bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-work-conserving effects in MapReduce
Authors: Tan Jian , Wang Yandong , Yu Weikuan , Zhang Li
Published: July 2014

Sequentially arriving jobs share a MapReduce cluster, each desiring a fair allocation of computing resources to serve its associated map and reduce tasks. The model of such a system consists of a processor sharing queue for the MapTasks and a multi-server queue for the ReduceTasks. These two queues are dependent through a constraint that the input data of each ReduceTask are fetched from the intermediate data generated by the MapTasks belonging to the same job. A more generalized form of MapReduce queueing model can capture the essence of other distributed data processing systems that contain interdependent processor sharing queues and multi-server queues.

Through theoretical modeling and extensive experiments, we show that, this dependence, if not carefully dealt with, can cause non-work-conserving effects that negatively impact system performance and scalability. First, we characterize the heavy-traffic approximation. Depending on how tasks are scheduled, the number of jobs in the system can even exhibit jumps in diffusion limits, resulting in prolonged job execution times. This problem can be mitigated through carefully applying a tie-breaking rule for ReduceTasks, which as a theoretical finding has direct engineering implications. Second, we empirically validate a criticality phenomenon using experiments. MapReduce systems experience an undesirable performance degradation when they have reached certain critical points, another finding that offers fundamental guidance on managing MapReduce systems.
IntroPerf
Authors: Kim Chung Hwan , Rhee Junghwan , Zhang Hui , Arora Nipun , Jiang Guofei , Zhang Xiangyu , Xu Dongyan
Published: July 2014

Performance bugs are frequently observed in commodity software. While profilers or source code-based tools can be used at development stage where a program is diagnosed in a well-defined environment, many performance bugs survive such a stage and affect production runs. OS kernel-level tracers are commonly used in post-development diagnosis due to their independence from programs and libraries; however, they lack detailed program-specific metrics to reason about performance problems such as function latencies and program contexts. In this paper, we propose a novel performance inference system, called IntroPerf, that generates fine-grained performance information -- like that from application profiling tools -- transparently by leveraging OS tracers that are widely available in most commodity operating systems. With system stack traces as input, IntroPerf enables transparent context-sensitive performance inference, and diagnoses application performance in a multi-layered scope ranging from user functions to the kernel. Evaluated with various performance bugs in multiple open source software projects, IntroPerf automatically ranks potential internal and external root causes of performance bugs with high accuracy without any prior knowledge about or instrumentation on the subject software. Our results show IntroPerf's effectiveness as a lightweight performance introspection tool for post-development diagnosis.
Traffic congestion
Authors: Mandayam Chinmoy V. , Prabhakar Balaji
Published: July 2014

We develop two models of highway traffic: (i) a deterministic fluid model based on conservation laws building on previous work and (ii) a mean-field model of a series of infinite server queues, where each stage in the tandem models a segment of highway. The models define the ``highway-map''---a transformation of time-varying arrival rate functions according to which vehicles arrive at the highway to the corresponding departure rate functions of vehicles exiting the highway. The two models are shown to be equivalent in that they obtain the same highway-map. The cost of congestion for vehicles traversing the highway is the total extra time they spend on the highway due to congestion. This cost is shown to be equal to the ``d-bar'' distance between the input and the output rate measures of the highway-map. This fact is used to formulate a convex optimization problem for determining the optimal way to shift users from peak to off-peak hours using incentives so that congestion costs are lowered.
Optimal energy source selection and capacity planning for green datacenters
Authors: Kong Fanxin , Liu Xue , Rao Lei
Published: July 2014

To reduce cost and emission, modern datacenter operators are beginning to incorporate green energy sources into datacenters' power supply. To improve service availability, they also back up datacenters using traditional (usually brown) energy sources. However, challenge arises due to distinct characteristics of energy sources used for different goals. How to select optimal energy sources and plan their capacity for datacenters to meet cost, emission and service availability requirement remains an open research problem. In this extended abstract, we briefly describe recent work in [4], which provides a holistic solution to address this problem. In [4], we present GreenPlanning, a framework to strike a judicious balance among multiple energy sources, the electrical grid and energy storage devices for a datacenter in terms of cost, emission, and service availability. GreenPlanning explores different features and operations of both green and traditional energy sources available to datacenters. The framework minimizes the lifetime total cost including both capital and operational cost for a datacenter. We conduct extensive experiments to evaluate GreenPlanning with real-life computational workload and meteorological data traces. Results demonstrate that GreenPlanning can reduce the lifetime total cost and emission by more than 50% compared to traditional configurations without integration of green energy, while still meeting service availability requirement.
Multi-source multipath HTTP (mHTTP)
Authors: Kim Juhoon , Chen Yung-Chih , Khalili Ramin , Towsley Don , Feldmann Anja
Published: July 2014

Today, most devices have multiple network interfaces. Coupled with wide-spread replication of popular content at multiple locations, this provides substantial path diversity in the Internet. We propose Multi-source Multipath HTTP, mHTTP, which takes advantage of all existing types of path diversity in the Internet. mHTTP needs only client-side but not server-side or network modifications as it is a receiver-oriented mechanism. Moreover, the modifications are restricted to the socket interface. Thus, no changes are needed to the applications or to the kernel.
Online algorithms for joint application-VM-physical-machine auto-scaling in a cloud
Authors: Guo Yang , Stolyar Alexander L. , Walid Anwar
Published: July 2014

We develop
shadow routing
based online algorithms for the joint problem of application-to-VM and VM-to-PM assignments in a cloud environment. The asymptotic optimality of the shadow algorithm is proved and the performance is evaluated by simulations.
Measuring throughput of data center network topologies
Authors: Jyothi Sangeetha Abdu , Singla Ankit , Godfrey P. Brighten , Kolla Alexandra
Published: July 2014

High throughput is a fundamental goal of network design. While myriad network topologies have been proposed to meet this goal, particularly in data center and HPC networking, a consistent and accurate method of evaluating a design's throughput performance and comparing it to past proposals is conspicuously absent. In this work, we develop a framework to benchmark the throughput of network topologies and apply this methodology to reveal insights about network structure. We show that despite being commonly used, cut-based metrics such as bisection bandwidth are the wrong metrics: they yield incorrect conclusions about the throughput performance of networks. We therefore measure flow-based throughput directly and show how to evaluate topologies with nearly-worst-case traffic matrices. We use the flow-based throughput metric to compare the throughput performance of a variety of computer networks. We have made our evaluation framework freely available to facilitate future work on design and evaluation of networks.
A framework for extensible languages
Authors: Erdweg Sebastian , Rieger Felix
Published: July 2014

Extensible programming languages such as SugarJ or Racket enable programmers to introduce customary language features as extensions of the base language. Traditionally, systems that support language extensions are either (i) agnostic to the base language or (ii) only support a single base language. In this paper, we present a framework for language extensibility that turns a non-extensible language into an extensible language featuring library-based extensible syntax, extensible static analyses, and extensible editor support. To make a language extensible, our framework only requires knowledge of the base language's grammar, the syntax for import statements (which activate extensions), and how to compile base-language programs. We have evaluated the generality of our framework by instantiating it for Java, Haskell, Prolog, JavaScript, and System F
ω
, and by studying existing module-system features and their support in our framework.
Protein Homeostasis at the Plasma Membrane
Authors: Apaja Pirjo M. , Lukacs Gergely L.
Published: July 2014

The plasma membrane (PM) and endocytic protein quality control (QC) in conjunction with the endosomal sorting machinery either repairs or targets conformationally damaged membrane proteins for lysosomal/vacuolar degradation. Here, we provide an overview of emerging aspects of the underlying mechanisms of PM QC that fulfill a critical role in preserving cellular protein homeostasis in health and diseases.
Vitamin D Signaling in Myogenesis: Potential for Treatment of Sarcopenia
Authors: Wagatsuma Akira , Sakuma Kunihiro
Published: July 2014

Muscle mass and strength progressively decrease with age, which results in a condition known as sarcopenia. Sarcopenia would lead to physical disability, poor quality of life, and death. Therefore, much is expected of an effective intervention for sarcopenia. Epidemiologic, clinical, and laboratory evidence suggest an effect of vitamin D on muscle function. However, the precise molecular and cellular mechanisms remain to be elucidated. Recent studies suggest that vitamin D receptor (VDR) might be expressed in muscle fibers and vitamin D signaling via VDR plays a role in the regulation of myoblast proliferation and differentiation. Understanding how vitamin D signaling contributes to myogenesis will provide a valuable insight into an effective nutritional strategy to moderate sarcopenia. Here we will summarize the current knowledge about the effect of vitamin D on skeletal muscle and myogenic cells and discuss the potential for treatment of sarcopenia.
Efficiency and Droop Improvement in GaN-Based High-Voltage Flip Chip LEDs
Authors: Chiang Yen-Chih , Lin Bing-Cheng , Chen Kuo-Ju , Chiu Sheng-Huan , Lin Chien-Chung , Lee Po-Tsung , Shih Min-Hsiung , Kuo Hao-Chung
Published: July 2014

The GaN-based high-voltage flip chip light-emitting diode (HVFC-LED) is designed and developed for the purpose of efficiency enhancement. In our design, the distributed Bragg reflector (DBR) is deposited at the bonded substrate to increase the light extraction. After the flip chip process, the general current-voltage characteristics between the flip chip sample and the traditional sample are essentially the same. With the help of great thermal conductive silicon substrate and the bottom DBR, the HVFC-LED is able to enhance the power by 37.1% when compared to the traditional high-voltage LEDs. The wall-plug efficiencies of the HVFC-LED also show good droop reduction as high as 9.9% compared to the traditional devices.
Different Effects of Implanting Sensory Nerve or Blood Vessel on the Vascularization, Neurotization, and Osteogenesis of Tissue-Engineered Bone In Vivo
Authors: Fan Jun-jun , Mu Tian-wang , Qin Jun-jun , Bi Long , Pei Guo-xian
Published: July 2014

To compare the different effects of implanting sensory nerve tracts or blood vessel on the osteogenesis, vascularization, and neurotization of the tissue-engineered bone in vivo, we constructed the tissue engineered bone and implanted the sensory nerve tracts (group SN), blood vessel (group VB), or nothing (group Blank) to the side channel of the bone graft to repair the femur defect in the rabbit. Better osteogenesis was observed in groups SN and VB than in group Blank, and no significant difference was found between groups SN and VB at 4, 8, and 12 weeks postoperatively. The neuropeptides expression and the number of new blood vessels in the bone tissues were increased at 8 weeks and then decreased at 12 weeks in all groups and were highest in group VB and lowest in group Blank at all three time points. We conclude that implanting either blood vessel or sensory nerve tract into the tissue-engineered bone can significantly enhance both the vascularization and neurotization simultaneously to get a better osteogenesis effect than TEB alone, and the method of implanting blood vessel has a little better effect of vascularization and neurotization but almost the same osteogenesis effect as implanting sensory nerve.
Prophylactic Efficacy of Melatonin on Cyclophosphamide-Induced Liver Toxicity in Mice
Authors: Shokrzadeh Mohammad , Ahmadi Amirhossein , Naghshvar Farshad , Chabra Aroona , Jafarinejhad Mehdi
Published: July 2014

The current study aimed to evaluate the protective effects of melatonin, a pineal secretory product, against hepatotoxicity induced by cyclophosphamide (CP) in mice. Mice were pretreated with melatonin intraperitoneally for 7 consecutive days before the administration of a single intraperitoneal dose of 200 mg/kg CP. 24 hr after CP administration, the mice were anesthetized, blood was then removed, and serum toxicity enzymes activities were evaluated. After the blood sampling, all animals were killed, livers were then removed, and histological studies were conducted. Serum toxicity marker enzymes were significantly increased after CP treatment but restored in melatonin pretreated groups. In addition, administration of CP induced necrotic hepatocyte with small crushed nuclei, portal space with severe inflammation, and hepatocytes surrounded by lymphocytic infiltration in hepatic tissues. However, melatonin effectively protected against CP-induced histopathological abnormalities in the liver tissues. Our results reveal that melatonin produces a potent hepatoprotective mechanism against CP. Therefore, melatonin could be a potent candidate to use concomitantly as a supplement agent against hepatotoxicity of CP for the patients undergoing chemotherapy.
Intensified Adjuvant Treatment of Prostate Carcinoma: Feasibility Analysis of a Phase I/II Trial
Authors: Mantini Giovanna , Fersino Sergio , Alitto Anna Rita , Frascino Vincenzo , Massaccesi Mariangela , Fionda Bruno , Iorio Vincenzo , Luzi Stefano , Balducci Mario , Mattiucci Gian Carlo , Di Nardo Francesco , De Belvis Antonio , Morganti Alessio Giuseppe , Valentini Vincenzo
Published: July 2014

Purpose. To perform a preliminary feasibility acute and late toxicity evaluation of an intensified and modulated adjuvant treatment in prostate cancer (PCa) patients after radical prostatectomy.Material and Methods. A phase I/II has been designed. Eligible patients were 79 years old or younger, with an ECOG of 0–2, previously untreated, histologically proven prostate adenocarcinoma with no distant metastases, pT2–4 N0-1, and with at least one of the following risk factors: capsular perforation, positive surgical margins, and seminal vesicle invasion. All patients received a minimum dose on tumor bed of 64.8 Gy, or higher dose (70.2 Gy; 85.4%), according to the pathological stage, pelvic lymph nodes irradiation (57.7%), and/or hormonal therapy (69.1%).Results. 123 patients were enrolled and completed the planned treatment, with good tolerance. Median follow-up was 50.6 months. Grade 3 acute toxicity was only 2.4% and 3.3% for genitourinary (GU) and gastrointestinal (GI) tract, respectively. No patient had late grade 3 GI toxicity, and the GU grade 3 toxicity incidence was 5.8% at 5 years. 5-year BDSF was 90.2%.Conclusions. A modulated and intensified adjuvant treatment in PCa was feasible in this trial. A further period of observation can provide a complete assessment of late toxicity and confirm the BDSF positive results.
Identification of a Novel Methylated Gene in Nasopharyngeal Carcinoma: TTC40
Authors: Ayadi Wajdi , Allaya Nesrine , Frikha Hanèn , Trigui Emna , Khabir Abdelmajid , Ghorbel Abdelmonem , Daoud Jamel , Frikha Mounir , Gargouri Ali , Mokdad-Gargouri Raja
Published: July 2014

To further explore the epigenetic changes in nasopharyngeal carcinoma (NPC), methylation-sensitive arbitrarily primed PCR was performed on NPC biopsies and nontumor nasopharyngeal samples. We have shown mainly two DNA fragments that appeared to be differentially methylated in NPCs versus nontumors. The first, defined as hypermethylated, corresponds to a CpG island at the 5′-end of the tetratricopeptide repeat domain 40 (TTC40) gene, whereas the second, defined as hypo-methylated, is located on repetitive sequences at chromosomes 16p11.1 and 13.1. Thereafter, the epigenetic alteration on the 5′-TTC40 gene was confirmed by methylation-specific PCR, showing a significant aberrant methylation in NPCs, compared to nontumors. In addition, the bisulfite sequencing analysis has shown a very high density of methylated cytosines in C15, C17, and X666 NPC xenografts. To assess whether TTC40 gene is silenced by aberrant methylation, we examined the gene expression by reverse transcription-PCR. Our analysis showed that the mRNA expression was significantly lower in tumors than in nontumors, which is associated with 5′-TTC40 gene hypermethylation. In conclusion, we found that the 5′-TTC40 gene is frequently methylated and is associated with the loss of mRNA expression in NPCs. Hypermethylation of 5′-TTC40 gene might play a role in NPC development; nevertheless, other studies are needed.
Endoscopic Measurement of Polyp Size Using a Novel Calibrated Hood
Authors: Kume Keiichiro , Watanabe Tatsuyuki , Yoshikawa Ichiro , Harada Masaru
Published: July 2014

Background. Although the size of colon polyps is an important risk factor for colorectal cancer, a standardized measurement technique has yet to be determined. In clinical practice, most endoscopists estimate polyp size by uncertain visual estimation; however, colonoscopic polypectomy is indicated for adenomatous polyps more than 5 mm in diameter. We have therefore developed a novel calibrated hood that enables accurate measurement of polyp size during colonoscopy.Method. We compared prepolypectomy estimates using the calibrated hood against measurements of preformalin-fixed samples immediately after polypectomy.Results. Sixty-five polyps removed from 44 patients were included in the present study. The mean size of polyps was significantly larger at prepolypectomy (6.06 ± 1.23 mm) than after polypectomy (5.48 ± 1.31 mm,P<0.05).Conclusion. Accurately measuring the size of polyps during colonoscopy is important, since polyps are shrunk by polypectomy. Attaching the calibrated hood appears useful in the measurement of polyp size to determine indications for polypectomy in patients with colon polyps.
Development and Validation of Stability Indicating LC-PDA Method for Mycophenolate Mofetil in Presence of Mycophenolic Acid and Its Application for Degradation Kinetics and pH Profile Study
Authors: Choudhari Vishnu P. , Nikalje Anna Pratima G.
Published: July 2014

Factorial design tool applied for development of isocratic reversed-phase stability-indicating HPLC method for the analysis of mycophenolate mofetil (MMF) and its degradation products. MMF stress degradation products mycophenolate acid (MPA) and DP3 (USP impurity H) were isolated and used for quantitation. Separation achieved on a Symmetry C18 (250 mm × 4.6 mm, 5.0 μ) column using a methanol: acetate buffer (75 : 25 v/v), pH 6.0 (adjusted with acetic acid), at 0.5 mL flow rate, column maintained at 55°C, and data integrated at 251 nm. MMF is subjected to hydrolysis, oxidation, heat degradation, and so forth; under all these conditions degraded products are well separated. The method validation characteristics included accuracy, precision, linearity, range, specificity, and sensitivity. Robustness testing is conducted to evaluate the effect of minor changes to the chromatographic conditions and to establish appropriate system suitability parameters. The proposed method is used to investigate kinetics of acid, alkali hydrolysis and oxidation process. Major degradation products MPA and DP3 were isolated and quantitated. Characterization of MPA by NMR and LC-MS/MS and other degraded products by LC-MS/MS is attempted successfully. The method is used successfully for the quality assessment of three MMF drug commercial formations and its acid, alkali, and oxidative degradation kinetics study.
Antimicrobial and Antiproliferative Potential of Anadenanthera colubrina (Vell.) Brenan
Authors: Lima Rennaly de Freitas , Alves Érika Ponchet , Rosalen Pedro Luiz , Ruiz Ana Lúcia Tasca Gois , Teixeira Duarte Marta Cristina , Góes Vivian Fernandes Furletti , de Medeiros Ana Cláudia Dantas , Pereira Jozinete Vieira , Godoy Gustavo Pina , Melo de Brito Costa Edja Maria
Published: July 2014

The aim of the present study was to perform an in vitro analysis of the antimicrobial and antiproliferative potential of an extract from Anadenanthera colubrina (Vell.) Brenan (angico) and chemically characterize the crude extract. Antimicrobial action was evaluated based on the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration, and the inhibition of formation to oral biofilm. Cell morphology was determined through scanning electron microscopy (SEM). Six strains of tumor cells were used for the determination of antiproliferative potential. The extract demonstrated strong antifungal activity against Candida albicans ATCC 18804 (MIC = 0.031 mg/mL), with similar activity found regarding the ethyl acetate fraction. The extract and active fraction also demonstrated the capacity to inhibit the formation of Candida albicans to oral biofilm after 48 hours, with median values equal to or greater than the control group, but the difference did not achieve statistical significance (P > 0.05). SEM revealed alterations in the cell morphology of the yeast. Regarding antiproliferative activity, the extract demonstrated cytostatic potential in all strains tested. The present findings suggest strong antifungal potential for Anadenanthera colubrina (Vell.) Brenan as well as a tendency toward diminishing the growth of human tumor cells.
IL15RA Drives Antagonistic Mechanisms of Cancer Development and Immune Control in Lymphocyte-Enriched Triple-Negative Breast Cancers
Authors: Marra Pierfrancesco , Mathew Sumi , Grigoriadis Anita , Wu Yin , Kyle-Cezar Fernanda , Watkins Johnathan , Rashid Mamunur , De Rinaldis Emanuele , Hessey Sonya , Gazinska Patrycja , Hayday Adrian , Tutt Andrew
Published: July 2014

Despite its aggressive nature, triple-negative breast cancer (TNBC) often exhibits leucocyte infiltrations that correlate with favorable prognosis. In this study, we offer an explanation for this apparent conundrum by defining TNBC cell subsets that overexpress the IL15 immune receptor IL15RA. This receptor usually forms a heterotrimer with the IL2 receptors IL2RB and IL2RG, which regulates the proliferation and differentiation of cytotoxic T cells and NK cells. However, unlike IL15RA, the IL2RB and IL2RG receptors are not upregulated in basal-like TNBC breast cancer cells that express IL15RA. Mechanistic investigations indicated that IL15RA signaling activated JAK1, STAT1, STAT2, AKT, PRAS40, and ERK1/2 in the absence of IL2RB and IL2RG, whereas neither STAT5 nor JAK2 were activated. RNAi-mediated attenuation of IL15RA established its role in cell growth, apoptosis, and migration, whereas expression of the IL15 cytokine in IL15RA-expressing cells stimulated an autocrine signaling cascade that promoted cell proliferation and migration and blocked apoptosis. Notably, coexpression of IL15RA and IL15 was also sufficient to activate peripheral blood mononuclear cells upon coculture in a paracrine signaling manner. Overall, our findings offer a mechanistic explanation for the paradoxical association of some high-grade breast tumors with better survival outcomes, due to engagement of the immune stroma. Cancer Res; 74(17); 4908–21. ©2014 AACR.
Infusions of Allogeneic Natural Killer Cells as Cancer Therapy
Authors: Leung Wing
Published: July 2014

Natural killer (NK) cells are normal white blood cells capable of killing malignant cells without prior sensitization. Allogeneic NK cell infusions are attractive for cancer therapy because of non–cross-resistant mechanisms of action and minimal overlapping toxicities with standard cancer treatments. Although NK therapy is promising, many obstacles will need to be overcome, including insufficient cell numbers, failure of homing to tumor sites, effector dysfunction, exhaustion, and tumor cell evasion. Capitalizing on the wealth of knowledge generated by recent NK cell biology studies and the advancements in biotechnology, substantial progress has been made recently in improving therapeutic efficiency and reducing side effects. A multipronged strategy is essential, including immunogenetic-based donor selection, refined NK cell bioprocessing, and novel augmentation techniques, to improve NK function and to reduce tumor resistance. Although data from clinical trials are currently limited primarily to hematologic malignancies, broader applications to a wide spectrum of adult and pediatric cancers are under way. The unique properties of human NK cells open up a new arena of novel cell-based immunotherapy against cancers that are resistant to contemporary therapies. Clin Cancer Res; 20(13); 3390–400. ©2014 AACR.
GSK-3β–Regulated N-Acetyltransferase 10 Is Involved in Colorectal Cancer Invasion
Authors: Zhang Hong , Hou Wei , Wang Hua-Li , Liu Hai-Jing , Jia Xin-Ying , Zheng Xing-Zheng , Zou Yong-Xin , Li Xin , Hou Lin , McNutt Michael A. , Zhang Bo
Published: July 2014

Purpose: NAT10 (N-acetyltransferase 10) is a nucleolar protein, but may show subcellular redistribution in colorectal carcinoma. In this study, we evaluated membranous staining of NAT10 in colorectal carcinoma and its clinical implications, and explored the mechanism of regulation of NAT10 redistribution.

Experimental Design: The expression and subcellular redistribution of NAT10, β-catenin, E-cadherin, and GSK-3β were evaluated by immunohistochemistry in 222 cases of colorectal carcinoma. Regulation of NAT10 and its influence on cell motility were analyzed with inhibitors of GSK-3β, transfection of wild-type or kinase-inactivated GSK-3β, or expression of various domains of NAT10, and evaluated with immunofluorescence, Western blotting, and Transwell assays.

Results: NAT10 localized mainly in the nucleoli of normal tissues, and was redistributed to the membrane in cancer cells, particularly at the invasive “leading edge” of the tumor. This correlated well with nuclear accumulation of β-catenin (P < 0.001; χ2 = 68.213). In addition, NAT10 membrane staining reflected the depth of invasion and tendency to metastasize (all P values < 0.001), and was associated with a poorer prognosis (P = 0.023; χ2 = 5.161). Evaluation of the mechanism involved demonstrated that subcellular redistribution of NAT10 may result from its increased stability and nuclear export, which is brought about by inhibition of GSK-3β. Moreover, redistribution of NAT10 induces alteration of cytoskeletal dynamics and increases cancer cell motility.

Conclusion: The subcellular redistribution of NAT10 can be induced by decreases in GSK-3β activity. This redistribution increases cancer cell motility, and is, thus, correlated with invasive potential and poorer clinical outcome. This finding suggests that NAT10 may be a useful prognostic marker and potential therapeutic target in colorectal carcinoma. Clin Cancer Res; 20(17); 4717–29. ©2014 AACR.
Combined Screening for Serum Anti-Nuclear and Anti-Aquaporin-4 Antibodies Improves Diagnostic Accuracy for Distinguishing Neuromyelitis Optica from Multiple Sclerosis
Authors: Wu Lei , Huang Dehui , Yang Yang , Wu Weiping
Published: July 2014

Background/Aims: Neuromyelitis optica spectrum disorders (NMOSDs) and multiple sclerosis (MS) are distinct clinical entities but are poorly distinguished by serum markers, including serum anti-aquaporin-4 (AQP4-Ab). We examined if testing for serum anti-nuclear antibodies (ANAs) and AQP4-Ab improved diagnostic sensitivity for NMOSDs. Methods: Chinese patients with NMOSDs (n = 74) or MS (n = 49) were screened for serum ANAs (all patients) and AQP4-Ab (58/74 NMOSDs and 45/49 MS patients). The NMOSDs group included patients with neuromyelitis optica (NMO; n = 53), recurrent longitudinally extensive transverse myelitis (rLETM; n = 20), and recurrent optic neuritis (n = 1). Results: The seroprevalence rate for ANAs was significantly higher in the NMOSDs group than the MS group (45.9 vs. 2%; p < 0.01). Similarly, AQP4-Ab seroprevalence was higher in NMOSDs than MS (56.9 vs. 4.4%; p < 0.01). Sensitivities and specificities for diagnosing NMOSDs were 51.7 and 97.8% using ANAs, 56.9 and 95.6% using AQP4-Ab, and 74.1 and 93.3% using both assays. Conclusion: Patients with NMO or rLETM had higher ANA seroprevalence than MS patients. Combined detection of both ANAs and AQP4-Ab improves the sensitivity of NMOSDs diagnosis without compromising specificity.
Height, Muscle, Fat and Bone Response to Growth Hormone in Short Children with Very Low Birth Weight Born Appropriate for Gestational Age and Small for Gestational Age
Authors: Berndt Cornelia , Schweizer Roland , Ranke Michael B. , Binder Gerhard , Martin David D.
Published: July 2014

Background/Aims: Growth hormone (GH) treatment is approved for short children born SGA but not for AGA. Our aim was to study the effect of GH in short VLBW SGA and AGA children. Methods: The study group comprised 44 prepubertal short children with a birth weight <1,500 g: 27 AGA (12 females) and 17 SGA (6 females). Mean values at GH start were (AGA, SGA): age 6.94, 7.14 years, height standard deviation score (SDS) -3.33, -3.33, and GH dose (mean ± SD) 54 ± 12, 51 ± 11 µg/kg/day. Arm and calf cross-sectional muscle area using peripheral quantitative computer tomography, body composition data using dual-energy X-ray absorptiometry and body impedance assessment, maximal isometric grip force and skin fold thickness, IGF-1 and IGFBP-3 were measured at the start and after 12 months of GH. Results: At GH start, both groups had similar characteristics with low height, weight, height velocity, muscle mass, bone thickness and content. The first year of GH treatment led to changes in muscle area SDS (AGA, SGA) -2.23 to -0.73 (p = 0.0010), -3.18 to -1.17 (p = 0.060) (AGA vs. SGA p = 0.61), fat area SDS -1.06 to -1.83 (p = 0.054), -0.62 to -1.75 (p = 0.12) (AGA vs. SGA p = 0.65) and height velocity SDS -0.0015 to 4.2 (p < 0.0001), -0.18 to 3.3 (p < 0.0001) (AGA vs. SGA p = 0.36). Conclusions: Growth, muscle and fat mass are similarly impaired in short prepubertal AGA and SGA VLBW children. The children born AGA show a similar or better response to GH compared to those born SGA. These results reveal the arbitrary nature of using the criterion ‘SGA' for eligibility to GH treatment in children born with a birth weight <1,500 g.
Apathy and Leukoaraiosis in Mild Cognitive Impairment and Alzheimer's Disease: Multicenter Diagnostic Criteria according to the Latest Studies
Authors: Sarabia-Cobo Carmen María , Pérez Victoria , Hermosilla Carmen , Nuñez María José , de Lorena Pablo
Published: July 2014

Aims: The aim is to study the prevalence and possible relationship of apathy and leukoaraiosis in cases of cognitive impairment of varying severity in Spain. Methods: We conducted a cross-sectional, descriptive, multicenter study involving 109 patients with Alzheimer's disease (AD) and 59 with mild cognitive impairment (MCI). Results: The older group with AD had a higher prevalence of leukoaraiosis and apathy, with significant differences compared to the MCI group. Conclusions: To our knowledge, this is the first multicenter study in our country that jointly analyzes the presence of apathy and leukoaraiosis in the institutionalized elderly with varying degrees of cognitive impairment according to the most recent criteria for detecting apathy in dementia.
Conjunctival Metastasis from Pleural Mesothelioma
Authors: Chung Andrew , Mudhar Hardeep Singh
Published: July 2014

Purpose of the Study: To describe the ophthalmic and pathological features of a conjunctival tumour in a 76-year-old male with terminal pleural mesothelioma who developed a rapidly growing mass on the bulbar conjunctiva. Procedures: The patient presented with a rapidly growing, pink nodule on the right nasal bulbar conjunctiva. His past medical history included biopsy-confirmed pleural malignant mesothelioma treated unsuccessfully with chemoradiotherapy. By the time he presented with his ocular signs, the systemic management plan was palliative. An incisional biopsy of the conjunctival lesion was performed, stained with haematoxylin and eosin and exposed to immunohistochemistry. Results: The histology showed a solid and pseudo-papillary tumour. The tumour was positive for cytokeratin (AE1/AE3), calretinin, WT1 and mesothelin, confirming metastatic mesothelioma to the conjunctiva. Conclusions and Message of the Paper: The clinical features mimicked metastatic carcinoma, and furthermore, the tumour's immunohistochemical positivity for cytokeratin could have led to an erroneous diagnosis of carcinoma rather than mesothelioma. The two key messages are (1) that metastatic mesothelioma can mimic metastatic carcinoma clinically and (2) that any cytokeratin-positive, rapidly growing conjunctival tumour with unusual morphology should be stained immunohistochemically with a mesothelioma panel to exclude metastatic mesothelioma.
Effects of a Long-Term Treatment With Aliskiren or Ramipril on Structural Alterations of Subcutaneous Small-Resistance Arteries of Diabetic Hypertensive Patients
Authors: De Ciuceis Carolina , Savoia Carmine , Arrabito Emanuele , Porteri Enzo , Mazza Monica , Rossini Claudia , Duse Sarah , Semeraro Francesco , Agabiti Rosei Claudia , Alonzo Alessandro , Sada Lidia , La Boria Elisa , Sarkar Annamaria , Petroboni Beatrice , Mercantini Paolo , Volpe Massimo , Rizzoni Damiano , Agabiti Rosei Enrico
Published: July 2014

Structural alterations of subcutaneous small-resistance arteries are associated with a worse clinical prognosis in hypertension and non–insulin-dependent diabetes mellitus. The effects of the direct renin inhibitor aliskiren on microvascular structure were never previously evaluated. Therefore, we investigated the effects of aliskiren in comparison with those of an extensively used angiotensin-converting enzyme inhibitor, ramipril, on peripheral subcutaneous small-resistance artery morphology, retinal arteriolar structure, and capillary density in a population of patients with non–insulin-dependent diabetes mellitus. Sixteen patients with mild essential hypertension and with a previous diagnosis of non–insulin-dependent diabetes mellitus were included in the study. Patients were then randomized to 1 of the 2 active treatments (aliskiren 150 mg once daily, n=9; or ramipril 5 mg once daily, n=7). Each patient underwent a biopsy of the subcutaneous fat from the gluteal region, an evaluation of retinal artery morphology (scanning laser Doppler flowmetry), and capillary density (capillaroscopy), at baseline and after 1 year of treatment. Subcutaneous small arteries were dissected and mounted on a pressurized micromyograph, and the media-to-lumen ratio was evaluated. A similar office blood pressure–lowering effect and a similar reduction of the wall-to-lumen ratio of retinal arterioles were observed with the 2 drugs. Aliskiren significantly reduced media-to-lumen ratio of subcutaneous small-resistance arteries, whereas ramipril-induced reduction of media to lumen ratio was not statistically significant. No relevant effect on capillary density was observed. In conclusion, treatment with aliskiren or ramipril was associated with a correction of microvascular structural alterations in patients with non–insulin-dependent diabetes mellitus.
Thresholds for Conventional and Home Blood Pressure by Sex and Age in 5018 Participants From 5 Populations
Authors: Nomura Kyoko , Asayama Kei , Thijs Lutgarde , Niiranen Teemu J. , Lujambio Inés , Boggia José , Hozawa Atsushi , Ohkubo Takayoshi , Hara Azusa , Johansson Jouni K. , Sandoya Edgardo , Kollias Anastasios , Stergiou George S. , Tsuji Ichiro , Jula Antti M. , Imai Yutaka , Staessen Jan A.
Published: July 2014

Whether blood pressure thresholds for hypertension should differ according to sex or age remains debated. We did a subject-level meta-analysis of 5018 people untreated for hypertension and randomly recruited from 5 populations (women, 56.7%; ≥60 years, 42.3%). We used multivariable-adjusted Cox regression and a bootstrap procedure to determine home blood pressure (HBP) levels yielding 10-year cardiovascular risks similar to those associated with established systolic/diastolic thresholds (140–160/80–100 mm Hg) for the conventional blood pressure (CBP). Conversely, we estimated CBP thresholds providing 10-year cardiovascular risks similar to those associated established HBP levels (125–135/80–85 mm Hg). All analyses were stratified for sex and age (<60 versus ≥60 years). During 8.3 years (median), 414 participants experienced a cardiovascular event. The sex differences between HBP thresholds derived from CBP and between CBP thresholds derived from HBP were all nonsignificant (
P
≥0.24), ranging from −4.6 to 3.6 mm Hg systolic and from −4.3 to 2.1 mm Hg diastolic. The age differences between HBP thresholds derived from CBP and between CBP thresholds derived from HBP ranged from −6.7 to 8.4 mm Hg systolic and from −1.9 to 1.7 mm Hg diastolic and were nonsignificant (
P
≥0.08), except for HBP thresholds derived from CBP levels of 140 mm Hg systolic and 80 mm Hg diastolic (
P
≤0.04). Sensitivity analyses based on cardiac or cerebrovascular complications were confirmatory. In conclusion, our findings based on outcome-driven criteria support contemporary guidelines that propose single blood pressure thresholds that can be indiscriminately applied in both sexes and across the age range.
The Evolution of Sin
Authors: Etzelmüller Gregor
Published: July 2014

The article develops a theological concept of the evolution of sin. In dialogue with evolutionary biology, the article clarifies how sin evolves out of the shadow side of creation. Therefore, we need to acknowledge how sin, already before the evolution of human beings, influences life. What this means for the understanding of human sin, is worked out in dialogue with evolutionary psychology on the one side and the Pauline understanding of flesh on the other side. From this perspective, sin appears as the human failure to live up to one’s divine calling by not transcending the evolutionary advance socialisation. Finally, the article addresses boundary cases in the dialogue, which undergird the specific potential of a theological understanding of sin. Theology can show how the power of sin endangers those cultural entities upon which the hopes of modernity rest in the struggle to overcome violence.
Introduction
Authors: van den Heever Gerhard
Published: July 2014

In this introductory essay to the theme issue “Intersections of Discourses – Pliable Body, the Making of Religion, and Social Definition,” we sketch the main contours of thinking about human bodiliness in religion. This relates both to the way in which bodies and ways of bodiliness feature in religious discourse and practice but also to the way in which scholarly theorising deal with human bodies in religion. Our argument is based on two main points of departure, namely that bodies are constructed products of discourse and that “religion” is a set of somaticising practices. After a long neglect, the body was rediscovered as a core topic for religious studies in the wake of four intersecting force fields, namely the interest in human bodies in anthropology and sociology, the intellectual legacy of Michel Foucault, the emergence of spirituality as lived religion, and interest in religious experience as study field. In sum, it is argued that the essays presented here constitute a reminder that religious discourses are not languages “out of this world”, but are very much human languages effecting human intentional (and unintentional) outcomes in interactional social and cultural settings.
A Multiplicity of Washing Rites and a Multiplicity of Experiences
Authors: van den Heever Gerhard
Published: July 2014

If experience can be defined as the affectively charged interaction with the world by means of the body as agency or medium, various sites of such affectively charged interaction mapped on to the body may be fruitfully analysed to explain the operations of religion as discourse. Baptism is one such site. In fact, baptism as the shorthand for of collective noun denoting a spectrum of ritual practices is a particularly apposite example. Baptism as ritual practice has had a varied history, both in terms of originary context as well as interpretive or discursive trajectories. This essay primarily tracks two such significant trajectories: the one being baptismal practices as purification rites operating in socially ‘heterodox’ early Jewish and early Christian groups within an apocalyptic, dissociative framework; the other being ‘orthodox’ baptismal discourse as expressed in, for instance, Cyril of Jerusalem’s Mystagogical Catheceses. In the former, the strong affect of dissociation is coupled with visionary experiences, hence its embeddedness in apocalyptic trajectories with their strongly dismissive stance to the surrounding world. In the case of the latter, the dramatic performances of the Easter liturgy, arguably, created the experience of salvation and resurrection. In both instances, the intersection of ritual, bodily experience, religious discourse, and social imaginaire provides the explanatory framework for baptism as foundational ritual practice in the making and maintenance of religious discourse and its attendant experiential effects. In this sense, such is the argument pursued in the essay, baptism is a core facet of early Jewish and early Christian religious experience.
Alien seed beetles (Coleoptera: Chrysomelidae: Bruchinae) in Europe
Authors: YUS-RAMOS RAFAEL , VENTURA DANIEL , BENSUSAN KEITH , COELLO-GARCÍA PEDRO , GYÖRGY ZOLTÁN , STOJANOVA ANELIA
Published: July 2014

Under the framework of the DAISIE consortium, whose main mission is to make an inventory of the alien invasive species of Europe and its islands, we review the current state of knowledge and provide an up-to-date catalogue and distributional status for alien seed beetles (Coleoptera: Chrysomelidae: Bruchinae) in Europe. This work is based on studies of the species detected from the last century to the present, but with greater emphasis on the beginning of the 21st century, during which new biological studies have been carried out and findings made in European countries. The main objective of this paper is to focus on this last fact, which has promoted new views on the existing and potential threat of exotic bruchids in relation to climate change. This must now be regarded as a matter of concern for European agricultural and environmental policies. Only species of exotic origin introduced in European regions outside their native range were considered. Therefore, species of European origin spreading to new countries within Europe are not treated. Also, we provide a new approach to classifying alien seed beetle species according to their ability to become established, distinguishing between the well-established and those that may appear in seed stores but are not capable of invading natural and agricultural ecosystems. We present a taxonomic characterization of the alien bruchids found in Europe, providing an illustrated key based on external morphological characters of adults. The key facilitates the identification of the sixteen most frequently recorded genera, which represent 37 of the 42 species of exotic species recorded in Europe up to the present, whether established, not established or occasional. Finally, we provide a summary of the state of knowledge of the taxonomy and biology of the 20 most worrying species as pests, both established and non-established. This includes, where appropriate, an illustrated key for the identification of species. The study reveals that the majority of exotic bruchid species in Europe originate in Asia and Africa, from host plant species imported for ornamental or forestry purposes, and that a greater effort in European customs control is advisable.
The complete larval development of the mud shrimp Upogebia vasquezi (Gebiidea: Upogebiidae) reared in the laboratory
Authors: DE OLIVEIRA DANIELLY BRITO , MARTINELLI-LEMOS JUSSARA MORETTO , ABRUNHOSA FERNANDO ARAÚJO
Published: July 2014

The larval development of Upogebia vasquezi consists of four zoeal stages and a megalopa. In the present study, each larval stage was described and illustrated in detail. The first two stages are re-described in order to provide a detailed comparison with the data available for this species recorded in a previous study. The morphological features of all the stages are compared with those of the larvae of other Upogebia species reported previously in the literature. Broad morphological similarities and distinctions were found among most Upogebia species. The main interspecific variations in the morphology of the zoeal stages are the segmentation pattern of the antennular endopod and number of aesthetascs, the number of setae on the scaphognathite and the presence or absence of a mandibular palp.
Three new species of Baeoentedon Girault (Hymenoptera: Eulophidae) from China, with the first record of whitefly host association (Hemiptera: Aleyrodidae)
Authors: WANG ZHU-HONG , HUANG JIAN , POLASZEK ANDREW
Published: July 2014

Three new species of Baeoentedon Girault (Hymenoptera: Eulophidae) are described from China, Baeoentedon balios Wang, Huang & Polaszek sp. nov., Baeoentedon bouceki Wang, Huang & Polaszek sp. nov. and Baeoentedon virgatus Wang, Huang & Polaszek sp. nov. Both female and male of Baeoentedon balios were reared from the whitefly Pealius spina (Singh) (Hemiptera: Aleyrodidae) on the bodhi tree Ficus religiosa L. (Urticales: Moraceae). The male and the whitefly host association of Baeoentedon are recorded for the first time. A key is also provided to females of the world species of the genus.
You Gotta Work at It
Authors: Siegle Greg J. , Price Rebecca B. , Jones Neil P. , Ghinassi Frank , Painter Tiffany , Thase Michael E.
Published: July 2014

Treatments for severe depression have moderate success rates, often take many weeks to yield responses, and are often followed by relapse or recurrence. Neurobehavioral interventions address these limitations by targeting mechanisms of cognitive and emotional dysregulation directly. This study extends data and observations from a pilot study examining effects of 2 weeks (6 sessions) of adjunctive cognitive control training exercises added to medication and psychotherapy in severely depressed patients. We examined acute effects and predictors of change in rumination, and long-term effects on service utilization. Compared with treatment as usual, exercises were associated with decreases in rumination and decreased use of intensive outpatient services in the following year. Responses were strongest among patients who displayed physiological indicators (pupillary oscillations at the task frequency) of task engagement before the intervention. These indices changed following intervention, suggesting that the intervention required capitalization on relevant attentional mechanisms and addressed fundamental emotional processes through their cognitive substrates.