bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of Microphysical Processes Occurring in Isolated Convection during NAME
Authors: Rowe Angela K. , Rutledge Steven A. , Lang Timothy J. 
Published: September 2010

AbstractTo address questions regarding microphysical processes occurring in the core North American monsoon region, data from NCAR’s S-band polarimetric Doppler radar (S-Pol) deployed during the North American Monsoon Experiment (NAME) in the summer of 2004, were used to investigate the location, size, and type of hydrometeors in convection. A cell identification and tracking algorithm was applied to this data over 100 h of microphysical scans, characterized by increased temporal and vertical resolution, to locate and track individual convective elements. Only isolated cells over land were included for this study to investigate potential elevation-dependent trends in microphysical processes in this region.Examples of intense, isolated convection over all elevations revealed deep cells and polarimetric signatures comparable to other studies of tropical and midlatitude convection. A case over the low terrain highlighted deep, isolated convection with precipitation-sized ice extending to 15 km. In addition, the presence of differential reflectivity ZDR columns in these cells indicated the lofting of supercooled water above the melting level, and an enhanced linear depolarization ratio LDR “cap” above the column implied subsequent freezing to produce graupel. Similar features were also observed in an isolated cell over the western slopes, highlighting the combined roles of collision–coalescence and melting precipitation-sized ice for producing intense rainfall over the lower elevations. Despite previous observations of weaker and shallower cells with less precipitation ice over the Sierra Madre Occidental (SMO), case studies and general statistics using polarimetric data reveal the potential for accretional processes to also play an important role in producing intense rainfall over these higher elevations. For these isolated SMO cells, reduced warm-cloud depths, increased ice mass observed just above the melting level, and a narrower distribution of drop sizes suggest a reduced role of warm-rain processes compared to intense cells over the lower terrain. A potential relationship between microphysical processes and degree of organization is also hypothesized and will be the focus of a future study.
Zymogen-like factor Xa variants restore thrombin generation and effectively bypass the intrinsic pathway in vitro
Authors: Bunce Matthew W. , Toso Raffaella , Camire Rodney M. 
Published: September 2010

AbstractInhibitory antibodies to factors VIII or IX represent a serious complication for hemophilia patients. Treatment involves products that bypass the intrinsic pathway and promote thrombin generation. Direct infusion of factor Xa should also restore hemostasis; however, it has a short half-life in plasma and could activate systemic coagulation in an uncontrolled fashion. Here we show that factor Xa mutants with zymogen-like properties (FXaI16L and FXaV17A) circumvent these limitations. In the absence of factor Va, the FXa variants are poor enzymes for a range of physiological ligands and are resistant to inactivation by antithrombin III and tissue factor pathway inhibitor. Notably, assembly of FXaI16L and FXaV17A on activated platelets with factor Va to form prothrombinase completely restores biologic activity. In hemophilic plasma, FXaI16L and FXaV17A have prolonged half-lives compared with wild-type factor Xa (approximately 60 minutes vs approximately 1 minute) and promote robust thrombin generation that bypasses the intrinsic pathway. The variants require factor Va generated in situ for procoagulant function, and cofactor inactivation by the protein C pathway regulates their activity. The efficacy, extended half-life, and mechanism of action suggest that novel zymogen-like forms of factor Xa might prove useful as new therapeutic procoagulants to treat deficiencies upstream of the common pathway.
Differential detection of alternatively spliced variants of Ciz1 in normal and cancer cells using a custom exon-junction microarray
Authors: Rahman Faisal A , Aziz Naveed , Coverley Dawn 
Published: September 2010

Abstract

Background
Ciz1 promotes initiation of mammalian DNA replication and is present within nuclear matrix associated DNA replication factories. Depletion of Ciz1 from normal and cancer cells restrains entry to S phase and inhibits cell proliferation. Several alternative splicing events with putative functional consequences have been identified and reported, but many more variants are predicted to exist based on publicly available mRNAs and expressed sequence tags.

Methods
Here we report the development and validation of a custom exon and exon-junction microarray focused on the human CIZ1 gene, capable of reproducible detection of differential splice-variant expression.

Results
Using a pair of paediatric cancer cell lines and a pool of eight normal lines as reference, the array identified expected and novel CIZ1 splicing events. One novel variant (delta 8-12) that encodes a predicted protein lacking key functional sites, was validated by quantitative RT-PCR and found to be over-represented in a range of other cancer cell lines, and over half of a panel of primary lung tumours.

Conclusions
Expression of CIZ1 delta 8-12 appears to be restricted to cancer cells, and may therefore be a useful novel biomarker
Down-regulation of the Nucleotide Excision Repair gene XPG as a new mechanism of drug resistance in human and murine cancer cells
Authors: Sabatino Maria Antonietta , Marabese Mirko , Ganzinelli Monica , Caiola Elisa , Geroni Cristina , Broggini Massimo 
Published: September 2010

Abstract

Background
Drug resistance is one of the major obstacles limiting the activity of anticancer agents. Activation of DNA repair mechanism often accounts for increase resistance to cancer chemotherapy.

Results
We present evidence that nemorubicin, a doxorubicin derivative currently in clinical evaluation, acts through a mechanism of action different from classical anthracyclines, requiring an intact nucleotide excision repair (NER) system to exert its activity. Cells made resistant to nemorubicin show increased sensitivity to UV damage. We have analysed the mechanism of resistance and discovered a previously unknown mechanism resulting from methylation-dependent silencing of the XPG gene. Restoration of NER activity through XPG gene transfer or treatment with demethylating agents restored sensitivity to nemorubicin. Furthermore, we found that a significant proportion of ovarian tumors present methylation of the XPG promoter.

Conclusions
Methylation of a NER gene, as described here, is a completely new mechanism of drug resistance and this is the first evidence that XPG gene expression can be influenced by an epigenetic mechanism. The reported methylation of XPG gene could be an important determinant of the response to platinum based therapy. In addition, the mechanism of resistance reported opens up the possibility of reverting the resistant phenotype using combinations with demethylating agents, molecules already employed in the clinical setting.
Linoleic acid suppresses colorectal cancer cell growth by inducing oxidant stress and mitochondrial dysfunction
Authors: Lu Xiaofeng , Yu Haining , Ma Qi , Shen Shengrong , Das Undurti N 
Published: September 2010

Abstract
Some polyunsaturated fatty acids (PUFAs), if not all, have been shown to have tumoricidal action, but their exact mechanism(s) of action is not clear. In the present study, we observed that n-6 PUFA linoleic acid (LA) inhibited tumor cell growth at high concentrations (above 300 μM); while low concentrations (100-200 μM) promoted proliferation. Analysis of cell mitochondrial membrane potential, reactive oxygen species (ROS) formation, malondialdehyde (MDA) accumulation and superoxide dismutase (SOD) activity suggested that anti-cancer action of LA is due to enhanced ROS generation and decreased cell anti-oxidant capacity that resulted in mitochondrial damage. Of the three cell lines tested, semi-differentiated colorectal cancer cells RKO were most sensitive to the cytotoxic action of LA, followed by undifferentiated colorectal cancer cell line (LOVO) while the normal human umbilical vein endothelial cells (HUVEC) were the most resistant (the degree of sensitivity to LA is as follows: RKO > LOVO > HUVEC). LA induced cell death was primed by mitochondrial apoptotic pathway. Pre-incubation of cancer cells with 100 μM LA for 24 hr enhanced sensitivity of differentiated and semi-differentiated cells to the subsequent exposure to LA. The relative resistance of LOVO cells to the cytotoxic action of LA is due to a reduction in the activation of caspase-3. Thus, LA induced cancer cell apoptosis by enhancing cellular oxidant status and inducing mitochondrial dysfunction.
The role of the JAK2-STAT3 pathway in pro-inflammatory responses of EMF-stimulated N9 microglial cells
Authors: Yang Xuesen , He Genlin , Hao Yutong , Chen Chunhai , Li Maoquan , Wang Yuan , Zhang Guangbin , Yu Zhengping 
Published: September 2010

AbstractBackgroundIn several neuropathological conditions, microglia can become overactivated and cause neurotoxicity by initiating neuronal damage in response to pro-inflammatory stimuli. Our previous studies have shown that exposure to electromagnetic fields (EMF) activates cultured microglia to produce tumor necrosis factor (TNF)-α and nitric oxide (NO) through signal transduction involving the activator of transcription STAT3. Here, we investigated the role of STAT3 signaling in EMF-induced microglial activation and pro-inflammatory responses in more detail than the previous study.MethodsN9 microglial cells were treated with EMF exposure or a sham treatment, with or without pretreatment with an inhibitor (Pyridone 6, P6) of the Janus family of tyrosine kinases (JAK). The activation state of microglia was assessed via immunoreaction using the microglial marker CD11b. Levels of inducible nitric oxide synthase (iNOS), TNF-α and NO were measured using real-time reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and the nitrate reductase method. Activation of JAKs and STAT3 proteins was evaluated by western blotting for specific tyrosine phosphorylation. The ability of STAT3 to bind to DNA was detected with an electrophoresis mobility shift assay (EMSA).ResultsEMF was found to significantly induce phosphorylation of JAK2 and STAT3, and DNA-binding ability of STAT3 in N9 microglia. In addition, EMF dramatically increased the expression of CD11b, TNF-α and iNOS, and the production of NO. P6 strongly suppressed the phosphorylation of JAK2 and STAT3 and diminished STAT3 activity in EMF-stimulated microglia. Interestingly, expression of CD11b as well as gene expression and production of TNF-α and iNOS were suppressed by P6 at 12 h, but not at 3 h, after EMF exposure.ConclusionsEMF exposure directly triggers initial activation of microglia and produces a significant pro-inflammatory response. Our findings confirm that the JAK2-STAT3 pathway may not mediate this initial microglial activation but does promote pro-inflammatory responses in EMF-stimulated microglial cells. Thus, the JAK2-STAT3 pathway might be a therapeutic target for reducing pro-inflammatory responses in EMF-activated microglia.
COMT Val158Met polymorphism, cognitive stability and cognitive flexibility: an experimental examination
Authors: Rosa Elise C , Dickinson Dwight , Apud José , Weinberger Daniel R , Elvevåg Brita 
Published: September 2010

Abstract

Background
Dopamine in prefrontal cortex (PFC) modulates core cognitive processes, notably working memory and executive control. Dopamine regulating genes and polymorphisms affecting PFC - including Catechol-O-Methyltransferase (COMT) Val158Met - are crucial to understanding the molecular genetics of cognitive function and dysfunction. A mechanistic account of the COMT Val158Met effect associates the Met allele with increased tonic dopamine transmission underlying maintenance of relevant information, and the Val allele with increased phasic dopamine transmission underlying the flexibility of updating new information. Thus, consistent with some earlier work, we predicted that Val carriers would display poorer performance when the maintenance component was taxed, while Met carriers would be less efficient when rapid updating was required.

Methods
Using a Stroop task that manipulated level of required cognitive stability and flexibility, we examined reaction time performance of patients with schizophrenia (n = 67) and healthy controls (n = 186) genotyped for the Val/Met variation.

Results
In both groups we found a Met advantage for tasks requiring cognitive stability, but no COMT effect when a moderate level of cognitive flexibility was required, or when a conflict cost measure was calculated.

Conclusions
Our results do not support a simple stability/flexibility model of dopamine COMT Val/Met effects and suggest a somewhat different conceptualization and experimental operationalization of these cognitive components.
Silencing of RhoA and RhoC expression by RNA interference suppresses human colorectal carcinoma growth in vivo
Authors: Wang Haibo , Zhao Gang , Liu Xiangping , Sui Aihua , Yang Kun , Yao Ruyong , Wang Zongbao , Shi Qiang 
Published: September 2010

Abstract

Background

RhoA and RhoC have been proved to be over-expressed in many solid cancers, including colorectal cancer. The reduction of RhoA and RhoC expression by RNA interference (RNAi) resulted growth inhibition of cancer cells. The present study was to evaluate the effect of silencing of RhoA and RhoC expression by RNAi on growth of human colorectal carcinoma (CRC) in tumor-bearing nude mice in vivo.

Methods
To establish HCT116 cell transplantable model, the nude mice were subcutaneously inoculated with 1.0 × 107 HCT116 cells and kept growing till the tumor xenografts reached 5-7 mm in diameter. Then the mice were randomly assigned to three groups(seven mice in each group): (1) normal saline(NS) group, (2)replication-defective recombinant adenovirus carrying the negative control shRNA (Ad-HK) group and (3)replication-defective recombinant adenovirus carrying the 4-tandem linked RhoA and RhoC shRNAs (Ad-RhoA-RhoC) group. Ad-HK (4 × 108 pfu, 30 ul/mouse), Ad-RhoA-RhoC (4 × 108 pfu, 30 ul/mouse) or PBS (30 ul/mouse) was injected intratumorally four times once every other day. The weight and volumes of tumor xenografts were recorded. The levels of RhoA and RhoC mRNA transcripts and proteins in tumor xenografts were detected by reverse quantitative transcription polymerase chain reaction (QRT-PCR) and immunohistochemical staining respectively. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was used to detect the death of cells.

Results
The xenografts in mice could be seen at 5th day from the implantation of HCT116 cells and all had reached 5-7 mm in size at 9th day. After injection intratumorally, the growth speed of tumor xenografts in Ad-RhoA-RhoC group was significantly delayed compared with those in NS and Ad-HK group(P < 0.05). The results of QRT-PCR showed that mRNA levels of RhoA and RhoC reduced more in Ad-RhoA-RhoC group than those in NS and Ad-HK group. The relative RhoA and RhoC mRNA transcripts were decreased to 48% and 43% respectively (P < 0.05). Immunohistochemical analyses of tumor xenograft sections also revealed the decreased RhoA and RhoC expression in Ad-RhoA-RhoC group. TUNEL assay also showed higher death of tumor xenograft tissue cells in Ad-RhoA-RhoC group.

Conclusion
Recombinant adenovirus mediated RhoA and RhoC shRNA in tandem linked expression may inhibit the growth of human colorectal tumor xenografts in vivo. These results indicate that RhoA and RhoC might be potential targets for gene therapy in colorectal cancer.
Aortic elastic properties in patients with venous thromboembolism
Authors: Duran N E , Oğuz E , Duran I , Aykan A Ç , Ertürk E , Bayram Z , Gürsoy M O , Biteker M , Karavelioğlu Y , Kaya H , Özkan M 
Published: September 2010

Objectives The relationship between venous thrombosis (VT) and atherosclerosis is controversial in recent studies. Aortic elastic properties have a predictive value in detecting early stages of atherosclerosis. The aim of this study is to evaluate the relationship between aortic elastic properties and VT. Methods Elastic properties of aorta in patients with spontaneous VT, without history of known cardiovascular disease and cardiovascular risk factors ( n: 31), and in healthy subjects without cardiovascular risk factors ( n: 30) were compared. Elastic properties of the aorta were assessed with transthoracic echocardiography. Results A significant increase in aortic stiffness index (6.5 ± 1.0 versus 6 ± 0.7, P = 0.03) and a significant decrease in aortic strain and aortic distensibility were found in patients with VT compared with healthy subjects (8.4 ± 7 versus 13 ± 8, P = 0.01, 4.9 ± 4.8 versus 6.5 ± 4.4, P = 0.03, respectively). Conclusions Elastic properties of aorta in patients with spontaneous VT were impaired. These results may support the role of endothelial dysfunction in the pathogenesis of VT.
Epidemiology and risk factors for varicose veins among older people: cross-sectional population study in the UK
Authors: Clark A , Harvey I , Fowkes F G R 
Published: September 2010

Background There are many hypotheses concerning risk factors for the development of varicose veins based mostly on pathophysiological plausibility. Population studies have been carried out mostly on the middle aged with relatively few on elderly populations. Objectives To investigate epidemiological risk factors for varicose veins in an elderly population in the UK. Methods The South Wales Skin Cancer study – an examination survey undertaken between 1988 and 1991 of a random sample ( n = 792) drawn from all patients aged 60 and over registered with a general practitioner in South Glamorgan. Exposure variables were obtained from a structured administered questionnaire combined with clinical examination. Unadjusted and adjusted odds ratios were estimated using logistic regression. Results The response rate was 71% with an average age of 71 years (range 60–97). The age-adjusted prevalence of trunk varices was 63.2% (95% confidence interval [CI] 57.9–68.4%) in men and 57.0% (95% CI 50.6–63.4%) in women. In a multiple logistic regression the significant risk factors for varicose veins were increasing age ( P value = 0.001), obesity (odds ratio [OR] 3.28, 95% CI 1.25–8.63, P = 0.042), self-reported history of deep vein thrombosis (DVT) (OR 3.19, 1.16–8.78, P = 0.024) and history of hypertension (OR 0.58, 0.38–0.89, P = 0.013). The results for gender suggested that women were at greater risk than men, but this was not statistically significant (OR 1.53, 0.99–2.38, P = 0.056). Conclusion Trunk varices occur very commonly in older age groups with increasing age, obesity and possibly female sex as risk factors. Associations found with DVT and hypertension were based on history alone and must be interpreted with caution.
Duplex scanning is no substitute for surgical expertise in identifying the saphenopopliteal junction: results following short saphenous vein surgery
Authors: Sonnenberg S , Gowland-Hopkins N F 
Published: September 2010

Objectives Short saphenous vein (SSV) surgery carries a high risk of failure to identify the saphenopopliteal junction (SPJ). We assessed the impact of surgical expertise on anatomical outcome from SSV surgery and the role of preoperative duplex SPJ marking in improving outcome for vascular and non-vascular specialists. Methods A retrospective analysis identified patients (30 limbs) who had undergone SSV surgery. These were recalled for duplex scanning of the SPJ. In a prospective study, 187 limbs had preoperative duplex marking of SPJ and postoperative duplex to assess outcome. Grade of operating surgeon was recorded in both retrospective and prospective analysis. Results In both retrospective and prospective analysis, vascular specialists were significantly more likely than non-vascular specialists to correctly identify the SPJ ( P < 0.0001). Preoperative SPJ marking did not improve outcome for the vascular specialist or the non-vascular specialist. Conclusion Preoperative SPJ marking is no substitute for surgical expertise. Competence in SSV surgery should be assessed prior to surgeons proceeding to independent practice.
Triple-lumen double-balloon catheter for foam sclerotherapy of the great saphenous vein: critical review on preliminary results
Authors: Reich-Schupke S , Altmeyer P , Stücker M 
Published: September 2010

Background Different catheters (angiography, single-balloon) have been used for foam sclerotherapy of the great saphenous vein (GSV). Objective Is there greater efficacy and safety in the use of a double-balloon catheter? Methods Twenty patients were treated with a double-balloon catheter and 3% polidocanol foam. Follow-up after one day, one and six weeks, six and 12 months. Results Up to week six complete success was seen in 95% (19/20) patients. Only eight patients attended the checks after six and 12 months. The occlusion rates were 75% (6/8, 6 months) resp. 50% (4/8, 12 months). A further 10 patients refused these checks as they were free of symptoms but could be questioned. Side-effects were haematoma (100%), limited phlebitis (15%) and one extended thrombophlebitis followed by hyperpigmentation. Conclusion A double-balloon catheter is a safe treatment option for foam sclerotherapy of the GSV. However, in this case series efficacy is not superior to the use of an angiography-catheter, a single-balloon catheter or just the direct puncture of the vein.
Pathophysiology of visual disturbances occurring after foam sclerotherapy
Authors: Gillet J L , Donnet A , Lausecker M , Guedes J M , Guex J J , Lehmann P 
Published: September 2010

Background Visual disturbances (VDs) are reported with an average rate of 1.4% after foam sclerotherapy (FS). Some clinical clues indicate that they could correspond to migraine with aura (MA). Aims To validate the hypothesis that VDs occurring after FS correspond to MA and are not transient ischaemic cerebro-vascular events. Method A prospective multicentre study was carried out by the French Society of Phlebology in collaboration with the Neurology Department of the Marseille University Hospital (France). We included prospectively and consecutively all patients who experienced VDs after FS using air to make the foam. The patients were assessed (1) clinically with a specific form describing procedures of FS and recording neurological symptoms, later analysed by a neurologist specialized in migraine; and (2) by a brain diffusion-weighted magnetic resonance imaging (MRI) (T1, T2, T2*, diffusion) carried out within two weeks and analysed by a neuroradiologist. Results Twenty patients, 16 women and four men, were included in 11 phlebology clinics. All kinds of veins were treated. VDs occurred in average seven minutes after FS. Clinical assessment showed that VDs presented characteristics of MA in all patients, with headache in 10 and without in 10. Paresthesia was observed in five patients and dysphasic speech disturbance in one. Fifteen patients (75%) had a personal history of migraine. Fifteen MRIs were performed within two weeks (mean: 8 days) and three were late (26 days). All of them were normal. MRI was not performed in two patients. Conclusion These results show that VDs occurring after FS correspond to MA and are not transient ischaemic cerebro-vascular events. We suggest a pathophysiological hypothesis resting on the release of endothelin that would reach the cerebral cortex through a paten foramen ovale.