bluuebunny/crossref_metadata_2025 huggingface dataset:
Jun Dimerization Protein 2 Controls Senescence and Differentiation via Regulating Histone Modification
Authors: Huang Yu-Chang , Hasegawa Hitomi , Wang Shin-Wei , Ku Chia-Chen , Lin Ying-Chu , Chiou Shyh-Shin , Hou Ming-Feng , Wu Deng-Chyang , Tsai Eing-Mei , Saito Shigeo , Yamaguchi Naoto , Yokoyama Kazunari K.
Published: December 2010

Transcription factor, Jun dimerization protein 2 (JDP2), binds directly to histones and DNAs and then inhibits the p300‐mediated acetylation both of core histones and of reconstituted nucleosomes that contain JDP2 recognition DNA sequences. JDP2 plays a key role as a repressor of adipocyte differentiation by regulation of the expression of the gene
C/EBPδ
via inhibition of histone acetylation. Moreover, JDP2‐deficient mouse embryonic fibroblasts (JDP2−/− MEFs)
are resistant to replicative senescence. JDP2 inhibits the recruitment of polycomb repressive complexes (PRC1 and PRC2) to the promoter
of the gene encoding p16Ink4a, resulting from the inhibition of methylation of lysine 27 of histone H3 (H3K27). Therefore, it seems that chromatin‐remodeling factors, including the PRC complex controlled by JDP2, may be important players in the senescence program. The novel mechanisms that underline the action of JDP2 in inducing cellular senescence and suppressing adipocyte differentiation are reviewed.
The Ecology of Coral Reef Top Predators in the Papahānaumokuākea Marine National Monument
Authors: Dale Jonathan J. , Meyer Carl G. , Clark Christian E.
Published: December 2010

Coral reef habitats in the Papahānaumokuākea Marine National Monument (PMNM) are characterized by abundant top-level predators such as sharks and jacks. The predator assemblage is dominated both numerically and in biomass by giant trevally (Caranx ignobilis) and Galapagos sharks (Carcharhinus galapagensis). A lower diversity of predatory teleosts, particularly groupers and snappers, distinguishes the PMNM from other remote, unfished atolls in the Pacific. Most coral reef top predators are site attached to a “home” atoll, but move extensively within these atolls. Abundances of the most common sharks and jacks are highest in atoll fore reef habitats. Top predators within the PMNM forage on a diverse range of prey and exert top-down control over shallow-water reef fish assemblages. Ecological models suggest ecosystem processes may be most impacted by top predators through indirect effects of predation. Knowledge gaps are identified to guide future studies of top predators in the PMNM.
Fracture Toughness of Carbon Nanotube-Reinforced Metal- and Ceramic-Matrix Composites
Authors: Chen Y. L. , Liu B. , Huang Y. , Hwang K. C.
Published: December 2010

Hierarchical analysis of the fracture toughness enhancement of carbon nanotube- (CNT-) reinforced hard matrix composites is carried out on the basis of shear-lag theory and facture mechanics. It is found that stronger CNT/matrix interfaces cannot definitely lead to the better fracture toughness of these composites, and the optimal interfacial chemical bond density is that making the failure mode just in the transition from CNT pull-out to CNT break. For hard matrix composites, the fracture toughness of composites with weak interfaces can be improved effectively by increasing the CNT length. However, for soft matrix composite, the fracture toughness improvement due to the reinforcing CNTs quickly becomes saturated with an increase in CNT length. The proposed theoretical model is also applicable to short fiber-reinforced composites.
Dietary, Anthropometric, and Biochemical Determinants of Plasma High-Density Lipoprotein-Cholesterol in Free-Living Adults
Authors: de Oliveira Erick Prado , Manda Rodrigo Minoru , Torezan Gabriel Augusto , Corrente José Eduardo , Burini Roberto Carlos
Published: December 2010

The level of high-density lipoprotein is thought to be critical in inhibiting lesion formation as well as reducing the lipid load of preexisting atherosclerotic lesions. With the aim of determining the main determinants of plasma HDL-cholesterol (HDL-c) in free-living adults, 997 individuals (52.3 ± 10 years, 67% females) were selected for a descriptive cross-sectional study. The used data corresponded to the baseline obtained from participants clinically selected for a lifestyle modification program. Covariables of clinical, anthropometry, food intake, aerobic fitness, and plasma biochemistry were analyzed against plasma HDL-c either as continuous or categorized variables. After adjustments for age, gender, and BMI the excess of abdominal fat along with high carbohydrate-energy intake and altered plasma triglycerides were the stronger predictors of reduced plasma HDL-c. In conclusion lifestyle interventions aiming to normalize abdominal fatness and plasma triglycerides are recommended to restore normal levels of HDL-c in these free-living adults.
Iterative Algorithms for Finding Common Solutions to Variational Inclusion Equilibrium and Fixed Point Problems
Authors: Tan JF , Chang SS
Published: December 2010

The main purpose of this paper is to introduce an explicit iterative algorithm to study the existence problem and the approximation problem of solution to the quadratic minimization problem. Under suitable conditions, some strong convergence theorems for a family of nonexpansive mappings are proved. The results presented in the paper improve and extend the corresponding results announced by some authors.
Delivery of NKG2D Ligand Using an Anti-HER2 Antibody-NKG2D Ligand Fusion Protein Results in an Enhanced Innate and Adaptive Antitumor Response
Authors: Cho Hyun-Mi , Rosenblatt Joseph D. , Tolba Khaled , Shin Sarah J. , Shin Daniel S. , Calfa Carmen , Zhang Yu , Shin Seung-Uon
Published: December 2010

NKG2D ligands link the innate and adapative immune response by activating the receptors expressed on effector cells of both the innate (NK) and adaptive immune systems (CD8+ T cells). In this study, we explored the potential therapeutic utility of this intersection by fusing the murine NKG2D ligand Rae-1β to the 3′ end of an anti-HER2 IgG3 antibody containing an intact Fc domain (anti-HER2 IgG3-Rae-1β), thereby targeting an NK cell activation signal to HER2+ breast tumor cells. The antitumor efficacy of this anti-HER2-Rae-1β fusion protein was examined in a mouse mammary tumor model engineered to express HER2 (EMT6-HER2 cells). We observed an enhanced cytotoxic response of NK effectors against EMT-HER2 cells in vitro. Mice implanted on one flank with EMT6-HER2 cells and contralaterally with control EMT6 cells exhibited rapid regression of EMT6-HER2 tumors but delayed regression of contralateral EMT6 tumors. IFNγ was implicated, given a lack of antitumor efficacy in IFNγ−/− mice. Depletion of either NK cells or CD8+ T cells abrogated tumor growth inhibition, suggesting essential roles for each in the observed antitumor activity. Mice rejecting EMT6-HER2 tumors after anti-HER2-Rae-1β treatment showed markedly decreased tumor growth when rechallenged with EMT6-HER2 or EMT6 cells, whereas both EMT6 and EMT6-HER2 cells grew in control mice, indicating the development of an adaptive memory response. Our findings demonstrate that administration of an antibody-NKG2D ligand fusion protein can enhance innate and adaptive immune antitumor responses, also evoking additional nontargeted antigens to enhance the potential clinical utility of this approach. Cancer Res; 70(24); 10121–30. ©2010 AACR.
The Inflammasome Component Nlrp3 Impairs Antitumor Vaccine by Enhancing the Accumulation of Tumor-Associated Myeloid-Derived Suppressor Cells
Authors: van Deventer Hendrik W. , Burgents Joseph E. , Wu Qing Ping , Woodford Rita-Marie T. , Brickey W. June , Allen Irving C. , McElvania-Tekippe Erin , Serody Jonathan S. , Ting Jenny P.-Y.
Published: December 2010

The inflammasome is a proteolysis complex that generates the active forms of the proinflammatory cytokines interleukin (IL)-1β and IL-18. Inflammasome activation is mediated by NLR proteins that respond to microbial and nonmicrobial stimuli. Among NLRs, NLRP3 senses the widest array of stimuli and enhances adaptive immunity. However, its role in antitumor immunity is unknown. Therefore, we evaluated the function of the NLRP3 inflammasome in the immune response using dendritic cell vaccination against the poorly immunogenic melanoma cell line B16-F10. Vaccination of Nlrp3−/− mice led to a relative 4-fold improvement in survival relative to control animals. Immunity depended on CD8+ T cells and exhibited immune specificity and memory. Increased vaccine efficacy in Nlrp3−/− hosts did not reflect differences in dendritic cells but rather differences in myeloid-derived suppressor cells (MDSC). Although Nlrp3 was expressed in MDSCs, the absence of Nlrp3 did not alter either their functional capacity to inhibit T cells or their presence in peripheral lymphoid tissues. Instead, the absence of Nlrp3 caused a 5-fold reduction in the number of tumor-associated MDSCs found in host mice. Adoptive transfer experiments also showed that Nlrp3−/− MDSCs were less efficient in reaching the tumor site. Depleting MDSCs with an anti–Gr-1 antibody increased the survival of tumor-bearing wild-type mice but not Nlrp3−/− mice. We concluded that Nlrp3 was critical for accumulation of MDSCs in tumors and for inhibition of antitumor T-cell immunity after dendritic cell vaccination. Our findings establish an unexpected role for Nlrp3 in impeding antitumor immune responses, suggesting novel approaches to improve the response to antitumor vaccines by limiting Nlrp3 signaling. Cancer Res; 70(24); 10161–9. ©2010 AACR.
A Unique Metastasis Gene Signature Enables Prediction of Tumor Relapse in Early-Stage Hepatocellular Carcinoma Patients
Authors: Roessler Stephanie , Jia Hu-Liang , Budhu Anuradha , Forgues Marshonna , Ye Qing-Hai , Lee Ju-Seog , Thorgeirsson Snorri S. , Sun Zhongtang , Tang Zhao-You , Qin Lun-Xiu , Wang Xin Wei
Published: December 2010

Metastasis-related recurrence often occurs in hepatocellular carcinoma (HCC) patients who receive curative therapies. At present, it is challenging to identify patients with high risk of recurrence, which would warrant additional therapies. In this study, we sought to analyze a recently developed metastasis-related gene signature for its utility in predicting HCC survival, using 2 independent cohorts consisting of a total of 386 patients who received radical resection. Cohort 1 contained 247 predominantly HBV-positive cases analyzed with an Affymetrix platform, whereas cohort 2 contained 139 cases with mixed etiology analyzed with the NCI Oligo Set microarray platform. We employed a survival risk prediction algorithm with training, test, and independent cross-validation strategies and found that the gene signature is predictive of overall and disease-free survival. Importantly, risk was significantly predicted independently of clinical characteristics and microarray platform. In addition, survival prediction was successful in patients with early disease, such as small (<5 cm in diameter) and solitary tumors, and the signature predicted particularly well for early recurrence risk (<2 years), especially when combined with serum alpha fetoprotein or tumor staging. In conclusion, we have shown in 2 independent cohorts with mixed etiologies and ethnicity that the metastasis gene signature is a useful tool to predict HCC outcome, suggesting the general utility of this classifier. We recommend the use of this classifier as a molecular diagnostic test to assess the risk that an HCC patient will develop tumor relapse within 2 years after surgical resection, particularly for those with early-stage tumors and solitary presentation. Cancer Res; 70(24); 10202–12. ©2010 AACR.
Targeting γδ T Lymphocytes for Cancer Immunotherapy: From Novel Mechanistic Insight to Clinical Application
Authors: Gomes Anita Q. , Martins Duarte S. , Silva-Santos Bruno
Published: December 2010

Abundant interferon-γ secretion, potent cytotoxicity, and major histocompatibility complex–independent targeting of a large spectrum of tumors make γδ T cells attractive mediators of cancer immunotherapy. However, a better understanding of the molecular mechanisms involved in tumor cell recognition and γδ T-cell activation is required to improve the limited success of γδ T-cell–mediated treatments. Here, we review key advances in basic knowledge made over the past 3 years, and summarize the results of γδ T-cell–based clinical trials concluded to date. We also highlight new research directions on the basis of the modulation of receptors that control the function of γδ T cells. Cancer Res; 70(24); 10024–7. ©2010 AACR.
AZ960, a Novel Jak2 Inhibitor, Induces Growth Arrest and Apoptosis in Adult T-Cell Leukemia Cells
Authors: Yang Jing , Ikezoe Takayuki , Nishioka Chie , Furihata Mutsuo , Yokoyama Akihito
Published: December 2010

Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive disease in which the Jak2/Stat5 pathway is constitutively activated. This study found that AZ960, a novel inhibitor of Jak2 kinase, effectively induced growth arrest and apoptosis of human T-cell lymphotropic virus type 1, HTLV-1–infected T cells (MT-1 and MT-2) in parallel with downregulation of the phosphorylated forms of Jak2 and Bcl-2 family proteins including Bcl-2 and Mcl-1. Interestingly, AZ960 increased levels of Bcl-xL in MT-1 and MT-2 cells in association with accumulation of cAMP response element-binding protein bound to the Bcl-xL promoter as measured by chromatin immunoprecipitation assay. Importantly, genetic inhibition of Bcl-xL by a small interfering RNA potentiated antiproliferative effects of AZ960 in MT-1 cells. Taken together, Jak2 is an attractive molecular target for treatment of ATL. Concomitant blockade of Jak2 and Bcl-xL may be a promising treatment strategy for this lethal disease. Mol Cancer Ther; 9(12); 3386–95. ©2010 AACR.
Contrasting Effects of Nutlin-3 on TRAIL- and Docetaxel-Induced Apoptosis Due to Upregulation of TRAIL-R2 and Mcl-1 in Human Melanoma Cells
Authors: Tseng Hsin-Yi , Jiang Chen Chen , Croft Amanda , Tay Kwang Hong , Thorne Rick Francis , Yang Fan , Liu Hao , Hersey Peter , Zhang Xu Dong
Published: December 2010

Wild-type p53 is commonly expressed in melanoma but does not appear to be effective in the induction of apoptosis. One explanation is that p53 is targeted for degradation by the E3 ligase MDM2. However, we found in this study that blockade of the interaction of p53 and MDM2 by the MDM2 antagonist nutlin-3 in melanoma cells did not induce apoptosis, even though it upregulated p53 and its proapoptotic targets. Nevertheless, nutlin-3 enhanced TRAIL-induced apoptosis as a result of p53-mediated upregulation of TRAIL-R2. Unexpectedly, nutlin-3 upregulated Mcl-1, which attenuated apoptotic signaling triggered by TRAIL, and inhibited apoptosis induced by the microtubule-targeting drug docetaxel. The increase in Mcl-1 was related to a p53-independent transcriptional mechanism, but stabilization of the Mcl-1 protein played a dominant role, as nutlin-3 upregulated the Mcl-1 protein to a much greater extent than the Mcl-1 mRNA, and this was associated with prolonged half-life time and reduced ubiquitination of the protein. Knockdown of p53 blocked the upregulation of the Mcl-1 protein, indicating that p53 plays a critical role in the stabilization of Mcl-1. The contrasting effects of nutlin-3 on TRAIL- and docetaxel-induced apoptosis were confirmed in fresh melanoma isolates. Collectively, these results show that nutlin-3 may be a useful agent in combination with TRAIL and, importantly, uncover a novel regulatory effect of p53 on the expression of Mcl-1 in melanoma cells on treatment with nutlin-3, which may antagonize the therapeutic efficacy of other chemotherapeutic drugs in addition to docetaxel in melanoma. Mol Cancer Ther; 9(12); 3363–74. ©2010 AACR.
Chemoprevention of Chemically Induced Skin Tumorigenesis by Ligand Activation of Peroxisome Proliferator–Activated Receptor-β/δ and Inhibition of Cyclooxygenase 2
Authors: Zhu Bokai , Bai Robert , Kennett Mary J. , Kang Boo-Hyon , Gonzalez Frank J. , Peters Jeffrey M.
Published: December 2010

Ligand activation of peroxisome proliferator–activated receptor-β/δ (PPARβ/δ) and inhibition of cyclooxygenase-2 (COX2) activity by nonsteroidal anti-inflammatory drugs (NSAID) can both attenuate skin tumorigenesis. The present study examined the hypothesis that combining ligand activation of PPARβ/δ with inhibition of COX2 activity will increase the efficacy of chemoprevention of chemically induced skin tumorigenesis over that observed with either approach alone. To test this hypothesis, wild-type and Pparβ/δ-null mice were initiated with 7,12-dimethylbenz[a]anthracene (DMBA), topically treated with 12-O-tetradecanoylphorbol-13-acetate to promote tumorigenesis, and then immediately treated with topical application of the PPARβ/δ ligand GW0742, dietary administration of the COX2 inhibitor nimesulide, or both GW0742 and nimesulide. Ligand activation of PPARβ/δ with GW0742 caused a PPARβ/δ-dependent delay in the onset of tumor formation. Nimesulide also delayed the onset of tumor formation and caused inhibition of tumor multiplicity (46%) in wild-type mice but not in Pparβ/δ-null mice. Combining ligand activation of PPARβ/δ with dietary nimesulide resulted in a further decrease of tumor multiplicity (58%) in wild-type mice but not in Pparβ/δ-null mice. Biochemical and molecular analysis of skin and tumor samples show that these effects were due to the modulation of terminal differentiation, attenuation of inflammatory signaling, and induction of apoptosis through both PPARβ/δ-dependent and PPARβ/δ-independent mechanisms. Increased levels and activity of PPARβ/δ by nimesulide were also observed. These studies support the hypothesis that combining ligand activation of PPARβ/δ with inhibition of COX2 activity increases the efficacy of preventing chemically induced skin tumorigenesis as compared with either approach alone. Mol Cancer Ther; 9(12); 3267–77. ©2010 AACR.
Assessing the Role of the Non-Pneumatic Anti-Shock Garment in Reducing Mortality from Postpartum Hemorrhage in Nigeria
Authors: Ojengbede Oladosu A. , Morhason-Bello Imran Oludare , Galadanci Hadiza , Meyer Carinne , Nsima David , Camlin Carol , Butrick Elizabeth , Miller Suellen
Published: December 2010

Background/Aims: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality. The non-pneumatic anti-shock garment (NASG), a first-aid lower-body pressure device, may decrease mortality. Methods: This pre-intervention/NASG study of 288 women was conducted in four referral facilities in Nigeria, 2004–2008. Entry criteria: women with PPH due to uterine atony, retained placenta, ruptured uterus, vaginal or cervical lacerations or placenta accreta with estimated blood loss of ≧750 ml and one clinical sign of shock. Differences in demographics, conditions on study entry, treatment and outcomes were examined. t tests and relative risks with 95% confidence intervals were calculated for primary outcomes – measured blood loss and mortality. Multiple logistic regression analysis was performed to examine independent association of the NASG with mortality. Results: Mean measured blood loss decreased by 80% between phases. Women experienced 350 ml of median blood loss after study entry in the pre-intervention and 50 ml in the NASG phase (p < 0.0001). Mortality decreased from 18% pre-intervention to 6% in the NASG phase (RR = 0.31, 95% CI 0.15–0.64, p = 0.0007). In a multiple logistic regression model, the NASG was associated with reduced mortality (odds ratio 0.30; 95% CI 0.13–0.68, p = 0.004). Conclusion: The NASG shows promise for reducing mortality from PPH in referral facilities in Nigeria.
Novel Treatment Immediately after Myelomeningocele Repair Applying Low-Level Laser Therapy in Newborns: A Pilot Study
Authors: Pinto Fernando C. , Chavantes M. Cristina , Pinto Nathali C. , Alho Eduardo J.L. , Yoshimura Elisabeth M. , Matushita Hamilton , Krebs Vera L.J. , Teixeira Manoel J.
Published: December 2010

Background/Aims: The use of low-level laser therapy (LLLT) in neurosurgery is still hardly disseminated and there are situations in which the effects of this therapeutic tool would be extremely relevant in this medical field. The aim of the present study is to analyze the effect of LLLT on tissue repair after the corrective surgical incision in neonates with myelomeningocele, in an attempt to diminish the incidence of postoperative dehiscences following surgical repair performed immediately after birth. Materials and Methods: Prospective pilot study with 13 patients submitted to surgery at birth who received adjuvant treatment with LLLT (group A). A diode laser CW, λ = 685 nm, p = 21 mW, was applied punctually along the surgical incision, with 0.19 J delivered per point, accounting for a total of 4–10 J delivered energy per patient, according to the surgical wound area and then compared with the results obtained in 23 patients who underwent surgery without laser therapy (group B). Results: This pilot study disclosed a significant decline in dehiscences of the surgical wounds in neonates who were submitted to LLLT (7.69 vs. 17.39%). Conclusion: This new adjuvant therapeutic modality with LLLT aided the healing of surgical wounds, preventing morbidities, as well as shortening the period of hospital stay, which implies a reduction of costs for patients and for the institution.
Eosinophil Activation in the Cerebrospinal Fluid of Children with Shunt Obstruction
Authors: Heidemann Sabrina M. , Fiore Michael , Sood Sandeep , Ham Steven
Published: December 2010

Objective: To determine if eosinophils are activated to release the cationic proteins, eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) in shunt obstruction, and to find out if these proteins are associated with ventriculoperitoneal shunt failure. Patients and Methods: This was a prospective observational study carried out in a 20-bed tertiary pediatric intensive care unit. Patients studied were children aged 0–18 years with suspected ventriculoperitoneal shunt malfunction requiring shunt revision. No interventions were performed. Cerebrospinal fluid (CSF) was analyzed for cell count and EDN and ECP concentrations. Patients were prospectively followed for 6 months to evaluate shunt failure. Results: In a 2-month period, 56 shunt revisions were performed on 56 children. Three children had culture-proven infection. Eosinophilia, defined as ≧5% eosinophils in the CSF, was present in 9 out of 53 children (17%). The 3 patients with infection did not have eosinophilia and were excluded from further analysis. Patients with CSF eosinophilia had higher concentrations of ECP (1.38 ± 0.66 vs. 0.41 ± 0.15 ng/ml; p = 0.013) and EDN (16.94 ± 5.83 vs. 4.69 ± 1.33 ng/ml; p = 0.011). Patients with CSF eosinophilia did not have more ventriculoperitoneal shunt revisions within 6 months (6 of 9) compared to those who did not have eosinophilia (21 of 44; p = 0.50). However, patients with higher levels of ECP in the CSF required more shunt revisions within 6 months of their surgeries (p < 0.05). Conclusions: In patients with malfunctioning ventriculoperitoneal shunts, CSF eosinophils are activated and release ECP and EDN. The presence of ECP is associated with a shorter shunt life.
A Clinical Study of Pregnancy-Associated Renal Insufficiency
Authors: Wang Feng , Xing Tao , Wang Niansong , Huang Yajuan
Published: December 2010

Background/Aim: This study aimed to explore the causes, incidence and outcome of renal insufficiency during pregnancy. Methods: All pregnant women admitted to our hospital from September 2004 to August 2007 were retrospectively screened for renal function. Patients were divided into 3 groups according to the serum creatinine (Scr) level (mild renal insufficiency: Scr 70–123 µmol/l; moderate: Scr 124–220 µmol/l; severe: Scr >221 µmol/l). Results: Seventy-five cases (2.51%) of renal insufficiency were identified. Twenty-two cases (0.73%) had evidence of chronic kidney disease before pregnancy. Compared to the moderate and severe groups, the mild group had the lowest blood pressure. In 29 recorded cases with multiple observations throughout pregnancy, the deterioration of renal function progressed during the course of pregnancy; on average, Scr changed from 177 ± 109 µmol/l in the early phase of pregnancy to 194 ± 149 µmol/l (p < 0.001) in the third trimester, and mean blood pressure increased from 97 ± 11 to 120 ± 19 mm Hg (p < 0.001). There were 37 cases with preeclampsia (49%). Fourteen cases showed a decrease in glomerular filtration rate (GFR) in the third trimester; 4 of these patients suffered a severe decrease in GFR (over 25%). The rate of obstetrical complications was high among pregnancies with renal impairment. Conclusion: Renal insufficiency associated with pregnancy is not rare, and renal function may deteriorate during the course of pregnancy.
Cellular Mechanisms Underlying the Formation of Circulating Microparticles
Authors: Morel Olivier , Jesel Laurence , Freyssinet Jean-Marie , Toti Florence
Published: December 2010

Microparticles (MPs) derived from platelets, monocytes, endothelial cells, red blood cells, and granulocytes may be detected in low concentrations in normal plasma and at increased levels in atherothrombotic cardiovascular diseases. The elucidation of the cellular mechanisms underlying the generation of circulating MPs is crucial for improving our understanding of their pathophysiological role in health and disease. The flopping of phosphatidylserine (PS) to the outer leaflet of the plasma membrane is the key event that will ultimately lead to the shedding of procoagulant MPs from activated or apoptotic cells. Research over the last few years has revealed important roles for calcium-, mitochondrial-, and caspase-dependent mechanisms leading to PS exposure. The study of Scott cells has unraveled different molecular mechanisms that may contribute to fine-tuning of PS exposure and MP release in response to a variety of specific stimuli. The pharmacological modulation of MP release may have a substantial therapeutic impact in the management of atherothrombotic vascular disorders. Because PS exposure is a key feature in pathological processes different from hemostasis and thrombosis, the most important obstacle in the field of MP-modulating drugs seems to be carefully targeting MP release to relevant cell types at an optimal level, so as to achieve a beneficial action and limit possible adverse effects.
Cell-Derived Microparticles in the Pathogenesis of Cardiovascular Disease
Authors: Tushuizen Maarten E. , Diamant Michaela , Sturk Augueste , Nieuwland Rienk
Published: December 2010

Microparticles are ascribed important roles in coagulation, inflammation, and endothelial function. These processes are mandatory to safeguard the integrity of the organism, and their derangements contribute to the development of atherosclerosis and cardiovascular disease. More recently, the presumed solely harmful role of microparticles has been challenged because microparticles may also be involved in the maintenance and preservation of cellular homeostasis and in promoting defense mechanisms. Here, we summarize recent studies revealing these 2 faces of microparticles in cardiovascular disease.
Comparison of a Novel, Single-Lead Atrial Sensing System With a Dual-Chamber Implantable Cardioverter-Defibrillator System in Patients Without Antibradycardia Pacing Indications
Authors: Sticherling Christian , Zabel Markus , Spencker Sebastian , Meyerfeldt Udo , Eckardt Lars , Behrens Steffen , Niehaus Michael ,   for the ADRIA Investigators
Published: December 2010

Background—

Supraventricular tachyarrhythmias are the main cause for inappropriate therapy by implantable cardioverter-defibrillators (ICDs). For better rhythm discrimination, an atrial electrogram is helpful and usually obtained from an additional atrial lead, even in the absence of sinus node or atrioventricular nodal disease. An A+-ICD system with integrated atrial sensing rings mounted 15 to 18 cm from the tip of an ICD lead may obviate the need to implant a separate atrial lead. The aim of the study was to compare the novel A+-ICD and a conventional dual-chamber (DR)-ICD.

Methods and Results—

Two hundred forty-nine patients with standard ICD indications but no requirement for antibradycardia pacing were randomized to receive an A+-ICD (n=124) or a DR-ICD (n=125). Implantation details, need for ICD system revision, long-term sensing, documented arrhythmia episodes, and the respective rhythm discrimination during follow-up were analyzed. The implantation time was significantly shorter in the A+-ICD group (67±30 vs 79±30 minutes,
P
=0.003). Mean P-wave amplitudes were 3.5±0.8 mV (A+-ICD) and 3.2±0.6 mV (DR-ICD) and remained stable during the follow-up period of 12 months. Surgical revision was necessary in 13 patients in the DR-ICD and 10 in the A+-ICD group. All 593 ventricular tachyarrhythmia episodes were correctly discriminated. Sensitivity and specificity of supraventricular tachyarrhythmia discrimination were not different between the study groups.

Conclusions—

The novel A+-ICD system can be implanted faster and is equivalent to a standard DR-ICD with regard to the detection of ventricular tachyarrhythmias and supraventricular tachyarrhythmias. It represents a useful alternative to obtain atrial sensing.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00324662.
Isoproterenol Administration During General Anesthesia for the Evaluation of Children With Ventricular Preexcitation
Authors: Moore Jeremy P. , Kannankeril Prince J. , Fish Frank A.
Published: December 2010

Background—

Rapid anterograde conduction in the setting of ventricular preexcitation is associated with an increased risk of sudden cardiac death. The effect of isoproterenol in this setting is unclear, particularly in younger anesthetized patients. The aim of this study was to determine the effect of isoproterenol on accessory-pathway conduction in children undergoing general anesthesia and its role in the risk-stratification process.

Methods and Results—

The records of 151 pediatric patients with preexcitation undergoing electrophysiologic study under propofol anesthesia during a 5-year period were reviewed. Data included accessory-pathway effective refractory period, minimum 1:1 accessory pathway conduction with atrial pacing, and shortest preexcited R-R interval in atrial fibrillation. Measurements were repeated after administration of low-dose isoproterenol (mean, 0.013 μg/kg per min; range, 0.003 to 0.027). All accessory-pathway characteristics were significantly shortened with isoproterenol (
P
<0.001). Accessory-pathway effective refractory period increased modestly with age, both in the baseline state (
r
=0.172,
P
=0.04) and with isoproterenol (
r
=0.267,
P
<0.01) as did minimum 1:1 accessory pathway conduction with atrial pacing (
r
=0.178,
P
=0.034, and
r
=0.175,
P
<0.01, respectively). Accessory-pathway effective refractory period ≤250 ms was observed in only 5% of patients at baseline vs 25% after isoproterenol, and Shortest preexcited R-R interval in atrial fibrillation ≤250 ms was noted in 16% vs 41%. Tachycardia was induced in 48 of 151 patients before and in 102 of 151 after isoproterenol.

Conclusions—

In anesthetized children with ventricular preexcitation, accessory pathways display shorter conduction properties at younger ages and important adrenergic sensitivity at all ages. Use of low-dose isoproterenol resulted in a substantial increase in the number of patients who would otherwise meet typical criteria for ablation.
The Effect of the Sea Ice Freshwater Flux on Southern Ocean Temperatures in CCSM3: Deep-Ocean Warming and Delayed Surface Warming
Authors: Kirkman Clark H. , Bitz Cecilia M.
Published: December 2010

This study explores the role of sea ice freshwater and salt fluxes in modulating twenty-first-century surface warming in the Southern Ocean via analysis of sensitivity experiments in the Community Climate System Model, version 3 (CCSM3). In particular, the role of a change in these fluxes in causing surface cooling, expanding sea ice, and increasing deep oceanic storage of heat in the Southern Ocean is investigated. The results indicate that in response to the doubling of CO2 concentrations in the atmosphere in CCSM3, net freshwater input from sea ice to the ocean increases south of 58°S (owing to less growth) and decreases from 48° to 58°S (owing to less melt). The freshwater source from changing precipitation in the model is considerably less than from sea ice south of 58°S, but it serves to compensate for the reduction in sea ice melt near the ice edge, leaving almost no net freshwater flux change between about 48° and 58°S. As a result, freshwater input principally from sea ice reduces ocean convection, which in turns reduces the entrainment of heat into the mixed layer and reduces the upward heat transport along isopycnals below about 1000 m. The reduced upward heat transport (from all sources) causes deep-ocean heating south of 60°S and below 500-m depth, with a corresponding surface cooling in large parts of the Southern Ocean in the model. These results indicate that changing sea ice freshwater and salt fluxes are a major component of the twenty-first-century delay in surface warming of the Southern Ocean and weak reduction in Antarctic sea ice in model projections.
Cotidal Charts near Hawaii Derived from TOPEX/Poseidon Altimetry Data
Authors: Fan Li-Li , Wang Bin , Lv Xian-Qing
Published: December 2010

Harmonic analysis of 10 yr of Ocean Topography Experiment (TOPEX)/Poseidon (T/P) along-track altimetry is performed to derive the semidiurnal and diurnal tides (M2, S2, N2, K2, K1, O1, P1, and Q1) near Hawaii. The T/P solutions are evaluated through intercomparison for crossover points of the ascending and descending tracks and comparison with the data of tidal stations, which show that the T/P solutions in the study area are reliable. By using a suitable order polynomial to fit the T/P solutions along every track, the harmonic constants of any point on T/P tracks are acquired. A new fitting method, which is characterized by applying the harmonics from T/P tracks to produce directly empirical cotidal charts, is developed. The harmonic constants derived by this fitting method show good agreement with the data of tidal stations, the results of National Astronomical Observatory 99b (NAO.99b), TOPEX/Poseidon 7.2 (TPXO7.2), and Finite Element Solutions 2004 (FES2004) models, which suggests that the fitting method is reasonable, and the highly accurate cotidal chart could be directly acquired from T/P altimetry data by this fitting method.
Observability of Flow-Dependent Structure Functions for Use in Data Assimilation
Authors: Lupu Cristina , Gauthier Pierre
Published: December 2010

One of the objectives of data assimilation is to produce initial conditions that will improve the quality of forecasts. Studies on singular vectors and sensitivity studies have shown that small changes to the initial conditions can sometimes lead to exponential error growth. This has motivated research to include flow-dependent structures within the assimilation that would have the characteristics to correctly predict the growth or decay of meteorological systems. This relates to the characterization of precursors to atmospheric instability. In this paper, the observability of such structures by observations is discussed. Several studies have shown that deploying observations over regions where changes in the initial conditions may impact the forecast the most do not lead to the expected benefit. In this paper, it is shown that given the small magnitude of the signal to be detected, it is important to take into account the accuracy of the observations. If the signal-to-noise ratio is too low, observations cannot detect and characterize precursors to forecast error growth. From that perspective, the assimilation only has the possibility to extract information about evolved structures of error growth. Experiments with a simple one-dimensional variational data assimilation (1D-Var) system are presented and, then, an adapted three-dimensional variational data assimilation (3D-Var) system with different sensitivity structure functions is used. The results have been obtained by adapting the variational assimilation system of Environment Canada.
Sexual Cues Emanating From the Anchorette Chair: Implications for Perceived Professionalism, Fitness for Beat, and Memory for News
Authors: Grabe Maria Elizabeth , Samson Lelia
Published: December 2010

The experimental study reported here employed one of the most compelling visual cues of female sexual attractiveness (low waist-to-hip ratio) to test the influence of news anchor sexualization on audience evaluations of her as a professional and their memory for the news that she presents. Male participants saw the sexualized version of the anchor as less suited for war and political reporting. They also encoded less news information presented by the sexualized than her unsexualized version. Conclusions were drawn in line with evolutionary psychology expectations of men’s cognitive susceptibility to visual sex cues. Women participants, on the other hand, did not vary across conditions in their assessments of the anchor’s competence to report on war and political news. Moreover, they encoded more news information presented by the sexualized than unsexualized anchor condition.
Why Are Some Ethnic Groups More Violent Than Others? The Role of Friendship Network’s Ethnic Composition
Authors: Rabold Susann , Baier Dirk
Published: December 2010

Ethnic differences in violent behavior can be found in official crime statistics, as well as in surveys on juvenile delinquency. To explain these differences, research mainly focuses on factors like parental violence, violence legitimizing norms of masculinity, or socio-economic status. Little research has examined the role of friendship network’s ethnic composition on ethnic differences in violent behavior, although different sociological and criminological theories suggest that the composition of friendship networks can play an important role for attitudes and behavior of its members. Using data of a survey conducted in 2006 among all ninth-grade pupils in Hanover (Germany), we investigated the influence of friendship network’s ethnic composition on violent behavior in general, and on ethnic differences in violent behavior in particular. Due to the specific sampling procedure, it was also possible to look for neighborhood effects both on (ethnic differences in) juvenile delinquency and friendship network composition. Findings indicate that there are significant differences in the network composition across the ethnic groups. After controlling for these network characteristics, ethnic differences in violent behavior disappeared. Furthermore, the results show that the friendship network’s ethnic composition also depends on community characteristics.
Unraveling the Relative Contributions of His, Her, and Their Drinking to the Likelihood of Arrest in Intimate Partner Violence Cases
Authors: Hirschel David , Hutchison Ira
Published: December 2010

The nexus between substance abuse and intimate partner violence has been studied in depth. The interrelationship between drinking, intimate partner violence, and an officer’s decision to make an arrest has not received as much attention. The issue is complicated by the fact that either or both of the involved parties may have been drinking and the effects may vary depending on who has been drinking. In this article, the authors examine the relative contributions of his, her, and their drinking to the likelihood of arrest.
Building Knowledge Stocks Locally
Authors: Groen Jeffrey A.
Published: December 2010

There is increasing evidence that the stock of college-educated labor in an area has fundamental effects on state and local economies through its association with wages, economic growth, personal incomes, and tax revenues. As a result, policy makers in many states attempt to increase the percentage of the state’s population (or workforce) that has a college degree through the use of various higher education policies that have the potential to influence the supply side of the labor market. This article reviews evidence on the effectiveness of these policies in achieving that goal. The author discusses several types of policies related to the finance and production of undergraduate education within a state, including expansions in degree production, merit-based scholarships, location-contingent financial aid, adjustments to the composition of enrollment by residency or by field of study, and internships with state-based employers.
Validity of the Montreal Cognitive Assessment (MoCA) as a Screening Test for Mild Cognitive Impairment (MCI) in a Cardiovascular Population
Authors: McLennan S.N. , Mathias J.L. , Brennan L.C. , Stewart S.
Published: December 2010

While rates of mild cognitive impairment (MCI) are relatively high in populations with cardiovascular diseases and risk factors, screening tests for MCI have not been evaluated in this patient group. This study investigated the sensitivity and specificity of the Montreal Cognitive Assessment (MoCA) tool for detecting MCI in 110 patients (mean age 67.9 + 11.7 years; 60% female) recruited from hospital cardiovascular outpatient clinics. Mean MoCA performance was relatively low (22.8 + 3.8) in this group, with 72.1% of participants scoring below the recommended cutoff for cognitive impairment (<26). The presence of MCI was determined using the Neuropsychological Assessment Battery Screening Module (NAB-SM). Both amnestic MCI and multiple-domain MCI were identified. The optimum MoCA cutoff for detecting MCI in this group was <24. At this cutoff, the MoCA’s sensitivity for detecting amnestic MCI was 100% and for multiple-domain MCI it was 83.3%. Specificity rates for amnestic MCI and multiple-domain MCI were 50.0% and 52% respectively. The poor specificity of the MoCA suggests that it will have limited value as a screening test for MCI in settings where the overall prevalence of MCI is low.
Postural Effects of the Horizon on Land and at Sea
Authors: Mayo Anthony M. , Wade Michael G. , Stoffregen Thomas A.
Published: December 2010

Motion of a ship at sea creates challenges for control of the body. Anecdotal reports suggest that the body can be stabilized by standing on the open deck and looking at the horizon. This advice contrasts with land-based findings that looking at the horizon leads to increased body sway. We measured standing body sway in experienced maritime crew members on land and at sea. On land, body sway was greater when subjects looked at the horizon than when they did not—the classical effect. At sea, body sway was greater in a closed cabin than on the open deck. On the open deck, body sway when looking at the horizon was reduced relative to sway when looking at middistance targets on the ship. The results are consistent with centuries of anecdotal advice given to sea travelers and raise new questions about the referents that are used for the control of standing posture.
Costs and Benefits of Stem Cell Research and Treatment: Media Presentation and Audience Understanding in Hungary
Authors: Vicsek Lilla
Published: December 2010

This study examined the press coverage and audience understanding of the costs and benefits of stem cell research/treatment in Hungary. A content analysis of five newspapers and a focus group study was conducted. The way participants talked about the costs and benefits in many aspects echoed the dominant framing of the issue in the press (medical benefits = main benefit, high expense of treatment = dominant negative aspect). Even though participants applied analogical reasoning to formulate some risks that were missing from the reporting on stem cells, many gaps of the media coverage were echoed in gaps in lay discussions.
(Even Radical) Illustration Requires (Normalizing) Convention: The Case of ‘Genre Art’ in Early Modern Japan
Authors: Berry Mary Elizabeth
Published: December 2010

Pictures that portray the ‘now’ of a lived reality from the vantage of witnesses emerged in Japan during the 17th century, when the mundane social life of contemporary commoners blasted into the visual repertoire of illustrated books. This change, a revolutionary one, belongs to the broader experience of early modernity, from Amsterdam to Nanjing, as seismic economic transitions helped occasion a new immediacy in social representation. Yet the radical newness of the imagery was quickly tamed by convention, which the author argues is indispensable to the legibility of all illustration. The visual conventions explored here include the ‘ordinary pictorial site’ (in the Japanese case such public spaces as theaters and bathhouses but quintessentially the street) that artists treated in a style of ‘generic factuality’ (combining a loving attention to material detail with stereotypical renderings of faces and bodies). Not so paradoxically, the very tropes and treatments used to convert novelty into normalcy also enforced inertia. If banality is one risk of convention, normativity is the greater problem. Training viewers to see one kind of world, illustrators elide any other.
Successful Glue Embolization of a Late Type 1a Endoleak Causing Abdominal Aortic Aneurysm Rupture
Authors: Rusius Victoria C. , Davies Robert S. M. , Hopkins Jonathan D. , Duddy Martin J. , Smith Simon R. G.
Published: December 2010

We describe the successful treatment with n-butyl cyanoacrylate embolization of a ruptured infrarenal abdominal aortic aneurysm caused by a late type-1A endoleak 10 years after endovascular aneurysm repair (EVAR).
High shear–dependent loss of membrane integrity and defective platelet adhesion following disruption of the GPIbα-filamin interaction
Authors: Cranmer Susan L. , Ashworth Katrina J. , Yao Yu , Berndt Michael C. , Ruggeri Zaverio M. , Andrews Robert K. , Jackson Shaun P.
Published: December 2010

Platelets have evolved a highly specialized membrane skeleton that provides stability to the plasma membrane and facilitates adhesion under high shear stress. The cytoskeletal anchorage of glycoprotein (GP) Ibα plays an important role in regulating the membrane skeleton. However, its role in regulating membrane stability remains unknown. To investigate this role, we have developed a new mouse model that expresses wild-type human GPIbα (hGPIbαWT), or a mutant form of human GPIbα that has a selective defect in its ability to bind filamin A and anchor to the membrane skeleton (hGPIbαFW–Phe568Ala and Trp570Ala substitutions). Our study demonstrates that the link between platelet GPIb and the cytoskeleton does not alter the intrinsic ligand binding function of GPIbα or the ability of the receptor to stimulate integrin αIIbβ3-dependent spreading. However, exposure of hGPIbαFW platelets to pathologic shear rate levels (5000 to 40 000 s−1) leads to the development of unstable membrane tethers, defective platelet adhesion, and loss of membrane integrity, leading to complete disintegration of the platelet cell body. These outcomes suggest that the GPIbα–filamin A interaction not only regulates the architecture of the membrane skeleton, but also maintains the mechanical stability of the plasma membrane under conditions of high shear.