bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-Dimensional Parameterized Matching
Authors: Cole Richard , Hazay Carmit , Lewenstein Moshe , Tsur Dekel
Published: October 2014

Two equal-length strings, or two equal-sized two-dimensional texts,
parameterize match
(
p-match
) if there is a one-one mapping (relative to the alphabet) of their characters.
Two-dimensional parameterized matching
is the task of finding all
m
×
m
substrings of an
n
×
n
text that p-match an
m
×
m
pattern. This models searching for color images with changing of color maps, for example. We present two algorithms that solve the two-dimensional parameterized matching problem. The time complexities of our algorithms are
O
(
n
2
log
2
m
) and
O
(
n
2
+
m
2.5
polylog(
m
)). Our algorithms are faster than the
O
(
n
2
m
log
2
m
log log
m
) time algorithm for this problem of Amir et al. [2006].

A key step in both of our algorithms is to count the number of distinct characters in every
m
×
m
substring of an
n
×
n
string. We show how to solve this problem in
O
(
n
2
) time. This result may be of independent interest.
Kernelization Lower Bounds Through Colors and IDs
Authors: Dom Michael , Lokshtanov Daniel , Saurabh Saket
Published: October 2014

In parameterized complexity, each problem instance comes with a parameter
k
, and a parameterized problem is said to admit a
polynomial kernel
if there are polynomial time preprocessing rules that reduce the input instance to an instance with size polynomial in
k
. Many problems have been shown to admit polynomial kernels, but it is only recently that a framework for showing the nonexistence of polynomial kernels for specific problems has been developed by Bodlaender et al. [2009] and Fortnow and Santhanam [2008]. With few exceptions, all known kernelization lower bounds results have been obtained by directly applying this framework. In this article, we show how to combine these results with combinatorial reductions that use colors and IDs in order to prove kernelization lower bounds for a variety of basic problems. To follow we give a summary of our main results. All results are under the assumption that the polynomial hierarchy does not collapse to the third level.

—We show that the
Steiner Tree
problem parameterized by the number of terminals and solution size
k
, and the
Connected Vertex Cover
and
Capacitated Vertex Cover
problems do not admit a polynomial kernel. The two latter results are surprising because the closely related
Vertex Cover
problem admits a kernel with at most 2
k
vertices.

—Alon and Gutner [2008] obtain a
k

poly
(
h
)

kernel for

Dominating Set in
H
-Minor Free Graphs

parameterized by
h
= |
H
| and solution size
k
, and ask whether kernels of smaller size exist. We partially resolve this question by showing that

Dominating Set in
H
-Minor Free Graphs

does not admit a kernel with size polynomial in
k
+
h
.

—Harnik and Naor [2007] obtain a “compression algorithm” for the
Sparse Subset Sum
problem. We show that their algorithm is essentially optimal by showing that the instances cannot be compressed further.

—The
Hitting Set
and
Set Cover
problems are among the most-studied problems in algorithmics. Both problems admit a kernel of size
k

O
(
d
)

when parameterized by solution size
k
and maximum set size
d
. We show that neither of them, along with the
Unique Coverage
and
Bounded Rank Disjoint Sets
problems, admits a polynomial kernel.

The existence of polynomial kernels for several of the problems mentioned previously was an open problem explicitly stated in the literature [Alon and Gutner 2008; Betzler 2006; Guo and Niedermeier 2007; Guo et al. 2007; Moser et al. 2007]. Many of our results also rule out the existence of compression algorithms, a notion similar to kernelization defined by Harnik and Naor [2007], for the problems in question.
The vocal chorder
Authors: Unander-Scharin Carl , Unander-Scharin Åsa , Höök Kristina , Elblaus Ludvig
Published: October 2014

Probing stamina in an interactive artifact through opera rehearsals.
Anti-oppressive design
Authors: Smyth Thomas , Dimond Jill
Published: October 2014

Community + Culture features practitioner perspectives on designing technologies for and with communities. We highlight compelling projects and provocative points of view that speak to both community technology practice and the interaction design field as a whole.
---Christopher A. Le Dantec, Editor
Designing for sustainable development in a remote Mexican community
Authors: Rocha Mario Alberto Moreno , Sandoval Carlos Alberto Martínez
Published: October 2014

In this forum we celebrate research that helps to successfully bring the benefits of computing technologies to children, older adults, people with disabilities, and other populations that are often ignored in the design of mass-marketed products.
---Juan Pablo Hourcade, Editor
Infantile hypertrophic pyloric stenosis (IHPS): A study of its pathophysiology utilizing the newborn hph-1 mouse model of the disease
Authors: Welsh Christopher , Shifrin Yulia , Pan Jingyi , Belik Jaques
Published: October 2014

Infantile hypertrophic pyloric stenosis (IHPS) is a common disease of unknown etiology. The tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia-1 ( hph-1) newborn mouse has a similar phenotype to the human condition. For hph-1 and wild-type control animals, pyloric tissue agonist-induced contractile properties, reactive oxygen species (ROS) generation, cGMP, neuronal nitric oxide synthase (nNOS) content, and Rho-associated protein kinase 2 (ROCK-2) expression and activity were evaluated. Primary pyloric smooth muscle cells from wild-type newborn animals were utilized to evaluate the effect of BH4 deficiency. One-week-old hph-1 mice exhibited a fourfold increase ( P < 0.01) in the pyloric sphincter muscle contraction magnitude but similar relaxation values when compared with wild-type animals. The pyloric tissue nNOS expression and cGMP content were decreased, whereas the rate of nNOS uncoupling increased ( P < 0.01) in 1-wk-old hph-1 mice when compared with wild-type animals. These changes were associated with increased pyloric tissue ROS generation and elevated ROCK-2 expression/activity ( P < 0.05). At 1–3 days of age and during adulthood, the gastric emptying rate of the hph-1 mice was not altered, and there were no genotype differences in pyloric tissue ROS generation, nNOS expression, or ROCK-2 activity. BH4 inhibition in pyloric smooth muscle cells resulted in increased ROS generation ( P < 0.01) and ROCK-2 activity ( P < 0.05). Oxidative stress upregulated ROCK-2 activity in pyloric tissue, but no changes were observed in newborn fundal tissue in vitro. We conclude that ROS-induced upregulation of ROCK-2 expression accounts for the increased pyloric sphincter tone and nNOS downregulation in the newborn hph-1 mice. The role of ROCK-2 activation in the pathogenesis of IHPS warrants further study.
Type I Cytokines Synergize with Oncogene Inhibition to Induce Tumor Growth Arrest
Authors: Acquavella Nicolas , Clever David , Yu Zhiya , Roelke-Parker Melody , Palmer Douglas C. , Xi Liqiang , Pflicke Holger , Ji Yun , Gros Alena , Hanada Ken-ichi , Goldlust Ian S. , Mehta Gautam U. , Klebanoff Christopher A. , Crompton Joseph G. , Sukumar Madhusudhanan , Morrow James J. , Franco Zulmarie , Gattinoni Luca , Liu Hui , Wang Ena , Marincola Francesco , Stroncek David F. , Lee Chyi-Chia R. , Raffeld Mark , Bosenberg Marcus W. , Roychoudhuri Rahul , Restifo Nicholas P.
Published: October 2014

Both targeted inhibition of oncogenic driver mutations and immune-based therapies show efficacy in treatment of patients with metastatic cancer, but responses can be either short lived or incompletely effective. Oncogene inhibition can augment the efficacy of immune-based therapy, but mechanisms by which these two interventions might cooperate are incompletely resolved. Using a novel transplantable BRAFV600E-mutant murine melanoma model (SB-3123), we explored potential mechanisms of synergy between the selective BRAFV600E inhibitor vemurafenib and adoptive cell transfer (ACT)–based immunotherapy. We found that vemurafenib cooperated with ACT to delay melanoma progression without significantly affecting tumor infiltration or effector function of endogenous or adoptively transferred CD8+ T cells, as previously observed. Instead, we found that the T-cell cytokines IFNγ and TNFα synergized with vemurafenib to induce cell-cycle arrest of tumor cells in vitro. This combinatorial effect was recapitulated in human melanoma–derived cell lines and was restricted to cancers bearing a BRAFV600E mutation. Molecular profiling of treated SB-3123 indicated that the provision of vemurafenib promoted the sensitization of SB-3123 to the antiproliferative effects of T-cell effector cytokines. The unexpected finding that immune cytokines synergize with oncogene inhibitors to induce growth arrest has major implications for understanding cancer biology at the intersection of oncogenic and immune signaling and provides a basis for design of combinatorial therapeutic approaches for patients with metastatic cancer. Cancer Immunol Res; 3(1); 37–47. ©2014 AACR.

See related commentary by Riddell, p. 23
Antioxidant Status and the Risk of Elevated C-Reactive Protein 12 Years Later
Authors: Julia Chantal , Galan Pilar , Touvier Mathilde , Meunier Nathalie , Papet Isabelle , Sapin Vincent , Cano Noël , Faure Patrice , Hercberg Serge , Kesse-Guyot Emmanuelle
Published: October 2014

Background/Aims: Low-grade inflammation is an independent risk factor for cardiovascular disease. Relationships between the antioxidant status and inflammatory biomarkers could give new insights into cardiovascular disease prevention. We investigated long-term associations between the antioxidant nutrient (vitamin C, α-tocopherol, β-carotene) status and C-reactive protein (CRP) in a population-based cohort. Methods: Subjects included in the French SU.VI.MAX trial study who had available data on baseline (1994-1995) blood nutrient concentrations and CRP measurements 12 years later (2007-2009) were included. Associations between baseline antioxidant circulating concentrations and elevated CRP (>3 mg/l) were investigated in multivariate logistic regression models. Subgroup analyses were performed according to gender, supplementation group of the initial trial, smoking status, and alcohol intake. Results: Serum α-tocopherol (n = 2,060) and vitamin C (n = 1,719) concentrations [odds ratio (OR) and 95% confidence interval (95% CI) quintile 5 vs. 1: OR 1.10 (95% CI 0.71-1.73), p for trend = 0.533, vs. OR 0.79 (95% CI 0.48-1.29), p for trend = 0.121, respectively] were not associated with elevated CRP concentrations. The β-carotene status (n = 2,048) was inversely associated with elevated CRP [adjusted OR quintile 5 vs. 1: OR 0.61 (95% CI 0.38-0.98), p for trend = 0.01]. Subgroup analyses showed that associations were stronger in women (p for trend = 0.004), never smokers (p for trend = 0.009) and subjects in the supplementation group (p for trend = 0.002). Conclusions: Our results suggest that the β-carotene status may be inversely associated with low-grade inflammation in the long term.
Evaluation of Endometrial Thickness and Bone Mineral Density Based on CYP2D6 Polymorphisms in Turkish Breast Cancer Patients Receiving Tamoxifen Treatment
Authors: Günaldı Meral , Erkisi Melek , Afşar Çiğdem Usul , Erçolak Vehbi , Paydas Semra , Kara I. Oguz , Şahin Berksoy , Gulec Umran Kucukgoz , Secilmis Ata
Published: October 2014

Background: Several previous studies have examined the effect of CYP2D6 gene polymorphism on the efficacy and metabolism of tamoxifen (Tamoxifen Teva, Nolvadex) in the treatment of breast cancer. In the present study, the metabolic profiles associated with various CYP2D6 genotypes were evaluated. Method: In the present study 92 Turkish breast cancer patients with early-stage hormone receptor-positive tumors treated with adjuvant tamoxifen (20 mg) were evaluated for CYP2D6 genotype and metabolic profiles. Known side effects of tamoxifen treatment, including endometrial thickening, changes in serum lipid levels and bone density, and hepatosteatosis, were evaluated according to the CYP2D6 polymorphism. Result: The distribution of metabolic characteristics in the Turkish population was as follows: 77.1% normal metabolism, 11.5% intermediate metabolism, 5.2% ultrarapid metabolism, and 2.1% poor metabolism. The CYP2D6 genotypes associated with rapid metabolism were CYP2D6 3X*1/*1 duplication (DUP) and CYP2D6 2X*1/*2, while poor metabolism was associated with the genotypes CYP2D6 *3/*4 and CYP2D6 *6/*6. There was no statistically significant relationship between metabolic characteristics and bone density or hepatosteatosis. A statistically significant difference in total cholesterol and triglycerides was detected in lipid profile analysis (p = 0.003, p = 0.02). Assessment of endometrial thickness revealed a significant association of hyperplasia and poor metabolism, and an association between atrophy and ultrarapid metabolism (p = 0.01). Conclusion: Significant development of endometrial hyperplasia was identified among individuals with poor tamoxifen metabolism. As a result, tamoxifen may be a significant predictor of endometrial thickening among individuals with poor metabolic characteristics.
Pharmacokinetics and Pharmacodynamics following Intravenous Administration of Recombinant Human Hepatocyte Growth Factor in Rats with Renal Injury
Authors: Adachi Eri , Hirose-Sugiura Tomoko , Kato Yukio , Ikebuchi Fumie , Yamashita Atsuko , Abe Tetsushi , Fukuta Kazuhiro , Adachi Kiichi , Matsumoto Kunio
Published: October 2014

Background/Aim: Hepatocyte growth factor (HGF) plays a role in the regeneration and protection of the kidney, but little information is available concerning the pharmacokinetics of therapeutic treatment with HGF. In this study, HGF was administered after the onset of renal injury, and pharmacokinetic analysis was performed simultaneously with an efficacious dose. Methods: For the study of pharmacodynamics, recombinant human HGF was intravenously administered to rats with glycerol-induced acute kidney injury (AKI). In the pharmacokinetic study, rats subjected to glycerol injection or renal ischemia-reperfusion were used as models of AKI, and rats subjected to 5/6 nephrectomy were used as models of chronic kidney disease (CKD). Results: After intravenous administration of HGF at doses of 0.5-2.0 mg/kg, the elevation of blood urea nitrogen was suppressed, indicating that HGF had a pharmacodynamic effect. However, no significant difference was seen in the pharmacokinetic parameters such as clearance, distribution volume and half-life between the normal, AKI and CKD groups. Conclusion: The intravenous administration of HGF after the onset of renal dysfunction exerted a pharmacological effect on AKI, and renal injury did not affect the clearance of plasma HGF. This unaffected profile may serve as a base for the safety of HGF during therapeutic administration.
Neuroinvasive Phlebovirus Infection in Greece: A Case Report
Authors: Papa Anna , Mallias John , Tsergouli Katerina , Markou Fani , Poulou Ageliki , Milidis Theodor
Published: October 2014

Objective: Sandfly fever phleboviruses are endemic in Mediterranean countries. We report a febrile phlebovirus case in a Greek patient who presented signs of neuroinvasive infection. Methods: In summer 2010, a 20-year-old male was admitted to hospital with fever and lethargy; he was a resident of central Macedonia, northern Greece, where a large outbreak of West Nile virus (WNV) infections occurred at that time. Since there was no laboratory evidence of WNV infection, the patient's serum and cerebrospinal fluid were tested for a probable phlebovirus infection. Results: High titers of IgM and IgG antibodies against Toscana virus were detected in serum and cerebrospinal fluid, while the titers against sandfly fever Naples virus were lower; no reactivity was detected against sandfly Sicilian and Cyprus viruses. Since neutralization assays were not performed and PCR resulted in being negative, it was concluded that the causative agent was a phlebovirus of the sandfly fever Naples serocomplex. Conclusion: The present case confirms results from previous seroprevalence studies showing that phleboviruses of the sandfly fever Naples serocomplex are present in Greece and provides evidence that they cause febrile neuroinvasive disease in humans, prompting for inclusion of phleboviral infections in the differential diagnosis of acute febrile cases during the time when sandflies are active.
Accuracy of Resting Energy Expenditure Calculations in Unselected Overweight and Obese Patients
Authors: Schusdziarra Volker , Wolfschläger Karl , Hausmann Margit , Wagenpfeil Stefan , Erdmann Johannes
Published: October 2014

Aims: Measurements of resting energy expenditure (REE) were compared with the data of 14 equations to determine their accuracy. Methods: REE measurements by indirect calorimetry in 1,032 unselected overweight and obese men (n = 306) and women (n = 726) were compared with calculations by 14 different formulas. Results: The mean (± SD) values calculated with the Owen, Robertson and Reid and WHO-I equations were not significantly different from our measurement of 1,682 ± 441.9 kcal/24 h. The values obtained with the Livingston, Mifflin, Müller and Bernstein equations were significantly different but still within a range of ±100 kcal/24 h. For females, the best comparison was observed with the Müller equation which, however, differed substantially in males. For men, the Cunningham equation was best, but it gave the worst comparison in women. A good individual match was only obtained with the equation of Robertson and Reid in 34% of the men and with the Owen equation in 38% of the women. All other formulas were less accurate. Drug treatment for 55% of the subjects had no effect on the mismatch between calculated and measured data. Conclusion: Calculations of REE with most equations seem to be valid in a group analysis but they are not helpful for the estimation of an obese patient's individual energy expenditure.
Spontaneous Arterial Calcification: A Possible Etiology for Spontaneous Splenic Rupture in a Patient on Maintenance Hemodialysis
Authors: Hou Yi-Chou , Chen Yen-Lin , Lu Kuo-Cheng
Published: October 2014

Spontaneous splenic rupture (SSR) is a rare condition in contrast to traumatic splenic hematoma, and vascular abnormality has rarely mentioned as an etiology in SSR with patients who had chronic kidney disease. We reported a 80-year-old female whose SSR might be related to splenic arterial calcification. i 2014 S. Karger AG, Basel
Role of the rs6923761 Gene Variant in Glucagon-Like Peptide 1 Receptor Gene on Cardiovascular Risk Factors and Weight Loss after Biliopancreatic Diversion Surgery
Authors: de Luis Daniel Antonio , Pacheco David , Aller Rocío , Izaola Olatz
Published: October 2014

Background: Studies of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) have been directed at identifying polymorphisms in the GLP-1R gene that may be a contributing factor in the pathogenesis of obesity. Objective: We decided to investigate the role of the rs6923761 GLP-1R polymorphism on outcomes after biliopancreatic diversion. Design: A sample of 137 morbidly obese patients was operated. Weight, blood pressure, basal glucose and lipid profile were measured at the basal visit and at each following visit (basal, 3, 9, 12 and 18 months). Results: Body mass index, weight and waist circumference were lower in non-A allele carriers than A allele carriers 12 and 18 months after surgery. The initial weight percent loss at 12 months (45.6 vs. 39.8%; p < 0.05) or 18 months (49.6 vs. 41.3%; p < 0.05) was higher in patients with GG genotype than A allele carriers. Conclusion: Our study showed a higher weight loss 12 and 18 months after bariatric surgery in GG variant than A allele carriers. The biochemical parameters and cardiovascular comorbidity rates improved similarly in both genotypes.
Body Composition, Hemodynamic, and Biochemical Parameters of Young Female Normal-Weight Oligo-Amenorrheic and Eumenorrheic Athletes and Nonathletes
Authors: Singhal Vibha , de Lourdes Eguiguren Maria , Eisenbach Lindsey , Clarke Hannah , Slattery Meghan , Eddy Kamryn , Ackerman Kathryn E. , Misra Madhusmita
Published: October 2014

Aims: Low-weight hypogonadal conditions such as anorexia nervosa are associated with marked changes in body composition, hemodynamic and hematological parameters, and liver enzymes. The impact of athletic activity in normal-weight adolescents with/without amenorrhea on these parameters has not been assessed. Our aim was to examine these parameters in normal-weight athletes and nonathletes and determine any associations with body composition, oligo-amenorrhea, and exercise intensity. Methods: We assessed vital signs, complete blood counts, liver enzymes, and regional body composition in 43 oligo-amenorrheic athletes (OAA), 24 eumenorrheic athletes (EA), and 23 nonathletes aged 14-21 years. Results: The BMI was lower in OAA than in EA. Systolic and pulse pressure and temperature were lowest in OAA. Blood counts did not differ among groups. Aspartate aminotransferase (AST) was higher in both groups of athletes, while alanine aminotransferase (ALT) was higher in OAA than in EA and nonathletes. Total and regional fat were lower in OAA than in other groups, and these factors were associated positively with heart rate and inversely with liver enzymes. Conclusions: Athletic activity is associated with higher AST levels, whereas menstrual dysfunction is associated with lower total and regional fat and higher ALT levels. Higher liver enzymes are associated with reductions in total and regional fat.
A Deep-Sequencing Method Detects Drug-Resistant Mutations in the Hepatitis B Virus in Indonesians
Authors: Widasari Dewiyani Indah , Yano Yoshihiko , Heriyanto Didik Setyo , Utsumi Takako , Yamani Laura Navika , Rinonce Hanggoro Tri , Wasityastuti Widya , Lusida Maria Inge , Soetjipto  , Okada Rina , Murakami Yoshiki , Tanahashi Toshihito , Azuma Takeshi , Hayashi Yoshitake
Published: October 2014

Objective: The long-term administration of a nucleos(t)ide analogue (NA) for the treatment of chronic hepatitis B may encourage the emergence of viral mutations associated with drug resistance. Minor populations of viruses may exist before treatment, but are difficult to detect because of technological limitations. Identifying minor viral quasispecies should be useful in the clinical management of hepatitis B virus (HBV) infection. Methods: Six treatment-naïve Indonesian patients with chronic HBV infection participated in this study. The polymerase region of the HBV genome, including regions with known drug-resistant mutations, was subjected to capillary sequencing and MiSeq sequencing (Illumina). Mutations were analyzed with Genomics Workbench software version 6.0.1 (CLC bio). Results: The mean mapping reads for the six samples was 745,654, and the mean number of amplified fragments ranged from 17,926 to 25,336 DNA reads. Several known drug-resistant mutations in the reverse transcriptase region were identified in all patients, although the frequencies were low (0.12-1.06%). The proportions of the total number of reads containing mutations I169L/M, S202R, M204I/L or N236S were >1.0%. Conclusion: Several known NA-resistant mutations were detected in treatment-naïve patients in Indonesia using deep sequencing. Careful management of such patients is essential to prevent drug-resistant mutations from spreading to other patients.
Best Anthropometric and Atherogenic Predictors of Metabolic Syndrome in the Chinese Han Population in Xinjiang: The Cardiovascular Risk Survey
Authors: Chen Bang-Dang , He Chun-Hui , Ma Yi-Tong , Yang Yi-Ning , Liu Fen , Pan Shuo , Ma Xiang , Li Xiao-Mei , Fu Zhen-Yan , Xie Xiang , Zheng Ying-Ying
Published: October 2014

Objective: This study aimed to identify the best predictor of metabolic syndrome (MetS) by comparing the predicting ability of various anthropometric and atherogenic parameters in the Chinese Han population in Xinjiang. Methods: A representative, cross-sectional sample of 5,757 Chinese Han adults were selected from the Cardiovascular Risk Survey conducted from October 2007 to March 2010. MetS prevalence, area under the curve (AUC), distance on the receiver operating characteristic curve and the cut-offs of each variable were compared for the presence of MetS. Results: According to the criteria of the International Diabetes Federation (IDF), the Joint Interim Statement (JIS) and the Third Adult Treatment Panel (ATPIII), 32.1, 48.5, 39.3% of men and 38.0, 45.1, 44.9% of women had MetS in Xinjiang. According to the IDF criteria, the waist-to-height ratio (WHtR) had the highest AUC value in men (0.836) and women (0.837), with the optimal cut-off of 0.54 in men and 0.53 in women. According to both the JIS and ATPIII criteria, triglycerides/high-density lipoprotein cholesterol TG/HDL-C had the highest AUC value in men (0.830 and 0.833, respectively) and women (0.832 and 0.827, respectively), with the optimal cut-offs being 1.6 and 1.2 in men and 1.1 and 1.1 in women, respectively. Conclusion: WHtR was the best predictor of MetS according to the IDF criteria while TG/HDL-C was the best predictor of MetS according to the JIS and ATPIII criteria.
The Role of Combined 68Ga-DOTANOC and 18FDG PET/CT in the Management of Patients with Pancreatic Neuroendocrine Tumors
Authors: Partelli Stefano , Rinzivillo Maria , Maurizi Angela , Panzuto Francesco , Salgarello Matteo , Polenta Vanessa , Delle Fave Gianfranco , Falconi Massimo
Published: October 2014

Purpose: The aim of this study was to evaluate the effect of combined 68Ga and 18F-FDG PET/CT on treatment management for patients with pancreatic neuroendocrine tumor (PNET). Methods: Between January 2012 and April 2014, 49 consecutive patients with a cytologically and/or histologically proven diagnosis of PNET underwent combined 68Ga and 18FDG PET/CT on the same day. Results: The study group consisted of 21 males and 28 females with a median age of 59 years. Disease detection was achieved in 48 out of the 49 cases with 68Ga imaging, and in 36 of the 49 cases with 18FDG PET/CT. These results corresponded to sensitivities of 98% for 68Ga versus 73% for 18FDG PET/CT. Patients with NET-G1/NET-G2 had a positive 68Ga and negative 18FDG PET/CT in 13 cases, whereas both 68Ga and 18FDG PET/CT were positive in 27 cases. Patients with NEC-G3 were positive by both 68Ga and 18FDG PET/CT in 7 cases and positive only by 18FDG in 1 case. Another NEC-G3 patient was only positive by 68Ga PET/CT. The median Ki67 was 7% for 68Ga PET/CT-positive tumors and 10% for tumors with both 68Ga and 18FDG PET/CT positivity (p = 0.130). Half of the patients with a prevalent uptake of 18FDG (n = 7) had an NEC-G3 compared with 12% of patients with a prevalent uptake of 68Ga (p = 0.012). There were no significant differences between patients with positive 68Ga and those with positive 18FDG with regards to treatment choice. Conclusions: The association of 18FDG slightly increases sensitivity of 68Ga PET/CT alone in the diagnosis of PNET. A combined dual tracer PET/CT does not influence the choice of treatment strategy.
Decline of Renal Function and Progression of Left Ventricular Hypertrophy Are Independently Determined in Chronic Kidney Disease Stages 3-5
Authors: Suzuki Hiromichi , Inoue Tsutomu , Dogi Mami , Kikuta Tomohiro , Takenaka Tsuneo , Okada Hirokazu
Published: October 2014

Invasive and noninvasive methods for evaluating the effects of hemodynamics on progression of left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD) have been proposed. Central aortic pressure (CAP) has been reported to be the best among selected measures of hemodynamics for predicting LVH. However, there are few studies examining the relation between longitudinal changes in CAP and renal dysfunction in patients with CKD. Methods: Sixty-seven patients with CKD stages 3-5 (female/male ratio: 26/41, age: 61.5 ± 13.1 years) were followed for 5 years. Before and at the end of the 5-year period, CAP was recorded by an automated tonometric system (HEM-9000 AI; Omron Healthcare, Kyoto, Japan). Second systolic aortic blood pressure (SBP2) was employed as an index of CAP. Results: Throughout the study, systolic blood pressure (SBP) was well controlled. Renal function followed by estimated glomerular filtration rate (eGFR) gradually worsened as a whole. Ten patients had renal replacement therapy, 3 patients developed cardiovascular diseases and 2 patients were found to have a neoplasm during the 5-year observation period. SBP2 increased from 120 ± 19 to 125 ± 33 mm Hg and eGFR decreased from 38.2 ± 18.2 to 29.5 ± 16.3 ml/min/1.73 m2; however, these differences did not achieve significance. The left ventricular mass (LVM) index significantly increased from 115.5 ± 10.5 to 131.2 ± 11.7 g/m2 (p < 0.05). Although the changes in SBP2 and eGFR looked like a mirror image, there was no significant correlation between the two factors. Moreover, multivariate regression analysis did not reveal a close correlation between SBP2 and CKD progression. In contrast to the decline of renal function, the baseline value of SBP2 predicted an increase in the LVM index. Conclusion: Worsening of renal dysfunction is not solely dependent on hemodynamics. Other factors might be involved in a complex manner. © 2014 S. Karger AG, Basel
High Plasma Levels of Heparin-Binding Epidermal Growth Factor Are Associated With a More Stable Plaque Phenotype and Reduced Incidence of Coronary Events
Authors: Rattik Sara , Wigren Maria , Björkbacka Harry , Fredrikson Gunilla Nordin , Hedblad Bo , Siegbahn Agneta , Bengtsson Eva , Schiopu Alexandru , Edsfeldt Andreas , Dunér Pontus , Grufman Helena , Gonçalves Isabel , Nilsson Jan
Published: October 2014

Objective—

Rupture of atherosclerotic plaques is the major cause of acute coronary events (CEs). Plaque destabilization is the consequence of an imbalance between inflammatory-driven degradation of fibrous tissue and smooth muscle cell–dependent tissue repair. Proinflammatory factors have been documented extensively as biomarkers of cardiovascular risk but factors that contribute to stabilization of atherosclerotic plaques have received less attention. The present study aimed to investigate whether plasma levels of the smooth muscle cell growth factor epidermal growth factor (EGF), heparin-binding-EGF (HB-EGF), and platelet-derived growth factor correlate with plaque phenotype and incidence of CEs.

Approach and Results—

HB-EGF, EGF and platelet-derived growth factor were measured in plasma from 202 patients undergoing carotid endarterectomy and in 384 incident CE cases and 409 matched controls recruited from the Malmö Diet and Cancer cohort. Significant positive associations were found between the plasma levels of all 3 growth factors and the collagen and elastin contents of the removed plaques. CE cases in the Malmö Diet and Cancer cohort had lower levels of HB-EGF in plasma, whereas no significant differences were found for EGF and platelet-derived growth factor. After adjusting for cardiovascular risk factors in a Cox proportional hazard model, the hazard ratio for the highest HB-EGF tertile was 0.61 (95% confidence interval, 0.47–0.82;
P
<0.001).

Conclusions—

The associations between high levels of smooth muscle cell growth factors in plasma and a more fibrous plaque phenotype as well as the association between low levels of HB-EGF and incident CEs point to a potential clinically important role for factors that contribute to plaque stabilization by stimulating smooth muscle cells.
Protein Kinase C δ Deficiency Enhances Megakaryopoiesis and Recovery From Thrombocytopenia
Authors: Kostyak John C. , Bhavanasi Dheeraj , Liverani Elisabeta , McKenzie Steven E. , Kunapuli Satya P.
Published: October 2014

Objective—

We previously determined that protein kinase C δ (PKCδ) regulates platelet function. However, the function of PKCδ in megakaryopoiesis is unknown.

Approach and Results—

Using PKCδ
-/-
and wild-type littermate mice, we found that deficiency of PKCδ caused an increase in white blood cells and platelet counts, as well as in bone marrow and splenic megakaryocytes (
P
<0.05). Additionally, the megakaryocyte number and DNA content were enhanced in PKCδ
-/-
mouse bone marrow after culturing with exogenous thrombopoietin compared with wild-type (
P
<0.05). Importantly, thrombopoietin-induced signaling was also altered with PKCδ deletion because both extracellular signal-regulated kinase and Akt308 phosphorylation were heightened in PKCδ
-/-
megakaryocytes compared with wild-type. Finally, PKCδ
-/-
mice recovered faster and had a heightened rebound thrombocytosis after thrombocytopenic challenge.

Conclusions—

These data suggest that PKCδ is an important megakaryopoietic protein, which regulates signaling induced by thrombopoietin and represents a potential therapeutic target.
Transdifferentiation of Human Fibroblasts to Endothelial Cells
Authors: Sayed Nazish , Wong Wing Tak , Ospino Frank , Meng Shu , Lee Jieun , Jha Arshi , Dexheimer Phillip , Aronow Bruce J. , Cooke John P.
Published: October 2014

Background—

Cell fate is fluid and may be altered experimentally by the forced expression of master regulators mediating cell lineage. Such reprogramming has been achieved with the use of viral vectors encoding transcription factors. We recently discovered that the viral vectors are more than passive vehicles for transcription factors because they participate actively in the process of nuclear reprogramming to pluripotency by increasing epigenetic plasticity. On the basis of this recognition, we hypothesized that small-molecule activators of toll-like receptor 3, together with external microenvironmental cues that drive endothelial cell (EC) specification, might be sufficient to induce transdifferentiation of fibroblasts into ECs (induced ECs).

Methods and Results—

We show that toll-like receptor 3 agonist Poly I:C, combined with exogenous EC growth factors, transdifferentiated human fibroblasts into ECs. These induced ECs were comparable to human dermal microvascular ECs in immunohistochemical, genetic, and functional assays, including the ability to form capillary-like structures and to incorporate acetylated low-density lipoprotein. Furthermore, induced ECs significantly improved limb perfusion and neovascularization in the murine ischemic hindlimb. Finally, using genetic knockdown studies, we found that the effective transdifferentiation of human fibroblasts to ECs requires innate immune activation.

Conclusions—

This study suggests that manipulation of innate immune signaling may be generally used to modify cell fate. Because similar signaling pathways are activated by damage-associated molecular patterns, epigenetic plasticity induced by innate immunity may play a fundamental role in transdifferentiation during wound healing and regeneration. Finally, this study is a first step toward development of a small-molecule strategy for therapeutic transdifferentiation for vascular disease.
L-Kynurenine/Aryl Hydrocarbon Receptor Pathway Mediates Brain Damage After Experimental Stroke
Authors: Cuartero María I. , Ballesteros Iván , de la Parra Juan , Harkin Andrew L. , Abautret-Daly Aine , Sherwin Eoin , Fernández-Salguero Pedro , Corbí Ángel L. , Lizasoain Ignacio , Moro María A.
Published: October 2014

Background—

Aryl hydrocarbon receptor (AhR) is a transcription factor that belongs to the basic helix-loop-helix PAS (Per-Arnt-Sim homology domain) family known to mediate the toxic and carcinogenic effects of xenobiotics. Interestingly, AhR is widely expressed in the central nervous system, but its physiological and pathological roles are still unclear.

Methods and Results—

To define the role of AhR in stroke, we used middle cerebral artery occlusion in mice and oxygen-glucose deprivation in rat cortical neurons. The results presented here show that the ischemic insult increases total and nuclear AhR levels and AhR transcriptional activity in neurons in vivo and in vitro. We also show that AhR has a causal role in acute ischemic damage because pharmacological or genetic loss-of-function approaches result in neuroprotection. Inhibition of cAMP response element-binding protein–dependent signaling may participate in the deleterious actions of AhR. Finally, we have also found that L-kynurenine, a tryptophan metabolite with AhR agonistic properties, is an endogenous ligand that mediates AhR activation in the brain after middle cerebral artery occlusion.

Conclusions—

Our data demonstrate that an L-kynurenine/AhR pathway mediates acute brain damage after stroke and open new possibilities for the diagnosis and treatment of this pathology.
Impact of Atrial Fibrillation on Healthcare Utilization in the Community: The Atherosclerosis Risk in Communities Study
Authors: Bengtson Lindsay G. S. , Lutsey Pamela L. , Loehr Laura R. , Kucharska‐Newton Anna , Chen Lin Y. , Chamberlain Alanna M. , Wruck Lisa M. , Duval Sue , Stearns Sally C. , Alonso Alvaro
Published: October 2014

Background

Atrial fibrillation (
AF
) is associated with increased risk of hospitalization. Little is known about the impact of
AF
on utilization of noninpatient health care or about sex or race differences in
AF
‐related utilization. We examined rates of inpatient and outpatient utilization by
AF
status in the Atherosclerosis Risk in Communities study.

Methods and Results

Participants with incident
AF
enrolled in fee‐for‐service Medicare for at least 12 continuous months between 1991 and 2009 (n=932) were matched on age, sex, race and field center with up to 3 participants without
AF
(n=2729). Healthcare utilization was ascertained from Medicare claims and classified by primary International Classification of Diseases, ninth revision code. The average annual numbers of days hospitalized were 13.2 (95% CI 11.6 to 15.0) and 2.8 (95%
CI
2.5 to 3.1) for those with and without
AF
, respectively. The corresponding numbers of annual outpatient claims were 53.3 (95%
CI
50.5 to 56.3) and 22.9 (95%
CI
22.1 to 23.8) for those with and without
AF
, respectively. Most utilization among
AF
patients was attributable to non‐
AF
conditions. The adjusted rate ratio for annual days hospitalized for other cardiovascular disease–related reasons was 4.58 (95%
CI
: 3.41 to 6.16) for those with AF versus those without
AF
. The association between
AF
and healthcare utilization was similar among men and women and among white and black participants.

Conclusions

Participants with
AF
had considerably greater healthcare utilization, and the difference in utilization for other
cardiovascular disease
–related reasons was substantial. In addition to rate or rhythm treatment,
AF
management should focus on the accompanying cardiovascular comorbidities.
Varying Definitions for Periprocedural Myocardial Infarction Alter Event Rates and Prognostic Implications
Authors: Idris Hanan , Lo Sidney , Shugman Ibrahim M. , Saad Yousef , Hopkins Andrew P. , Mussap Christian , Leung Dominic , Thomas Liza , Juergens Craig P. , French John K.
Published: October 2014

Background

Periprocedural myocardial infarction (
PMI
) has had several definitions in the last decade, including the Society for Cardiovascular Angiography and Interventions (
SCAI
) definition, that requires marked biomarker elevations congruent with surgical
PMI
criteria.

Methods and Results

The aim of this study was to examine the definition‐based frequencies of
PMI
and whether they influenced the reported association between
PMI
and increased rates of late death/ myocardial infarction (
MI
). We studied 742 patients; 492 (66%) had normal troponin T (TnT) levels and 250 (34%) had elevated, but stable or falling, TnT levels.
PMI
, using the 2007 and the 2012 universal definition, occurred in 172 (23.2%) and in 99 (13.3%) patients, respectively, whereas 19 (2.6%) met the
SCAI PMI
definition (
P
<0.0001). Among patients with
PMI
using the 2012 definition, occlusion of a side branch ≤1 mm occurred in 48 patients (48.5%) and was the most common angiographic finding for
PMI
. The rates of death/
MI
at 2 years in patients with, compared to those without,
PMI
was 14.7% versus 10.1% (
P
=0.087) based on the 2007 definition, 16.9% versus 10.3% (
P
=0.059) based on the 2012 definition, and 29.4% versus 10.7% (
P
=0.015) based on the
SCAI
definition.

Conclusion

In this study,
PMI
, according to the
SCAI
definition, was associated with more‐frequent late death/
MI
, with ≈20% of all patients, who had
PMI
using the 2007 universal
MI
definition, not having
SCAI
‐defined
PMI
. Categorizing these latter patients as
SCAI
‐defined no
PMI
did not alter the rate of death/
MI
among no‐
PMI
patients.
Turning to the Goddess: Anachronism, Secularity, and the Late Style of Tyeb Mehta and K. G. Subramanyan
Authors: Zitzewitz Karin
Published: October 2014

At nearly the same late-1980s moment, two of the most important artists of India's twentieth century, Tyeb Mehta (1925–2009) and K. G. Subramanyan (b. 1924), turned to the goddess as a subject for painting. Although Mehta and Subramanyan represented different strands of Indian modernism, they had both hitherto largely limited themselves to secular subject matter. This essay accounts for the significance of their goddess turn by discussing it as an example of late style, as theorized by Edward Said. It finds in these paintings the intransigence, anachronism, and negative intervention championed by Said, but also a critique of the secularism that he argued was the root of late style. Mehta and Subramanyan's intervention came at a crucial moment in Indian art history, as modernism began to be undermined by a rising group of narrative painters supported by the critic Geeta Kapur. The older artists’ embrace of the religious image sits uneasily in Kapur's influential narration of post-colonial Indian art history.
Seeing a World Apart: Visual Reality in Michelangelo Antonioni's Chung Kuo/Cina
Authors: Lin Jenny
Published: October 2014

This essay examines Michelangelo Antonioni's Chung Kuo Cina (China) (1972), a documentary made in and about the People's Republic of China during the height of the Cultural Revolution. Detailing the documentary's controversial reception and analyzing Chung Kuo’s emphasis on visual reality in opposition to the PRC's official socialist realism, I argue that Chung Kuo constituted a critical cross-cultural project, while providing a unique portrayal of quotidian life in Maoist China.
Of Cultural Diplomacy, Culture Games, and Curation of Non-Western Art
Authors: Karimi Pamela
Published: October 2014

This essay is a review of the Iran Modern Exhibition, which took place at the Asia Society in New York from September 6, 2013, to January 5, 2014. The show was the first major international retrospective of Iranian art of the 1960s and 1970s. While shedding light on the featured art from a period that is lesser known outside of Iran, this essay mainly elaborates on the curatorial strategies at work in the exhibit.
Composing Perceivable Time
Authors: Kirby Jenn
Published: October 2014

Time is an integral element in music. The chronometric duration of a piece of music often differs from the duration perceived by the listener. This paper presents a composition that aims to manipulate the listener’s perception of time and presents the research findings that influenced the compositional decisions.
Weather as Medium: Art and Meteorological Science
Authors: Randerson Janine , Salmond Jennifer , Manford Chris
Published: October 2014

The recent artworks Albedo of Clouds and Neighbourhood Air adopt weather as primary material for sensory experiences. The art installations included the contributions of scientists, programmers, instrument technicians, social online networks and the vagaries of the weather itself. The projects suggest that creative engagement with meteorological science can activate eco-political “networks” in Latour’s sense, productive of knowledge and potentially transformative. In such “meteorological art,” digital networks not only distribute facts about atmospheric data; they also generate affective forms. Multi-directional flows between weather instrumentation, digital data, media art and meteorological science are enacted in the pursuit of a creative outcome.
Karakuri: Subtle Trickery in Device Art and Robotics Demonstrations at Miraikan
Authors: Shea Michael
Published: October 2014

Based on museological participant-observation conducted at the Miraikan National Museum of Emerging Science and Innovation in Tokyo, this article considers the role of karakuri, or subtle trickery, referring to devices that evoke a sense of awe and wonderment through concealment of their inner workings. The author critically assesses Miraikan’s Tearoom of Zero/One gallery space as well as its ASIMO demonstrations in terms of their utilization of this quality.
Synesthesia: From Cross-Modal to Modality-Free Learning and Knowledge
Authors: Williams Roy , Gumtau Simone , Mackness Jenny
Published: October 2014

In an integrated view of perception and action, learning involves all the senses, their interaction and cross-modality, rather than multi-modality alone. This can be referred to as synesthetic enactive perception, which forms the basis for more abstract, modality-free knowledge and a potential underpinning for innovative learning design. The authors explore this mode of learning in two case studies: The first focuses on children in Montessori preschools and the second on MEDIATE, an interactive space designed for children on the autistic spectrum that offers a “whole-body” engagement with the world.
Ibn Khaldūn, Ibn al-Khaṭīb and Their Milieu: A Community of Letters in the Fourteenth-Century Mediterranean
Authors: Fromherz Allen
Published: October 2014

Despite the calamities of the fourteenth century, the Black Death, the disintegration of political power, and the destructive rivalry between North African and Andalusī rulers, the correspondence of two scholars and ministers, Ibn al-Khaṭīb and Ibn Khaldūn, reveals a network of intellectual contacts maintained above the fray. As Ibn al-Khaṭīb’s famous essay, the “Art of Being a Minister,” made clear, the intelligentsia saw itself as both within and above the political milieu. The conferring of diplomas from teacher to student was based as much on personal loyalty as on scholarship. In the same century, however, many members of the intellectual club, including Ibn Khaldūn and his teachers, complained that rulers limited the traditional freedoms of the scholars and ministers. Ibn Khaldūn articulated these moves as assaults on true scholarship. The intellectuals writing the history of the fourteenth-century Mediterranean were not simply agents of the rulers they worked for; rather, even as rivals they saw themselves as guardians in a family of letters, linked more by the ijāza than by blood. They were, or at least aspired to be, members of an intellectual class that transcended political and, sometimes, religious boundaries.
The Great Ruling Family of the Fourteenth Century: Muṣāhara in the Age of Ibn al-Khaṭīb
Authors: Ženka Josef
Published: October 2014

Muṣāhara (affinity/relation by marriage) represented one of the essential distinctions of the ruling elite of fourteenth-century Granada. Ibn al-Khaṭīb understood its importance for life in Granada and he felt the need to mention it whenever two people were related by marriage. His perception has been taken as one of the most fundamental for historical research, as he drew on his personal experience in Granada. This study first defines the concept of the ruling elite of fourteenth-century Granada. Within this group, the concept of muṣāhara as understood by Ibn al-Khaṭīb is further elaborated. The definition of muṣāhara is followed by the description of its actual use among the families close to the office of the vizier (wazīr) and by Ibn al-Khaṭīb himself. The history of one of these families (al-Fihrī) has been hailed as an exceptional example of the “ruling elite family” that included contemporaries and adversaries of Ibn al-Khaṭīb. The example of the al-Fihrī family shows how strong and active their position was during the rule of every fourteenth-century emir. Consequently, this study demonstrates that the extensive Granadan families similar to those known from the fifteenth century had existed and cooperated with each other before this time.