bluuebunny/crossref_metadata_2025 huggingface dataset:
Innate Response Activator B Cells Protect Against Microbial Sepsis
Authors: Rauch Philipp J. , Chudnovskiy Aleksey , Robbins Clinton S. , Weber Georg F. , Etzrodt Martin , Hilgendorf Ingo , Tiglao Elizabeth , Figueiredo Jose-Luiz , Iwamoto Yoshiko , Theurl Igor , Gorbatov Rostic , Waring Michael T. , Chicoine Adam T. , Mouded Majd , Pittet Mikael J. , Nahrendorf Matthias , Weissleder Ralph , Swirski Filip K.
Published: January 2012

Immune Sentinels

A classic paradigm in immunology holds that the immune response occurs in two waves: Rapidly responding cells of the innate immune system help to contain the invading pathogen and alert lymphocytes. These cells of the adaptive immune system then help to clear the infection and go on to form long-lasting memory. However, some specialized populations of lymphocytes can also respond quickly to an infection and carry out functions that overlap with the innate immune system. Now,

Rauch
et al.

(p.
597
, published online 12 January) describe one such cell type—innate response activator (IRA) B cells. IRA B cells recognize bacterial liposaccharide through Toll-like receptor 4 and, in response, produce the cytokine GM-CSF, which activates other innate immune cells. Deletion of IRA B cells in mice impaired their ability to clear a bacterial infection and promoted septic shock.
Polarographic and voltammetric determination of genotoxic 2-aminofluoren-9-one at mercury electrodes
Authors: Hájková Andrea , Vyskočil Vlastimil , Daňhel Aleš , Wang Joseph , Barek Jiří
Published: January 2012

Electrochemical behavior of genotoxic 2-aminofluoren-9-one (2-AFN) was investigated by DC tast polarography (DCTP) and differential pulse polarography (DPP), both at a classical dropping mercury electrode (DME), and by DC voltammetry (DCV), differential pulse voltammetry (DPV), and adsorptive stripping differential pulse voltammetry (AdSDPV), all at a miniaturized hanging mercury drop minielectrode (HMDmE), in buffered aqueous-methanolic solutions. Optimum conditions were found for the determination of 2-AFN by DCTP at DME in the concentration range from 1 × 10–6to 1 × 10–4mol l–1(with a limit of quantification (LQ) of 5 × 10–7mol l–1), by DPP at DME (from 1 × 10–7to 1 × 10–4mol l–1;LQ ≈ 1 × 10–7mol l–1), by DCV and DPV at HMDmE (both from 1 × 10–7to 1 × 10–4mol l–1;LQs ≈ 2 × 10–7and 1 × 10–7mol l–1for DCV and DPV, respectively), and by AdSDPV at HMDmE (from 2 × 10–9to 1 × 10–7mol l–1;LQ ≈ 4 × 10–9mol l–1). Practical applicability of the developed methods was verified on the direct determination of 2-AFN in model samples of drinking and river water in nanomolar to micromolar concentrations.
Dangerous dads? Ecological and longitudinal analyses of paternity leave and risk for child injury
Authors: Laflamme Lucie , Månsdotter Anna , Lundberg Michael , Magnusson Cecilia
Published: January 2012

Background

In 1974, Sweden became the first country to permit fathers to take paid parental leave. Other countries are currently following suit issuing similar laws. While this reform supports the principles of the United Nations convention of the right for children to be with both parents and enshrines the ethos of gender equality, there has been little systematic examination of its potential impact on child health. Instead, there is uninformed debate that fathers may expose their children to greater risks of injury than mothers. In this Swedish national study, the authors therefore assess whether fathers' parental leave can be regarded as a more serious risk factor for child injuries than that of mothers.

Methods

Nationwide register-based ecological and longitudinal studies of hospitalisation due to injury (and intoxication) in early childhood, involving the Swedish population in 1973–2009 (ecological design), and children born in 1988 and 1989 (n=118 278) (longitudinal design).

Results

An increase in fathers' share of parental leave over time was parallelled by a downward trend in child injury rates (age 0–4 years). At the individual level, the crude incidence of child injury (age 0–2 years) was lower during paternity as compared with maternity leave. This association was, however, explained by parental socio-demographic characteristics (multivariate HR 0.96, 95% CI 0.74 to 1.2).

Conclusion

There is no support for the notion that paternity leave increases the risk of child injury.
Educational inequalities in blood pressure and cholesterol screening in nine European countries
Authors: Rodin Danielle , Stirbu Irina , Ekholm Ola , Dzurova Dagmar , Costa Giuseppe , Mackenbach Johan P , Kunst Anton E
Published: January 2012

Background

To perform the first European overview of educational inequalities in the use of blood pressure and cholesterol screening.

Methods

Data were obtained on the use of screening services according to educational level from nationally representative cross-sectional surveys in Belgium, Czech Republic, Denmark, Estonia, Finland, Hungary, Italy, Latvia and Lithuania. Screening rates were examined in the preceding 12 months and 5 years, for respondents 35+ years (45+ for women). ORs comparing low- to high-educated respondents were estimated using logistic regression controlling for age.

Results

Inequalities in cholesterol screening favouring higher socioeconomic groups were demonstrated with statistical significance among men in four countries, whereby men with higher education were more likely to receive screening, with 1.22 as the highest OR. Among women, a similar pattern was found. Inequalities in blood pressure screening were even smaller and less often statistically significant. Hungary was the only country with higher rates of both types of screening in the low-educated group. In other countries, pro-high inequalities were slightly increased after controlling for self-rated health.

Conclusions

All European countries in this study had small educational inequalities in the utilisation of blood pressure and cholesterol screening. These inequalities are smaller than those previously observed in the USA. Further comparative studies need to distinguish between screening for preventive purposes and screening for treatment and control.
LOCAL ANALYTIC CONJUGACY OF SEMI-HYPERBOLIC MAPPINGS IN TWO VARIABLES, IN THE NON-ARCHIMEDEAN SETTING
Authors: JENKINS ADRIAN , SPALLONE STEVEN
Published: January 2012

In this note, we consider locally invertible analytic mappings of a two-dimensional space over a non-archimedean field. Such a map is called semi-hyperbolic if its Jacobian has eigenvalues λ1 and λ2 so that λ1 = 1 and |λ2| ≠ 1. We prove that two analytic semi-hyperbolic maps are analytically equivalent if and only if they are formally equivalent, applying a generalized version of an estimation scheme from our earlier work [A. Jenkins and S. Spallone, A p-adic approach to local dynamics: Analytic flows and analytic maps tangent to the identity, Ann. Fac. Sci. Toulouse Math. (6) 18(3) (2009) 611–634].
LIMITS OF MULTIPOLE PLURICOMPLEX GREEN FUNCTIONS
Authors: MAGNÚSSON JÓN I. , RASHKOVSKII ALEXANDER , SIGURDSSON RAGNAR , THOMAS PASCAL J.
Published: January 2012

Let Ω be a bounded hyperconvex domain in ℂn, 0 ∈ Ω, and Sε a family of N poles in Ω, all tending to 0 as ε tends to 0. To each Sε we associate its vanishing ideal [Formula: see text] and pluricomplex Green function [Formula: see text].

Suppose that, as ε tends to 0, [Formula: see text] converges to [Formula: see text] (local uniform convergence), and that (Gε)ε converges to G, locally uniformly away from 0; then [Formula: see text]. If the Hilbert–Samuel multiplicity of [Formula: see text] is strictly larger than its length (codimension, equal to N here), then (Gε)ε cannot converge to [Formula: see text]. Conversely, if [Formula: see text] is a complete intersection ideal, then (Gε)ε converges to [Formula: see text]. We work out the case of three poles.
FAMILIES OF STABLE AND METASTABLE SOLITONS IN COUPLED SYSTEM OF SCALAR FIELDS
Authors: RIAZI NEMATOLLAH , PEYRAVI MARZIEH
Published: January 2012

In this paper, we obtain stable and metastable soliton solutions of a coupled system of two real scalar fields with five discrete points of vacua. These solutions have definite topological charges and rest energies and show classical dynamical stability. From a quantum point of view, however, the V-type solutions are expected to be unstable and decay to D-type solutions. The induced decay of a V-type soliton into two D-type ones is calculated numerically, and shown to be chiral, in the sense that the decay products do not respect left–right symmetry.
Internet Information Relevance of Financial Institutions: Evidence from Taiwan
Authors: Chou Shuching , Yen Tze-Yu , Kuo Yen-Hui
Published: January 2012

This study investigates the perception of factors that are likely to influence the Internet information relevance of financial institutions. The media richness theory and stakeholder theory point out that the extent of information and stakeholder communication will influence the utilization of online information, while not many of these discussions are associated with financial institutions. This study integrates seven information categories into three constructs: sufficiency, stakeholder communication and external supervision, using a structural equation model to examine whether the three constructs relate to information utilization. The results show that stakeholder communication and external oversight are significantly related to the user's intention to utilize online information of financial institutions, while information sufficiency is not. These findings correspond to stakeholder theory as well as international guidelines that emphasize external oversight of financial institutions.
Applied Rough Set Logics for Multi-Criteria Decision Analysis in Stock Index Volatility Projection
Authors: Ho Wen-Rong Jerry
Published: January 2012

The main purpose of this paper is to advocate a rule-based forecasting technique for anticipating stock index volatility. This paper intends to set up a stock index indicators projection prototype by using a multiple criteria decision making model consisting of the cluster analysis (CA) technique and Rough Set Theory (RST) to select the important attributes and forecast TSEC Capitalization Weighted Stock Index. The projection prototype was then released to forecast the stock index in the first half of 2009 with an accuracy of 66.67%. The results point out that the decision rules were authenticated to employ in forecasting the stock index volatility appropriately.
SHEEP: A TOOL FOR DESCRIPTION OF β-SHEETS IN PROTEIN 3D STRUCTURES
Authors: AKSIANOV EVGENIY , ALEXEEVSKI ANDREI
Published: January 2012

The description of a protein fold is a hard problem due to significant variability of main structural units, β-sheets and α-helixes, and their mutual arrangements. An adequate description of the structural units is an important step in objective protein structure classification, which to date is based on expert judgment in a number of cases. Explicit determination and description of structural units is more complicated for β-sheets than for α-helixes due to β-sheets variability both in composition and geometry. We have developed an algorithm that can significantly modify β-sheets detected by commonly used DSSP and Stride algorithms and represent the result as a “β-sheet map,” a table describing certain β-sheet features. In our approach, β-sheets (rather than β-strands) are considered as holistic objects. Both hydrogen bonds and geometrical restrains are explored for the determination of β-sheets. The algorithm is implemented in SheeP program. It was tested for prediction architectures of domains from 93 well-defined all-β and α/β SCOP protein domain families, and showed 93% of correct results. The Web-service http://mouse.belozersky.msu.ru/sheep allows to detect β-sheets in a given protein structure, visualize β-sheet maps, as well as input three-dimensional structures with highlighted β-sheets and their structural features.
FUTURE ASPECT OF REFRIGERANTS: CONSIDERING THERMOPHYSICAL PROPERTIES AND CYCLE PERFORMANCE
Authors: KAGAWA NOBORU
Published: January 2012

Refrigeration, air conditioning and heat pump equipments (generally known as heat pumps) are very important for the civilized society. However, discharged refrigerants from heat pumps and exhausted carbon dioxide to drive heat pumps result in serious environmental problems. For this reason, fluorocarbon refrigerants are limited or regulated. To alleviate the problems, new refrigerants with lower GWP and higher cycle performance must be developed and used. In this paper, calculated thermophysical properties of hydrofluoroolefin refrigerants using databases are evaluated with experimental data. Then, the fundamental cycle performance of air conditioning by using major refrigerants is studied based on their thermophysical properties. The results show that there is no adequate refrigerant for air conditioning applications. Heat pumps with new refrigerants including refrigerant mixtures must be developed as fast as possible. It leads to that HFC refrigerants must be used taking care until the new refrigerants will be available.
Mitochondrial permeability transition in rat hepatocytes after anoxia/reoxygenation: role of Ca2+-dependent mitochondrial formation of reactive oxygen species
Authors: Kim Jae-Sung , Wang Jin-Hee , Lemasters John J.
Published: January 2012

Onset of the mitochondrial permeability transition (MPT) is the penultimate event leading to lethal cellular ischemia-reperfusion injury, but the mechanisms precipitating the MPT after reperfusion remain unclear. Here, we investigated the role of mitochondrial free Ca2+ and reactive oxygen species (ROS) in pH- and MPT-dependent reperfusion injury to hepatocytes. Cultured rat hepatocytes were incubated in anoxic Krebs-Ringer-HEPES buffer at pH 6.2 for 4 h and then reoxygenated at pH 7.4 to simulate ischemia-reperfusion. Some cells were loaded with the Ca2+ chelators, BAPTA/AM and 2-[(2-bis-[carboxymethyl]aono-5-methoxyphenyl)-methyl-6-methoxy-8-bis[carboxymethyl]aminoquinoline, either by a cold loading protocol for intramitochondrial loading or by warm incubation for cytosolic loading. Cell death was assessed by propidium iodide fluorometry and immunoblotting. Mitochondrial Ca2+, inner membrane permeability, membrane potential, and ROS formation were monitored with Rhod-2, calcein, tetramethylrhodamine methylester, and dihydrodichlorofluorescein, respectively. Necrotic cell death increased after reoxygenation. Necrosis was blocked by 1 μM cyclosporin A, an MPT inhibitor, and by reoxygenation at pH 6.2. Confocal imaging of Rhod-2, calcein, and dichlorofluorescein revealed that an increase of mitochondrial Ca2+ and ROS preceded onset of the MPT after reoxygenation. Intramitochondrial Ca2+ chelation, but not cytosolic Ca2+ chelation, prevented ROS formation and subsequent necrotic and apoptotic cell death. Reoxygenation with the antioxidants, desferal or diphenylphenylenediamine, also suppressed MPT-mediated cell death. However, inhibition of cytosolic ROS by apocynin or diphenyleneiodonium chloride failed to prevent reoxygenation-induced cell death. In conclusion, Ca2+-dependent mitochondrial ROS formation is the molecular signal culminating in onset of the MPT after reoxygenation of anoxic hepatocytes, leading to cell death.
Clathrin mediates endocytosis of progastrin and activates MAPKs: role of cell surface annexin A2
Authors: Sarkar Shubhashish , Kantara Carla , Singh Pomila
Published: January 2012

Cell-surface-associated annexin A2 (CS-ANXA2) is a nonconventional “receptor” for progastrin; expression levels of both are elevated in colon cancers, and downregulation of either reduces tumorigenic potential of cells. We recently reported internalization of progastrin in target cells. Here, mechanisms mediating internalization of progastrin were examined. Initially, we confirmed that cell-surface ANXA2 mediates binding and internalization of progastrin in intestinal cells. Progastrin, covalently linked to sepharose beads, failed to activate p38MAPK/ERKs, suggesting internalization of progastrin was required for eliciting biological effects; importantly annexin A2 expression and availability of CS-ANXA2 were required for internalization of progastrin. Clathrin expression and formation of clathrin-coated pits were critically required for endocytotic internalization of progastrin; in the absence of clathrin, progastrin failed to activate p38MAPK/ERKs. Downregulation of caveolin had no effect on binding or internalization of progastrin. We therefore demonstrate for the first time that progastrin binds CS-ANXA2 and is rapidly internalized via clathrin-mediated endocytotic pathway, resulting in activation of MAPKinases. Targeting clathrin-mediated endocytosis of progastrin may thus inhibit previously reported co-carcinogenic/tumorigenic effects of progastrin on intestinal cells.
RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter
Authors: Rattan Satish , Singh Jagmohan
Published: January 2012

The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10−8to 10−4M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC20in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC20, before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.
High-intensity training improves airway responsiveness in inactive nonasthmatic children: evidence from a randomized controlled trial
Authors: Rosenkranz Sara K. , Rosenkranz Richard R. , Hastmann Tanis J. , Harms Craig A.
Published: January 2012

Purpose: the relationship between physical activity and airway health in children is not well understood. The purpose of this study was to determine whether 8 wk of high-intensity exercise training would improve airway responsiveness in prepubescent, nonasthmatic, inactive children. Methods: 16 healthy, prepubescent children were randomized [training group (TrG) n = 8, control group (ConG) n = 8]. Prior to and following 8 wk of training (or no training), children completed pulmonary function tests (PFTs): forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory flow at 25–75% of vital capacity (FEF25–75), and exhaled nitric oxide (FENO). Children completed an incremental cycle V̇o2maxtest, eucapnic voluntary hyperventilation (EVH), anthropometric tests, and blood tests to determine fasting blood glucose, total cholesterol, HDL, LDL, and triglycerides. Body fat percentage was determined using dual-energy X-ray absorptiometry pretraining and bioelectrical impedance pre- and posttraining. Results: there were no differences ( P > 0.05) in anthropometric measures or PFTs between TrG and ConG at baseline. In the TrG, there was a significant increase in V̇o2max(∼24%) and a decrease in total cholesterol (∼13%) and LDL cholesterol (∼35%) following training. There were improvements ( P < 0.05) in ΔFEV1both postexercise (pre: −7.60 ± 2.10%, post: −1.10 ± 1.80%) and post-EVH (pre: −6.71 ± 2.21%, post: −1.41 ± 1.58%) with training. The ΔFEF25–75pre-post exercise also improved with training (pre: −16.10 ± 2.10%, post: −6.80 ± 1.80%; P < 0.05). Lower baseline body fat percentages were associated with greater improvements in pre-post exercise ΔFEV1following training ( r = −0.80, P < 0.05). Conclusion: these results suggest that in nonasthmatic prepubescent children, inactivity negatively impacts airway responsiveness, which can be improved with high-intensity training. Excess adiposity, however, may constrain these improvements.
Variation in the uncoupling protein 2 and 3 genes and human performance
Authors: Dhamrait Sukhbir S. , Williams Alun G. , Day Stephen H. , Skipworth James , Payne John R. , World Michael , Humphries Steve E. , Montgomery Hugh E.
Published: January 2012

Uncoupling proteins 2 and 3 (UCP2 and UCP3) may negatively regulate mitochondrial ATP synthesis and, through this, influence human physical performance. However, human data relating to both these issues remain sparse. Examining the association of common variants in the UCP3/2 locus with performance phenotypes offers one means of investigation. The efficiency of skeletal muscle contraction, delta efficiency (DE), was assessed by cycle ergometry in 85 young, healthy, sedentary adults both before and after a period of endurance training. Of these, 58 were successfully genotyped for the UCP3-55C>T (rs1800849) and 61 for the UCP2-866G>A (rs659366) variant. At baseline, UCP genotype was unrelated to any physical characteristic, including DE. However, the UCP2-866G>A variant was independently and strongly associated with the DE response to physical training, with UCP2-866A allele carriers exhibiting a greater increase in DE with training (absolute change in DE of −0.2 ± 3.6% vs. 1.7 ± 2.8% vs. 2.3 ± 3.7% for GG vs. GA vs. AA, respectively; P = 0.02 for A allele carriers vs. GG homozygotes). In multivariate analysis, there was a significant interaction between UCP2-866G>A and UCP3-55C>T genotypes in determining changes in DE (adjusted R2 = 0.137; P value for interaction = 0.003), which was independent of the effect of either single polymorphism or baseline characteristics. In conclusion, common genetic variation at the UCP3/2 gene locus is associated with training-related improvements in DE, an index of skeletal muscle performance. Such effects may be mediated through differences in the coupling of mitochondrial energy transduction in human skeletal muscle, but further mechanistic studies are required to delineate this potential role.
A threshold lung volume for optimal mechanical effects on upper airway airflow dynamics: studies in an anesthetized rabbit model
Authors: Kairaitis Kristina , Verma Manisha , Amatoury Jason , Wheatley John R. , White David P. , Amis Terence C.
Published: January 2012

Increasing lung volume improves upper airway airflow dynamics via passive mechanisms such as reducing upper airway extraluminal tissue pressures (ETP) and increasing longitudinal tension via tracheal displacement. We hypothesized a threshold lung volume for optimal mechanical effects on upper airway airflow dynamics. Seven supine, anesthetized, spontaneously breathing New Zealand White rabbits were studied. Extrathoracic pressure was altered, and lung volume change, airflow, pharyngeal pressure, ETP laterally (ETPlat) and anteriorly (ETPant), tracheal displacement, and sternohyoid muscle activity (EMG%max) monitored. Airflow dynamics were quantified via peak inspiratory airflow, flow limitation upper airway resistance, and conductance. Every 10-ml lung volume increase resulted in caudal tracheal displacement of 2.1 ± 0.4 mm (mean ± SE), decreased ETPlat by 0.7 ± 0.3 cmH2O, increased peak inspiratory airflow of 22.8 ± 2.6% baseline (all P < 0.02), and no significant change in ETPant or EMG%max. Flow limitation was present in most rabbits at baseline, and abolished 15.7 ± 10.5 ml above baseline. Every 10-ml lung volume decrease resulted in cranial tracheal displacement of 2.6 ± 0.4 mm, increased ETPant by 0.9 ± 0.2 cmH2O, ETPlat was unchanged, increased EMG%max of 11.1 ± 0.3%, and a reduction in peak inspiratory airflow of 10.8 ± 1.0%baseline (all P < 0.01). Lung volume, resistance, and conductance relationships were described by exponential functions. In conclusion, increasing lung volume displaced the trachea caudally, reduced ETP, abolished flow limitation, but had little effect on resistance or conductance, whereas decreasing lung volume resulted in cranial tracheal displacement, increased ETP and increased resistance, and reduced conductance, and flow limitation persisted despite increased muscle activity. We conclude that there is a threshold for lung volume influences on upper airway airflow dynamics.
High-Risk Ovarian Cancer Based on 126-Gene Expression Signature Is Uniquely Characterized by Downregulation of Antigen Presentation Pathway
Authors: Yoshihara Kosuke , Tsunoda Tatsuhiko , Shigemizu Daichi , Fujiwara Hiroyuki , Hatae Masayuki , Fujiwara Hisaya , Masuzaki Hideaki , Katabuchi Hidetaka , Kawakami Yosuke , Okamoto Aikou , Nogawa Takayoshi , Matsumura Noriomi , Udagawa Yasuhiro , Saito Tsuyoshi , Itamochi Hiroaki , Takano Masashi , Miyagi Etsuko , Sudo Tamotsu , Ushijima Kimio , Iwase Haruko , Seki Hiroyuki , Terao Yasuhisa , Enomoto Takayuki , Mikami Mikio , Akazawa Kohei , Tsuda Hitoshi , Moriya Takuya , Tajima Atsushi , Inoue Ituro , Tanaka Kenichi
Published: January 2012

Purpose: High-grade serous ovarian cancers are heterogeneous not only in terms of clinical outcome but also at the molecular level. Our aim was to establish a novel risk classification system based on a gene expression signature for predicting overall survival, leading to suggesting novel therapeutic strategies for high-risk patients.

Experimental Design: In this large-scale cross-platform study of six microarray data sets consisting of 1,054 ovarian cancer patients, we developed a gene expression signature for predicting overall survival by applying elastic net and 10-fold cross-validation to a Japanese data set A (n = 260) and evaluated the signature in five other data sets. Subsequently, we investigated differences in the biological characteristics between high- and low-risk ovarian cancer groups.

Results: An elastic net analysis identified a 126-gene expression signature for predicting overall survival in patients with ovarian cancer using the Japanese data set A (multivariate analysis, P = 4 × 10−20). We validated its predictive ability with five other data sets using multivariate analysis (Tothill's data set, P = 1 × 10−5; Bonome's data set, P = 0.0033; Dressman's data set, P = 0.0016; TCGA data set, P = 0.0027; Japanese data set B, P = 0.021). Through gene ontology and pathway analyses, we identified a significant reduction in expression of immune-response–related genes, especially on the antigen presentation pathway, in high-risk ovarian cancer patients.

Conclusions: This risk classification based on the 126-gene expression signature is an accurate predictor of clinical outcome in patients with advanced stage high-grade serous ovarian cancer and has the potential to develop new therapeutic strategies for high-grade serous ovarian cancer patients. Clin Cancer Res; 18(5); 1374–85. ©2012 AACR.
Disseminated Prostate Cancer Cells Can Instruct Hematopoietic Stem and Progenitor Cells to Regulate Bone Phenotype
Authors: Joseph Jeena , Shiozawa Yusuke , Jung Younghun , Kim Jin Koo , Pedersen Elisabeth , Mishra Anjali , Zalucha Janet Linn , Wang Jingcheng , Keller Evan T. , Pienta Kenneth J. , Taichman Russell S.
Published: January 2012

Prostate cancer metastases and hematopoietic stem cells (HSC) frequently home to the bone marrow, where they compete to occupy the same HSC niche. We have also shown that under conditions of hematopoietic stress, HSCs secrete the bone morphogenetic proteins (BMP)-2 and BMP-6 that drives osteoblastic differentiation from mesenchymal precursors. As it is not known, we examined whether metastatic prostate cancer cells can alter regulation of normal bone formation by HSCs and hematopoietic progenitor cells (HPC). HSC/HPCs isolated from mice bearing nonmetastatic and metastatic tumor cells were isolated and their ability to influence osteoblastic and osteoclastic differentiation was evaluated. When the animals were inoculated with the LNCaP C4-2B cell line, which produces mixed osteoblastic and osteolytic lesions in bone, HPCs, but not HSCs, were able to induced stromal cells to differentiate down an osteoblastic phenotype. Part of the mechanism responsible for this activity was the production of BMP-2. On the other hand, when the animals were implanted with PC3 cells that exhibits predominantly osteolytic lesions in bone, HSCs derived from these animals were capable of directly differentiating into tartrate-resistant acid phosphatase–positive osteoclasts through an interleukin-6–mediated pathway. These studies for the first time identify HSC/HPCs as novel targets for future therapy involved in the bone abnormalities of prostate cancer. Mol Cancer Res; 10(3); 282–92. ©2012 AACR.
A New Arteriovenous Fistula Model to Study the Development of Neointimal Hyperplasia
Authors: Manning Eddie , Skartsis Nikolaos , Orta Armando M. , Velazquez Omaida C. , Liu Zhao-Jun , Asif Arif , Salman Loay H. , Vazquez-Padron Roberto I.
Published: January 2012

This study describes an alternative arteriovenous fistula (AVF) model in the rat in which the animals develop significant neointimal hyperplasia (NIH) not only at the distal anastomotic site, but also throughout the fistula body. This aortocaval fistula was established by anastomosing the distal end of the renal vein to the abdominal aorta after unilateral nephrectomy. The increased hemodynamic stress resulting from exposing the renal vein to the arterial circulation induced venous NIH as early as 7 days after surgery. This experimental AVF was characterized by the early lack of endothelium, the accumulation of proliferating vascular smooth muscle cells and the neovascularization of the fistula adventitia. In summary, we have described an informative animal model to study the pathobiology of NIH in native AVF.
Clinical and Economic Aspects of KRAS Mutational Status as Predictor for Epidermal Growth Factor Receptor Inhibitor Therapy in Metastatic Colorectal Cancer Patients
Authors: Königsberg Robert , Hulla Wolfgang , Klimpfinger Martin , Reiner-Concin Angelika , Steininger Tanja , Büchler Wilfried , Terkola Robert , Dittrich Christian
Published: January 2012

Treatment of metastasized colorectal cancer (mCRC) patients with anti-epidermal growth factor receptor (EGFR)-directed monoclonal antibodies is driven by the results of the KRAS mutational status (wild type [WT]/mutated [MUT]). To find out as to what extent the treatment selection based on the KRAS status had impact on overall costs, a retrospective analysis was performed. Of 73 mCRC patients 31.5% were MUT carriers. Costs of EGFR inhibitor treatment for WT patientswere significantly higher compared to those for patients with MUT (p = 0.005). Higher treatment costs in WT carriers reflect a significantly higher number of treatment cycles (p = 0.012) in this cohort of patients. Savings of drug costs minus the costs for the determination of KRAS status accounted for EUR 779.42 (SD ±336.28) per patient per cycle. The routine use of KRAS screening is a cost-effective strategy. Costs of unnecessary monoclonal EGFR inhibitor treatment can be saved in MUT patients.
Feasibility and Reproducibility of Transvaginal, Transabdominal, and 3D Volume Reconstruction Sonography for Measurement of the Corpus Callosum at Different Gestational Ages
Authors: Miguelote Rui F. , Vides Belisa , Santos Ricardo F. , Matias Alexandra , Sousa Nuno
Published: January 2012

Objective: To compare the feasibility and reproducibility of transvaginal and transabdominal approaches, and 3D volume reconstruction sonography for measurement of corpus callosum (CC) length at different gestational ages. Methods: Forty-six normal fetuses were examined by 2D and 3D ultrasound at 23-25, 27-28 and 31-32 weeks of gestation. Direct mid-sagittal views were obtained by either a transabdominal and/or transvaginal approach. 3D reconstructed mid-sagittal views were obtained by 3D multiplanar manipulations and Volume Contrast Imaging in the C-plane technique (VCI-C) from volumes acquired in axial planes. Results: The CC could be measured in 91% of transvaginal acquisitions, in 52% of transabdominal acquisitions, in 92% of multiplanar reconstructions, and in 86% of VCI-C reconstructions. The success rate was independent of gestational age for transvaginal acquisition and slightly dependent on gestational age for 3D reconstruction techniques. Transabdominal acquisition was dependent on gestational age and fetal presentation. Inter- and intra-observer agreement was slightly better for measurements obtained from direct mid-sagittal views with either transvaginal or transabdominal acquisition than in views obtained by volume reconstruction. The reproducibility of measurements taken in reconstructed mid-sagittal views decreased with gestational age. Conclusion: 3D volume reconstruction techniques allow visualization and measurement of the CC in a high percentage of cases, with good reproducibility.
Lack of Neurofibromatosis Type 2 Gene Promoter Methylation in Sporadic Vestibular Schwannomas
Authors: Koutsimpelas D. , Ruerup G. , Mann W.J. , Brieger J.
Published: January 2012

Background: Vestibular schwannomas (VS) are benign tumors of the nervous system that are usually sporadic but also occur in the inherited disorder neurofibromatosis type 2 (NF2). In VS, losses of chromosomal material and mutations of the NF2 gene have been established to be causative. For a subset of VS without detectable gene alterations, promoter inactivation by hypermethylation has been suggested. However, published data are very limited and contradictory. Methods: We analyzed NF2 gene promoter methylation in 35 sporadic VS by methylation-specific PCR. Results: Twenty-three of the tumors were informative, showing no promoter methylation. In the remaining 12 tumors, promoter methylation could neither be verified nor excluded. Conclusions: Our study suggests that NF2 gene inactivation by promoter hypermethylation is a rare or very uncommon mechanism of NF2 gene inactivation in sporadic VS. Other mechanisms destabilizing the NF2 gene product, yet to be identified, might play a role in the genesis of VS apart from the loss or mutation of the NF2 gene.
Fractalkine: A Survivor's Guide
Authors: White Gemma E. , Greaves David R.
Published: January 2012

Chemokines are a family of low-molecular-weight proteins essential to the directed migration of cells under homeostatic and pathological conditions. Fractalkine (CX3CL1) is an unusual chemokine that can act as either a soluble or membrane-bound mediator and signals through the G protein–coupled chemokine receptor CX3CR1, expressed on monocytes, natural killer cells, T cells, and smooth muscle cells. Accumulating evidence suggests that fractalkine, in addition to its role in chemotaxis and adhesion of leukocytes, supports the survival of multiple cell types during homeostasis and inflammation. This review presents the evidence obtained from several disease models implying an antiapoptotic function for fractalkine and shows how this is relevant to the pathology of atherosclerosis and other vascular diseases. We discuss whether the key role of fractalkine, unlike other chemokines, is the promotion of cell survival and whether this has implications for vascular disease.
Making Sense of CO2: Putting Carbon in Context
Authors: Moolna Adam
Published: January 2012

Human-driven climate change resulting from carbon emissions threatens major environmental disturbance. However, the problems we face are the environmental costs of the changing climate, not the presence of CO2 molecules as such. This essay argues that present climate action strategies dangerously fail to appreciate the environmental, socioeconomic and climate context of carbon. Reducing action on climate to the management of carbon emissions, while favored by governments and businesses, threatens to create a myriad of wider environmental and social problems. This has been exacerbated by the subsequent transformation, made possible by this carbon reductionism, of carbon into a commodity. Consideration of context is effectively prevented, even if one tries to factor in environmental values, because tradable carbon credits depend on treating carbon in the abstract as a commodity. Contesting the decontextualization of carbon requires researchers to explain the importance of environmental context, to develop potential models for the transition to a “climate clean” global economy, and to explore the political levers for such structural change.
Global Banks, the Environment, and Human Rights: The Impact of the Equator Principles on Lending Policies and Practices
Authors: Wright Christopher
Published: January 2012

The Equator Principles are a set of operational principles and standards adopted by more than 70 public and private financial institutions to manage environmental and social risks in project financing. This article assesses the impact of the voluntary framework on lending policies and practices, and the environmental and social accountability of financial institutions. It finds that the direct link between the Equator Principles and the International Finance Corporation (IFC), the World Bank Group's private sector financing division, enhances the legitimacy and potential impact of the framework. However, development of lending policies across financial institutions is greatly uneven, and the framework has not stopped lending to projects with significant environmental and social costs. Although the framework has improved relations between financial institutions and stakeholders, a lack of transparency undermines external accountability. The conclusion considers the scope for increased harmonization of environmental and social lending policies in international banking.
The Evolution of Environment-Conflict Research: Toward a Livelihood Framework
Authors: Deligiannis Tom
Published: January 2012

The focus of qualitative environment-conflict research since the early 1990s on the state level of analysis has led to considerable uncertainty about the validity of hypothesized connections and under-specification of existing pathways inhuman-environmental change interactions. As a corrective, this article proposes a household-livelihood framework for qualitative environment-conflict research. This approach begins at the local level and then scales the analysis of social-political effects to higher levels. A household-livelihood framework also improves our understanding of many previously-ignored violent conflicts at the local level that have roots in human-environmental change.
La notoriété de l’appellation d’origine et du nom commercial, deux signes distinctifs. Étude comparée de droit français et jordanien
Authors: Al-Shammari Mohammad , Hattab Rasha
Published: January 2012

Résumé

L’évolution du concept de notoriété relevant de la continuité, celui qui en entreprendrait l’étude ne serait pas près d’aboutir. S’agissant du domaine des signes distinctifs, le concept a d’abord fait son entrée à plusieurs reprises en droit des marques. Ensuite, et récemment, la notoriété a commencé à jouer un rôle d’importance dans la protection d’autres signes distinctifs, en affectant les règles du droit et de la jurisprudence. La présente étude cherche à mettre en lumière l’influence de la notoriété sur le mécanisme juridique mis en place pour protéger deux signes distinctifs: les appellations d’origine et les noms commerciaux. Les points de mire de la recherche ont été la présence de la notoriété dans les règles de droit concernées et le rôle de la notoriété dans l’extension de la protection conférée aux deux signes. La question est traitée sous un angle d’une comparaison entre deux législations – la législation française et la législation jordanienne.
Compliance with Philosophy of Exemption from Notification at Termination of Contract: Study in Light of Jordanian Labour Law
Authors: Kasassbeh Firas Y.
Published: January 2012

Abstract

Under the Jordanian Labour Code 1996, it is not permissible for an employer to terminate a contract without giving the employee at least 1-month notice before the date of termination, because sudden dismissal would catch the worker unaware. However, there are cases in which an employer is exempted from giving prior notice, due to either the nature of the contract (e.g., definite-period contracts or employment under probation) or the nature of termination (e.g., due to the employee’s conduct resulting in a major error or due to technical or economic justifications such as redundancy). This study is devoted to examining all such cases in order to bring to light to what extent such cases truly reflect the philosophy behind exemption from notice.
Surface Temperature Gradients as Diagnostic Indicators of Midlatitude Circulation Dynamics
Authors: Karamperidou Christina , Cioffi Francesco , Lall Upmanu
Published: January 2012

Zonal and meridional surface temperature gradients are considered to be determinants of large-scale atmospheric circulation patterns. However, there has been limited investigation of these gradients as diagnostic aids. Here, the twentieth-century variability in the Northern Hemisphere equator-to-pole temperature gradient (EPG) and the ocean–land temperature contrast (OLC) is explored. A secular trend in decreasing EPG and OLC is noted. Decadal and interannual (ENSO-related) variations in the joint distribution of EPG and OLC are identified, hinting at multistable climate states that may be indigenous to the climate or due to changing boundary forcings. The NH circulation patterns for cases in the tails of the joint distribution of EPG and OLC are also seen to be different. Given this context, this paper extends past efforts to develop insights into jet stream dynamics using the Lorenz-1984 model, which is forced directly and only by EPG and OLC. The joint probability distribution of jet stream and eddy energy, conditional on EPG and OLC scenarios, is investigated. The scenarios correspond to (i) warmer versus colder climate conditions and (ii) polarized ENSO phases. The latter scenario involves the use of a heuristic ENSO model to drive the Lorenz-1984 model via a modulation of the EPG or the OLC. As with GCMs, the low-order model reveals that the response to El Niño forcing is not similar to an anthropogenic warming signature. The potential uses of EPG and OLC as macro-level indicators of climate change and variability and for comparing results across GCMs and observations are indicated.
Can Oceanic Freshwater Flux Amplify Global Warming?
Authors: Zhang Liping , Wu Lixin
Published: January 2012

The roles of freshwater flux (defined as evaporation minus precipitation) changes in global warming are studied using simulations of a climate model in which the freshwater flux changes are suppressed in the presence of a doubling of CO2 concentration. The model simulations demonstrate that the warm climate leads to an acceleration of the global water cycle, which causes freshening in the high latitudes and salinification in the subtropics and midlatitudes. It is found that the freshwater flux changes tend to amplify rather than suppress global warming. Over the global scale, this amplification is largely associated with high-latitude freshening in a warm climate, which leads to a shoaling of the mixed layer depth, a weakening of the vertical mixing, and thus a trapping of CO2-induced warming in the surface ocean. The latitudinal distribution of SST changes due to the effects of freshwater flux changes in a warm climate is complicated, involving anomalous advection induced by both salinity and wind stress changes. In addition, atmospheric feedbacks associated with global warming also amplify the SST warming.
Causes of the Rapid Warming of the North Atlantic Ocean in the Mid-1990s
Authors: Robson Jon , Sutton Rowan , Lohmann Katja , Smith Doug , Palmer Matthew D.
Published: January 2012

In the mid-1990s, the subpolar gyre of the North Atlantic underwent a remarkable rapid warming, with sea surface temperatures increasing by around 1°C in just 2 yr. This rapid warming followed a prolonged positive phase of the North Atlantic Oscillation (NAO) but also coincided with an unusually negative NAO index in the winter of 1995/96. By comparing ocean analyses and carefully designed model experiments, it is shown that this rapid warming can be understood as a delayed response to the prolonged positive phase of the NAO and not simply an instantaneous response to the negative NAO index of 1995/96. Furthermore, it is inferred that the warming was partly caused by a surge and subsequent decline in the meridional overturning circulation and northward heat transport of the Atlantic Ocean. These results provide persuasive evidence of significant oceanic memory on multiannual time scales and are therefore encouraging for the prospects of developing skillful predictions.
Using WSR-88D Data and Insolation Estimates to Determine Convective Boundary Layer Depth
Authors: Elmore Kimberly L. , Heinselman Pamela L. , Stensrud David J.
Published: January 2012

Prior work shows that Weather Surveillance Radar-1988 Doppler (WSR-88D) clear-air reflectivity can be used to determine convective boundary layer (CBL) depth. Based on that work, two simple linear regressions are developed that provide CBL depth. One requires only clear-air radar reflectivity from a single 4.5° elevation scan, whereas the other additionally requires the total, clear-sky insolation at the radar site, derived from the radar location and local time. Because only the most recent radar scan is used, the CBL depth can, in principle, be computed for every scan. The “true” CBL depth used to develop the models is based on human interpretation of the 915-MHz profiler data. The regressions presented in this work are developed using 17 summer days near Norman, Oklahoma, that have been previously investigated. The resulting equations and algorithms are applied to a testing dataset consisting of 7 days not previously analyzed. Though the regression using insolation estimates performs best, errors from both models are on the order of the expected error of the profiler-estimated CBL depth values. Of the two regressions, the one that uses insolation yields CBL depth estimates with an RMSE of 208 m, while the regression with only clear-air radar reflectivity yields CBL depth estimates with an RMSE of 330 m.
Calcium Chloride and Sodium Phosphate in Neonatal Parenteral Nutrition Containing TrophAmine
Authors: Migaki Evelyn A. , Melhart Brian J. , Dewar Christina J. , Huston Robert K.
Published: January 2012

Objectives: The objectives were to determine concentrations of calcium chloride (CaCl) and sodium phosphate (NaPhos) that can be safely added to TrophAmine‐based parenteral nutrition (PN) and to measure aluminum (Al) concentrations in PN solutions containing CaCl and NaPhos vs those containing calcium gluconate (CaGlu) and potassium phosphate (KPhos). Methods: In study A, PN solutions containing varying amounts of TrophAmine, CaCl, and NaPhos were compounded and then evaluated visually for precipitation. In study B, Al concentrations were measured in PN solutions containing CaCl and NaPhos (S1), CaGlu and NaPhos (S2), or CaGlu and KPhos (S3). Results: Study A showed that a maximum phosphorus concentration of 15 mmol/L could be added to a solution containing 12.5 mmol/L of calcium without evidence of precipitation when the amino acid (AA) concentration reached ≥3 g/dL (3%). In study B, the mean (range) Al concentrations were S1 = 2.2 (1.9–2.4), S2 = 8.5 (7.8–9.3), and S3 = 11.7 (10.8–12.2) µmol/L (means of 6.0, 22.9, and 31.5 micrograms/dL, respectively). Conclusions: The data can provide a guide for compounding neonatal PN solutions containing TrophAmine, CaCl, and NaPhos. More studies are needed to determine the long‐term effects of substituting CaCl for CaGlu in PN solutions for neonates. Substituting CaCl and NaPhos for CaGlu and KPhos significantly decreases Al concentrations in PN and potential Al exposure of neonatal patients.