bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Performance through REST Open API Grouping for Wireless Sensor Network
Authors: Choi Min , Jeong Young-Sik , Park Jong Hyuk
Published: November 2013

With this growth of the Internet, it is expected that every device, including computers, will be connected to the Internet, as it is called IoT. For example, smartphones and even refrigerators require an address to connect to the Internet. In this research, we design Internet of things architecture, especially for wireless sensor networks. The architecture consists of wireless sensor networks with a microcontroller at the very bottom level. They are connected to smart devices at the next level. However, the computing capability of the smart devices is generally less powerful than that of the conventional devices. Thus, it is necessary to offload the computation-intensive part by careful partitioning of application functions. In this research, we focus on designing the concept of MapReduce like approach through the web service grouping of several web services into one. We propose two methods: REST API grouping and REST API caching. First, the web service composition results in reducing energy consumption and communication latency by composing two or more REST web services into one. Second, the web service caching technique provides fast access that is recently accessed or frequently accessed. We conducted the experiments with Jersey REST web service server. Experimental result shows that our approach outperforms conventional approaches.
Secondary Merkel Cell Carcinoma Manifested in the Parotid
Authors: Basati M. , Kassam K. , Messiha A.
Published: November 2013

Background. Merkel cell carcinoma of the head and neck is a rare and aggressive malignant tumour. Both the dermatological and surgical colleagues should be aware of this entity as lesions usually present on sun exposed areas of the skin such as the head and neck.Main Observation and Treatment. A 69-year-old male originally presented to the maxillofacial surgery department with a growing lesion on the left eyebrow. Histological analysis confirmed Merkel cell carcinoma and consequently surgical excision was carried out. A follow-up PET/CT scan 2 years later demonstrated a hotspot in the left parotid gland. Fine needle aspiration and cytology revealed Merkel cell carcinoma. A subtotal parotidectomy left side with ipsilateral selective neck dissection levels I to III was carried out.Conclusions. Potential secondary Merkel cell carcinoma in the head and neck region should be taken into account when planning short- and long-term follow up for previously diagnosed patients. This followup should involve both dermatological and surgical colleagues.
Mitochondrial Dysfunctions and Altered Metals Homeostasis: New Weapons to Counteract HCV-Related Oxidative Stress
Authors: Arciello Mario , Gori Manuele , Balsano Clara
Published: November 2013

The hepatitis C virus (HCV) infection produces several pathological effects in host organism through a wide number of molecular/metabolic pathways. Today it is worldwide accepted that oxidative stress actively participates in HCV pathology, even if the antioxidant therapies adopted until now were scarcely effective. HCV causes oxidative stress by a variety of processes, such as activation of prooxidant enzymes, weakening of antioxidant defenses, organelle damage, and metals unbalance. A focal point, in HCV-related oxidative stress onset, is the mitochondrial failure. These organelles, known to be the “power plants” of cells, have a central role in energy production, metabolism, and metals homeostasis, mainly copper and iron. Furthermore, mitochondria are direct viral targets, because many HCV proteins associate with them. They are the main intracellular free radicals producers and targets. Mitochondrial dysfunctions play a key role in the metal imbalance. This event, today overlooked, is involved in oxidative stress exacerbation and may play a role in HCV life cycle. In this review, we summarize the role of mitochondria and metals in HCV-related oxidative stress, highlighting the need to consider their deregulation in the HCV-related liver damage and in the antiviral management of patients.
Highlights on Novel Technologies for the Detection of Antibodies to Ro60, Ro52, and SS-B
Authors: Infantino M. , Bentow C. , Seaman A. , Benucci M. , Atzeni F. , Sarzi-Puttini P. , Olivito B. , Meacci F. , Manfredi M. , Mahler M.
Published: November 2013

Objective. We aimed to compare a chemiluminescent immunoassay (CIA, QUANTA Flash) on BIO-FLASH with a multiplex flow immunoassay (MFI) on BioPlex 2200 for the detection of antibodies to Ro60, Ro52, and SS-B.Methods. The study included 241 samples, from patients suffering from systemic autoimmune diseases (n=108) as well as disease controls (n=133). All samples were tested for anti-Ro52, anti-Ro60, and anti-SS-B (La) antibodies on QUANTA Flash (INOVA Diagnostics, San Diego, USA) and BioPlex 2200 (Bio-Rad Laboratories Inc., Hercules, USA). Discrepant samples were tested by two independent methods: BlueDot/ANA and QUANTRIX Microarray (both D-tek, Belgium).Results. The overall qualitative agreements were 95.4% (95% confidence interval, CI 92.0–97.7%) for anti-Ro52, 98.8% (95% CI 96.4–99.7%) for anti-Ro60, and 91.7% (95% CI 87.5–94.9%) for anti-SS-B antibodies. There were 34 discrepant samples among all assays (20 anti-SS-B, 11 anti-Ro52, 3 anti-Ro60). 30/33 of retested samples (by D-tek dot blot) agreed with the QUANTA Flash results. Similar findings were obtained with QUANTRIX Microarray kit.Conclusion. QUANTA Flash and BioPlex 2200 show good qualitative agreement. The clinical performances were similar for anti-Ro52 and anti-Ro60 autoantibodies while differences were observed for anti-SS-B (La) antibodies.
Blocking SDF-1α/CXCR4 Downregulates PDGF-B and Inhibits Bone Marrow–Derived Pericyte Differentiation and Tumor Vascular Expansion in Ewing Tumors
Authors: Hamdan Randala , Zhou Zhichao , Kleinerman Eugenie S.
Published: November 2013

Bone marrow cells (BMC) are critical to the expansion of the tumor vessel network that supports Ewing sarcoma growth. BMCs migrate to the tumor and differentiate into endothelial cells and pericytes. We recently demonstrated that stromal-derived growth factor 1α (SDF-1α) regulates platelet-derived growth factor B (PDGF-B) and that this pathway plays a critical role in bone marrow–derived pericyte differentiation in vitro. We investigated the role of SDF-1α/PDGF-B in the tumor microenvironment in vivo in promoting bone marrow–derived pericyte differentiation in Ewing tumors. The CXCR4 antagonist AMD 3100 was used to disrupt the SDF-1α/CXCR4 axis in vivo in two xenograft Ewing tumor models. BMCs from GFP+ transgenic mice were transplanted into lethally irradiated nude mice to track BMC migration to the tumor site. Following BMC engraftment, tumor-bearing mice received daily subcutaneous injections of either PBS or AMD 3100 for 3 weeks. Tumors were resected and tumor sections were analyzed by immunohistochemistry. AMD 3100 inhibited BMC differentiation into desmin+ and NG2+ pericytes, affected the morphology of the tumor vasculature, decreased perfusion, and increased tumor cell apoptosis. We observed smaller vessels with tiny lumens and a decrease in the microvessel density. AMD 3100 also inhibited PDGF-B protein expression in vitro and in vivo. SDF-1α in the tumor microenvironment plays a critical role in promoting pericyte formation and Ewing sarcoma tumor neovascularization by regulating PDGF-B expression. Interfering with this pathway affects tumor vascular morphology and expansion. Mol Cancer Ther; 13(2); 483–91. ©2013 AACR.
Regular Aspirin Use and Risk of Multiple Myeloma: A Prospective Analysis in the Health Professionals Follow-up Study and Nurses' Health Study
Authors: Birmann Brenda M. , Giovannucci Edward L. , Rosner Bernard A. , Colditz Graham A.
Published: November 2013

Multiple myeloma is a lethal malignancy with an unknown etiology and no prevention strategy. Aspirin inhibits several pathways mediated by NF-κB, COX-2, or their targets that are important in multiple myeloma pathogenesis. We conducted prospective analyses in the Health Professionals Follow-up Study and Nurses' Health Study cohorts to examine whether regular aspirin use influences multiple myeloma risk. We used biennially updated data to characterize aspirin use from baseline through a cancer diagnosis, death, or 2008. We applied a 4-year lag in exposure classification to diminish the influence of preclinical multiple myeloma on aspirin use habits. We obtained HRs and 95% confidence intervals (CI) from multivariable proportional hazard models to assess the association of aspirin use with multiple myeloma risk. We tested for trend across increasing quantity and duration of use. During 2,395,458 person-years, we confirmed 328 incident multiple myeloma diagnoses, including 265 with prospective information on typical aspirin dose and frequency. Participants with a cumulative average of ≥5 adult strength (325 mg) tablets per week had a 39% lower multiple myeloma risk than nonusers (HR; 95% CI, 0.61, 0.39–0.94; tablets per week, Ptrend = 0.06). Persons with ≥11 years of continuous regular aspirin use also had a lower multiple myeloma risk (HR; 95% CI, 0.63, 0.41–0.95; duration, Ptrend = 0.17). The associations appeared stronger in men than in women, possibly reflecting gender differences in aspirin use patterns. This prospective study of aspirin use and multiple myeloma supports an etiologic role for aspirin-inhibited (i.e., NF-κB- or COX-2 mediated) pathways. The utility of aspirin for multiple myeloma chemoprevention warrants further evaluation. Cancer Prev Res; 7(1); 33–41. ©2013 AACR.
The Timing of Reconstruction in Severe Mechanical Trauma
Authors: Kuhn Ferenc
Published: November 2013

Serious ocular trauma involving the posterior segment remains rather common and, despite many technological advances in recent years, continues to represent a significant management challenge to the ophthalmologist. One of these challenges is to identify the most optimal timing for the ultimate reconstruction, namely vitrectomy. While it is fairly obvious that suture-closure of the wound of open-globe injuries should be done as soon as possible, it is less clear whether vitrectomy should be performed in the same surgical session (primary comprehensive reconstruction) or be deferred (staged approach), and if so for how long. In this review, 4 options for staging are offered: early (days 2-4); delayed (days 5-7); late (days 8-14), and very late (past 2 weeks). The earlier the vitrectomy, the higher the risk of intraoperative complications. Conversely, the later the vitrectomy, the higher the incidence and severity of postoperative complications, of which proliferative vitreoretinopathy is the most damaging.
Quantitative Computed Tomographic Coronary Angiography
Authors: Rossi Alexia , Papadopoulou Stella-Lida , Pugliese Francesca , Russo Brunella , Dharampal Anoeshka S. , Dedic Admir , Kitslaar Pieter H. , Broersen Alexander , Meijboom W. Bob , van Geuns Robert-Jan , Wragg Andrew , Ligthart Jurgen , Schultz Carl , Petersen Steffen E. , Nieman Koen , Krestin Gabriel P. , de Feyter Pim J.
Published: November 2013

Background—

Coronary lesions with a diameter narrowing ≥50% on visual computed tomographic coronary angiography (CTCA) are generally considered for referral to invasive coronary angiography. However, similar to invasive coronary angiography, visual CTCA is often inaccurate in detecting functionally significant coronary lesions. We sought to compare the diagnostic performance of quantitative CTCA with visual CTCA for the detection of functionally significant coronary lesions using fractional flow reserve (FFR) as the reference standard.

Methods and Results—

CTCA and FFR measurements were obtained in 99 symptomatic patients. In total, 144 coronary lesions detected on CTCA were visually graded for stenosis severity. Quantitative CTCA measurements included lesion length, minimal area diameter, % area stenosis, minimal lumen diameter, % diameter stenosis, and plaque burden [(vessel area−lumen area)/vessel area×100]. Optimal cutoff values of CTCA-derived parameters were determined, and their diagnostic accuracy for the detection of flow-limiting coronary lesions (FFR ≤0.80) was compared with visual CTCA. FFR was ≤0.80 in 54 of 144 (38%) coronary lesions. Optimal cutoff values to predict flow-limiting coronary lesion were 10 mm for lesion length, 1.8 mm
2
for minimal area diameter, 73% for % area stenosis, 1.5 mm for minimal lumen diameter, 48% for % diameter stenosis, and 76% for plaque burden. No significant difference in sensitivity was found between visual CTCA and quantitative CTCA parameters (
P
>0.05). The specificity of visual CTCA (42%; 95% confidence interval [CI], 31%–54%) was lower than that of minimal area diameter (68%; 95% CI, 57%–77%;
P
=0.001), % area stenosis (76%; 95% CI, 65%–84%;
P
<0.001), minimal lumen diameter (67%; 95% CI, 55%–76%;
P
=0.001), % diameter stenosis (72%; 95% CI, 62%–80%;
P
<0.001), and plaque burden (63%; 95% CI, 52%–73%;
P
=0.004). The specificity of lesion length was comparable with that of visual CTCA.

Conclusions—

Quantitative CTCA improves the prediction of functionally significant coronary lesions compared with visual CTCA assessment but remains insufficient. Functional assessment is still required in lesions of moderate stenosis to accurately detect impaired FFR.
Evaluation of the taxonomic status of the genus Aliella (Compositae, Gnaphalieae): a recircumscription of the genus Phagnalon
Authors: MONTES-MORENO NOEMÍ , GARCIA-JACAS NÚRIA , BENEDÍ CARLES , SÁEZ LLORENÇ
Published: November 2013

A taxonomic evaluation of the genus Aliella, endemic to the Moroccan Atlas Mountains, is presented. We evaluate the taxonomic status of Aliella using a morphologic and molecular approach. Firstly, we discuss the variability and usefulness of its morphological diagnostic characters. Secondly, we analyse nuclear ETS and ITS, and chloroplast ycf3-trnS and trnT-trnL spacers. Phylogenetic analyses of the nrDNA and cpDNA spacers suggest the paraphyly of Aliella and Phagnalon. Two species of Aliella, A. ballii and A. embergeri, form a strongly supported clade. In contrast, relationships of A. platyphylla to A. ballii and A. embergeri are only weakly supported, and A. iminouakensis do not form a group with the other species and shows two different haplotypes. The morphological and diagnostic characters of Aliella are described and compared with an extensive sampling of the closely related genus Phagnalon. Our results strongly suggest that Aliella should be merged into Phagnalon. For each accepted taxon, taxonomical, chorological, and ecological data are provided. Six taxa are recognized, three species and three subspecies. Three lectotypifications of specific names and three new combinations are proposed. New descriptions and distribution maps of the recognized taxa are given.
Tersilochinae of Western Amazonia (Hymenoptera: Ichneumonidae). Genus Stethantyx Townes, part 1
Authors: KHALAIM ANDREY I. , SÄÄKSJÄRVI ILARI E. , BORDERA SANTIAGO
Published: November 2013

Sixteen species of the genus Stethantyx Townes having first and second sections of radius meeting at obtuse angle are recorded from Peru and Ecuador in Western Amazonia. Ten species, S. amazonica Khalaim & Sääksjärvi, sp. nov., S. aurantia Khalaim & Sääksjärvi, sp. nov., S. juninensis Khalaim & Bordera, sp. nov., S. loretosa Khalaim & Sääksjärvi, sp. nov., S. neopropodeator Khalaim & Sääksjärvi, sp. nov., S. orellana Khalaim & Sääksjärvi, sp. nov., S. sinuata Khalaim & Sääksjärvi, sp. nov., S. tiputinia Khalaim & Sääksjärvi, sp. nov., S. trepida Khalaim & Sääksjärvi, sp. nov. and S. voluptaria Khalaim & Sääksjärvi, sp. nov., are described as new. Six species, previously known only from Costa Rica,           S. alajuela Khalaim & Broad, S. heredia Khalaim & Broad, S. orosia Khalaim & Broad, S. propodeator Khalaim & Broad, S. puntarenasa Khalaim & Broad and S. sanjosea Khalaim & Broad, are recorded from South America for the first time. A partial key to Western Amazonian species of Stethantyx is given.
Two Species of Thienemanniella Kieffer from Oriental China (Diptera: Chironomidae: Orthocladiinae)
Authors: FU YUE , FANG XIANGLIANG , WANG XINHUA
Published: November 2013

A new species from Oriental China, Thienemanniella curva sp. n. is described and illustrated as adult males. T. nipponica which belong to eye bare species group in Thienemanniella from Guangdong Province is re-described. A revised key to known males of the world is provided.
A replacement name for Macrobrachium aemulum madhusoodani Pillai & Unnikrishnan, 2013, a junior homonym of Macrobrachium madhusoodani Unnikrishnan, Pillai & Jayachandran, 2011 (Decapoda: Palaemonidae)
Authors: PILLAI P. M. , UNNIKRISHNAN V.
Published: November 2013

Macrobrachium aemulum madhusoodani Pillai & Unnikrishnan (2013) was recently described based on material from the Neyyar River, Kerala, India as a new subspecies of M. aemulum (Nobili, 1906).  As however, both species and subspecies names are considered part of the species-group for nomenclatorial purposes (ICZN, Art. 45.1), the name is a junior homonym of Macrobrachium madhusoodani Unnikrishnan, Pillai & Jayachandran (2011) and requires a replacement name.
The Fate of the Dramatic in Modern Society: Social Theory and the Theatrical Avant-Garde
Authors: Alexander Jeffrey C
Published: November 2013

Avant-garde theatre is often invoked as the bellwether for a society that has become postdramatic – fragmented, alienated, and critical of efforts to create collectively shared meanings. A theatre whose sequenced actions have no narrative (so the story goes) mirrors a social world where the most conflictual situations no longer appear as drama but merely as spectacle: a society where audiences look on without any feeling or connection. Because only half right, these theses about postdramatic theatre and society are fundamentally wrong. As modern societies have expanded and differentiated, the elements that compose performances have become separated and often fragmented in both theatre and society. If they can be brought back together again, performances are viewed as authentic and meaningful. If (re)fusion cannot be achieved, performances fail to communicate meaning. The aim of this essay is to demonstrate that a shared ambition to (re)fuse fragmented performative elements has defined the most important strain of avant-garde theatre over the last two centuries. Most radical theatrical innovation has sought to open live drama back up to the telos of myth and ritual. Neither in theatre nor social life can the world transcend dramaturgy; it is fundamental to the search for meaning in a world beyond cosmological religion.
Formative Evaluation of a Practice-Based Smoking Cessation Program for Diverse Populations
Authors: Mahoney Martin C. , Erwin Deborah O. , Widman Christy , Masucci Twarozek Annamaria , Saad-Harfouche Frances G. , Underwood Willie , Fox Chester H.
Published: November 2013

Background. Smoking rates are higher among those living at or below poverty and among persons with lower levels of education. We report on a formative research project examining patient perceptions of tobacco cessation strategies among diverse, low socioeconomic, urban smokers cared for in community-based primary care medical offices. Method. We conducted 10 focus groups among low socioeconomic status participants recruited from urban primary care medical offices in Buffalo and Niagara Falls, New York. Participants included current or former smokers, who were stratified by age-group (18-39 years and 40+ years). The focus groups discussed perceptions of tobacco cessation strategies, previous quit attempts, and use/attitudes regarding technology and social media as potential platforms for cessation support. Results. Participants ( n = 96) included predominantly African Americans ( n = 62, 65%) and European Americans ( n = 16, 16%); 56% were older than 40 years and 92% were low income. Most participants were supportive of cessation message delivery via phone; however, the age-groups varied in their attitudes on quitting smoking, desired frequency of phone contacts, and social media usage. Participants aged 18 to 39 years reported more Internet use, greater use of text messaging, and were more open to health information via social media. Conclusions. Based on significant variation between younger and older smokers’ perceptions of tobacco addiction and use of communication technologies, it appears reasonable to stratify the content and platform of health messaging by the target age-group.
Characterization of Plp, a phosphatidylcholine-specific phospholipase and hemolysin of Vibrio anguillarum
Authors: Li Ling , Mou Xiangyu , Nelson David R
Published: November 2013

Background

Vibrio anguillarum is the causative agent of vibriosis in fish. Several extracellular proteins secreted by V. anguillarum have been shown to contribute to virulence. While two hemolysin gene clusters, vah1-plp and rtxACHBDE, have been previously identified and described, the activities of the protein encoded by the plp gene were not known. Here we describe the biochemical activities of the plp-encoded protein and its role in pathogenesis.

Results

The plp gene, one of the components in vah1 cluster, encodes a 416-amino-acid protein (Plp), which has homology to lipolytic enzymes containing the catalytic site amino acid signature SGNH. Hemolytic activity of the plp mutant increased 2-3-fold on sheep blood agar indicating that plp represses vah1; however, hemolytic activity of the plp mutant decreased by 2-3-fold on fish blood agar suggesting that Plp has different effects against erythrocytes from different species. His6-tagged recombinant Plp protein (rPlp) was over-expressed in E. coli. Purified and re-folded active rPlp exhibited phospholipase A2 activity against phosphatidylcholine and no activity against phosphatidylserine, phosphatidylethanolamine, or sphingomyelin. Characterization of rPlp revealed broad optimal activities at pH 5–9 and at temperatures of 30-64°C. Divalent cations and metal chelators did not affect activity of rPlp. We also demonstrated that Plp was secreted using thin layer chromatography and immunoblot analysis. Additionally, rPlp had strong hemolytic activity towards rainbow trout erythrocytes, but not to sheep erythrocytes suggesting that rPlp is optimized for lysis of phosphatidylcholine-rich fish erythrocytes. Further, only the loss of the plp gene had a significant effect on hemolytic activity of culture supernatant on fish erythrocytes, while the loss of rtxA and/or vah1 had little effect. However, V. anguillarum strains with mutations in plp or in plp and vah1 exhibited no significant reduction in virulence compared to the wild type strain when used to infect rainbow trout.

Conclusion

The plp gene of V. anguillarum encoding a phospholipase with A2 activity is specific for phosphatidylcholine and, therefore, able to lyse fish erythrocytes, but not sheep erythrocytes. Mutation of plp does not affect the virulence of V. anguillarum in rainbow trout.
High incidence of Aggregatibacter actinomycetemcomitansinfection in patients with cerebral infarction and diabetic renal failure: a cross-sectional study
Authors: Murakami Minoru , Suzuki Jun-ichi , Yamazaki Satoshi , Ikezoe Masaya , Matsushima Rintaro , Ashigaki Norihiko , Aoyama Norio , Kobayashi Naho , Wakayama Kouji , Akazawa Hiroshi , Komuro Issei , Izumi Yuichi , Isobe Mitsuaki
Published: November 2013

Background

Recent epidemiological studies suggest that periodontitis is a major risk factor for renal failure and cerebral infarction. The aim of this study was to evaluate the association among periodontitis, renal failure, and cerebral infarction, focusing on microbiological and immunological features.

Methods

Twenty-one patients treated with hemodialysis (HD) were enrolled in this study. They were 8 with diabetic nephropathy and 13 with non-diabetic nephropathy. Blood examination, periodontal examination, brain magnetic resonance image (MRI), and dental radiography were performed on all patients. Subgingival plaque, saliva, and blood samples were analyzed for the periodontal pathogens, Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Porphyromonas gingivalis (P. gingivalis), and Prevotella intermedia (P. intermedia) using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA).

Results

We found that the patients with diabetic nephropathy had more A. actinomycetemcomitans compared with non-diabetic nephropathy (P = 0.038) in dental plaque. Furthermore, the patients with diabetic nephropathy showed a significantly higher incidence of cerebral infarction compared with those with non-diabetic nephropathy (P = 0.029). Clinical oral and radiographic scores tended to be higher among patients in the diabetic nephropathy group than in the non-diabetic nephropathy group.

Conclusions

Periodontal pathogens, particularly A. actinomycetemcomitans, may play a role, at least a part, in the development of cerebral infarction in Japanese HD patients with diabetic nephropathy.
Method of quasilinearization for a nonlocal singular boundary value problem in weighted spaces
Authors: Agarwal Ravi P , Ahmad Bashir , Alsaedi Ahmed
Published: November 2013

This paper studies the existence and uniqueness of solutions for a nonlocal singular boundary value problem of second-order integro-differential equations in weighted spaces. The method of quasilinearization is applied to obtain monotone sequences of approximate solutions converging uniformly and quadratically to a unique solution of the problem at hand. An illustrative example is presented.

MSC:34A45, 34B16, 45J05.
Impaired Noradrenaline Homeostasis in Rats with Painful Diabetic Neuropathy as a Target of Duloxetine Analgesia
Authors: Kinoshita Jun , Takahashi Yukari , Watabe Ayako M , Utsunomiya Kazunori , Kato Fusao
Published: November 2013

Background

Painful diabetic neuropathy (PDN) is a serious complication of diabetes mellitus that affects a large number of patients in many countries. The molecular mechanisms underlying the exaggerated nociception in PDN have not been established. Recently, duloxetine (DLX), a serotonin and noradrenaline re-uptake inhibitor, has been recommended as one of the first-line treatments of PDN in the United States Food and Drug Administration, the European Medicines Agency and the Japanese Guideline for the Pharmacologic Management of Neuropathic pain. Because selective serotonin re-uptake inhibitors show limited analgesic effects in PDN, we examined whether the potent analgesic effect of DLX contributes toward improving the pathologically aberrant noradrenaline homeostasis in diabetic models.

Results

In streptozotocin (STZ) (50 mg/kg, i.v.)-induced diabetic rats that exhibited robust mechanical allodynia and thermal hyperalgesia, DLX (10 mg/kg, i.p.) significantly and markedly increased the nociceptive threshold. The analgesic effect of DLX was nullified by the prior administration of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) (50 mg/kg, i.p.), which drastically eliminated dopamine-beta-hydroxylase- and norepinephrine transporterimmunopositive fibers in the lumbar spinal dorsal horn and significantly reduced the noradrenaline content in the lumbar spinal cord. The treatment with DSP-4 alone markedly lowered the nociceptive threshold in vehicle-treated non-diabetic rats; however, this pro-nociceptive effect was occluded in STZ-treated diabetic rats. Furthermore, STZ-treated rats exhibited a higher amount of dopamine-beta-hydroxylase- and norepinephrine transporterimmunopositive fibers in the dorsal horn and noradrenaline content in the spinal cord compared to vehicle-treated rats.

Conclusions

Impaired noradrenaline-mediated regulation of the spinal nociceptive network might underlie exaggerated nociception in PDN. DLX might exert its analgesic effect by selective enhancement of noradrenergic signals, thus counteracting this situation.
A modified VMAT adaptive radiotherapy for nasopharyngeal cancer patients based on CT-CT image fusion
Authors: Jin Xiance , Han Ce , Zhou Yongqiang , Yi Jinling , Yan Huawei , Xie Congying
Published: November 2013

Background

To investigate the feasibility and benefits of a modified adaptive radiotherapy (ART) by replanning in the initial CT (iCT) with new contours from a repeat CT (rCT) based on CT-CT image fusion for nasopharyngeal cancer (NPC) patients underwent volumetric modulated arc radiotherapy (VMAT).

Materials and methods

Nine NPC patients underwent VMAT treatment with a rCT at 23rd fraction were enrolled in this study. Dosimetric differences for replanning VMAT plans in the iCT and in the rCT were compared. Volumetric and dosimetric changes of gross tumor volume (GTV) and organs at risk (OARs) of this modified ART were also investigated.

Results

No dosimetric differences between replanning in the iCT and in the rCT were observed. The average volume of GTV decreased from 78.83 ± 38.42 cm3 in the iCT to 71.44 ± 37.46 cm3 in the rCT, but with no significant difference (p = 0.42).The average volume of the left and right parotid decreased from 19.91 ± 4.89 cm3 and 21.58 ± 6.16 cm3 in the iCT to 11.80 ± 2.79 cm3 and 13.29 ± 4.17 cm3 in the rCT (both p < 0.01), respectively. The volume of other OARs did not shrink very much. No significant differences on PTVGTV and PTVCTV coverage were observed for replanning with this modified ART. Compared to the initial plans, the average mean dose of the left and right parotid after re-optimization were decreased by 62.5 cGy (p = 0.05) and 67.3 cGy (p = 0.02), respectively, and the V5 (the volume receiving 5 Gy) of the left and right parotids were decreased by 7.8% (p = 0.01) and 11.2% (p = 0.001), respectively. There was no significant difference on the dose delivered to other OARs.

Conclusion

Patients with NPC undergoing VMAT have significant anatomic and dosimetric changes to parotids. Repeat CT as an anatomic changes reference and re-optimization in the iCT based on CT-CT image fusion was accurate enough to identify the volume changes and to ensure safe dose to parotids.
Presurgical therapy with axitinib for advanced renal cell carcinoma: a case report
Authors: Koie Takuya , Ohyama Chikara , Okamoto Akiko , Yamamoto Hayato , Imai Atsushi , Hatakeyama Shingo , Yoneyama Takahiro , Hashimoto Yasuhiro
Published: November 2013

Background

Targeted therapy with tyrosine kinase inhibitors has been shown to reduce tumor volumes and prolong the survival of patients with metastatic renal cell carcinoma. Tyrosine kinase inhibitors, particularly sunitinib, have recently been used in neoadjuvant and presurgical settings. Axitinib is a promising second-line therapy option for advanced or metastatic renal cell carcinoma. Herein, we report a patient with advanced renal cell carcinoma who received presurgical treatment with axitinib.

Case presentation

A 73-year-old man was transported by ambulance to a community hospital with chief complaints of high fever and a gait disorder. Computed tomography screening revealed a hypervascular tumor (size, 9 × 8.5 cm) in the lower pole of the left kidney. Upon admission to our hospital, his general condition was poor and his performance status was judged as 3, based on the Eastern Cooperative Oncology Group performance status criteria. After biopsy for the renal tumor, he received 5 mg of axitinib twice daily for 3 months. No serious adverse events were reported during this treatment. The tumor diameter shrank by 56%. Left radical nephrectomy was performed, and there were no intraoperative or postoperative complications. Pathological examination indicated a pT3aN0M0, Furman grade 3, clear cell renal cell carcinoma with necrosis, hyaline degeneration, and hemosiderosis. The patient was asymptomatic and disease-free at 1 year post-diagnosis.

Conclusion

This case study demonstrate that presurgical therapy with axitinib is feasible and might have several potential advantages for patients with advanced renal cell carcinoma.
Molecular dynamics simulation of the specific heat capacity of water-Cu nanofluids
Authors: Rajabpour Ali , Akizi Farrokh Yousefi , Heyhat Mohammad Mahdi , Gordiz Kiarash
Published: November 2013

This paper presents molecular dynamics (MD) modeling for calculating the specific heat of nanofluids containing copper nanoparticles. The Cu nanoparticles with 2-nm diameter were considered to be dispersed in water as base liquid. The MD modeling procedure presented and implemented to calculate the specific heat of nanofluids with volume fractions of 2 to 10%. Obtained results show that the specific heat capacity of Cu-water nanofluids decreases gradually with increasing volume concentration of nanoparticles. The simulation results are compared with two existing applied models for prediction of the specific heat of the nanofluid. The obtained specific heat results from the MD simulation and the prediction from the thermal equilibrium model for calculating specific heat of nanofluids exhibit good agreement and the other simple mixing model fails to predict the specific heat capacity of Cu-water nanofluids particularly at high volume fractions.
Nanoparticulate flurbiprofen reduces amyloid-β42 generation in an in vitro blood–brain barrier model
Authors: Meister Sabrina , Zlatev Iavor , Stab Julia , Docter Dominic , Baches Sandra , Stauber Roland H , Deutsch Mordechai , Schmidt Reinhold , Ropele Stefan , Windisch Manfred , Langer Klaus , Wagner Sylvia , von Briesen Hagen , Weggen Sascha , Pietrzik Claus U
Published: November 2013

Introduction

The amyloid-β42 (Aβ42) peptide plays a crucial role in the pathogenesis of Alzheimer’s disease (AD), the most common neurodegenerative disorder affecting the elderly. Over the past years, several approaches and compounds developed for the treatment of AD have failed in clinical studies, likely in part due to their low penetration of the blood–brain barrier (BBB). Since nanotechnology-based strategies offer new possibilities for the delivery of drugs to the brain, this technique is studied intensively for the treatment of AD and other neurological disorders.

Methods

The Aβ42 lowering drug flurbiprofen was embedded in polylactide (PLA) nanoparticles by emulsification-diffusion technique and their potential as drug carriers in an in vitro BBB model was examined. First, the cytotoxic potential of the PLA-flurbiprofen nanoparticles on endothelial cells and the cellular binding and uptake by endothelial cells was studied. Furthermore, the biological activity of the nanoparticulate flurbiprofen on γ-secretase modulation as well as its in vitro release was examined. Furthermore, the protein corona of the nanoparticles was studied as well as their ability to transport flurbiprofen across an in vitro BBB model.

Results

PLA-flurbiprofen nanoparticles were endocytosed by endothelial cells and neither affected the vitality nor barrier function of the endothelial cell monolayer. The exposure of the PLA-flurbiprofen nanoparticles to human plasma occurred in a rapid protein corona formation, resulting in their decoration with bioactive proteins, including apolipoprotein E. Furthermore, luminally administered PLA-flurbiprofen nanoparticles in contrast to free flurbiprofen were able to modulate γ-secretase activity by selectively decreasing Aβ42 levels in the abluminal compartment of the BBB model.

Conclusions

In this study, we were able to show that flurbiprofen can be transported by PLA nanoparticles across an in vitro BBB model and most importantly, the transported flurbiprofen modulated γ-secretase activity by selectively decreasing Aβ42 levels. These results demonstrate that the modification of drugs via embedding in nanoparticles is a promising tool to facilitate drug delivery to the brain, which enables future development for the treatment of neurodegenerative disorders like AD.
Direct repression of MYB by ZEB1 suppresses proliferation and epithelial gene expression during epithelial-to-mesenchymal transition of breast cancer cells
Authors: Hugo Honor J , Pereira Lloyd , Suryadinata Randy , Drabsch Yvette , Gonda Thomas J , Gunasinghe N P A Devika , Pinto Cletus , Soo Eliza TL , van Denderen Bryce JW , Hill Prue , Ramsay Robert G , Sarcevic Boris , Newgreen Donald F , Thompson Erik W
Published: November 2013

Introduction

Epithelial-to-mesenchymal transition (EMT) promotes cell migration and is important in metastasis. Cellular proliferation is often downregulated during EMT, and the reverse transition (MET) in metastases appears to be required for restoration of proliferation in secondary tumors. We studied the interplay between EMT and proliferation control by MYB in breast cancer cells.

Methods

MYB, ZEB1, and CDH1 expression levels were manipulated by lentiviral small-hairpin RNA (shRNA)-mediated knockdown/overexpression, and verified with Western blotting, immunocytochemistry, and qRT-PCR. Proliferation was assessed with bromodeoxyuridine pulse labeling and flow cytometry, and sulforhodamine B assays. EMT was induced with epidermal growth factor for 9 days or by exposure to hypoxia (1% oxygen) for up to 5 days, and assessed with qRT-PCR, cell morphology, and colony morphology. Protein expression in human breast cancers was assessed with immunohistochemistry. ZEB1-MYB promoter binding and repression were determined with Chromatin Immunoprecipitation Assay and a luciferase reporter assay, respectively. Student paired t tests, Mann–Whitney, and repeated measures two-way ANOVA tests determined statistical significance (P < 0.05).

Results

Parental PMC42-ET cells displayed higher expression of ZEB1 and lower expression of MYB than did the PMC42-LA epithelial variant. Knockdown of ZEB1 in PMC42-ET and MDA-MB-231 cells caused increased expression of MYB and a transition to a more epithelial phenotype, which in PMC42-ET cells was coupled with increased proliferation. Indeed, we observed an inverse relation between MYB and ZEB1 expression in two in vitro EMT cell models, in matched human breast tumors and lymph node metastases, and in human breast cancer cell lines. Knockdown of MYB in PMC42-LA cells (MYBsh-LA) led to morphologic changes and protein expression consistent with an EMT. ZEB1 expression was raised in MYBsh-LA cells and significantly repressed in MYB-overexpressing MDA-MB-231 cells, which also showed reduced random migration and a shift from mesenchymal to epithelial colony morphology in two dimensional monolayer cultures. Finally, we detected binding of ZEB1 to MYB promoter in PMC42-ET cells, and ZEB1 overexpression repressed MYB promoter activity.

Conclusions

This work identifies ZEB1 as a transcriptional repressor of MYB and suggests a reciprocal MYB-ZEB1 repressive relation, providing a mechanism through which proliferation and the epithelial phenotype may be coordinately modulated in breast cancer cells.
Characterization of chromosomal architecture in Arabidopsisby chromosome conformation capture
Authors: Grob Stefan , Schmid Marc W , Luedtke Nathan W , Wicker Thomas , Grossniklaus Ueli
Published: November 2013

Background

The packaging of long chromatin fibers in the nucleus poses a major challenge, as it must fulfill both physical and functional requirements. Until recently, insights into the chromosomal architecture of plants were mainly provided by cytogenetic studies. Complementary to these analyses, chromosome conformation capture technologies promise to refine and improve our view on chromosomal architecture and to provide a more generalized description of nuclear organization.

Results

Employing circular chromosome conformation capture, this study describes chromosomal architecture in Arabidopsis nuclei from a genome-wide perspective. Surprisingly, the linear organization of chromosomes is reflected in the genome-wide interactome. In addition, we study the interplay of the interactome and epigenetic marks and report that the heterochromatic knob on the short arm of chromosome 4 maintains a pericentromere-like interaction profile and interactome despite its euchromatic surrounding.

Conclusion

Despite the extreme condensation that is necessary to pack the chromosomes into the nucleus, the Arabidopsis genome appears to be packed in a predictive manner, according to the following criteria: heterochromatin and euchromatin represent two distinct interactomes; interactions between chromosomes correlate with the linear position on the chromosome arm; and distal chromosome regions have a higher potential to interact with other chromosomes.
Influence of frequency and saturation on AVO attributes for patchy saturated rocks
Authors: Dupuy Bastien , Stovas Alexey
Published: November 2013

Partially saturated rocks are considered to be major sources of seismic wave velocity dispersion and attenuation in recorded real data. From the physical description of partially saturated gas-water and oil-water reservoirs, we use upscaling theories to compute an equivalent frequency-dependent porous medium. These homogenization methods are associated with mesoscale description of attenuation and dispersion coming from wave-induced flow phenomena. To compute wave propagation, we use numerical codes in the frequency domain that allow us to take into account all the frequency-dependent parameters without approximation or local time steps. In this way, the Biot slow compressional wave is well modeled and its partially diffusive, partially propagative behavior is completely considered. The attenuation and dispersion of the waves in such media are coming partly from the wave mode conversion into diffusive slow waves, not visible on seismograms. But the amplitude of propagative P- and S-waves are mainly affected by these energy losses at interfaces. Using full waveform modeling, we investigate the amplitude versus offset (AVO) attributes with respect to saturation and frequency. For a simple three-layer case, we compute poroelastic wave propagation, extract maximum amplitude with respect to angle, and, through a least-square fitting method, we obtain the AVO attributes for PP- and PS-reflected events. Due to the influence of mesoscale induced-flow phenomena and relatively to the regime of the Biot slow wave, the main results show a strong variability of the AVO attributes with the frequency and a lower variability with the saturation for reflected PP or PS events. We show that gas-water and oil-water systems have similar behaviors. Strong differences between patchy saturation and effective fluid phase theories are highlighted, especially at high frequency, for PP events and for gas-water systems. Then, we conclude that these AVO attributes carry information about the saturation that can be used to estimate the saturation variations in time-lapse studies.
Geophysical monitoring and reactive transport simulations of bioclogging processes induced by Leuconostoc mesenteroides
Authors: Wu Yuxin , Surasani Vikranth Kumar , Li Li , Hubbard Susan Sharpless
Published: November 2013

Although bioclogging has been used for various applications, its performance has been unpredictable. We carried out a bioclogging experiment and developed a reactive transport model to understand and quantify geophysical responses to the production of a biopolymer (dextran) in a silica sand porous medium. The developed model was used to predict effectiveness of bioclogging and the associated geophysical signature under different treatment conditions. The porosity reduction calculated from the reactive transport modeling matched the concurrent increase in electrical resistivity and confirmed the dominant contribution of pore fluid conductivity to the bulk electrical conductivity. Correlations between measured electrical phase signals and predicted mineral surface area reduction indicated the controlling effect of mineral surface area on polarization. The joint use of the two methods quantitatively estimated the extent of decrease in porosity as well as effective mineral surface area, both of which are challenging to measure nondestructively in biological systems. The joint use of the geophysical methods and reactive transport modeling provided a better understanding of the dominant processes that govern dextran-based bioclogging and the associated geophysical responses. This opens new opportunities for quantifying changes associated with bioclogging processes and can potentially lead to new conceptual models that relate hydraulic property changes to the porosity and mineral surface area, which will enhance prediction, monitoring, and control of applications that use bioclogging.
Beckett's Philosophical Imagination: Democritus versus Pythagoras and Plato in Comment C'est/How It Is
Authors: Cordingley Anthony
Published: November 2013

This article elucidates the dialectic between Pythagorean-Platonic and Democritean ideas latent in Beckett's final work of long prose, Comment c'est/How It Is (1961/1964), and measures the importance of Beckett's perception of philosophy gained through his study of Wilhelm Windelband's primer, A History of Philosophy. Unearthing Beckett's reaction to the nineteenth-century Kantian's grand narrative of the progress of reason, this article maps the poetics of appropriation that marks Beckett's quintessentially late modernist aesthetics. In no way can Beckett's poetics edify the Tradition (à la Pound or Eliot), but neither can it simply deny, subvert, or pastiche it. To ask whether or not Beckett escapes into nihilism, to wonder if he finds a philosophically satisfactory solution to his rejection of a faith in reason, or to look for his synthesis of the Ancient dialectic he entertains is in each case to miss the point. Beckett's use of allusive discourse is demonstrated to be a vector through which he explores the mechanisms of listening, memory, and creativity. This article therefore offers the precise example of Beckett's use of Ancient philosophy to illustrate how his aesthetics defines a limit point of modernism.
Indigeneity and Mestizaje in Ana Castillo'sThe Mixquiahuala Lettersand Leslie Marmon Silko'sAlmanac of the Dead
Authors: Szeghi Tereza M.
Published: November 2013

This article argues that conceptions of indigeneity and mestizaje conveyed in Ana Castillo's The Mixquiahuala Letters and Leslie Marmon Silko's Almanac of the Dead are influenced (differentially) by the very colonialist assumptions the novels otherwise aim to dismantle. I compare how indigeneity and mestizaje are defined in Letters and Almanac (with particular attention to their oppositional features), addressing relationships between these definitions, popular colonialist discourse, and anti-colonial articulations of identity that have developed in American Indian and Chicana/o communities. Significantly (and tragically), Letters' Chicana protagonist, Teresa, envisions her recovery of a cohesive cultural identity as a return to a distant indigenous past (via traveling from the U.S. to Mexico) — which, I demonstrate, places Letters in conversation with Mexican indigenismo, the myth of the Vanishing Indian, and the myth of Mexico as an Infernal Paradise. Almanac's Menardo, by contrast, grows up with a strong sense of Mexican indigenous ideologies but cuts his family ties and conceals his cultural identity after discovering that identification as Indian will disqualify him for entrance into Mexican high society. Through Menardo, introduced as “the mestizo,” Almanac critiques Mexican mestizaje as a cultural construct, and I consider whether this critique functions as the sort of exclusionary gesture Castillo has ascribed to some North American Indians when it comes to Chicana/o claims to indigeneity. At the same time, I consider how Teresa's inherited presuppositions about indigeneity perpetuate discourses that have functioned to bar indigenous peoples from the full rights of citizenship and self-determination. That Menardo eschews what Teresa strives to recover can best be understood, I argue, in the context of the different national circumstances in which they grow up, the consequences of Chicana/o diaspora, and traditional versus colonially influenced American Indian standards for tribal identification.