bluuebunny/crossref_metadata_2025_split huggingface dataset:
The selective poly(ADP-ribose) polymerase-1(2) inhibitor, CEP-8983, increases the sensitivity of chemoresistant tumor cells to temozolomide and irinotecan but does not potentiate myelotoxicity
Authors: Miknyoczki Sheila , Chang Hong , Grobelny Jennifer , Pritchard Sonya , Worrell Candace , McGann Natalie , Ator Mark , Husten Jean , Deibold James , Hudkins Robert , Zulli Allison , Parchment Ralph , Ruggeri Bruce 
Published: August 2007

Abstract
The effect of the potent and selective poly(ADP-ribose) (PAR) polymerase-1 [and PAR polymerase-2] inhibitor CEP-8983 on the ability to sensitize chemoresistant glioblastoma (RG2), rhabdomyosarcoma (RH18), neuroblastoma (NB1691), and colon carcinoma (HT29) tumor cells to temozolomide- and camptothecin-induced cytotoxicity, DNA damage, and G2-M arrest and on the potentiation of chemotherapy-induced myelotoxicity was evaluated using in vitro assays. In addition, the effect of the prodrug CEP-9722 in combination with temozolomide and/or irinotecan on PAR accumulation and tumor growth was also determined using glioblastoma and/or colon carcinoma xenografts relative to chemotherapy alone. CEP-8983 sensitized carcinoma cells to the growth-inhibitory effects of temozolomide and/or SN38 increased the fraction of and/or lengthened duration of time tumor cells accumulated in chemotherapy-induced G2-M arrest and sensitized tumor cells to chemotherapy-induced DNA damage and apoptosis. A granulocyte-macrophage colony-forming unit colony formation assay showed that coincubation of CEP-8983 with temozolomide or topotecan did not potentiate chemotherapy-associated myelotoxicity. CEP-9722 (136 mg/kg) administered with temozolomide (68 mg/kg for 5 days) or irinotecan (10 mg/kg for 5 days) inhibited significantly the growth of RG2 tumors (60%) or HT29 tumors (80%) compared with temozolomide or irinotecan monotherapy, respectively. In addition, CEP-9722 showed “stand alone” antitumor efficacy in these preclinical xenografts. In vivo biochemical efficacy studies showed that CEP-9722 attenuated PAR accumulation in glioma xenografts in a dose- and time-related manner. These data indicate that CEP-8983 and its prodrug are effective chemosensitizing agents when administered in combination with select chemotherapeutic agents against chemoresistant tumors. [Mol Cancer Ther 2007;6(8):2290–302]
Development of a fluorescence-based assay to screen antiviral drugs against Kaposi's sarcoma–associated herpesvirus
Authors: Nun Tamara K. , Kroll David J. , Oberlies Nicholas H. , Soejarto Djaja D. , Case Ryan J. , Piskaut Pius , Matainaho Teatulohi , Hilscher Chelsey , Wang Ling , Dittmer Dirk P. , Gao Shou-Jian , Damania Blossom 
Published: August 2007

Abstract
Tumors associated with Kaposi's sarcoma–associated herpesvirus infection include Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Virtually all of the tumor cells in these cancers are latently infected and dependent on the virus for survival. Latent viral proteins maintain the viral genome and are required for tumorigenesis. Current prevention and treatment strategies are limited because they fail to specifically target the latent form of the virus, which can persist for the lifetime of the host. Thus, targeting latent viral proteins may prove to be an important therapeutic modality for existing tumors as well as in tumor prevention by reducing latent virus load. Here, we describe a novel fluorescence-based screening assay to monitor the maintenance of the Kaposi's sarcoma–associated herpesvirus genome in B lymphocyte cell lines and to identify compounds that induce its loss, resulting in tumor cell death. [Mol Cancer Ther 2007;6(8):2360–70]
Targeting the AKT protein kinase for cancer chemoprevention
Authors: Crowell James A. , Steele Vernon E. , Fay Judith R. 
Published: August 2007

Abstract
The AKT protein kinase transduces signals from growth factors and oncogenes to downstream targets that control crucial elements in tumor development. The AKT pathway is one of the most frequently hyperactivated signaling pathways in human cancers. Available data are reviewed herein to support targeting the AKT kinase for cancer prevention. This review will present data to show that AKT is up-regulated in preneoplastic lesions across a broad range of target tissues, briefly describe drug development efforts in this area, and present evidence that down-regulation of AKT signaling may be a viable strategy to prevent cancer. [Mol Cancer Ther 2007;6(8):2139–48]
A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells
Authors: van der Luit Arnold H. , Vink Stefan R. , Klarenbeek Jeffrey B. , Perrissoud Daniel , Solary Eric , Verheij Marcel , van Blitterswijk Wim J. 
Published: August 2007

Abstract
Single-chain alkylphospholipids, unlike conventional chemotherapeutic drugs, act on cell membranes to induce apoptosis in tumor cells. We tested four different alkylphospholipids, i.e., edelfosine, perifosine, erucylphosphocholine, and compound D-21805, as inducers of apoptosis in the mouse lymphoma cell line S49. We compared their mechanism of cellular entry and their potency to induce apoptosis through inhibition of de novo biosynthesis of phosphatidylcholine at the endoplasmic reticulum. Alkylphospholipid potency closely correlated with the degree of phosphatidylcholine synthesis inhibition in the order edelfosine &gt; D-21805 &gt; erucylphosphocholine &gt; perifosine. In all cases, exogenous lysophosphatidylcholine, an alternative source for cellular phosphatidylcholine production, could partly rescue cells from alkylphospholipid-induced apoptosis, suggesting that phosphatidylcholine biosynthesis is a direct target for apoptosis induction. Cellular uptake of each alkylphospholipid was dependent on lipid rafts because pretreatment of cells with the raft-disrupting agents, methyl-β-cyclodextrin, filipin, or bacterial sphingomyelinase, reduced alkylphospholipid uptake and/or apoptosis induction and alleviated the inhibition of phosphatidylcholine synthesis. Uptake of all alkylphospholipids was inhibited by small interfering RNA (siRNA)–mediated blockage of sphingomyelin synthase (SMS1), which was previously shown to block raft-dependent endocytosis. Similar to edelfosine, perifosine accumulated in (isolated) lipid rafts independent on raft sphingomyelin content per se. However, perifosine was more susceptible than edelfosine to back-extraction by fatty acid-free serum albumin, suggesting a more peripheral location in the cell due to less effective internalization. Overall, our results suggest that lipid rafts are critical membrane portals for cellular entry of alkylphospholipids depending on SMS1 activity and, therefore, are potential targets for alkylphospholipid anticancer therapy. [Mol Cancer Ther 2007;6(8):2337–45]
Very stable 188Re-S4 chelates for labelling biomolecules
Authors: Jentsche C. , Bergmann R. , Pietzsch H.-J. , Wunderlich G. , Kotzerke J. , Steinbach J. , Seifert S. 
Published: August 2007

SummaryAim: The preparation and stability of a new 188Re-S4-complex [S4 = (1-aza-18-crown-6)(O)C-C(SH)-C(SH)- C(O)NH-(CH2)3-NH-(CH2)3-NHC(O)-C(SH)-C(SH)- C(O)(1-aza-18-crown-6] was studied at therapeutic relevant radioactive concentrations. The results were compared with 188Re-MAG3 (MAG3: mercaptoacetyltriglycine) and 188Re-DMSA preparations (DMSA: dimercaptosuccinic acid) performed with the same highly concentrated [188Re]perrhenate solution (12-15 GBq/ml). Methods: The 188Re complexes were prepared by direct reduction of perrhenate (188Re-S4-complex) as well as via the 188Re- EDTA precursor complex (188Re-MAG3, 188Re-DMSA). The preparations were stabilised with 15 mg of ascorbic acid and analysed after 1, 2, and 24 hours by TLC and HPLC. Additionally, in vitro and in vivo stability studies were performed with the purified complexes. Results: After stabilisation with 15 mg of ascorbic acid, all of the complexes were nearly stable under nitrogen for hours, and only 2–8 % of perrhenate was observed after 24 h. In contrast, only the 188Re-S4 complex was completely stable in vitro and in all investigated in vivo samples after separation of ligand excess and reducing agent by HPLC. Conclusion: The bridging amine group or free carboxylic groups of the S4-ligand framework make available reactive positions for coupling biomolecules to the chelate. Thus it appears that the new 188Re-S4 complexes offer the possibility of stable and high specific activity labelling of biomolecules for therapeutic application.
Procedure guidelines for radioiodine therapy of differentiated thyroid cancer (version 3)
Authors: Dressler J. , Eschner W. , Grünwald F. , Lassmann M. , Leisner B. , Luster M. , Moser E. , Reiners Chr. , Schicha H. , Schober O. , Dietlein M. 
Published: August 2007

SummaryThe procedure guideline for radioiodine therapy (RIT) of differentiated thyroid cancer (version 3) is the counterpart to the procedure guideline for 131I whole-body scintigraphy (version 3) and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. Recommendation for ablative 131I therapy is given for all differentiated thyroid carcinoma (DTC) >1 cm. Regarding DTC ≤1 cm 131I ablation may be helpful in an individual constellation. Preparation for 131I ablation requires low iodine diet for two weeks and TSHstimulation by withdrawal of thyroid hormone medication or by use of recombinant human TSH (rhTSH). The advantages of rhTSH (no symptoms of hypothyroidism, lower blood activity) and the advantages of endogenous TSHstimulation (necessary for 131I-therapy in patients with metastases, higher sensitivity of 131I whole-body scan) are discussed. In most centers standard activities are used for 131I ablation. If pretherapeutic dosimetry is planned, the diagnostic administration of 131I should not exceed 1–10 MBq, alternative tracers are 123I or 124I. The recommendations for contraception and family planning are harmonized with the recommendation of ATA and ETA. Regarding the best possible protection of salivary glands the evidence is insufficient to recommend a specific setting. To minimize the risk of dental caries due to xerostomia patients should use preventive strategies for dental hygiene.
The Dynamics of Northern Hemisphere Stratospheric Final Warming Events
Authors: Black Robert X. , McDaniel Brent A. 
Published: August 2007

A lag composite analysis is performed of the zonal-mean structure and dynamics of Northern Hemisphere stratospheric final warming (SFW) events. SFW events are linked to distinct zonal wind deceleration signatures in the stratosphere and troposphere. The period of strongest stratospheric decelerations (SD) is marked by a concomitant reduction in the high-latitude tropospheric westerlies. However, a subsequent period of tropospheric decelerations (TD) occurs while the stratospheric circulation relaxes toward climatological conditions. During SFW onset, a wavenumber-1 disturbance at stratospheric altitudes evolves into a circumpolar anticyclonic circulation anomaly. Transformed Eulerian-mean dynamical diagnoses reveal that the SD period is characterized by an anomalous upward Eliassen–Palm (EP) signature at high latitudes extending from the surface to the middle stratosphere. The associated wave-driving pattern consists of zonal decelerations extending from the upper troposphere to the midstratosphere. Piecewise potential vorticity tendency analyses further indicate that zonal wind decelerations in the lower and middle troposphere result, at least in part, from the direct response to latitudinal redistributions of potential vorticity occurring in the lower stratosphere. The TD period exhibits a distinct dynamical behavior with anomalous downward EP fluxes in the high-latitude stratosphere as the zero zonal wind line descends toward the tropopause. This simultaneously allows the stratospheric polar vortex to radiatively recover while providing anomalous upper-tropospheric zonal decelerations (as tropospheric Rossby wave activity is vertically trapped in the high-latitude troposphere). The tropospheric decelerations that occur during the TD period are regarded as a subsequent indirect consequence of SFW events.
Evaluation of Three-Beam and Four-Beam Profiler Wind Measurement Techniques Using a Five-Beam Wind Profiler and Collocated Meteorological Tower
Authors: Adachi Ahoro , Kobayashi Takahisa , Gage Kenneth S. , Carter David A. , Hartten Leslie M. , Clark Wallace L. , Fukuda Masato 
Published: August 2007

Abstract
In this paper a five-beam wind profiler and a collocated meteorological tower are used to estimate the accuracy of four-beam and three-beam wind profiler techniques in measuring horizontal components of the wind. In the traditional three-beam technique, the horizontal components of wind are derived from two orthogonal oblique beams and the vertical beam. In the less used four-beam method, the horizontal winds are found from the radial velocities measured with two orthogonal sets of opposing coplanar beams. In this paper the observations derived from the two wind profiler techniques are compared with the tower measurements using data averaged over 30 min. Results show that, while the winds measured using both methods are in overall agreement with the tower measurements, some of the horizontal components of the three-beam-derived winds are clearly spurious when compared with the tower-measured winds or the winds derived from the four oblique beams. These outliers are partially responsible for a larger 30-min, three-beam standard deviation of the profiler/tower wind speed differences (2.2 m s−1), as opposed to that from the four-beam method (1.2 m s−1). It was also found that many of these outliers were associated with periods of transition between clear air and rain, suggesting that the three-beam technique is more sensitive to small-scale variability in the vertical Doppler velocity because of its reliance on the point measurement from the vertical beam, while the four-beam method is surprisingly robust. Even after the removal of the rain data, the standard deviation of the wind speed error from the three-beam method (1.5 m s−1) is still much larger than that from the four-beam method. Taken together, these results suggest that the spatial variability of the vertical airflow in nonrainy periods or hydrometeor fall velocities in rainy periods makes the vertical beam velocities significantly less representative over the area across the three beams, and decreases the precision of the three-beam method. It is concluded that profilers utilizing the four-beam wind profiler technique have better reliability than wind profilers that rely on the three-beam wind profiler technique.
Cloud-Resolving Model Simulations over the ARM SGP
Authors: Wu Xiaoqing , Liang Xin-Zhong , Park Sunwook 
Published: August 2007

Abstract
This study aims to combine the cloud-resolving model (CRM) simulations with the Department of Energy’s Atmospheric Radiation Measurement Program (ARM) observations to provide long-term comprehensive and physically consistent data that facilitate quantifying the effects of subgrid cloud–radiation interactions and ultimately to develop physically based parameterization of these interactions in general circulation models. The CRM is applied here to simulate the midlatitude cloud systems observed at the ARM southern Great Plains (SGP) site during the 1997 intensive observation period. As in the Tropical Ocean Global Atmosphere Coupled Ocean–Atmosphere Response Experiment (TOGA COARE), the CRM-simulated ensemble mean quantities such as cloud liquid water, cloud fraction, precipitation, and radiative fluxes are generally in line with the surface measurements, satellite, and radar retrievals. The CRM differences from the ARM estimates, when averaged over the entire period, are less than 5 W m−2 in both longwave and shortwave radiative fluxes at the top of the atmosphere and surface. Because of the different large-scale forcing and surface heat fluxes in ARM and TOGA COARE, the CRM produces different cloud distributions over the midlatitude continent and tropical ocean. However, diagnostic analyses show that the subgrid cloud variability has similar impact on the domain-averaged radiative fluxes and heating rates in ARM as in TOGA COARE.
Conservative Split-Explicit Time Integration Methods for the Compressible Nonhydrostatic Equations
Authors: Klemp J. B. , Skamarock W. C. , Dudhia J. 
Published: August 2007

Abstract
Historically, time-split schemes for numerically integrating the nonhydrostatic compressible equations of motion have not formally conserved mass and other first-order flux quantities. In this paper, split-explicit integration techniques are developed that numerically conserve these properties by integrating prognostic equations for conserved quantities represented in flux form. These procedures are presented for both terrain-following height and hydrostatic pressure (mass) vertical coordinates, two potentially attractive frameworks for which the equation sets and integration techniques differ significantly. For each set of equations, the linear dispersion equation for acoustic/gravity waves is derived and analyzed to determine which terms must be solved in the small (acoustic) time steps and how these terms are represented in the time integration to achieve stability. Efficient techniques for including numerical filters for acoustic and external modes are also presented. Simulations for several idealized test cases in both the height and mass coordinates are presented to demonstrate that these integration techniques appear robust over a wide range of scales, from subcloud to synoptic.
Effects of an intensive rehabilitation programme on patients with Huntington's disease: a pilot study
Authors: Zinzi Paola , Salmaso Dario , De Grandis Rosa , Graziani Graziano , Maceroni Stefano , Bentivoglio Annarita , Zappata Paolo , Frontali Marina , Jacopini Gioia 
Published: August 2007

Objective: To investigate the effects of an intensive, inpatient rehabilitation programme on individuals affected by Huntington's disease. Design: A pilot study. Within-subjects design. Setting: Inpatient rehabilitation home of the Italian welfare system. Subjects: Forty patients, early and middle stage of the disease, were recruited to an intensive, inpatient rehabilitation protocol. Interventions: The treatment programme included respiratory exercises and speech therapy, physical and occupational therapy and cognitive rehabilitation exercises. The programme involved three-week admission periods of intensive treatment that could be repeated three times a year. Main measures: A standard clinical assessment was performed at the beginning of each admission using the Zung Depression Scale, Mini-Mental State Examination (MMSE), Barthel Index, Tinetti Scale and Physical Performance Test (PPT). Tinetti and PPT were also used at the end of each admission to assess the outcomes in terms of motor and functional performance. Results: Each three-week period of treatment resulted in highly significant ( P < 0.001) improvements of motor performance and daily life activities. The average increase was 4.7 for Tinetti and 5.21 for PPT scores. No carry-over effect from one admission to the next was apparent but at the same time, no motor decline was detected over two years, indicating that patients maintained a constant level of functional, cognitive as well as motor performance. Conclusions: Intensive rehabilitation treatments may positively influence the maintenance of functional and motor performance in patients with Huntington's disease.
Selection of reference genes for gene expression studies in pig tissues using SYBR green qPCR
Authors: Nygard Ann-Britt , Jørgensen Claus B , Cirera Susanna , Fredholm Merete 
Published: August 2007

Abstract

Background
Real-time quantitative PCR (qPCR) is a method for rapid and reliable quantification of mRNA transcription. Internal standards such as reference genes are used to normalise mRNA levels between different samples for an exact comparison of mRNA transcription level. Selection of high quality reference genes is of crucial importance for the interpretation of data generated by real-time qPCR.

Results
In this study nine commonly used reference genes were investigated in 17 different pig tissues using real-time qPCR with SYBR green. The genes included beta-actin (ACTB), beta-2-microglobulin (B2M), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), hydroxymethylbilane synthase (HMBS), hypoxanthine phosphoribosyltransferase 1 (HPRT1), ribosomal protein L4 (RPL4), succinate dehydrogenase complex subunit A (SDHA), TATA box binding protein (TPB)and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta polypeptide (YWHAZ). The stability of these reference genes in different pig tissues was investigated using the geNorm application. The range of expression stability in the genes analysed was (from the most stable to the least stable): ACTB/RPL4, TBP, HPRT, HMBS, YWHAZ, SDHA, B2M and GAPDH.

Conclusion
Expression stability varies greatly between genes. ACTB, RPL4, TPB and HPRT1 were found to have the highest stability across tissues. Based on both expression stability and expression level, our data suggest that ACTB and RPL4 are good reference genes for high abundant transcripts while TPB and HPRT1 are good reference genes for low abundant transcripts in expression studies across different pig tissues.
Longitudinal increases in mitochondrial DNA levels in blood cells are associated with survival in critically ill patients
Authors: Côté Hélène CF , Day Andrew G , Heyland Daren K 
Published: August 2007

Abstract
Background
Mitochondrial dysfunction may be causally related to the pathogenesis of organ failure in critically ill patients. Decreased mitochondrial DNA (mtDNA) levels have been associated with mitochondrial dysfunction and were investigated here in relation to short-term (31-day) survival.

Methods
This was a prospective longitudinal cohort study of 28 mechanically ventilated critically ill adults admitted to a single center tertiary care intensive care unit (ICU) with hypotension secondary to cardiogenic (N = 13), septic (N = 14) or hypovolemic (N = 1) disease processes. Clinical data and blood were collected at baseline and patients were followed until they expired or left the ICU. Blood was collected every Monday, Wednesday and Friday, and the buffycoat relative mtDNA/nuclear DNA (nDNA) ratio was determined. An archived pool of healthy controls was also studied.

Results
At baseline, the patients' mtDNA/nDNA ratio was 30% lower than a pool of 24 healthy controls (0.76 versus 1.09) and was not different between short-term survivors and non-survivors (0.74 ± 0.05 (N = 16) versus 0.79 ± 0.06 (N = 12), p = 0.49). By day 4, the percent mtDNA/nDNA change from baseline in survivors was significantly different from that in non-survivors (+29.5% versus -5.7%, p = 0.03). It also tended to be higher in survivors at last measurement (+38.4% versus +7.1%, p = 0.06). There was a weak correlation between within patient mtDNA/nDNA and platelet count (r = 0.20, p = 0.03) but not with Sequential Organ Failure Assessment (SOFA) scores (r = 0.12, p = 0.23). The mtDNA associations remained after adjustment for platelet.

Conclusion
Blood mtDNA levels appeared initially low, increased over time in patients who ultimately survived, and remained low in those who did not. This is consistent with mitochondrial recovery being associated with survival and warrants further investigation as a marker of mitochondrial alterations and outcome in critical illness.