bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carfilzomib Interacts Synergistically with Histone Deacetylase Inhibitors in Mantle Cell Lymphoma Cells In Vitro and In Vivo
Authors: Dasmahapatra Girija , Lembersky Dmitry , Son Minkyeong P. , Attkisson Elisa , Dent Paul , Fisher Richard I. , Friedberg Jonathan W. , Grant Steven 
Published: July 2011

Abstract
Interactions between the proteasome inhibitor carfilzomib and the histone deacetylase (HDAC) inhibitors vorinostat and SNDX-275 were examined in mantle cell lymphoma (MCL) cells in vitro and in vivo. Coadministration of very low, marginally toxic carfilzomib concentrations (e.g., 3–4 nmol/L) with minimally lethal vorinostat or SNDX-275 concentrations induced sharp increases in mitochondrial injury and apoptosis in multiple MCL cell lines and primary MCL cells. Enhanced lethality was associated with c-jun-NH,-kinase (JNK) 1/2 activation, increased DNA damage (induction of λH2A.X), and ERK1/2 and AKT1/2 inactivation. Coadministration of carfilzomib and histone deacetylase inhibitors (HDACI) induced a marked increase in reactive oxygen species (ROS) generation and G2–M arrest. Significantly, the free radical scavenger tetrakis(4-benzoic acid) porphyrin (TBAP) blocked carfilzomib/HDACI-mediated ROS generation, λH2A.X formation, JNK1/2 activation, and lethality. Genetic (short hairpin RNA) knockdown of JNK1/2 significantly attenuated carfilzomib/HDACI-induced apoptosis, but did not prevent ROS generation or DNA damage. Carfilzomib/HDACI regimens were also active against bortezomib-resistant MCL cells. Finally, carfilzomib/vorinostat coadministration resulted in a pronounced reduction in tumor growth compared with single agent treatment in an MCL xenograft model associated with enhanced apoptosis, λH2A.X formation, and JNK activation. Collectively, these findings suggest that carfilzomib/HDACI regimens warrant attention in MCL. Mol Cancer Ther; 10(9); 1686–97. ©2011 AACR.
Inhibition of Dynamin by Dynole 34-2 Induces Cell Death following Cytokinesis Failure in Cancer Cells
Authors: Chircop Megan , Perera Swetha , Mariana Anna , Lau Hui , Ma Maggie P.C. , Gilbert Jayne , Jones Nigel C. , Gordon Christopher P. , Young Kelly A. , Morokoff Andrew , Sakoff Jennette , O'Brien Terence J. , McCluskey Adam , Robinson Phillip J. 
Published: July 2011

Abstract
Inhibitors of mitotic proteins such as Aurora kinase and polo-like kinase have shown promise in preclinical or early clinical development for cancer treatment. We have reported that the MiTMAB class of dynamin small molecule inhibitors are new antimitotic agents with a novel mechanism of action, blocking cytokinesis. Here, we examined 5 of the most potent of a new series of dynamin GTPase inhibitors called dynoles. They all induced cytokinesis failure at the point of abscission, consistent with inhibition of dynamin while not affecting other cell cycle stages. All 5 dynoles inhibited cell proliferation (MTT and colony formation assays) in 11 cancer cell lines. The most potent GTPase inhibitor, dynole 34-2, also induced apoptosis, as revealed by cell blebbing, DNA fragmentation, and PARP cleavage. Cell death was induced specifically following cytokinesis failure, suggesting that dynole 34-2 selectively targets dividing cells. Dividing HeLa cells were more sensitive to the antiproliferative properties of all 5 dynoles compared with nondividing cells, and nontumorigenic fibroblasts were less sensitive to cell death induced by dynole 34-2. Thus, the dynoles are a second class of dynamin GTPase inhibitors, with dynole 34-2 as the lead compound, that are novel antimitotic compounds acting specifically at the abscission stage. Mol Cancer Ther; 10(9); 1553–62. ©2011 AACR.
Epigallocatechin-gallate Suppresses Tumorigenesis by Directly Targeting Pin1
Authors: Urusova Darya V. , Shim Jung-Hyun , Kim Dong Joon , Jung Sung Keun , Zykova Tatyana A. , Carper Andria , Bode Ann M. , Dong Zigang 
Published: July 2011

AbstractThe most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG). The human peptidyl prolyl cis/trans isomerase (Pin1) plays a critical role in oncogenic signaling. Herein, we report the X-ray crystal structure of the Pin1/EGCG complex resolved at 1.9 Å resolution. Notably, the structure revealed the presence of EGCG in both the WW and PPIase domains of Pin1. The direct binding of EGCG with Pin1 was confirmed and the interaction inhibited Pin1 PPIase activity. In addition, proliferation of cells expressing Pin1 was inhibited and tumor growth in a xenograft mouse model was suppressed. The binding of EGCG with Arg17 in the WW domain prevented the binding of c-Jun, a well-known Pin1 substrate. EGCG treatment corresponded with a decreased abundance of cyclin D1 and diminution of 12-O-tetradecanoylphorbol-l3-acetate–induced AP-1 or NF-κB promoter activity in cells expressing Pin1. Overall, these results showed that EGCG directly suppresses the tumor-promoting effect of Pin1. Cancer Prev Res; 4(9); 1366–77. ©2011 AACR.
Convective Activity over Africa and the Tropical Atlantic Inferred from 20 Years of Geostationary Meteosat Infrared Observations
Authors: Bennartz Ralf , Schroeder Marc 
Published: July 2011

Abstract
A 20-yr (1986–2005) time series of Meteosat Visible and Infrared Imager (MVIRI) geostationary infrared observations was used to study deep convection over Africa and the tropical Atlantic. The 20-yr time period is covered by six consecutive satellites (Meteosat-2–7). To correct for possible systematic differences between instruments on the different satellite platforms, a time series of Meteosat infrared observations over cloud-free ocean surfaces was compared to reanalysis-based radiative transfer results. Based on the comparison of simulations with observations, a homogenization was performed for the MVIRI infrared channel. The homogenized 20-yr dataset was then subjected to a tracking analysis for deep convection over Africa and the tropical Atlantic for the boreal summer months of July–September.
The mean state of convection as well as anomalies for high– and low–Sahel rainfall years were studied. Comparisons with the Global Precipitation Climatology Center’s (GPCC) rainfall estimates were performed for the Sahel region and interannual variability was evaluated comparing convection for the five driest and five wettest Sahel years. Results support earlier findings that precipitation in the Sahel region is strongly linked to the latitudinal position of the African Easterly Jet with deep convection being triggered more strongly if the jet is displaced northward. A relationship between the jet position and long-lived convective systems over the tropical Atlantic was found as well.
Geographical Dependence Observed in Blocking High Influence on the Stratospheric Variability through Enhancement and Suppression of Upward Planetary-Wave Propagation
Authors: Nishii Kazuaki , Nakamura Hisashi , Orsolini Yvan J. 
Published: July 2011

Abstract
Previous studies have suggested the importance of blocking high (BH) development for the occurrence of stratospheric sudden warming (SSW), while there is a recent study that failed to identify their statistical linkage. Through composite analysis applied to high-amplitude anticyclonic anomaly events observed around every grid point over the extratropical Northern Hemisphere, the present study reveals a distinct geographical dependence of BH influence on the upward propagation of planetary waves (PWs) into the stratosphere. Tropospheric BHs that develop over the Euro-Atlantic sector tend to enhance upward PW propagation, leading to the warming in the polar stratosphere and, in some cases, to major SSW events. In contrast, the upward PW propagation tends to be suppressed by BHs developing over the western Pacific and the Far East, resulting in the polar stratospheric cooling. This dependence is found to arise mainly from the sensitivity of the interference between the climatological PWs and upward-propagating Rossby wave packets emanating from BHs to their geographical locations. This study also reveals that whether a BH over the eastern Pacific and Alaska can enhance or reduce the upward PW propagation is case dependent. It is suggested that BHs that induce the stratospheric cooling can weaken the statistical relationship between BHs and SSWs.
Effect of early compensation of distal motor deficiency by the Chignon ankle-foot orthosis on gait in hemiplegic patients: a randomized pilot study
Authors: de Sèze Mathieu-Panchoa , Bonhomme Clément , Daviet Jean-Christophe , Burguete Emmanuel , Machat Hugues , Rousseaux Marc , Mazaux Jean Michel 
Published: July 2011

Objective: To compare the effect of the Chignon ankle-foot orthosis on gait versus a standard ankle-foot orthosis. Method: A multicentre randomized study was conducted in seven rehabilitation centres. Hemiplegic patients were recruited after unilateral stroke lasting less than six months. Exclusion criteria were: impossibility to stand for 10 seconds; ankle passive dorsiflexion <5 degrees with knee flexed to 90 degrees; triceps spasticity ≥3/4 on the Ashworth modified scale; diseases that might impair active participation in the study. Thirteen patients were randomized to the Chignon group and 15 to the control group. Included patients were given a standard ankle-foot orthosis or Chignon ankle-foot orthosis. The Chignon ankle-foot orthosis is an articulated double-stopped custom-made orthosis with elements to assist dorsiflexion and plantar flexion. Gait speed improvement (ten-metre test), kinematic assessment, and functional scales were assessed. Results: Gain ratio of walking speed with the orthosis increased significantly more in the Chignon group than in the control group at day 0 (27.2  ±  36% versus −0.8  ±  17%; P = 0.006), day 30 (39.9  ±  19% versus 7.5  ±  17%; P = 0.0004) and day 90 (44.6  ±  27% versus 17.1  ±  0.3%; P = 0.04). There was also a significant improvement in kinematic parameters and spasticity in the Chignon group. Conclusion: Early compensation of distal motor deficiency by the Chignon ankle-foot orthosis improves the immediate gait of hemiplegics more than the standard ankle-foot orthosis and seems to modify motor recovery processes in the legs after stroke.
Measurement of the effects of the exhaust gas recirculation delay on the nitrogen oxide emissions within a turbocharged passenger car diesel engine
Authors: Peckham M S , Campbell B W , Finch A 
Published: July 2011

Fast-response nitrogen oxide (NO x) and carbon dioxide (CO2) analysers have been used to study the effects of exhaust gas recirculation (EGR) delay within a modern diesel passenger car. These analysers have response times of the order of a few milliseconds, allowing the CO2 analyser to be used to study the effects of the EGR transit delay during engine transients and the effect of sudden EGR valve actuation during a drive cycle. The effect of the EGR system delays on the NO x emissions was measured with the fast-response NO x analyser. The results indicate that the EGR delay contributes to the sharp short-duration spikes of NO x. Tests have also been carried out to identify the transient cylinder-to-cylinder EGR distribution by comparing the CO2 concentrations in the inlet ports, again using the fast-response CO2 analyser. The results of these tests show a variation between the CO2 concentrations in the intake ports, suggesting a poor EGR distribution under certain conditions. Measurements have been recorded of the EGR in the intake port runner of just one of the engine’s cylinders and have been compared with the exhaust port NO x emissions. This provided some data on a cycle-by-cycle basis including the number of engine cycles required for the burned gas to complete the EGR circuit.
Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, alemtuzumab, and rituximab for high-risk chronic lymphocytic leukemia
Authors: Parikh Sameer A. , Keating Michael J. , O'Brien Susan , Wang Xuemei , Ferrajoli Alessandra , Faderl Stefan , Burger Jan , Koller Charles , Estrov Zeev , Badoux Xavier , Lerner Susan , Wierda William G. 
Published: July 2011

Abstract
Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) is associated with superior overall survival (OS) for patients with chronic lymphocytic leukemia (CLL). Alemtuzumab (A) was added to FCR (CFAR) in a phase 2 trial for high-risk untreated patients < 70 years with serum β-2 microglobulin (β2M) ≥ 4 mg/L. Sixty patients were enrolled; median age was 59 years (range, 42-69); 75% were male; median β2M was 5.1 mg/L (range, 4-11.6); and 51% were Rai III-IV. Complete remission (CR) was achieved in 70%, partial remission (PR) in 18%, nodular PR in 3%, for an overall response of 92%. Of 14 patients with 17p deletion, CR was achieved by 8 (57%). Of 57 BM samples evaluated by 3-color flow cytometry at the end of treatment, 41 (72%) were negative for residual disease. Grade 3-4 neutropenia and thrombocytopenia occurred with 33% and 13% courses, respectively. The median progression-free survival was 38 months and median OS was not reached. In conclusion, CFAR is an active frontline regimen for high-risk CLL. Response rates and survival are comparable with historic high-risk FCR-treated patients. CFAR may be a useful frontline regimen to achieve CR in patients with 17p deletion before allogeneic stem cell transplantation.
TRPC1 transcript variants, inefficient nonsense-mediated decay and low up-frameshift-1 in vascular smooth muscle cells
Authors: Dedman Alexandra M , Majeed Yasser , Tumova Sarka , Zeng Fanning , Kumar Bhaskar , Munsch Christopher , Bateson Alan N , Wittmann Jürgen , Jäck Hans-Martin , Porter Karen E , Beech David J 
Published: July 2011

Abstract

Background
Transient Receptor Potential Canonical 1 (TRPC1) is a widely-expressed mammalian cationic channel with functional effects that include stimulation of cardiovascular remodelling. The initial aim of this study was to investigate variation in TRPC1-encoding gene transcripts.

Results
Extensive TRPC1 transcript alternative splicing was observed, with exons 2, 3 and 5-9 frequently omitted, leading to variants containing premature termination codons. Consistent with the predicted sensitivity of such variants to nonsense-mediated decay (NMD) the variants were increased by cycloheximide. However it was notable that control of the variants by NMD was prominent in human embryonic kidney 293 cells but not human vascular smooth muscle cells. The cellular difference was attributed in part to a critical protein in NMD, up-frameshift-1 (UPF1), which was found to have low abundance in the vascular cells. Rescue of UPF1 by expression of exogenous UPF1 was found to suppress vascular smooth muscle cell proliferation.

Conclusions
The data suggest: (i) extensive NMD-sensitive transcripts of TRPC1; (ii) inefficient clearance of aberrant transcripts and enhanced proliferation of vascular smooth muscle cells in part because of low UPF1 expression.
Respiratory health effects and exposure to superabsorbent polymer and paper dust - an epidemiological study
Authors: Holm Mathias , Dahlman-Höglund Anna , Torén Kjell 
Published: July 2011

Abstract

Background
The primary aim of the present study was to investigate if exposure to dust from absorbent hygiene products containing superabsorbent polymer is related to symptoms from the airways and from the eyes. The secondary aim was to estimate the current exposure to superabsorbent polymer among production and maintenance workers in a plant producing hygiene products.

Methods
The cohort comprised 1043 workers of whom 689 were exposed to super absorbent polymer and 804 were exposed to paper dust (overlapping groups). There was 186 workers not exposed to either superabsorbent polymer or to paper dust They were investigated with a comprehensive questionnaire about exposure, asthma, rhinitis and symptoms from eyes and airways. The results were analyzed with logistic regression models adjusting for sex, age, atopy and smoking habits. An aerosol sampler equipped with a polytetrafluoroethylene filter with 1 μm pore size was used for personal samplings in order to measure inhalable dust and superabsorbent polymer.

Results
The prevalence of nasal crusts (OR 1.4, 95% CI 1.01-2.0) and nose-bleeding (OR 1.7, 95% CI 1.2-2.4) was increased among the paper dust exposed workers (adjusted for superabsorbent polymer exposure). There were no significant effects associated with exposure to superabsorbent polymer (adjusted for paper dust exposure). The average exposure to inhalable levels of total dust (paper dust) varied between 0.40 and 1.37 mg/m3. For superabsorbent polymer dust the average exposure varied between 0.02 and 0.81 mg/m3.

Conclusions
In conclusion, our study shows that workers manufacturing diapers in the hygiene industry have an increased prevalence of symptoms from the nose, especially nose-bleeding. There was no relation between exposure to superabsorbent polymer and symptoms from eyes, nose or respiratory tract, but exposure to paper dust was associated with nose-bleeding and nasal crusts. This group of workers had also a considerable exposure to superabsorbent polymer dust.
Simultaneous fabrication of line defects-embedded periodic lattice by topographically assisted holographic lithography
Authors: Choi Byung-Yeon , Pak Yusin , Kim Ki Seok , Lee Kwang-Ho , Jung Gun-Young 
Published: July 2011

Abstract
We have demonstrated simultaneous fabrication of designed defects within a periodic structure. For rapid fabrication of periodic structures incorporating nanoscale line-defects at large area, topographically assisted holographic lithography (TAHL) technique, combining the strength of hologram lithography and phase-shift interference, was proposed. Hot-embossing method generated the photoresist patterns with vertical side walls which enabled phase-shift mask effect at the edge of patterns. Embossing temperature and relief height were crucial parameters for the successful TAHL process. Periodic holes with a diameter of 600 nm at a 1 μm-pitch incorporating 250 nm wide line-defects were obtained simultaneously.
Intense ultraviolet emission from needle-like WO3 nanostructures synthesized by noncatalytic thermal evaporation
Authors: Park Sunghoon , Kim Hyunsu , Jin Changhyun , Lee Chongmu 
Published: July 2011

AbstractPhotoluminescence measurements showed that needle-like tungsten oxide nanostructures synthesized at 590°C to 750°C by the thermal evaporation of WO3 nanopowders without the use of a catalyst had an intense near-ultraviolet (NUV) emission band that was different from that of the tungsten oxide nanostructures obtained in other temperature ranges. The intense NUV emission might be due to the localized states associated with oxygen vacancies and surface states.
Genome-wide mapping of imprinted differentially methylated regions by DNA methylation profiling of human placentas from triploidies
Authors: Yuen Ryan KC , Jiang Ruby , Peñaherrera Maria S , McFadden Deborah E , Robinson Wendy P 
Published: July 2011

Abstract

Background
Genomic imprinting is an important epigenetic process involved in regulating placental and foetal growth. Imprinted genes are typically associated with differentially methylated regions (DMRs) whereby one of the two alleles is DNA methylated depending on the parent of origin. Identifying imprinted DMRs in humans is complicated by species- and tissue-specific differences in imprinting status and the presence of multiple regulatory regions associated with a particular gene, only some of which may be imprinted. In this study, we have taken advantage of the unbalanced parental genomic constitutions in triploidies to further characterize human DMRs associated with known imprinted genes and identify novel imprinted DMRs.

Results
By comparing the promoter methylation status of over 14,000 genes in human placentas from ten diandries (extra paternal haploid set) and ten digynies (extra maternal haploid set) and using 6 complete hydatidiform moles (paternal origin) and ten chromosomally normal placentas for comparison, we identified 62 genes with apparently imprinted DMRs (false discovery rate <0.1%). Of these 62 genes, 11 have been reported previously as DMRs that act as imprinting control regions, and the observed parental methylation patterns were concordant with those previously reported. We demonstrated that novel imprinted genes, such as FAM50B, as well as novel imprinted DMRs associated with known imprinted genes (for example, CDKN1C and RASGRF1) can be identified by using this approach. Furthermore, we have demonstrated how comparison of DNA methylation for known imprinted genes (for example, GNAS and CDKN1C) between placentas of different gestations and other somatic tissues (brain, kidney, muscle and blood) provides a detailed analysis of specific CpG sites associated with tissue-specific imprinting and gestational age-specific methylation.

Conclusions
DNA methylation profiling of triploidies in different tissues and developmental ages can be a powerful and effective way to map and characterize imprinted regions in the genome.
Role of TLR signaling inFrancisella tularensis-LPS-induced, antibody-mediated protection againstFrancisella tularensischallenge
Authors: Cole Leah E , Mann Barbara J , Shirey Kari Ann , Richard Katharina , Yang Yang , Gearhart Patricia J , Chesko Kirsty L , Viscardi Rose M , Vogel Stefanie N 
Published: July 2011

ABSTRACTImmunization with Ft-LPS provokes an antigen-specific, B-1a cell-derived antibody response that protects WT mice against an otherwise lethal challenge with Ft LVS. However, this same regimen offers limited protection to TLR2−/− mice, despite production of WT levels of anti-Ft-LPS antibodies. As Ft-LPS exhibits no TLR2 agonist activity, and macrophage-induced cytokine production in response to Ft LVS is overwhelmingly TLR2-dependent, we hypothesized that treatment of TLR2−/− mice with an alternative, MyD88-dependent TLR agonist would compensate for reduced recognition of Ft LVS in TLR2−/− mice and thereby, restore Ft-LPS-mediated protection. Administration of the nontoxic TLR4 agonist, synthetic Escherichia coli MPL, at the time of Ft-LPS immunization or Ft LVS challenge, fully protected TLR2−/− mice, whereas treatment of WT or TLR2−/− mice with MPL alone conferred partial protection. The TLR5 agonist, flagellin, also synergized with Ft-LPS to protect TLR2−/− mice from lethal Ft LVS challenge. In contrast to Ft LVS, Ft-LPS pretreatment failed to protect mice against i.n. challenge with Ft Schu S4, whereas MPL, administered in the absence or presence of Ft-LPS, conferred significant, albeit partial, protection. MPL treatment of macrophages increased the uptake of Ft LVS and decreased intracellular bacterial survival while shifting the macrophage-differentiation phenotype from “alternatively activated” to “classically activated”. Collectively, our data suggest that optimal, Ft-LPS-mediated protection against Ft LVS infection requires two discrete events, i.e., production of Ft-LPS-specific antibody, as well as TLR-mediated macrophage activation, to fully control Francisella infection.