bluuebunny/crossref_metadata_2025 huggingface dataset:
A mutation in the β-subunit of ENaC identified in a patient with cystic fibrosis-like symptoms has a gain-of-function effect
Authors: Rauh Robert , Soell Daniel , Haerteis Silke , Diakov Alexei , Nesterov Viatcheslav , Krueger Bettina , Sticht Heinrich , Korbmacher Christoph
Published: October 2012

In some patients with atypical cystic fibrosis (CF), only one allele of the CF transmembrane conductance regulator (CFTR) gene is affected. Mutations of the epithelial sodium channel (ENaC) may contribute to the pathophysiology of the disease in these patients. To functionally characterize a mutation in the β-subunit of ENaC (βV348M) recently identified in a patient with severe CF-like symptoms (Mutesa et al. 2009), we expressed wild-type (wt) αβγENaC or mutant αβV348MγENaC in Xenopus laevis oocytes. The βV348M mutation stimulated amiloride-sensitive whole-cell current (Δ Iami) by ∼40% but had no effect on surface expression or single-channel conductance of ENaC. Instead the mutation increased channel open probability ( Po). Proteolytic activation of mutant ENaC by chymotrypsin was reduced compared with that of wt ENaC (∼3.0-fold vs. ∼4.2-fold), which is consistent with the increased baseline Po of mutant ENaC. Similarly, the ENaC activator S3969 stimulated mutant ENaC currents to a lesser degree (by ∼2.6-fold) than wt ENaC currents (by ∼3.5-fold). The gain-of-function effect of the βV348M mutation was confirmed by whole-cell current measurements in HEK293 cells transiently transfected with wt or mutant ENaC. Computational channel modeling in combination with functional expression of different βV348 mutants in oocytes suggests that the βV348M mutation increases channel Po by destabilizing the closed channel state. Our findings indicate that the gain-of-function effect of the βV348M mutation may contribute to CF pathophysiology by inappropriately increasing sodium and fluid absorption in the respiratory tract.
Medulloblastoma with Excessive Nodularity: Radiographic Features and Pathologic Correlate
Authors: Yeh-Nayre L. A. , Malicki D. M. , Vinocur D. N. , Crawford J. R.
Published: October 2012

Medulloblastoma with extensive nodularity is a rare subtype of the most common malignant childhood brain tumor and has been associated with more favorable prognosis. The authors report the case of a 10-month-old girl with a posterior fossa tumor of excessive nodularity with decreased diffusivity on diffusion-weighted magnetic resonance imaging sequences and robust grape-like postgadolinium contrast enhancing features. The unique neuroradiographic features were confirmed by histopathology and a diagnosis of medulloblastoma with extensive nodularity was made. This case highlights the importance of recognizing this unique medulloblastoma subtype preoperatively, as the more favorable outcome may preclude less aggressive medical management.
Prevalence and Risk Factors for Bacterial Vaginosis and Other Vulvovaginitis in a Population of Sexually Active Adolescents from Salvador, Bahia, Brazil
Authors: Moreira Mascarenhas Rita Elizabeth , Sacramento Cunha Machado Márcia , Borges da Costa e Silva Bruno Fernando , Fernandes Weyll Pimentel Rodrigo , Teixeira Ferreira Tatiana , Silva Leoni Fernanda Maria , Grassi Maria Fernanda Rios
Published: October 2012

Bacterial vaginosis, trichomoniasis, and genital candidiasis are considered the main etiologies of vulvovaginitis. Few studies estimate the prevalence of vulvovaginitis among adolescents, especially in Brazil. This study aimed to determine the prevalence and main risk factors associated with bacterial vaginosis and genital infection byC. albicansandTrichomonas vaginalisamong a group of adolescents from Salvador, Bahia, Brazil. One hundred sexually active adolescents followed at an adolescent gynecology clinic were included. Endocervical and vaginal samples were obtained during gynecological examination. Nugent criteria were applied for the diagnosis of bacterial vaginosis. ForCandida albicansandTrichomonas vaginalisdetection, culture in Sabouraud agar plates and Papanicolaou cytology were used, respectively. The mean age of participants was16.6±1.6years. The prevalence of bacterial vaginosis was 20% (95% CI 12–28) and of genital infection byCandidawas 22% (95% CI 14–30). Vaginal cytology detectedTrichomonas vaginalisin one patient. Alcohol, tobacco, and illegal drug use (P=0.02) and multiple lifetime partners were statistically related to bacterial vaginosis (P=0.01). The prevalence of bacterial vaginosis and genital candidiasis was similar to other studies carried out among adolescents worldwide.
Investigations into Soil Composition and Texture Using Infrared Spectroscopy (2–14 μm)
Authors: Hewson Robert D. , Cudahy Thomas J. , Jones Malcolm , Thomas Matilda
Published: October 2012

The ability of thermal and shortwave infrared spectroscopy to characterise composition and texture was evaluated using both particle size separated soil samples and natural soils. Particle size analysis and separation into clay, silt, and sand-sized soil fractions was undertaken to examine possible relationships between quartz and clay mineral spectral signatures and soil texture. Spectral indices, based on thermal infrared specular and volume scattering features, were found to discriminate clay mineral-rich soil from mostly coarser quartz-rich sandy soil and to a lesser extent from the silty quartz-rich soil. Further investigations were undertaken using spectra and information on 51 USDA and other soils within the ASTER spectral library to test the application of shortwave, mid- and thermal infrared spectral indices for the derivation of clay mineral, quartz, and organic carbon content. A nonlinear correlation between quartz content and a TIR spectral index based on the 8.62 μm was observed. Preliminary efforts at deriving a spectral index for the soil organic carbon content, based on 3.4–3.5 μm fundamental H–C stretching vibration bands, were also undertaken with limited results.
Radix Entomolaris in Mandibular First Molars in Indian Population: A Review and Case Reports
Authors: Attam Kanika , Nawal Ruchika Roongta , Utneja Shivani , Talwar Sangeeta
Published: October 2012

Purpose. The aim of this paper is to present cases of mandibular first molars with an additional distolingual root and their management using appropriate instruments and techniques.Basic Procedures and Main Findings. Mandibular molars can sometimes present a variation called radix entomolaris, wherein the tooth has an extra root attached to its lingual aspect. This additional root may complicate the endodontic management of the tooth if it is misdiagnosed or maltreated. This paper reviews the prevalence of such cases in Indian population and reports the management of 6 such teeth.Principal Conclusions. (1) It is crucial to be familiar with variations in tooth/canal anatomy and characteristic features since such knowledge can aid location and negotiation of canals, as well as their subsequent management. (2) Accurate diagnosis and careful application of clinical endodontic skill can favorably alter the prognosis of mandibular molars with this root morphology.
The H1(R) Space Global Weak Solutions to the Weakly Dissipative Camassa‐Holm Equation
Authors: Sheng Zhaowei , Lai Shaoyong , Ma Yuan , Luo Xuanjun
Published: October 2012

The existence of global weak solutions to the Cauchy problem for a generalized Camassa‐Holm equation with a dissipative term is investigated in the space C([0, ∞) × R)∩L∞([0, ∞); H1(R)) provided that its initial value u0(x) belongs to the space H1(R). A one‐sided super bound estimate and a space‐time higher‐norm estimate on the first‐order derivatives of the solution with respect to the space variable are derived.
Neurotropic Melanoma: The Management of Localised Disease
Authors: Croker Jeremy , Burmeister Bryan , Foote Matthew
Published: October 2012

Neurotropic melanoma is a rare subtype of cutaneous malignant melanoma. Compared with conventional melanoma, it is more locally aggressive with an increased tendency for local recurrence but less likely for nodal or distant metastases. These tumours can be a diagnostic dilemma with a variety of morphological, histopathological, and immunophenotypical expressions. The often amelanotic, benign appearance may lead to treatment issues such as late presentation, diagnostic delay, misdiagnosis, insufficient surgical margins, and recurrence with resulting poor outcome. The neurotropic nature of the disease and prevalence in the head and neck region can result in perineural and neural invasion along named large nerves into the brain with resulting neuropathies. Wide local excision with adjuvant radiotherapy where indicated remains the current practice for treatment with chemotherapy predominately being reserved as a salvage treatment for patients with disseminated disease.
Desmoplasia in Pancreatic Cancer. Can We Fight It?
Authors: Merika E. E. , Syrigos K. N. , Saif M. W.
Published: October 2012

The hallmark of pancreatic tumours, the desmoplastic reaction, provides a unique microenvironment that affects pancreatic tumour behaviour, its ability to grow and metastasize as well as resist the effects of chemotherapy. Complex molecular interactions and pathways give rise to the desmoplastic reaction. Breakdown or penetration of the desmoplastic reaction may hold the key to overcoming the limits of delivery of efficacious chemotherapy or the development of new targeted treatments. Herein we discuss such new developments to fight the desmoplastic reaction, including inhibitors of the epidermal growth factor, fibroblast growth factor, the hedgehog pathway, as well as new molecular targets like CD40 agonist and its effects on T cells, extracellular matrix modifying enzymes such as LOXL2 inhibitor and novel tumour penetrating peptides for delivery of drugs.
Recent Advances in Multiband Printed Antennas Based on
Metamaterial Loading
Authors: Paredes F. , Zamora G. , Zufanelli S. , Herraiz-Martínez F. J. , Bonache J. , Martín F.
Published: October 2012

It is shown that printed antennas loaded with metamaterial resonators can be designed to exhibit multiband functionality. Two different antenna types and metamaterial loading are considered: (i) printed dipoles or monopoles loaded with open complementary split ring resonators (OCSRRs) and (ii) meander line or folded dipole antennas loaded with split ring resonators (SRRs) or spiral resonators (SRs). In the first case, multiband operation is achieved by series connecting one or more OCSRRs within the dipole/monopole. Such resonators force opens at their positions, and by locating them at a quarter wavelength (at the required operating frequencies) from the feeding point, it is possible to achieve multiple radiation bands. In the second case, dual-band functionality is achieved through the perturbation of the antenna characteristics caused by the presence of the metamaterial resonators. This latter strategy is specially suited to achieve conjugate matching between the antenna and the chip in radiofrequency identification (RFID) tags at two of the regulated UHF-RFID bands.
Modulation of the ATPase and Transport Activities of Broad-Acting Multidrug Resistance Factor ABCC10 (MRP7)
Authors: Malofeeva Ekaterina V. , Domanitskaya Natalya , Gudima Mariya , Hopper-Borge Elizabeth A.
Published: October 2012

The cell surface molecule ABCC10 is a broad-acting transporter of xenobiotics, including cancer drugs, such as taxanes, epothilone B, and modulators of the estrogen pathway. Abcc10−/− mice exhibit increased tissue sensitivity and lethality resulting from paclitaxel exposure compared with wild-type counterparts, arguing ABCC10 functions as a major determinant of taxane sensitivity in mice. To better understand the mechanistic basis of ABCC10 action, we characterized the biochemical and vectorial transport properties of this protein. Using crude membranes in an ABCC10 overexpression system, we found that the ABCC10 transport substrates estrogen estradiol-glucuronide (E217βG) and leukotriene C4 (LTC4) significantly stimulated ABCC10 beryllium fluoride (BeFx)-sensitive ATPase activity. We also defined the E217βG antagonist, tamoxifen, as a novel substrate and stimulator of ABCC10. In addition, a number of cytotoxic substrates, including docetaxel, paclitaxel, and Ara-C, increased the ABCC10 basal ATPase activity. We determined that ABCC10 localizes to the basolateral cell surface, using transepithelial well assays to establish that ABCC10-overexpressing LLC-PK1 cells exported [3H]-docetaxel from the apical to the basolateral side. Importantly, we found that the clinically valuable multikinase inhibitor sorafenib, and a natural alkaloid, cepharanthine, inhibited ABCC10 docetaxel transport activity. Thus, concomitant use of these agents might restore the intracellular accumulation and potency of ABCC10-exported cytotoxic drugs, such as paclitaxel. Overall, our work could seed future efforts to identify inhibitors and other physiologic substrates of ABCC10. Cancer Res; 72(24); 6457–67. ©2012 AACR.
Benign Breast Disease and the Risk of Subsequent Breast Cancer in African American Women
Authors: Cote Michele L. , Ruterbusch Julie J. , Alosh Barra , Bandyopadhyay Sudeshna , Kim Elizabeth , Albashiti Bassam , Sharaf Aldeen Bashar , Radisky Derek C. , Frost Marlene H. , Visscher Daniel W. , Hartmann Lynn C. , Nassar Warzecha Hind , Ali-Femhi Rouba
Published: October 2012

Benign breast disease (BBD) is an established risk factor for breast cancer among Caucasian women but less is known about BBD in African American women. As African American women suffer from disproportionate mortality due to breast cancer, special focus on pathologic characteristics that may influence disease risk is warranted.

Benign breast biopsies from African American women were identified by the University Pathology Group (Detroit, MI). African American women of ages 20 to 84 years, who underwent a breast biopsy from 1997 to 2000, were eligible for the study. Subsequent breast cancers were identified through a linkage with the Detroit Surveillance Epidemiology and End Results (SEER) program. The first biopsy was reviewed by the pathologist, and lesions were classified following Dupont and Page criteria along with involution and other histologic features. Logistic regression was used to estimate the risk of developing a subsequent breast cancer with the histologic characteristics of BBD.

A total of 1,406 BBD biopsies from African American women were included in this study with a median follow-up of 10.1 years. The majority (68%) showed nonproliferative disease, 29% had proliferative disease without atypia, and 3% had proliferative disease with atypia. Subsequent incident breast cancers occurred in 55 women (3.9%). Women whose biopsies showed proliferative disease with atypia were more than three-fold more likely to develop breast cancer as compared with women who had nonproliferative disease [relative risk (RR) 3.29, 95% confidence interval (CI) 1.21–8.93].

Better characterization of the risk of breast cancer among women with BBD, considering both ethnicity and detailed molecular findings, can lead to better surveillance, earlier diagnosis, and potentially improved survival. Cancer Prev Res; 5(12); 1375–80. ©2012 AACR.
Inhibition of Notch1 Signaling Reduces Abdominal Aortic Aneurysm in Mice by Attenuating Macrophage-Mediated Inflammation
Authors: Hans Chetan P. , Koenig Sara N. , Huang Nianyuan , Cheng Jeeyun , Beceiro Susana , Guggilam Anuradha , Kuivaniemi Helena , Partida-Sánchez Santiago , Garg Vidu
Published: October 2012

Objective—

Activation of inflammatory pathways plays a critical role in the development of abdominal aortic aneurysms (AAA). Notch1 signaling is a significant regulator of the inflammatory response; however, its role in AAA is unknown.

Methods and Results—

In an angiotensin II–induced mouse model of AAA, activation of Notch1 signaling was observed in the aortic aneurysmal tissue of
Apoe
−/−
mice, and a similar activation of Notch1 was observed in aneurysms of humans undergoing AAA repair.
Notch1
haploinsufficiency significantly reduced the incidence of AAA in
Apoe
−/−
mice in response to angiotensin II. Reconstitution of bone marrow–derived cells from
Notch1
+/−
;Apoe
−/−
mice (donor) in lethally irradiated
Apoe
−/−
mice (recipient) decreased the occurrence of aneurysm. Flow cytometry and immunohistochemistry demonstrated that
Notch1
haploinsufficiency prevented the influx of inflammatory macrophages at the aneurysmal site by causing defects in macrophage migration and proliferation. In addition, there was an overall reduction in the inflammatory burden in the aorta of the
Notch1
+/−
;Apoe
−/−
mice compared with the
Apoe
−/−
mice. Last, pharmacological inhibition of Notch1 signaling also prevented AAA formation and progression in
Apoe
−/−
mice.

Conclusion—

Our data suggest that decreased levels of Notch1 protect against the formation of AAA by preventing macrophage recruitment and attenuating the inflammatory response in the aorta.
Retinol-Binding Protein 4 Is an Independent Factor Associated With Triglycerides and a Determinant of Very Low-Density Lipoprotein–Apolipoprotein B100 Catabolism in Type 2 Diabetes Mellitus
Authors: Vergès Bruno , Guiu Boris , Cercueil Jean Pierre , Duvillard Laurence , Robin Isabelle , Buffier Perrine , Bouillet Benjamin , Aho Serge , Brindisi Marie Claude , Petit Jean Michel
Published: October 2012

Objective—

Retinol-binding protein 4 (rbp4) is an adipokine secreted by adipocytes and liver, whose levels are elevated in type 2 diabetes mellitus (T2DM). Plasma levels of rbp4 and triglycerides are strongly correlated in T2DM. However, we do not know whether this association is direct or indirect via liver fat content, and the link between rbp4 and triglyceride metabolism remains unknown.

Methods and Results—

Liver fat measurement by proton spectroscopy was performed in 221 patients with T2DM, and an in vivo kinetic study with stable isotopes was carried out in 14 patients with T2DM. In multivariate analysis, triglycerides were associated positively with rbp4 (β=0.273,
P
<0.0001), apolipoprotein (apo) B (β=0.258,
P
<0.0001), and liver fat (β=0.191,
P
=0.002) and negatively with high-density lipoprotein cholesterol (β=−0.442,
P
<0.0001). rbp4 was correlated positively with apoB100 very-low-density lipoprotein (VLDL) pool (
r
=0.62,
P
=0.017) and negatively with VLDL-apoB100 total fractional catabolic rate (
r
=−0.66,
P
=0.001). In multivariate analysis, rbp4 (
P
=0.015), plasma triglycerides (
P
=0.024), and sex (
P
=0.026) were independently associated with VLDL-apoB100 total fractional catabolic rate.

Conclusion—

In T2DM, plasma rbp4 level is associated with plasma triglycerides, independently of liver fat content. There is a strong independent negative correlation between plasma rbp4 and VLDL-apoB100 total fractional catabolic rate. These data suggest that rbp4 may be involved in the pathophysiology of hypertriglyceridemia in T2DM by reducing VLDL catabolism.
Mitochondrial Calcium and Reactive Oxygen Species Regulate Agonist-Initiated Platelet Phosphatidylserine Exposure
Authors: Choo Hyo-Jung , Saafir Talib B. , Mkumba Laura , Wagner Mary B. , Jobe Shawn M.
Published: October 2012

Objective—

To study the interactions of cytoplasmic calcium elevation, mitochondrial permeability transition pore (mPTP) formation, and reactive oxygen species formation in the regulation of phosphatidylserine (PS) exposure in platelets.

Methods and Results—

mPTP formation, but not the degree of cytoplasmic calcium elevation, was associated with PS exposure in wild-type, cyclophilin D–null, ionomycin-treated, and reactive oxygen species–treated platelets. In the absence of the mPTP regulator cyclophilin D, agonist-initiated mPTP formation and high-level PS exposure were markedly blunted, but cytoplasmic calcium transients were unchanged. Mitochondrial calcium (Ca
2+
mit
) transients and reactive oxygen species, key regulators of mPTP formation, were examined in strongly stimulated platelets. Increased reactive oxygen species production occurred in strongly stimulated platelets and was dependent on extracellular calcium entry, but not the presence of cyclophilin D. Ca
2+
mit
increased significantly in strongly stimulated platelets. Abrogation of Ca
2+
mit
entry, either by inhibition of the Ca
2+
mit
uniporter or mitochondrial depolarization, prevented mPTP formation and exposure but not platelet aggregation or granule release.

Conclusion—

Sustained cytoplasmic calcium levels are necessary, but not sufficient, for high-level PS exposure in response to agonists. Increased Ca
2+
mit
levels are a key signal initiating mPTP formation and PS exposure. Blockade of Ca
2+
mit
entry allows the specific inhibition of platelet procoagulant activity.
Induction of Anti-Anti-Idiotype Antibodies Against Sulfated Glycosaminoglycans Reduces Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Brito Víctor , Mellal Katia , Portelance Simon Giroux , Pérez Arlenis , Soto Yosdel , deBlois Denis , Ong Huy , Marleau Sylvie , Vázquez Ana María
Published: October 2012

Objective—

The pathogenesis of atherosclerosis is associated with the early retention of low-density lipoproteins that are trapped in the extracellular matrix of the arterial intima by interaction with glycosaminoglycan side chains of proteoglycans. Mutant mouse/human chimeric antibodies of the murine monoclonal antibody P3, which react with N-glycolyl–containing gangliosides and sulfated glycosaminoglycans, were tested for their potentially antiatherogenic properties through the induction of an idiotypic antibody network that may specifically interfere with the binding of low-density lipoproteins to proteoglycan side chains, low-density lipoprotein modification, and foam cell formation.

Methods and Results—

Apolipoprotein E–deficient mice fed a high-fat, high-cholesterol diet received 5 to 6 doses of chP3R99 or chP3S98 mutant antibodies, showing high and low reactivity, respectively, against their respective antigens. Both chimeric antibodies elicited an immunodominant anti-idiotypic response in the absence of adjuvant. A striking (40%–43%) reduction (
P
<0.01) in total lesion areas was observed in 18-week-old mice immunized with chP3R99, but not chP3S98, compared with PBS-treated mice. The antiatherosclerotic effect was associated with increased mice sera reactivity against heparin and sulfated glycosaminoglycans, including chondroitin and dermatan sulfate. In addition, purified IgG from chP3R99-immunized mice blocked the retention of apolipoprotein B–containing lipoproteins within the arterial wall of apolipoprotein E
−/−
mice.

Conclusion—

The present study supports use of active immunization and the mounting of an idiotypic antibody network response against glycosaminoglycans as a novel approach to target atherosclerosis.
Interference of the CD30–CD30L Pathway Reduces Atherosclerosis Development
Authors: Foks Amanda C. , Bot Ilze , Frodermann Vanessa , de Jager Saskia C.A. , ter Borg Mariette , van Santbrink Peter J. , Yagita Hideo , Kuiper Johan , van Puijvelde Gijs H.M.
Published: October 2012

Objective—

Costimulatory molecules tightly control immune responses by providing positive signals that promote T-cell activation or by transducing inhibitory signals that limit T-cell responses. CD30 and CD30L are members of the tumor necrosis factor receptor superfamily and are involved in the activation and proliferation of T and B cells, which have been implicated in the initiation and progression of atherosclerosis. In the present study, we thus aimed to determine the role of the CD30–CD30L pathway in the development of atherosclerosis.

Methods and Results—

Western-type diet–fed low-density lipoprotein receptor–deficient mice were treated with an anti-CD30L antibody for 8 weeks, which resulted in a reduction of atherosclerotic lesion formation in the aortic root by 35%. Reduced numbers of adventitial CD3
+
T cells were found in anti-CD30L–treated mice, whereas no differences were observed in collagen and macrophage content of the atherosclerotic lesions. B-cell and mast cell responses were also not affected on anti-CD30L treatment. Interestingly, splenocyte proliferation was reduced by 53%, whereas T-cell numbers were concomitantly reduced in anti-CD30L–treated mice compared with control mice. These data thus indicate that the CD30–CD30L pathway solely exerts its function via inhibition of T-cell responses.

Conclusion—

In the present study, we are the first to show that interruption of the CD30–CD30L pathway reduced initial atherosclerosis development by modulating T-cell function.
Hypertension Susceptibility Loci and Blood Pressure Response to Antihypertensives
Authors: Gong Yan , McDonough Caitrin W. , Wang Zhiying , Hou Wei , Cooper-DeHoff Rhonda M. , Langaee Taimour Y. , Beitelshees Amber L. , Chapman Arlene B. , Gums John G. , Bailey Kent R. , Boerwinkle Eric , Turner Stephen T. , Johnson Julie A.
Published: October 2012

Background—

To date, 39 single nucleotide polymorphisms (SNPs) have been associated with blood pressure (BP) or hypertension in genome-wide association studies in whites. Our hypothesis is that the loci/SNPs associated with BP/hypertension are also associated with BP response to antihypertensive drugs.

Methods and Results—

We assessed the association of these loci with BP response to atenolol or hydrochlorothiazide monotherapy in 768 hypertensive participants in the Pharmacogenomics Responses of Antihypertensive Responses study. Linear regression analysis was performed on whites for each SNP in an additive model adjusting for baseline BP, age, sex, and principal components for ancestry. Genetic scores were constructed to include SNPs with nominal associations, and empirical
P
values were determined by permutation test. Genotypes of 37 loci were obtained from Illumina 50K cardiovascular or Omni1M genome-wide association study chips. In whites, no SNPs reached Bonferroni-corrected α of 0.0014, 6 reached nominal significance (
P
<0.05), and 3 were associated with atenolol BP response at
P
<0.01. The genetic score of the atenolol BP-lowering alleles was associated with response to atenolol (
P
=3.3×10
–6
for systolic BP;
P
=1.6×10
–6
for diastolic BP). The genetic score of the hydrochlorothiazide BP-lowering alleles was associated with response to hydrochlorothiazide (
P
=0.0006 for systolic BP;
P
=0.0003 for diastolic BP). Both risk score
P
values were <0.01 based on the empirical distribution from the permutation test.

Conclusions—

These findings suggest that selected signals from hypertension genome-wide association studies may predict BP response to atenolol and hydrochlorothiazide when assessed through risk scoring.

Clinical Trial Registration Information—

clinicaltrials.gov
; Identifier: NCT00246519.
Immunoglobulins Against Tyrosine-Nitrated Epitopes in Coronary Artery Disease
Authors: Thomson Leonor , Tenopoulou Margarita , Lightfoot Richard , Tsika Epida , Parastatidis Ioannis , Martinez Marissa , Greco Todd M. , Doulias Paschalis-Thomas , Wu Yuping , Tang W.H. Wilson , Hazen Stanley L. , Ischiropoulos Harry
Published: October 2012

Background—

Several lines of evidence support a pathophysiological role of immunity in atherosclerosis. Tyrosine-nitrated proteins, a footprint of oxygen- and nitrogen-derived oxidants generated by cells of the immune system, are enriched in atheromatous lesions and in circulation of patients with coronary artery disease (CAD). However, the consequences of possible immune reactions triggered by the presence of nitrated proteins in subjects with clinically documented atherosclerosis have not been explored.

Methods and Results—

Specific immunoglobulins that recognize 3-nitrotyrosine epitopes were identified in human lesions, as well as in circulation of patients with CAD. The levels of circulating immunoglobulins against 3-nitrotyrosine epitopes were quantified in patients with CAD (n=374) and subjects without CAD (non-CAD controls, n=313). A 10-fold increase in the mean level of circulating immunoglobulins against protein-bound 3-nitrotyrosine was documented in patients with CAD (3.75±1.8 μg antibody Eq/mL plasma versus 0.36±0.8 μg antibody Eq/mL plasma), and was strongly associated with angiographic evidence of significant CAD.

Conclusions—

The results of this cross-sectional study suggest that posttranslational modification of proteins via nitration within atherosclerotic plaque-laden arteries and in circulation serve as neo-epitopes for the elaboration of immunoglobulins, thereby providing an association between oxidant production and the activation of the immune system in CAD.
Cerebrovascular Reserve and Stroke Risk in Patients With Carotid Stenosis or Occlusion
Authors: Gupta Ajay , Chazen J. Levi , Hartman Maya , Delgado Diana , Anumula Nikesh , Shao Huibo , Mazumdar Madhu , Segal Alan Z. , Kamel Hooman , Leifer Dana , Sanelli Pina C.
Published: October 2012

Background and Purpose—

Impairments in cerebrovascular reserve (CVR) have been variably associated with increased risk of ischemic events and may stratify stroke risk in patients with high-grade internal carotid artery stenosis or occlusion. The purpose of this study is to perform a systematic review and meta-analysis to summarize the association of CVR impairment and stroke risk.

Methods—

We performed a literature search evaluating the association of impairments in CVR with future stroke or transient ischemic attack in patients with high-grade internal carotid artery stenosis or occlusion. We included studies with a minimum of 1-year patient follow-up with baseline CVR measures performed by any modality and primary outcome measures of stroke and/or transient ischemic attack. A meta-analysis with assessment of study heterogeneity and publication bias was performed. Results were presented in a forest plot and summarized using a random-effects model.

Results—

Thirteen studies met the inclusion criteria, representing a total of 1061 independent CVR tests in 991 unique patients with a mean follow-up of 32.7 months. We found a significant positive relationship between impairment of CVR and development of stroke with a pooled random effects OR of 3.86 (95% CI, 1.99–7.48). Subset analysis showed that this association between CVR impairment and future risk of stroke/transient ischemic attack remained significant regardless of ischemic outcome measure, symptomatic or asymptomatic disease, stenosis or occlusion, or CVR testing method.

Conclusions—

CVR impairment is strongly associated with increased risk of ischemic events in carotid stenosis or occlusion and may be useful for stroke risk stratification.
Polarized Networks
Authors: Heaney Michael T. , Masket Seth E. , Miller Joanne M. , Strolovitch Dara Z.
Published: October 2012

Previous research has documented that the institutional behaviors (e.g., lobbying, campaign contributions) of political organizations reflect the polarization of these organizations along party lines. However, little is known about how these groups are connected at the level of individual party activists. Using data from a survey of 738 delegates at the 2008 Democratic and Republican national conventions, we use network regression analysis to demonstrate that co-membership networks of national party convention delegates are highly polarized by party, even after controlling for homophily due to ideology, sex/gender, race/ethnicity, age, educational attainment, income, and religious participation. Among delegates belonging to the same organization, only 1.78% of these co-memberships between delegates crossed party lines, and only 2.74% of the ties between organizations sharing common delegates were bipartisan in nature. We argue that segregation of organizational ties on the basis of party adds to the difficulty of finding common political ground between the parties.
The dynamics of word retrieval in major depression
Authors: Douglas Katie M , Porter Richard J , Knight Robert G , Alsop Brent
Published: October 2012

Objective:

Impairment in the retrieval of specific episodes from autobiographical memory is commonly observed in major depression. However, it is unclear whether impairment in retrieval processes is a general characteristic of major depression or is confined to the recollection of personal memories. This study examined the time course of the retrieval of words from semantic memory.

Method:

A letter fluency test was administered to 65 inpatients with major depression and 50 healthy controls. A two-parameter model was fit to the decay curve representing the production of words over a 90-second period. One parameter, N, is an estimate of the total number of words that would be generated if the respondent was given unlimited time. The other, tau, is the average of the difference in time between the first word generated and each subsequent word.

Results:

There was evidence of a deficit in the retrieval of words from long-term memory in depressed patients. The significant difference between groups suggested that even if given an extended period of time in which to respond to compensate for possible slowness, the depressed group would not retrieve as many words as the controls. The retrieval failure could not be attributed solely to cognitive slowing or the effects of antidepressant medication.

Conclusions:

The results extend findings of a deficit in the process of retrieving specific episodes from autobiographical memory and suggest that a generalised impairment in memory retrieval may be characteristic of major depression.
The Role of Conductor Facial Expression in Students’ Evaluation of Ensemble Expressivity
Authors: Silvey Brian A.
Published: October 2012

The purpose of this study was to explore whether conductor facial expression affected the expressivity ratings assigned to music excerpts by high school band students. Three actors were videotaped while portraying approving, neutral, and disapproving facial expressions. Each video was duplicated twice and then synchronized with one of three professional wind ensemble recordings. Participants ( N = 133) viewed nine 1-min videos of varying facial expressions, actors, and excerpts and rated each ensemble’s expressivity on a 10-point rating scale. Results of a one-way repeated measures ANOVA indicated that conductor facial expression significantly affected ratings of ensemble expressivity ( p < .001, partial η2 = .15). Post hoc comparisons revealed that participants’ ensemble expressivity ratings were significantly higher for excerpts featuring approving facial expressions than for either neutral or disapproving expressions. Participants’ mean ratings were lowest for neutral facial expression excerpts, indicating that an absence of facial affect influenced evaluations of ensemble expressivity most negatively.
Perceptions of Time Spent in Teacher Talk
Authors: Nápoles Jessica , Vázquez-Ramos Angel M.
Published: October 2012

The purpose of this study was to examine and compare self-estimates, peer estimates, and actual time preservice teachers spent talking in rehearsal. Participants ( N = 32) conducted a short choral rehearsal and estimated their teacher talk (expressed as a percentage of total rehearsal time). Their peers also reported estimates, and the researchers took data on actual time. Later, participants observed themselves on video and used stopwatches to compute teacher talk percentages on the same session. Participants then conducted a second rehearsal and again estimated their teacher talk percentage. Results indicated that by the second rehearsal, participants reduced their teacher talk by about half, and their estimates became closer to actual time. Significant differences were discovered between all estimates from the first rehearsal and the second rehearsal. Self-analysis through videotapes appears to be a useful tool for reducing teacher talk and increasing estimation accuracy.
Beyond the Hype
Authors: Schulz Armin W.
Published: October 2012

In this paper, I consider the recent resurgence of “evolutionary economics”—the idea that evolutionary theory can be very useful to push forward key debates in economics—and assess the extent to which it rests on a plausible foundation. To do this, I first distinguish two ways in which evolutionary theory can, in principle, be brought to bear on an economic problem—namely, evidentially and heuristically—and then apply this distinction to the three major hypotheses that evolutionary economists have come to defend: the implausibility of rational choice theory as an account of economic rationality, the idea that firms are autonomous economic agents, and the need for a more dynamic, less equilibrium-focused economic methodology. In each of these cases, I conclude negatively: the relevant evolutionary considerations neither suggest interesting and novel hypotheses to investigate further (the hallmark of heuristic devices) nor are backed up by the needed data to constitute genuine evidence. I end by distinguishing this criticism of evolutionary economics from others that have been put forward in the literature: in particular, I make clear that, unlike those of other critics, the arguments of this paper are based on epistemic—not structural—considerations and therefore leave more room for a plausible form of evolutionary economics to come about in the future.
The Causal Autonomy of Reason Explanations and How Not to Worry about Causal Deviance
Authors: Stueber Karsten R.
Published: October 2012

This essay will defend a causal conception of action explanations in terms of an agent’s reasons by delineating a metaphysical and epistemic framework that allows us to view folk psychology as providing us with causal and autonomous explanatory strategies of accounting for individual agency. At the same time, I will calm philosophical concerns about the issue of causal deviance that have been at the center of the recent debates between causalist and noncausalist interpretations of action explanations. For that purpose, it is important to realize that the domain of folk-psychological action explanation is also the domain of skillful and goal-directed bodily movements, a domain to which we have independent epistemic access.
Reframing the Responsibilities of Bystanders through Film
Authors: Esquith Stephen L.
Published: October 2012

Political responsibilities for systemic mass violence have been subordinated to the moral guilt and legal liability of perpetrators and collaborators, while the role of the bystander has been narrowly construed in terms of charitable rescue or negligence. This dominant victim–perpetrator framework ignores the complex political dimensions of bystander responsibilities for systemic mass violence, especially those responsibilities that stem from the benefits that bystanders receive. The films of Claude Lanzmann, Rithy Panh, and Yael Hersonski contain elements of an alternative framework of bystander responsibility and also can serve as catalysts for the political education of bystander beneficiaries and those from whom they have benefited.
Play and Democracy
Authors: Edwards Jason
Published: October 2012

In this essay I argue that the work of the Dutch historian Johan Huizinga is an important resource for contemporary democratic theory because his employment of the concept of play illustrates both the strengths and weaknesses of agonistic thought. I employ a reading of Huizinga to explore three central problems of contemporary agonism: the distinction between antagonism and agonism; the representative or expressive character of the agon; and the shaping and limiting of the space of the agon by the materials with which we play democratic games. Reading Huizinga reveals the importance of a consideration of the social relations and material conditions that shape the playful features of democratic contestation. But it also warns against the idealization of democratic contestation and the contesting subject that occurs in contemporary agonistic thought as a result of privileging the autonomy and priority of play and extruding it from the wider economy of agonism.
Expression and Significance of Hypoxia‐Inducible Factor–1α and Survivin in Laryngeal Carcinoma Tissue and Cells
Authors: Li Da‐wei , Zhou Liang , Jin Bin , Xie Jin , Dong Pin
Published: October 2012

Objective

The aim was to evaluate hypoxia‐inducible factor–1α (HIF‐1α) and survivin expression in laryngeal squamous cell carcinoma (LSCC) tissues and cell lines and to investigate whether HIF‐1α has an effect on the regulation of survivin gene expression in LSCC cells under hypoxia.

Study Design

Prospective, observational.

Setting

Shanghai Jiaotong University Affiliated First People’s Hospital.

Subjects and Methods

The expression of HIF‐1α and survivin protein in human LSCC tissues was analyzed by immunohistochemistry. HIF‐1α and survivin gene expression levels in Hep‐2 cells were detected by real‐time quantitative reverse transcription polymerase chain reaction (RT‐PCR) and Western blot under normoxic or hypoxic conditions. In hypoxic cells, HIF‐1α expression was inhibited by RNA interference.

Results

HIF‐1α and survivin were both highly expressed in LSCC tissues and significantly related to the clinical stage and lymph node metastasis (P <. 05). Meanwhile, a positive correlation existed between HIF‐1α and survivin expression (r = 0.456, P <. 01). In LSCC cells, HIF‐1α and survivin expression were obviously upregulated in response to hypoxia (P <. 05). The downregulation of HIF‐1α expression dramatically decreased survivin gene expression in hypoxic cells (P <. 05).

Conclusion

HIF‐1α could be considered as an important regulator for the upregulation of survivin gene expression induced by hypoxia in LSCC cells, and both proteins could be regarded as 2 key predictors of malignant progression and metastasis of LSCC.
Evaluating the fracture strength of welded joints based on their limit states under high-cycle stresses
Authors: Leonavičius Mindaugas , Stonkus Rimantas , Kliukas Romualdas , Petraitis Gediminas
Published: October 2012

The research presented here aims at evaluating the strength of the welded joints of spheroidal cast iron of large mineral crushers based on the limit states under very high-cycle loading. Several experiments were performed using semi-natural and standard specimens. This study derived the summary fracture process diagram, including the test results for compact tension specimens and semi-natural specimens, for all fracture process stages. A method for evaluating the strength of these welded joints based on safety factors, when the number of loading cycles exceeds 108, is proposed.
Autologous Gastrointestinal Reconstruction
Authors: Rege Aparna S. , Sudan Debra Lynn
Published: October 2012

Short bowel syndrome (SBS) results in loss of absorptive capacity of the development of gut, leading to malabsorption due to protein, energy, fluid, and electrolyte loss and imbalance while on enteral diet alone. Various nonsurgical and surgical therapeutic options that have emerged improve the survival outcome following SBS in both children and adults. An individualized, complex multidisciplinary approach to medical and surgical intestinal rehabilitation is needed to provide an opportunity for enteral autonomy to be possible in a patient with SBS. The remnant bowel plays a very pivotal role in autologous gastrointestinal reconstruction (AGIR) surgery. Intestinal transplantation, although promising and potentially life‐saving for SBS, should be reserved for patients with failed AGIR or those who have no prospect for autologous enteral autonomy. This article reviews the evolution of nontransplant surgical management of patients with SBS.
Review and Clinical Update on Parenteral Nutrition–Associated Liver Disease
Authors: Tillman Emma M.
Published: October 2012

Parenteral nutrition–associated liver disease (PNALD) is a complex disease that is diagnosed by clinical presentation, biochemical markers of liver injury, concurrent use of parenteral nutrition (PN), and negative workup for other causes of liver disease. Since the first case of PNALD was reported more than 30 years ago, clinicians have had few effective treatments for PNALD, and when disease progressed to liver cirrhosis, it was historically associated with poor outcomes. Within the past 5 years, there has been much excitement about new treatments for PNALD, including use of both parenteral and enteral ω‐3 polyunsaturated long‐chain fatty acids (ω‐3 PUFA) as well as restricting dosing of ω‐6 PUFA. Scientists are also interested in uncovering the mechanisms associated with liver injury seen in PNALD. This article reviews the recent literature relating to the pathophysiology and treatment of PNALD.
Collateral Punishments and Sentencing Policy
Authors: Levenson Jill S. , Shields Ryan T. , Singleton David A.
Published: October 2012

Residence restrictions, which prohibit sex offenders from living within close proximity to places where children congregate, have grown popular. Participants ( n = 255) were asked to participate in a survey rating and comparing their perceptions of residence restrictions for drunk drivers and sex offenders. Residence restrictions were seen as more punitive for DUI offenders than for sex offenders, though a majority of the sample viewed making either offender leave their home as punishment. Those who believed that most sex offenders would reoffend were significantly less likely to view these policies as punitive. Older respondents and those who knew someone convicted of a crime were also less likely to view residence restrictions as punitive. The results of the current study indicate that although many of the respondents were not optimistic about the effectiveness of residence restrictions in reducing victimization, those policies still garnered considerable support.
Experiments and zero D modeling studies using specific Wiebe coefficients for producer gas as fuel in spark-ignited engines
Authors: Shivapuji Anand M , Dasappa S
Published: October 2012

The paper addresses experiments and modeling studies on the use of producer gas, a bio-derived low energy content fuel in a spark-ignited engine. Producer gas, generated in situ, has thermo-physical properties different from those of fossil fuel(s). Experiments on naturally aspirated and turbo-charged engine operation and subsequent analysis of the cylinder pressure traces reveal significant differences in the heat release pattern within the cylinder compared with a typical fossil fuel. The heat release patterns for gasoline and producer gas compare well in the initial 50% but beyond this, producer gas combustion tends to be sluggish leading to an overall increase in the combustion duration. This is rather unexpected considering that producer gas with nearly 20% hydrogen has higher flame speeds than gasoline. The influence of hydrogen on the initial flame kernel development period and the combustion duration and hence on the overall heat release pattern is addressed. The significant deviations in the heat release profiles between conventional fuels and producer gas necessitates the estimation of producer gas-specific Wiebe coefficients. The experimental heat release profiles are used for estimating the Wiebe coefficients. Experimental evidence of lower fuel conversion efficiency based on the chemical and thermal analysis of the engine exhaust gas is used to arrive at the Wiebe coefficients. The efficiency factor a is found to be 2.4 while the shape factor m is estimated at 0.7 for 2% to 90% burn duration. The standard Wiebe coefficients for conventional fuels and fuel-specific coefficients for producer gas are used in a zero D model to predict the performance of a 6-cylinder gas engine under naturally aspirated and turbo-charged conditions. While simulation results with standard Wiebe coefficients result in excessive deviations from the experimental results, excellent match is observed when producer gas-specific coefficients are used. Predictions using the same coefficients on a 3-cylinder gas engine having different geometry and compression ratio(s) indicate close match with the experimental traces highlighting the versatility of the coefficients.