bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of Proinflammatory Cytokines in Functionalized Fullerene‐Exposed Dermal Keratinocytes
Authors: Gao Jun , Wang Hsing-Lin , Iyer Rashi
Published: February 2010

Initial experiments using differentially functionalized fullerenes, CD‐C60, hexa‐C60, and tris‐C60, suggested a properties dependent effect on cytotoxic and proliferative responses in human skin keratinocytes. In the present study we investigated the cytokine secretion profile of dermal epithelial cells exposed to functionalized fullerenes. Keratinocyte‐derived cytokines affect homing and trafficking of normal and malignant epidermal immune as well as nonimmune cells in vivo. These cytokines are critical for regulating activation, proliferation, and differentiation of epidermal cells. Our results indicate that tris‐C60 (size range <100 nm) significantly reduces inflammatory cytokine release in a dose‐ and time‐dependent manner. In contrast CD‐C60 demonstrated a relatively pro‐inflammatory cytokine response, while hexa‐C60 did not significantly perturb cytokine responses. Physical and chemical characterizations of these engineered nanomaterials suggest that the disparate biological responses observed may potentially be a function of the aggregation properties of these fullerenes.
Error Immune Logic for Low-Power Probabilistic Computing
Authors: Marr Bo , George Jason , Degnan Brian , Anderson David V. , Hasler Paul
Published: February 2010

Two novel theorems are developed which prove that certain logic functions are more robust to errors than others. These theorems are used to construct datapath circuits that give an increased immunity to error over other naive implementations. A link between probabilistic operation and ultra-low energy computing has been shown in prior work. These novel theorems and designs will be used to further improve probabilistic design of ultra-low power datapaths. This culminates in an asynchronous
design for the maximum amount of energy savings per a given error rate. Spice simulation results using a commercially available and well-tested 0.25 μm technology are given verifying the ultra-low power, probabilistic full-adder designs. Further, close to 6X energy savings is achieved for a probabilistic full-adder over the deterministic case.
Modeling Sequential Searches with Ancillary Target Dependencies
Authors: Wettergren Thomas A. , Baylog John G.
Published: February 2010

We develop a mathematical modeling approach to evaluate the effectiveness of a Bayesian search for objects in cases where the target exhibits ancillary dependencies. These dependencies occur in situations where there are multiple search passes of the same region, and they represent a change in search probability from that predicted using an assumption of independent scans. This variation from independent scans is typically found in situations of advanced detection processing due to fusion and/or collaboration between searchers. The framework developed is based upon the evaluation of a recursion process over spatial search cells, and the dependencies appear as additive utility components within the recursion. We derive expressions for evaluating this utility and illustrate in detail some specific instantiations of the dependency. Computational examples are provided to demonstrate the capabilities of the method.
Thermal and Mechanical Properties of Chitosan/SiO2 Hybrid Composites
Authors: Al-Sagheer F. , Muslim S.
Published: February 2010

Chitosan‐silica (CSSi) hybrid films have been fabricated by sol‐gel process using tetraethoxysilane (TEOS) as precursor. The structure of the resulting hybrid has been characterized by Fourier transform infrared spectroscopy (FTIR). Fracture surface has been revealed through a field emission‐scanning electron microscopy/energy dispersive spectrometer (FE‐SEM/EDS) to probe the dispersion degree and the size of SiO2 particle. Study of morphology using a SEM micrograph and the High Resolution Transmission Electron Microscopy (HRTEM) images of the nanocomposite films suggests that the SiO2 nanoparticles are within the range of 2–7 nm in diameter and are uniformly dispersed in the polymer matrix. Thermal properties of these composite materials have been studied as a function of silica, indicating that thermal stability of the chitosan film is enhanced. Dynamical mechanical thermal analysis (DMTA) has been carried out to measure the shift in the glass transition temperature (Tg) of the composites from the maxima of the α transition curves. The glass transition temperature and the storage modulus show an increase with increasing silica content. The maximum increase in the Tg value, that is, 159.37∘C, is seen with 30 wt% silica. A gradual increase of 3.0 GPa in the modulus relative to the pure polymer is observed.
Overweight among Four-Year-Old Children in Relation to Early Growth Characteristics and Socioeconomic Factors
Authors: Thorn Jörgen , Waller Maria , Johansson Maria , Mårild Staffan
Published: February 2010

Objectives. To assess early growth characteristics and socioeconomic factors of children in relation to body mass index (BMI) and presence of overweight among four-year-old children.Methods. Two Child Health Centres (CHC) participated in the study. They were selected to obtain two populations of children featuring divergent socio-economic characteristics. Growth data registered at the CHCs from birth to the 4-year check-up were recovered. Overweight was defined by the BMI cut-offs established by IOTF. BMI values expressed as BMI standard deviation score (BMISDS) were used for analysis.Results. At the 4-year check-up, the BMISDS and the proportion of children with overweight (including the obese) were significantly higher in the district with lower socio-economic status. High BMI at birth and low socio-economic status of the population in the CHC-district were shown to be independent determinants for overweight and BMISDS at four years of age.Conclusions. More research is needed to understand the mechanisms and how intervention programs should be designed in order to prevent the development of overweight and obesity in children.
Normal Structure and Common Fixed Point Properties for Semigroups of Nonexpansive Mappings in Banach Spaces
Authors: Lau AnthonyTo-Ming
Published: February 2010

In 1965, Kirk proved that if "Equation missing" is a nonempty weakly compact convex subset of a Banach space with normal structure, then every nonexpansive mapping "Equation missing" has a fixed point. The purpose of this paper is to outline various generalizations of Kirk's fixed point theorem to semigroup of nonexpansive mappings and for Banach spaces associated to a locally compact group.
Rhombencephalitis Caused byListeria monocytogenesin Humans and Ruminants: A Zoonosis on the Rise?
Authors: Oevermann Anna , Zurbriggen Andreas , Vandevelde Marc
Published: February 2010

Listeriosis is an emerging zoonotic infection of humans and ruminants worldwide caused byListeria monocytogenes(LM). In both host species, CNS disease accounts for the high mortality associated with listeriosis and includes rhombencephalitis, whose neuropathology is strikingly similar in humans and ruminants. This review discusses the current knowledge about listeric encephalitis, and involved host and bacterial factors. There is an urgent need to study the molecular mechanisms of neuropathogenesis, which are poorly understood. Such studies will provide a basis for the development of new therapeutic strategies that aim to prevent LM from invading the brain and spread within the CNS.
Gene Expression Profiling of Placentas Affected by Pre-Eclampsia
Authors: Hoegh Anne Mette , Borup Rehannah , Nielsen Finn Cilius , Sørensen Steen , Hviid Thomas V. F.
Published: March 2010

Several studies point to the placenta as the primary cause of pre-eclampsia. Our objective was to identify placental genes that may contribute to the development of pre-eclampsia. RNA was purified from tissue biopsies from eleven pre-eclamptic placentas and eighteen normal controls. Messenger RNA expression from pooled samples was analysed by microarrays. Verification of the expression of selected genes was performed using real-time PCR. A surprisingly low number of genes (21 out of 15,000) were identified as differentially expressed. Among these were genes not previously associated with pre-eclampsia as bradykinin B1 receptor and a 14-3-3 protein, but also genes that have already been connected with pre-eclampsia, for example, inhibin beta A subunit and leptin. A low number of genes were repeatedly identified as differentially expressed, because they may represent the endpoint of a cascade of events effectuated throughout gestation. They were associated with transcriptional regulation and vasoregulative pathways, along with a number of hypothetical proteins and gene sequences with unknown functions.
p53 Regulates the Ras Circuit to Inhibit the Expression of a Cancer-Related Gene Signature by Various Molecular Pathways
Authors: Buganim Yosef , Solomon Hilla , Rais Yoach , Kistner Daria , Nachmany Ido , Brait Mariana , Madar Shalom , Goldstein Ido , Kalo Eyal , Adam Nitzan , Gordin Maya , Rivlin Noa , Kogan Ira , Brosh Ran , Sefadia-Elad Galit , Goldfinger Naomi , Sidransky David , Kloog Yoel , Rotter Varda
Published: March 2010

In this study, we focus on the analysis of a previously identified cancer-related gene signature (CGS) that underlies the cross talk between the p53 tumor suppressor and Ras oncogene. CGS consists of a large number of known Ras downstream target genes that were synergistically upregulated by wild-type p53 loss and oncogenic H-RasG12V expression. Here we show that CGS expression strongly correlates with malignancy. In an attempt to elucidate the molecular mechanisms underling the cooperation between p53 loss and oncogenic H-RasG12V, we identified distinguished pathways that may account for the regulation of the expression of the CGS. By knocking-down p53 or by expressing mutant p53, we revealed that p53 exerts its negative effect by at least two mechanisms mediated by its targets B-cell translocation gene 2 (BTG2) and activating transcription factor 3 (ATF3). Whereas BTG2 binds H-RasG12V and represses its activity by reducing its GTP loading state, which in turn causes a reduction in CGS expression, ATF3 binds directly to the CGS promoters following p53 stabilization and represses their expression. This study further elucidates the molecular loop between p53 and Ras in the transformation process. Cancer Res; 70(6); 2274–84
Antibody-Maytansinoid Conjugates Designed to Bypass Multidrug Resistance
Authors: Kovtun Yelena V. , Audette Charlene A. , Mayo Michele F. , Jones Gregory E. , Doherty Heather , Maloney Erin K. , Erickson Hans K. , Sun Xiuxia , Wilhelm Sharon , Ab Olga , Lai Katharine C. , Widdison Wayne C. , Kellogg Brenda , Johnson Holly , Pinkas Jan , Lutz Robert J. , Singh Rajeeva , Goldmacher Victor S. , Chari Ravi V.J.
Published: March 2010

Conjugation of cytotoxic compounds to antibodies that bind to cancer-specific antigens makes these drugs selective in killing cancer cells. However, many of the compounds used in such antibody-drug conjugates (ADC) are substrates for the multidrug transporter MDR1. To evade the MDR1-mediated resistance, we conjugated the highly cytotoxic maytansinoid DM1 to antibodies via the maleimidyl-based hydrophilic linker PEG4Mal. Following uptake into target cells, conjugates made with the PEG4Mal linker were processed to a cytotoxic metabolite that was retained by MDR1-expressing cells better than a metabolite of similar conjugates prepared with the nonpolar linker N-succinimidyl-4-(maleimidomethyl)cyclohexane-1-carboxylate (SMCC). In accord, PEG4Mal-linked conjugates were more potent in killing MDR1-expressing cells in culture. In addition, PEG4Mal-linked conjugates were markedly more effective in eradicating MDR1-expressing human xenograft tumors than SMCC-linked conjugates while being tolerated similarly, thus showing an improved therapeutic index. This study points the way to the development of ADCs that bypass multidrug resistance. Cancer Res; 70(6); 2528–37
Wnt Inhibitory Factor 1 Decreases Tumorigenesis and Metastasis in Osteosarcoma
Authors: Rubin Elyssa M. , Guo Yi , Tu Khoa , Xie Jun , Zi Xiaolin , Hoang Bang H.
Published: March 2010

It has been reported that the progression of osteosarcoma was closely associated with the aberrant activation of canonical Wnt signaling. Wnt inhibitory factor-1 (WIF-1) is a secreted Wnt inhibitor whose role in human osteosarcoma remains unknown. In this study, WIF-1 expression in NHOst and osteosarcoma cell lines was determined by real-time reverse transcription-PCR, methylation-specific PCR, and Western blotting analysis. In addition, tissue array from patient samples was examined for WIF-1 expression by immunohistochemistry. Compared with normal human osteoblasts, WIF-1 mRNA and protein levels were significantly downregulated in several osteosarcoma cell lines. The downregulation of WIF-1 mRNA expression is associated with its promoter hypermethylation in these tested cell lines. Importantly, WIF-1 expression was also downregulated in 76% of examined osteosarcoma cases. These results suggest that the downregulation of WIF-1 expression plays a role in osteosarcoma progression. To further study the potential tumor suppressor function of WIF-1 in osteosarcoma, we established stable 143B cell lines overexpressing WIF-1. WIF-1 overexpression significantly decreased tumor growth rate in nude mice as examined by the s.c. injection of 143B cells stably transfected with WIF-1 and vector control. WIF-1 overexpression also markedly reduced the number of lung metastasis in vivo in an orthotopic mouse model of osteosarcoma. Together, these data suggest that WIF-1 exerts potent antiosteosarcoma effect in vivo in mouse models. Therefore, the reexpression of WIF-1 in WIF-1–deficient osteosarcoma represents a potential novel treatment and preventive strategy. Mol Cancer Ther; 9(3); 731–41
Phase I Combination of Sorafenib and Erlotinib Therapy in Solid Tumors: Safety, Pharmacokinetic, and Pharmacodynamic Evaluation from an Expansion Cohort
Authors: Quintela-Fandino Miguel , Le Tourneau Christophe , Duran Ignacio , Chen Eric X. , Wang Lisa , Tsao Ming , Bandarchi-Chamkhaleh Bizhan , Pham Nhu-Ann , Do Trevor , MacLean Martha , Nayyar Rakesh , Tusche Michael W. , Metser Ur , Wright John J. , Mak Tak W. , Siu Lillian L.
Published: March 2010

The aims of this study were to further define the safety of sorafenib and erlotinib, given at their full approved monotherapy doses, and to correlate pharmacokinetic and pharmacodynamic markers with clinical outcome. In addition, a novel pharmacodynamic marker based on the real-time measurement of RAF signal transduction capacity (STC) is described. Sorafenib was administered alone for a 1-week run-in period, and then both drugs were given together continuously. RAF STC was assessed in peripheral blood monocytes prior to erlotinib initiation. Epidermal growth factor receptor (EGFR) expression and K-RAS mutations were measured in archival tumor samples. Changes in pERK and CD31 were determined in fresh tumor biopsies obtained pretreatment, prior to erlotinib dosing, and during the administration of both drugs. In addition, positron emission tomography–computed tomography scans and pharmacokinetic assessments were done. Eleven patients received a total of 57 cycles (median, 5; range, 1–10). Only four patients received full doses of both drugs for the entire study course, with elevation of liver enzymes being the main reason for dose reductions and delays. Among 10 patients evaluable for response, 8 experienced tumor stabilization of ≥4 cycles. Pharmacokinetic analysis revealed no significant interaction of erlotinib with sorafenib. Sorafenib-induced decrease in RAF-STC showed statistically significant correlation with time-to-progression in seven patients. Other pharmacodynamic markers did not correlate with clinical outcome. This drug combination resulted in promising clinical activity in solid tumor patients although significant toxicity warrants close monitoring. RAF-STC deserves further study as a predictive marker for sorafenib. Mol Cancer Ther; 9(3); 751–60
CNK1 Promotes Invasion of Cancer Cells through NF-κB–Dependent Signaling
Authors: Fritz Rafael D. , Radziwill Gerald
Published: March 2010

Hallmarks of cancer cells are uncontrolled proliferation, evasion of apoptosis, angiogenesis, cell invasion, and metastasis, which are driven by oncogenic activation of signaling pathways. Herein, we identify the scaffold protein CNK1 as a mediator of oncogenic signaling that promotes invasion in human breast cancer and cervical cancer cells. Downregulation of CNK1 diminishes the invasiveness of cancer cells and correlates with reduced expression of matrix metalloproteinase 9 (MMP-9) and membrane-type 1 MMP (MT1-MMP). Ectopic expression of CNK1 elevates MT1-MMP promoter activity in a NF-κB–dependent manner. Moreover, CNK1 cooperates with the NF-κB pathway, but not with the extracellular signal–regulated protein kinase pathway, to promote cell invasion. Mechanistically, CNK1 regulates the alternative branch of the NF-κB pathway because knockdown of CNK1 interferes with processing of NF-κB2 p100 to p52 and its localization to the nucleus. In agreement with this, the invasion of CNK1-depleted cells is less sensitive to RelB downregulation compared with the invasion of control cells. Moreover, CNK1-dependent MT1-MMP promoter activation is blocked by RelB siRNA. Thus, CNK1 is an essential mediator of an oncogenic pathway involved in invasion of breast and cervical cancer cells and is therefore a putative target for cancer therapy. Mol Cancer Res; 8(3); 395–406
MLN8054, an Inhibitor of Aurora A Kinase, Induces Senescence in Human Tumor Cells Both In vitro and In vivo
Authors: Huck Jessica J. , Zhang Mengkun , McDonald Alice , Bowman Doug , Hoar Kara M. , Stringer Bradley , Ecsedy Jeffery , Manfredi Mark G. , Hyer Marc L.
Published: March 2010

Aurora A kinase is a serine/threonine protein kinase responsible for regulating several mitotic processes including centrosome separation, spindle assembly, and chromosome segregation. Small molecule inhibitors of Aurora A kinase are being pursued as novel anticancer agents, some of which have entered clinical trials. Despite the progress in developing these agents, terminal outcomes associated with Aurora A inhibition are not fully understood. Although evidence exists that Aurora A inhibition leads to apoptosis, other therapeutically relevant cell fates have not been reported. Here, we used the small molecule inhibitor MLN8054 to show that inhibition of Aurora A induces tumor cell senescence both in vitro and in vivo. Treatment of human tumor cells grown in culture with MLN8054 showed a number of morphologic and biochemical changes associated with senescence. These include increased staining of senescence-associated β-galactosidase, increased nuclear and cell body size, vacuolated cellular morphology, upregulation/stabilization of p53, p21, and hypophosphorylated pRb. To determine if Aurora A inhibition induces senescence in vivo, HCT-116 xenograft–bearing animals were dosed orally with MLN8054 for 3 weeks. In the MLN8054-treated animals, increased senescence-associated β-galactosidase activity was detected in tissue sections starting on day 15. In addition, DNA and tubulin staining of tumor tissue showed a significant increase in nuclear and cell body area, consistent with a senescent phenotype. Taken together, this data shows that senescence is a terminal outcome of Aurora A inhibition and supports the evaluation of senescence biomarkers in clinic samples. Mol Cancer Res; 8(3); 373–84
Metabolic Syndrome in Children: Comparison of the International Diabetes Federation 2007 Consensus with an Adapted National Cholesterol Education Program Definition in 300 Overweight and Obese French Children
Authors: Druet Céline , Ong Ken , Levy Marchal Claire
Published: March 2010

Background/Aims: Former definitions of metabolic syndrome (MS) in children have been adapted from adult MS definitions using age-related thresholds for each biochemical component, whereas the International Diabetes Federation (IDF) definition is based on absolute values. We compared the IDF childhood MS definition (IDF-MS) to the adapted National Cholesterol Education Program (adapted-NCEP) definition in overweight children. Methods: 300 overweight and obese children were included with a median age of 11 years and BMI SDS of +4.7. Results: Below 10 years of age, the frequency of MS according to the adapted-NCEP-MS definition was 18.6%, and 86.1% had abdominal obesity. In children aged 10 to <16 years (n = 214), the frequency of IDF-MS was 8.9% compared to 14.5% by adapted-NCEP. IDF-MS children had a larger waist circumference, and higher triglycerides, fasting insulin and tended to be older than the intermediate severity group of children with MS only according to adapted-NCEP. Children with MS only according to adapted-NCEP (IDF-MS negative), differed from non-MS children in systolic blood pressure, triglycerides and high-density lipoprotein cholesterol. Conclusions: The recent IDF-MS criterion in children represents a more severe definition and appears to identify a group of children with higher fasting insulin than the adapted-MS definition which uses age-related thresholds (90th percentile).
Clinical, Genetic and Functional Characteristics of Three Novel CYP17A1 Mutations Causing Combined 17α-Hydroxylase/17,20-Lyase Deficiency
Authors: Rosa S. , Steigert M. , Lang-Muritano M. , l’Allemand D. , Schoenle E.J. , Biason-Lauber A.
Published: March 2010

Background: P450c17 has two distinct activities: 17α-hydroxylase activity and 17,20-lyase activity. Combined 17α-hydroxylase/17,20-lyase deficiency leads to a severe defect in the production of cortisol and sex steroids. In affected males this results in impaired masculinization with ambiguous or female external genitalia. Female patients have normal genitalia but show a lack of pubertal development in adolescence. An increased production of mineralocorticoids often leads to hypertension and hypokalemia in both sexes. Methods: To better understand the mechanisms of P450c17 deficiency, we studied 2 patients (both 46,XY) with combined 17α-hydroxylase/17,20-lyase deficiency of different severity: one with complete lack of masculinization and one with ambiguous genitalia. Results: Four mutations were identified by sequencing of the CYP17A1 gene: I332T and A355T in the less severely affected patient; G111S and R440H in the patient with complete lack of masculinization. The three novel mutations were expressed in COS1 cells and all mutant proteins except I332T showed a complete loss of both enzymatic activities. I332T retained some residual 17α-hydroxylase as well as 17,20-lyase activity. Conclusion: We identified 2 patients with the phenotypical spectrum of P450c17 deficiency. Three novel mutations in the CYP17A1 gene were identified and their functional characterization provided a good phenotype-genotype correlation. The location of the mutated residues in the three-dimensional model of P450c17 gave some additional insights into its structure-function relationship.
Leucine-Rich Repeat Kinase 2 Gene-Associated Disease: Redefining Genotype-Phenotype Correlation
Authors: Wider Christian , Dickson Dennis W. , Wszolek Zbigniew K.
Published: March 2010

Background: Leucine-rich repeat kinase 2 (LRRK2) has emerged as the most prevalent genetic cause of Parkinson’s disease (PD) among Caucasians. Patients carrying an LRRK2 mutation display significant variability of clinical and pathologic phenotypes across and within affected families. Methods: Herein, we review available clinical and pathologic data on patients with an LRRK2 mutation who have come to autopsy. Results: Thirty-eight patients have been reported who presented clinically with PD; parkinsonism with resistance to levodopa, supranuclear gaze palsy, or autonomic dysfunction; or tremor and dementia. Pathology showed typical PD-type Lewy body disease (LBD) in most patients, whereas in others there was ‘pure’ nigral degeneration (one with TDP-43-positive inclusions), diffuse LBD, or tau-, α-synuclein- or ubiquitin-positive pathology reminiscent of progressive supranuclear gaze palsy, multisystem atrophy, and frontotemporal dementia with ubiquitin-positive inclusions. Conclusions: Such clinical and pathologic variability suggests Lrrk2 acts upstream from other proteins implicated in neurodegeneration. Specific mutations may be associated with alternative progressive supranuclear gaze palsy-like or ‘pure’ nigral degeneration phenotypes. A different effect on Lrrk2 kinase activity may play a role in such heterogeneity.
Incidence of Lobar and Non-Lobar Spontaneous Intracerebral Haemorrhage in a Predominantly Hispanic-Mestizo Population – The PISCIS Stroke Project: A Community-Based Prospective Study in Iquique, Chile
Authors: Lavados Pablo M. , Sacks Claudio , Prina Liliana , Escobar Arturo , Tossi Claudia , Araya Fernando , Feuerhake Walter , Gálvez Marcelo , Salinas Rodrigo , Álvarez Gonzalo
Published: March 2010

Background: The incidence of intracerebral haemorrhage (ICH) in Hispanics is high, especially of non-lobar ICH. Our aim was to ascertain prospectively the incidence of first-ever spontaneous ICH (SICH) stratified by localisation in a Hispanic-Mestizo population of the north of Chile. Methods: Between July 2000 and June 2002 all possible cases of ICH were ascertained from multiple overlapping sources. The cases were allocated according to localisation. Those with vascular malformations or non-identifiable localisations were excluded. Results: We identified a total of 69 cases of first-ever ICH. Of these, 64 (92.7%) had SICH, of which we allocated 58 cases (84%) to non-lobar or lobar localisation. The mean age was 57.3 ± 17 years, and 62.3% of the subjects were male. The age-adjusted incidence rates were 13.8 (non-lobar) and 4.9 (lobar) per 100,000 person-years. Non-lobar SICH was more frequent in young males and lobar SICH in older women. The non-lobar-to-lobar ratio was similar to previous findings in Hispanics. Hypertension was more frequent in non-lobar SICH and in diabetes, heavy drinking and antithrombotic use in lobar SICH, but in none significantly. There was no association between localisation and prognosis. Conclusions: The incidence of non-lobar SICH was high, but lower than in most non-white populations. This lower incidence could be due to a lower population prevalence of risk factors, a higher socioeconomic level in this population, or chance.
Continuous Monitoring of Intrathoracic Impedance and Right Ventricular Pressures in Patients With Heart Failure
Authors: Vanderheyden Marc , Houben Richard , Verstreken Sofie , Ståhlberg Marcus , Reiters Pascalle , Kessels Roger , Braunschweig Frieder
Published: March 2010

Background—

Hemodynamic monitoring using implantable devices may provide early warning of volume overload in patients with heart failure (HF). This study was designed to prospectively compare information from intrathoracic impedance monitoring and continuous right ventricular pressure measurements in patients with HF.

Methods and Results—

Sixteen patients with HF (age, 63.5±13.8 years; left ventricular ejection fraction, 23.2±11.3%; New York Heart Association, II and III) and a previous HF decompensation received both a cardiac resynchronization therapy defibrillator providing a daily average of intrathoracic impedance and an implantable hemodynamic monitor providing an estimate of the pulmonary artery diastolic pressure. At the end of a 6-month investigator-blinded period, baseline reference hemodynamic values were determined over 4 weeks during which the patient was clinically stable. A major HF event was defined as HF decompensation requiring hospitalization, IV diuretic treatment, or leading to death. Sixteen major HF events occurred in 10 patients. Within 30 days and 14 days before a major HF event, impedance decreased by 0.12±0.21 Ω/d and 0.20±0.20 Ω/d, respectively, whereas estimated pulmonary arterial diastolic pressure increased by 0.10±0.20 mm Hg/d and 0.16±0.15 mm Hg/d, respectively. During these periods, impedance decreased by 3.8±5.4 Ω (
P
<0.02) and 4.9±6.1 Ω (
P
<0.007), respectively, whereas estimated pulmonary arterial diastolic pressure increased by 5.8±5.7 mm Hg (
P
<0.002) and 6.8±6.1 mm Hg (
P
<0.001), respectively, compared with baseline. In all patients, impedance and estimated pulmonary arterial diastolic pressure were inversely correlated (
r
=−0.48±0.25). Within 30 days preceding a major HF event, this correlation improved to
r
=−0.58±0.24.

Conclusions—

Decompensated HF develops based on hemodynamic derangements and is preceded by significant changes in intrathoracic impedance and right ventricular pressures during the month prior to a major clinical event. Impedance and pressure changes are moderately correlated. Future research may establish the complementary contribution of both parameters to guide diagnosis and management of patients with HF by implantable devices.
Prognostic Value of Right Ventricular Function in Patients After Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention
Authors: Antoni M. Louisa , Scherptong Roderick W.C. , Atary Jael Z. , Boersma Eric , Holman Eduard R. , van der Wall Ernst E. , Schalij Martin J. , Bax Jeroen J.
Published: February 2010

Background—

Data on the association between right ventricular (RV) function and adverse events after acute myocardial infarction (AMI) are scarce. The purpose of the current study was to evaluate the relation between RV function and adverse events in patients treated with primary percutaneous coronary intervention for AMI.

Methods and Results—

Consecutive patients admitted with AMI treated with primary percutaneous coronary intervention underwent echocardiography within 48 hours of admission to assess left ventricular and RV function. RV function was quantified with RV fractional area change (RVFAC), tricuspid annular plane systolic excursion, and RV strain. The end point was defined as a composite of all-cause mortality, reinfarction, and hospitalization for heart failure. All patients (n=621) were followed prospectively, and during a mean follow-up of 24 months, 86 patients reached the composite end point. RVFAC, tricuspid annular plane systolic excursion, and RV strain were all univariable predictors of worse outcome. After multivariable analysis, only RVFAC (hazard ratio, 0.96; 95% CI, 0.92 to 0.99) and RV strain (hazard ratio, 1.08; 95% CI, 1.03 to 1.13) independently predicted the composite end point. In addition, RV strain provided incremental value to clinical information, infarct characteristics, left ventricular function, and RVFAC.

Conclusions—

RV function provides strong prognostic information in patients treated with primary percutaneous coronary intervention for AMI.
Rapid 3D Phenotyping of Cardiovascular Development in Mouse Embryos by Micro-CT With Iodine Staining
Authors: Degenhardt Karl , Wright Alexander C. , Horng Debra , Padmanabhan Arun , Epstein Jonathan A.
Published: February 2010

Background—

Microcomputed tomography (micro-CT) has been used extensively in research to generate high-resolution 3D images of calcified tissues in small animals nondestructively. It has been especially useful for the characterization of skeletal mutations but limited in its utility for the analysis of soft tissue such as the cardiovascular system. Visualization of the cardiovascular system has been largely restricted to structures that can be filled with radiopaque intravascular contrast agents in adult animals. Recent ex vivo studies using osmium tetroxide, iodinated contrast agents, inorganic iodine, and phosphotungstic acid have demonstrated the ability to stain soft tissues differentially, allowing for high intertissue contrast in micro-CT images. In the present study, we demonstrate the application of this technology for visualization of cardiovascular structures in developing mouse embryos using Lugol solution (aqueous potassium iodide plus iodine).

Methods and Results—

We show the optimization of this method to obtain ex vivo micro-CT images of embryonic and neonatal mice with excellent soft-tissue contrast. We demonstrate the utility of this method to visualize key structures during cardiovascular development at various stages of embryogenesis. Our method benefits from the ease of sample preparation, low toxicity, and low cost. Furthermore, we show how multiple cardiac defects can be demonstrated by micro-CT in a single specimen with a known genetic lesion. Indeed, a previously undescribed cardiac venous abnormality is revealed in a
PlexinD1
mutant mouse.

Conclusions—

Micro-CT of iodine-stained tissue is a valuable technique for the characterization of cardiovascular development and defects in mouse models of congenital heart disease.
Treatment With 5-Lipoxygenase Inhibitor VIA-2291 (Atreleuton) in Patients With Recent Acute Coronary Syndrome
Authors: Tardif Jean-Claude , L'Allier Philippe L. , Ibrahim Reda , Grégoire Jean C. , Nozza Anna , Cossette Mariève , Kouz Simon , Lavoie Marc-André , Paquin Janie , Brotz Tilmann M. , Taub Rebecca , Pressacco Josephine
Published: February 2010

Background—

Production of leukotrienes by 5-lipoxygenase (5-LO) has been linked to unstable atherosclerotic plaques and cardiovascular events. VIA-2291 is a potent 5-LO inhibitor.

Methods and Results—

In a double-blinded study, 191 patients were randomly assigned 3 weeks after an acute coronary syndrome to receive 25, 50, or 100 mg VIA-2291 or placebo daily for 12 weeks. The primary study end point, whole blood stimulated leukotriene LTB4 at trough drug level, was reduced in all VIA-2291 groups (
P
<0.0001) in a dose-dependent fashion, with approximately 80% inhibition in >90% of patients in the 100-mg group. A significant reduction of urine leukotriene LTE4 was obtained in all dose groups. No serious adverse events were considered related to study drug. A subset of 93 patients who had undergone a 64-slice coronary CT examination at baseline continued on study medication for a total of 24 weeks and underwent a repeat scan. Five of these patients withdrew or were noncompliant and 28 had nonevaluable scans. Among the 60 remaining patients, new coronary plaques were observed in 5 of 18 (27.8%) placebo-treated patients and in 2 of 42 (4.8%) VIA-2291–treated patients (
P
=0.01). A reduction in noncalcified plaque volume at 24 weeks versus placebo was observed in VIA-2291–treated groups in the 34 of these 60 patients in whom this end point was analyzable (
P
<0.01).

Conclusions—

VIA-2291 reduces leukotriene production at 12 weeks after an acute coronary syndrome. Preliminary data from the CT substudy suggest that such a reduction in leukotriene production may influence atherosclerosis; however, this requires confirmation in a larger study.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00358826.
How Deep a Transformation? Europeanization of Greek and Turkish Minority Policies
Authors: Onar Nora Fisher , Özgüneş Meriç
Published: February 2010

The article examines the Europeanization of Greece and Turkey's policies towards their respective Turkish/Muslim and Greek/Orthodox minorities. It begins with a comparative survey of nation-building processes in both countries. It shows that as bilateral tensions rose, minorities' rights as citizens were increasingly compromised by the perception that minorities were agents of their kin-states. Greek accession to the European Economic Community in 1981 catalyzed a slow process of internationalization of European norms of minority protection among policymakers, though pockets of resistance persist to this day. Turkey, meanwhile, became a candidate for membership in December 1999. The carrot-and-stick incentive structure of the accession process led to a rapid succession of taboo-shattering reforms, catalyzing a partial transformation of minority policies. By 2007, however, an altered calculus of domestic and international forces impeded the implementation of reform and consequently the transformation of minority treatment.
Is There Space for “Genuine Autonomy” for Tibetan Areas in the PRC's System of Nationalities Regional Autonomy?
Authors: Woodman Sophia , Ghai Yash , Loper Kelley
Published: February 2010

This article considers whether room exists within the current system of nationalities regional autonomy (NRA) in China to accommodate Tibetan aspirations for "genuine autonomy" under the People's Republic of China (PRC) sovereignty. It examines the legal framework for NRA in China, as well as Chinese government policy and practice toward autonomous areas, in terms of the limitations and possibilities they imply for realizing Tibetan aspirations for autonomy, highlighting specific areas of concern, opportunities and constraints. It explores the development of political and legal approaches toward autonomy since the 1930s, the nature of the current framework and how recent legal and political developments interact with that framework. It looks at options for autonomy under the Chinese Constitution and national legislation, particularly the self-government of nationality (minority) autonomous areas as well as Article 31 of the Constitution which has provided the basis for the establishment of special administrative regions (SARs). Since autonomous areas also exercise the general powers of local governments in the PRC, it describes the general system of local government at the provincial and lower administrative levels. The article examines the practical implementation and operation of minority autonomy and SARs including the apparent gap between law and practice. In particular, special attention is paid to the role of the Chinese Communist Party and its officials which have a significant impact on the exercise of state powers. It concludes that there are formidable obstacles to the autonomy that Tibetans seek in order to preserve their culture, values and identity.
Property Rights, Indigenous People and the Developing World: Issues from Aboriginal Entitlement to Intellectual Ownership Rights
Authors: Koivurova Timo
Published: February 2010

This book review essay will employ David Lea's interesting ideas over how indigenous and traditional societies should relate themselves to economic globalisation for self-reflection regarding how we international legal scholars in general approach indigenous issues. Moreover, because Lea also outlines his views on how indigenous and traditional societies should improve their situation, it gives a good basis to think of an alternative model from the international legal viewpoint on how indigenous governance could be improved.
Some Possible Chinese Records about Armenia and the Armenians in Mid-Qing Dynasty
Authors: Yang Xi
Published: February 2010

The Armenians arrived at Guangzhou (Canton) and Macao for trade, no later than the end of the 17th century. Their existence in the Pearl River Delta was noticed by westerners throughout the 18th century. However, due to several reasons, there is little evidence in Chinese sources showing that contemporary Chinese people were aware of such a small group in their homeland. Nevertheless, after a re-examination of existing Chinese records dated from 1751 to 1840, the author could find several pieces of evidence in support of the argument that the Chinese in mid-Qing period might have been informed about the Armenians, as well as the land of Armenia. The names by which the Chinese addressed these foreigners in that period might be of some interest for the research and interpretation of the Chinese texts as well.
The Lost Mosque(s) in the Citadel of Qajar Yerevan: Architecture and Identity, Iranian and Local Traditions in the Early 19th Century
Authors: Ritter Markus
Published: February 2010

The mosques in the citadel of Yerevan are lost today and almost unknown. Here, the most significant of them is reconstructed from visual and literary sources, documented by unpublished photographs, and related to the early Qajar period under the last Iranian governor Husayn Khān, prior to the Russian conquest of Yerevan in 1827. The second mosque in the citadel is attributed to the Ottoman period; the third one remains uncertain. While the type of the Qajar mosque is compared to earlier buildings in Yerevan, notably the 18th-century Gök Jāmi', stylistic elements are analysed with reference to early 19th-century architecture in Iran and a building at Qazvīn. The interpretation seeks to understand the different references of the Qajar mosque as the construction of a visual statement of local and Iranian identity in a period of change.
Marriage Customs in Lar: The Role of Women's Networks in Tradition and Change
Authors: Gianfortoni Emily Wells
Published: February 2010

One reason many traditional Lari customs celebrating life cycle events, such as births, marriages, and pilgrimages were preserved well into the 1970s is that women, particularly the older women, have been the keepers of this knowledge. They maintained the practice of these customs and passed on the knowledge to their daughters and younger members of their social networks. This paper examines Lari marriage practices in the 1970s and contrasts them with earlier customs as reported by older women. It discusses also the role of social networks in maintaining, changing, and passing on marriage customs.
Contemporary Armenian Community in Tbilisi
Authors: Mkrtchian Satenik
Published: February 2010

This paper seeks to present a comprehensive picture of the Armenian community of Tbilisi, based on extensive ethnographic field-work carried out in Tbilisi during 2006-2008. The paper aims to explore the following main aspects of the Tbilisi Armenian community: a) a brief history of the community's formation and its current social-demographic situation, and b) the community's structure and agents. In addition, the following questions will be addressed: What are the current problems and challenges faced by the community today (how the community actors see these challenges and what approaches they have to address the issues)? How do Tbilisi Armenians perceive Armenia? Components of the identity of the Armenian community in Tbilisi also will be addressed, such as ceremonial and holiday traditions, symbols, and so on.
A Hūra-Song in Kalhorī
Authors: Khanian-Sumari Hamid
Published: February 2010

Kalhorī is the less investigated dialect of Southern Kurdish. The paper introduces a Kalhorī folk-song of the hūra genre (with parallel English translation and commentaries), selected from the vast corpus of the Southern Kurdish dialect and folkloric materials, which have been collected from the Kalhor-inhabited regions of Western Iran.
TÜSİAD and the Armenian-Turkish Relations: Turkish Economy between Progress and National Identity
Authors: Kluge Pascal
Published: February 2010

In examining the endeavours of the Turkish entrepreneurs' association TÜSİAD, a politically embedded economic interest group, it becomes clear how highly discriminative it must act, and react, in its pursuit to deliver economic and political benefits to its members. This can be observed via the example of the association's attitude vis-à-vis the Armenian-Turkish rapprochement process. On the one hand, the association speaks up freely and acts independently, and it has supported and engaged in numerous Armenian-Turkish initiatives, thus promoting a dialogue through trade. Improving economic conditions in the eastern provinces of Turkey and taking steps in line with the European Union accession process have been the major impetus for these moves. On the other hand, when it comes to highly contentious issues considered to be of Turkish national interest, such as the Armenian Genocide debate, TÜSİAD has been strongly affected by nationalist sensibilities. Its approach in this matter is deadlocked and determined by historical legacy. It conforms to the state ideology, rejecting the term genocide for the Ottoman massacres of Armenians in 1915 and considering any contrary arguments as an attempt by foreign powers to damage Turkey's reputation. One of the reasons behind this attitude is the way that a particular Turkish identity was formulated in the transition between the Ottoman Empire and the Turkish Republic, in which a sole “national culture” was founded exclusive of ideological divergence. The state, as a historically powerful guardian of this identity, has consistently attempted to enforce the conformity of social actors and the public sphere with this “national culture”. However, along with continuing globalisation and a general trend of individualisation of society, TÜSİAD and other civil organisations are in a process of disengagement from these structures. Should this process continue, TÜSİAD could further contribute to a prosperity that extends beyond economic advancement in Turkey's eastern border provinces, leading to a sustainable reconciliation in the South Caucasian region.
An Inter-Ethnic Conflict in the Cultural Environment of the Baloch National Movement in Present-day Afghanistan
Authors: Bödeker Just
Published: February 2010

This article focuses on strategies of inter-ethnic conflict resolution in southwest Afghanistan under the circumstances of social changes in a tribal society. Field research was carried on in September and October 2008 in Kabul and Zaranj, the province centre of Nimruz. During ethnographic fieldwork focusing on transnational identities of the Baloch people in the Afghan-Iranian border region, I observed an informal inter-ethnic trial. The location of this trial was the town of Zaranj, the administrative centre of the south-western Afghan province of Nimruz. This province, beside Pashtun and Tajik populations, has a compact Baloch settlement area bordering the Baloch areas in Iran and Pakistan. The trial took place between my host, the chief of a Baloch cultural centre, and an Uzbek defendant. As my host was a representative of an emerging Baloch self-confidence since the decline of the Taliban regime, the trial has to be analysed in the broader socio-cultural context of the Baloch people in present-day Afghanistan. The paper first presents the sequence of events during the trial; then it deals with the social context considering some new developments in the self-conceptions of the Baloches in Afghanistan. Finally, the trial is analysed in the framework of this context.
Current Political Complexities of the Iraqi Turkmen
Authors: Strakes Jason
Published: February 2010

The Turkmen population of Iraq is a significant factor in linking the greater Caucasus region to Northern Mesopotamia. However, in the post-Saddam Hussein era, much conventional discourse has identified them as a politically and culturally marginalised group in relation to the Arab and Kurdish majorities. This study presents an alternative assessment of the Turkmen situation based on a survey of changes in the Iraqi political context over the past decade. This is applied in order to determine the precedents for Turkmen democratic activity in northern Iraq, as well as impediments to accommodation between Turkmen and other regional identities. These patterns are analysed at both the domestic level, including geographic distribution, popular mobilisation and party formation, and at the international level, which examines the impact of Turkey's external influence and sponsorship on these internal conditions. Several tentative conclusions are reached. First, the Iraqi Turkmen exhibit both high levels of mobilisation and pluralistic political organisation that contrast with other ethnic and sectarian minorities in Iraq. Second, sectarian and ideological cleavages within the Turkmen population along with sporadic violent attacks have motivated assimilation with the coalition politics that has evolved since the first post-Saddam national elections, rather than armed insurgency. Finally, the role of Turkey as a primary external patron has presented both obstacles and potential advantages for the political welfare of the Iraqi Turkmen community since 2003.