models was that Rb mutations did not cause tumorigenesis in murine retinas. Subsequently, the discovery that the p107 protein takes over the role of pRb in mice led to the development of several animal models that phenotypically and histologically resemble the human form. This paper summarizes the transgenic models that have been developed over the last three decades.
Intraocular Lymphoma Models
Authors: Aronow Mary E. , Shen Defen , Hochman Jacob , Chan Chi-Chao
Published: April 2015

Primary vitreoretinal lymphoma (PVRL) is a subtype of primary central nervous system lymphoma (PCNSL), a high-grade, extranodal, non-Hodgkin's lymphoma, predominantly of B-cell origin. PVRL is an aggressive disease with a poor prognosis. Human studies are not ideally suited for the study of intraocular lymphoma pathogenesis or treatment strategies due to the rare nature of the disease, its variable presentation, limited volume of available ocular fluids, and fragility of sampled lymphoma cells. Animal models have been critical in making progress in understanding intraocular lymphoma pathogenesis and investigating potential therapeutic strategies. Early murine models for intraocular lymphoma used intraperitoneal injection of mouse T-cell lymphomas. This was followed by intravitreal T-cell murine models. More recent murine models have used B-cell lymphomas to more closely mimic human disease. The most current B-cell lymphoma models employ a combined approach of inoculating both the mouse vitreous cavity and brain. The challenge in murine models for intraocular lymphoma lies in recreating the clinical features, disease behavior, molecular profile, systemic immunity, and the microenvironment observed in human disease. In the future, animal models will continue to be central to furthering our understanding of the disease and in the investigation of potential treatment targets.
Embryonic Zebrafish: Different Phenotypes after Injection of Human Uveal Melanoma Cells
Authors: van der Ent Wietske , Burrello Claudia , de Lange Mark J. , van der Velden Pieter A. , Jochemsen Aart G. , Jager Martine J. , Snaar-Jagalska B. Ewa
Published: April 2015

Although murine xenograft models for human uveal melanoma (UM) are available, they are of limited utility for screening large compound libraries for the discovery of new drugs. We need new preclinical models which can efficiently evaluate drugs that can treat UM metastases. The zebrafish embryonic model is ideal for drug screening purposes because it allows the investigation of potential antitumor properties of drugs within 1 week. The optical transparency of the zebrafish provides unique possibilities for live imaging of fluorescence-labelled cancer cells and their behavior. In addition, the adaptive immune response, which is responsible for the rejection of transplanted material, is not yet present in the early stages of fish development, and systemic immunosuppression is therefore not required to allow growth of tumor cells. We studied the behavior of UM cells following injection into zebrafish embryos and observed different phenotypes. We also analyzed cell migration, proliferation, formation of micrometastasis and interaction with the host microenvironment. Significant differences were noted between cell lines: cells derived from metastases showed more migration and proliferation than cells derived from the primary tumors. The addition of the c-Met inhibitor crizotinib to the water in which the larvae were kept reduced the migration and proliferation of UM cells expressing c-Met. This indicates the applicability of the zebrafish xenografts for testing novel inhibitory compounds and provides a fast and sensitive in vivo vertebrate model for preclinical drug screening to combat UM.
Dysfunctional Dopaminergic Neurones in Mouse Models of Huntington's Disease: A Role for SK3 Channels
Authors: Dallérac Glenn M. , Levasseur Grégoire , Vatsavayai Sarat C. , Milnerwood Austen J. , Cummings Damian M. , Kraev Igor , Huetz Chloé , Evans Karen A. , Walters Steve W. , Rezaie Payam , Cho Yoon , Hirst Mark C. , Murphy Kerry P.S.J.
Published: April 2015

Background: Huntington's disease (HD) is a late-onset fatal neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the gene coding for the protein huntingtin and is characterised by progressive motor, psychiatric and cognitive decline. We previously demonstrated that normal synaptic function in HD could be restored by application of dopamine receptor agonists, suggesting that changes in the release or bioavailability of dopamine may be a contributing factor to the disease process. Objective: In the present study, we examined the properties of midbrain dopaminergic neurones and dopamine release in presymptomatic and symptomatic transgenic HD mice. Methods and Results: Using intracellular sharp recordings and immunohistochemistry, we found that neuronal excitability was increased due to a loss of slow afterhyperpolarisation and that these changes were related to an apparent functional loss and abnormal distribution of SK3 channels (KCa2.3 encoded by the KCNN3 gene), a class of small-conductance calcium-activated potassium channels. Electrochemical detection of dopamine showed that this observation was associated with an enhanced dopamine release in presymptomatic transgenic mice and a drastic reduction in symptomatic animals. These changes occurred in the context of a progressive expansion in the CAG repeat number and nuclear localisation of mutant protein within the substantia nigra pars compacta. Conclusions: Dopaminergic neuronal dysfunction is a key early event in HD disease progression. The initial increase in dopamine release appears to be related to a loss of SK3 channel function, a protein containing a polyglutamine tract. Implications for polyglutamine-mediated sequestration of SK3 channels, dopamine-associated DNA damage and CAG expansion are discussed in the context of HD.
Towards an Ecumenical Theology of Religions through a Latin-American Lens
Authors: Ribeiro Claudio de Oliveira
Published: April 2015

This article reflects on how theology of religions needs to focus on two aspects when speaking of religious pluralism: the ability and capacity of religious groups to dialogue, and the challenges of human rights and inclusiveness. From the Latin-American theological context, the research was formulated around three topics: (i) the public importance of religion in both building peace as well as the promotion of justice, taking into account the importance of mysticism and otherness in the ecumenical formation of spiritualties and how they affect religious and social processes, allowing the emergence of new utopian, democratic and meaningful perspectives; (ii) the necessity of reshaping the theological lens with an intentional starting point in the realities of afro-indigenous cultures; and (iii) the contribution of feminist liberation theology to the debate of religious pluralism.
Réflexions critiques sur le statut juridique de la société en nom collectif en droit émirati à la lumière du droit français
Authors: Farah Ahmad Qasim
Published: April 2015

Cet article présente une analyse critique des dispositions actuelles sur la société en nom collectif, dans le cadre juridique des Émirats arabes unis. Il se limite, dans un premier temps, à mettre en exergue les faiblesses et imperfections législatives dans le droit émirati des sociétés commerciales concernant le cas particulier de la société en nom collectif et, dans un deuxième temps, à suggérer des solutions appropriées tout en profitant de l’expérience législative et jurisprudentielle française en la matière. Pour ce faire, nos réflexions seront axées d’une part, sur les critiques relatives à la substance de la société en nom collectif et d’autre part, sur celles qui concernent le fonctionnement de la société en nom collectif.
The Theory of ‘Promise’ (Waʿd) in Islamic Law
Authors: Abdullah Faruk , Rahman Asmak Ab
Published: April 2015

This article aims to clarify the concept of promise (waʿd) and questions whether a promise, albeit personal or transactional, is by nature binding on the promisor under Sharīʿah law. The term waʿd is also discussed in relation to other concepts involving promise: i.e., ʿaqd (contract), ʿahd (covenant or binding agreement), nudhur (vows), and juʿālah (payment for performing a service). A number of studies have concluded that waʿd is not obligatory on the promisor, unless the promisee incurs a loss due to a breach or deceptive promise. However, after reviewing the opinions of a number of classical Islamic scholars, this study concludes that under Sharīʿah law all promises are generally binding on the promisor, except in light of valid excuses or mitigating circumstances.
SPIELEN UND ZUSCHAUEN IN JAKOB BIDERMANNS PHILEMON MARTYR
Authors: Hagens Jan L.
Published: April 2015

Jacob Bidermann's (1578-1639) Jesuit drama, Philemon Martyr (1618), presents the world as a theater, not only within its plot, but also through structural and stylistic features. Ironically, precisely because of his dubious profession, the pagan comedian Philemon, as he plays a Christian, is granted , and grasps, the chance to convert. Though his perfect model may inspire the audience, Philemon can effect the play's moral only in tandem with Arrianus, his antagonist, who turns from pagan spectator to Christian actor: it is Arrianus' more realistic role conversion which assures the spectator that salvation is actually within reach. Through the ideas of play-acting and play-watching, Bidermann illustrates the Jesuit view, not only of secular theater and society, but also of religion, human nature, and our appropriate role in life. Going beyond a scena vitae, which would merely focus on human performance, the play constructs a more complex theatrum mundi, which includes divine director and spectator. In terms of dramatic genre, Bidermann advocates tragicomedy , in terms of attitude, a contemptus mundi. As school theater, Philemon Martyr provides an antidote to the rigid Jesuit conception of education, activating the students through a playful version of pedagogy.
DES MARTIN OPITZ EPICEDIUM AUF ERZHERZOG KARL VON 6STERREICH
Authors: Ludwig Walther
Published: April 2015

Als Specimen des von mehreren Mitarbeitem vorbereiteten Opitius Latinus, einer kommentierten Ausgabe der von Martin Opitz verfaßten lateinischen Texte, wird das lateinische Epicedium auf Erzherzog Karl von Österreich (1590-1624) ediert, übersetzt und unter Beachtung seiner Bezüge zur zeigenössischen Trauerdichtung und zur antiken Literatur interpretiert und dabei gezeigt, wie Opitz die konventioneilen Themen Trauer und Trost hier zu einem Panegyricus auf das mit Gott verbundene, weltbeherrschende und ideologisch an die antiken Kaiser anknüpfende Haus Österreich instrumentalisierte.
JOHANN GERHARD (1582-1637) UND EIN FORSCHUNGSPROJEKT
Authors: Steiger Johann Anselm
Published: April 2015

Innerhalb des Projektes "Johann Gerhard (1582-1637)" sind u.a. erstmals historisch-kritische Editionen von Schriften eines der bedeutendsten protestantischen Theologen des 17. Jahrhunderts erarbeitet worden. Darüber hinaus wurde eine umfangreiche Bibliographie sämtlicher Druckschriften Gerhards erstellt, die neben dem Kleinschrifttum auch Neuauflagen aller Werke bis in die Gegenwart berücksichtigt. Zudem wurde die Rekonstruktion der Bibliotheca Gerhardina, einer ihrem Charakter nach einmaligen Gelehrtenbibliothek, zum Abschluß gebracht. Somit ist ein Teilstück der in den vergangenen Jahren zunehmend in Gang kommenden Erforschung des barocken Luthertums und damit der Epoche zwischen der Reformationszeit und dem Pietismus geleistet worden.
DIE MUSEN ALS LEXIKOGRAPHEN
Authors: Kaminski Nicola
Published: April 2015

Johann Heinrich Zedlers Universal-Lexicon, von buch- und verlags geschichtlicher
Seite aus erschöpfend untersucht, ist der Literaturwissenschaft bislang nicht zum Problem geworden. Und doch ist es 'der Zedler' selbst, der seine Selbstlegitimierung auf das Feld der poetologischen Diskussion verschiebt, indem die Mitarbeiter des Lexikons als "die IX. Musen" vorgestellt werden. Rhetorisch scheint damit zweierlei gewonnen: daß Musen nicht einfach aus fremden Büchern abschreiben, versteht sich von selbst, und zudem bietet die imitatio-orientierte Poetik der Zeit für 'musisches Schreiben' sogar eine legitime Form des' Abschreibens'. Tatsächlich ist jedoch das Problem einer Begründung universallexikographischen Schreibens nicht aus der Welt. Daß 'der Zedler' dieses Dilemma in der le)(ikographischen Textur performativ in Szene setzt, soll die Analyse ausgewählter Lexikonartikel erweisen. Sichtbar wird in einer solchen poetischen Lektüre eine lexikographische Autoreflexivität, deren Radikalität sich in pragmatischer Perspektive am Rande des Kriminellen bewegt, überraschenderweise aber in Diderot und seiner Encyclopédie einen Komplizen findet.
"ES WERD NU WOL ZEIT, DAS SI WARTET, WAS EINEM FRUMEN EE WEIB ZU STUND"
Authors: Woodford Charlotte
Published: April 2015

When analysing women's literary activity, it is easy to overlook the fact that most writing by women was never destined for publication. Women wrote only a very small percentage of the printed pamphlets of the 1520s. However, there is much to suggest that they took issue with Reformation ideas in the letters they were accustomed to writing to family and friends. Nuns' families used letters to try to convert nuns to Lutheranism and persuade them to leave their convents. Four pamphlets containing letters to and from nuns suggest that such family debates could become polemical in nature. The reason why 'private' letters were printed are examined in this article, as weil as the different positions of the writers and recipients.
TEXTE UND TEXTILIEN
Authors: Schulz Armin
Published: April 2015

Die Liebesromane des 15. und 16. Jahrhunderts verlagern das erotische Begehren vom Körperlichen ins Kognitive. Im Zentrum des Begehrens steht nicht mehr der Körper des anderen, sondern das sichere Wissen über seine Liebe: Liebeshandlungen werden als semiotische Prozesse inszeniert, als Spiele von Zeichen und Interpretationen, die in Wickrams Goldfaden zugleich auf einer poetologischen Ebene lesbar werden.
PATRIOTISM AND THE PROMOTION OF GERM AN LANGUAGE AND CULTURE
Authors: Mast Thomas
Published: April 2015

The year 1642 constitutes a dernonstrable shift in the literary career of Johann Rist (1607-1667). With his Rettung der Edlen Teutschen Hauptsprache Rist joined the discourse about the national vernacular language as prornoted by the Fruchtbringende Gesellschaft, taking a firm stand against foreign corruption of German language and culture. A cornparison between Rist's text and that of Carl Gustav von Hille's Der Teutsche Palmbaum (1647), a history of the Fruchtbringende Gesellschaft, shows that both writers share sirnilar ideas and concerns. Although Rist was not yet a distinguished poet when his Rettung der Edlen Teutschen Hauptsprache was published, this text sheds light on the trajectory that his career was to follow both aesthetically and ideologically. Rist's Rettung der Edlen Teutschen Hauptsprache can thus be read in the context of his atternpt to gain the attention of, and to becorne accepted into, the Fruchtbringende Gesellschaft, an honor bestowed upon hirn in 1647.