bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation and evaluation of Cremophor-free paclitaxel solid dispersion by a supercritical antisolvent process
Authors: Park Jae-Hyun , Yan Yi-Dong , Chi Sang-Cheol , Hwang Doo Hyung , Shanmugam Srinivasan , Lyoo Won Seok , Woo Jong Soo , Yong Chul Soon , Choi Han-Gon 
Published: March 2011

Abstract

Objectives
To avoid the major adverse effects induced by Cremophor EL formulated in the commercial paclitaxel products of Taxol.

Methods
An injectable paclitaxel solid dispersion free of Cremophor was prepared by a supercritical antisolvent process and then was fully characterized and investigated with regard to its short-term and long-term stability. Pharmacokinetics in rats was also evaluated compared with the commercial product.

Key findings
The solid dispersion system at a 1/20/40 weight ratio of paclitaxel/HP-β-CD/HCO-40 had a paclitaxel solubility of about 10 mg/ml, an almost 10 000-fold increase over its aqueous solubility. This system was physically stable for at least six months or four weeks in accelerated conditions (40 ± 2°C; RH: 75 ± 5%) and stress conditions (60°C), respectively. The precipitation time of paclitaxel solid dispersion in 0.9% sodium chloride injection at a concentration of 1000 µg/ml was above 70 h at room temperature. Intravenous administration of paclitaxel solid dispersion at a dose of 6 mg/kg revealed no significant differences when compared with the commercial product. However, our results obtained at a dose of 12 mg/kg showed a striking non-linear increase in the plasma Cmax and AUCall with increased dose. In addition, the concentrations of paclitaxel in various organs in the solid dispersion group were found to be higher than those of Taxol at 6 mg/kg, and the paclitaxel levels in these organs increased proportionately with increasing dose.

Conclusions
Nano-scale paclitaxel solid dispersion without Cremophor EL provided advantageous results over Taxol with respect to the physicochemical properties, safety, clinic convenience and pharmacokinetic behaviour in rats.
The Polyomavirus BK Large T-Antigen-Derived Peptide Elicits an HLA-DR Promiscuous and Polyfunctional CD4+T-Cell Response
Authors: Ramaswami Bala , Popescu Iulia , Macedo Camila , Luo Chunqing , Shapiro Ron , Metes Diana , Chalasani Geetha , Randhawa Parmjeet S. 
Published: March 2011

ABSTRACTBK virus (BKV) nephropathy and hemorrhagic cystitis are increasingly recognized causes of disease in renal and hematopoietic stem cell transplant recipients, respectively. Functional characterization of the immune response to BKV is important for clinical diagnosis, prognosis, and vaccine design. A peptide mix (PepMix) and overlapping (OPP) or random (RPP) peptide pools derived from BKV large T antigen (LTA) were used to restimulate 14-day-expanded peripheral blood mononuclear cells (PBMC) from 27 healthy control subjects in gamma interferon (IFN-γ)-specific enzyme-linked immunospot (ELISPOT) assays. A T-cell response to LTA PepMix was detected in 15/27 subjects. A response was frequently observed with peptides derived from the helicase domain (9/15 subjects), while the DNA binding and host range domains were immunologically inert (0/15 subjects). For all nine subjects who responded to LTA peptide pools, the immune response could be explained largely by a 15-mer peptide designated P313. P313-specific CD4+T-cell clones demonstrated (i) stringent LTA peptide specificity; (ii) promiscuous recognition in the context of HLA-DR alleles; (iii) cross recognition of homologous peptides from the polyomavirus simian virus 40 (SV40); (iv) an effector memory phenotype, CD107a expression, and intracellular production of IFN-γ and tumor necrosis factor alpha (TNF-α); (v) cytotoxic activity in a chromium release assay; and (vi) the ability to directly present cognate antigen to autologous T cells. In conclusion, T-cell-mediated immunity to BKV in healthy subjects is associated with a polyfunctional population of CD4+T cells with dual T-helper and T-cytotoxic properties. HLA class II promiscuity in antigen presentation makes the targeted LTA peptide sequence a suitable candidate for inclusion in immunotherapy protocols.
Microbiological Screening of Irish Patients with Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Reveals Persistence of Candida albicans Strains, Gradual Reduction in Susceptibility to Azoles, and Incidences of Clinical Signs of Oral Candidiasis without Culture Evidence
Authors: McManus Brenda A. , McGovern Eleanor , Moran Gary P. , Healy Claire M. , Nunn June , Fleming Pádraig , Costigan Colm , Sullivan Derek J. , Coleman David C. 
Published: March 2011

ABSTRACT

Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) are prone to chronic mucocutaneous candidiasis, which is often treated with azoles. The purpose of this study was to characterize the oral
Candida
populations from 16 Irish APECED patients, who comprise approximately half the total number identified in Ireland, and to examine the effect of intermittent antifungal therapy on the azole susceptibility patterns of
Candida
isolates. Patients attended between one and four clinical evaluations over a 5-year period, providing oral rinses and/or oral swab samples each time.
Candida
was recovered from 14/16 patients, and
Candida albicans
was the only
Candida
species identified. Interestingly, clinical diagnosis of candidiasis did not correlate with microbiological evidence of
Candida
infection at 7/22 (32%) clinical assessments. Multilocus sequence typing analysis of
C. albicans
isolates recovered from the same patients on separate occasions identified the same sequence type each time. Fluconazole resistance was detected in isolates from one patient, and isolates exhibiting a progressive reduction in itraconazole and/or fluconazole susceptibility were identified in a further 3/16 patients, in each case correlating with the upregulation of
CDR
- and
MDR
-encoded efflux pumps. Mutations were also identified in the
ERG11
and the
TAC1
genes of isolates from these four patients; some of these mutations have previously been associated with azole resistance. The findings suggest that alternative
Candida
treatment options, other than azoles such as chlorhexidine, should be considered in APECED patients and that clinical diagnosis of oral candidiasis should be confirmed by culture prior to the commencement of anti-
Candida
therapy.
Characterization of an F1 Deletion Mutant of Yersinia pestis CO92, Pathogenic Role of F1 Antigen in Bubonic and Pneumonic Plague, and Evaluation of Sensitivity and Specificity of F1 Antigen Capture-Based Dipsticks
Authors: Sha Jian , Endsley Janice J. , Kirtley Michelle L. , Foltz Sheri M. , Huante Matthew B. , Erova Tatiana E. , Kozlova Elena V. , Popov Vsevolod L. , Yeager Linsey A. , Zudina Irina V. , Motin Vladimir L. , Peterson Johnny W. , DeBord Kristin L. , Chopra Ashok K. 
Published: March 2011

ABSTRACTWe evaluated two commercial F1 antigen capture-based immunochromatographic dipsticks, Yersinia Pestis (F1) Smart II and Plague BioThreat Alert test strips, in detecting plague bacilli by using whole-blood samples from mice experimentally infected withYersinia pestisCO92. To assess the specificities of these dipsticks, an in-frame F1-deficient mutant of CO92 (Δcaf) was generated by homologous recombination and used as a negative control. Based on genetic, antigenic/immunologic, and electron microscopic analyses, the Δcafmutant was devoid of a capsule. The growth rate of the Δcafmutant generally was similar to that of the wild-type (WT) bacterium at both 26 and 37°C, although the mutant's growth dropped slightly during the late phase at 37°C. The Δcafmutant was as virulent as WT CO92 in the pneumonic plague mouse model; however, it was attenuated in developing bubonic plague. Both dipsticks had similar sensitivities, requiring a minimum of 0.5 μg/ml of purified F1 antigen or 1 × 105to 5 × 105CFU/ml of WT CO92 for positive results, while the blood samples were negative for up to 1 × 108CFU/ml of the Δcafmutant. Our studies demonstrated the diagnostic potential of two plague dipsticks in detecting capsular-positive strains ofY. pestisin bubonic and pneumonic plague.
Validation and Diagnostic Application of NS and HA Gene-Specific Real-Time Reverse Transcription-PCR Assays for Detection of 2009 Pandemic Influenza A (H1N1) Viruses in Clinical Specimens
Authors: Rönkkö Esa , Ikonen Niina , Kontio Mia , Haanpää Minna , Kallio-Kokko Hannimari , Mannonen Laura , Lappalainen Maija , Julkunen Ilkka , Ziegler Thedi 
Published: March 2011

ABSTRACT
Real-time reverse transcription-PCR assays specific for the nonstructural (NS) and hemagglutinin (HA) genes of the 2009 pandemic influenza A (H1N1) virus were developed and evaluated with clinical samples from infected patients. The tests are characterized by high sensitivity and specificity and performed well throughout the first year of the 2009 pandemic.
Rapid Deletion-Based Subtyping System for the Manila Family of Mycobacterium tuberculosis
Authors: Frink Stephen , Qian Lishi , Yu Steven , Cruz Laura , Desmond Ed , Douglas James T. 
Published: March 2011

ABSTRACT

The Manila family of
Mycobacterium tuberculosis
is a group of clonal isolates seen throughout the Pacific Basin. Commonly used rapid molecular typing methods often leave large groups of Manila family isolates clustered together. Here we describe a simple deletion-based PCR method that improves the discrimination for Manila family isolates, with or without the use of mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) classification, and that is both rapid and affordable. Twenty-eight Manila family isolates, classified by spoligotyping, were collected from around the Pacific Basin from 1995 to 2003 and were tested for known genomic deletions. Nine of 15 regions of difference tested were identified as potentially discriminatory, with 18 distinct patterns; of these 9, 5 were selected for optimal discrimination using 61 Manila family isolates collected from California in 2009. For this geographically limited sample, the single large cluster was reduced to 14 distinct patterns. When the isolates were tested by spoligotyping and MIRU-VNTR, the addition of deletion analysis increased the number of distinct patterns from 43 to 56. In summary, the two study groups, which together form a single group of 89 isolates by spoligotyping, were segregated into 17 subgroups by our deletion-based subtyping system.
Prenatal Famine and Adult Health
Authors: Lumey L.H. , Stein Aryeh D. , Susser Ezra 
Published: March 2011

We review human studies on the relation between acute exposures to prenatal famine and adult physical and mental health. These studies are observational and include exposures to a famine environment by natural or man-made causes or, more commonly, from the interplay between natural and human factors. These natural experiments provide an opportunity to examine long-term outcomes after famine exposures by comparing exposed and nonexposed individuals. The studies show consistent associations between prenatal famine and adult body size, diabetes, and schizophrenia. For other measures of adult health, findings are less robust. A relation between prenatal famine and some reported epigenetic changes may provide a potential mechanism to explain specific associations. Much progress can be made if current separate studies are further analyzed with comparable definitions of exposures and outcomes and using common analytic strategies.
miR-34a Induces the Downregulation of BothE2F1andB-MybOncogenes in Leukemic Cells
Authors: Zauli Giorgio , Voltan Rebecca , di Iasio Maria Grazia , Bosco Raffaella , Melloni Elisabetta , Sana Maria Elena , Secchiero Paola 
Published: March 2011

AbstractPurpose: To elucidate new molecular mechanisms able to downregulate the mRNA levels of key oncogenes, such as B-Myb and E2F1, in a therapeutic perspective.Experimental Design: B-Myb and E2F1 mRNA levels were evaluated in primary B chronic lymphocytic leukemia (B-CLL, n = 10) and acute myeloid leukemia (AML, n = 5) patient cells, in a variety of p53wild-type and p53mutated/deleted leukemic cell lines, as well as in primary endothelial cells and fibroblasts. Knockdown experiments with siRNA for p53 and E2F1 and overexpression experiments with miR34a were conducted to elucidate the role of these pathways in promoting B-Myb downregulation.Results: In vitro exposure to Nutlin-3, a nongenotoxic activator of p53, variably downregulated the expression of B-Myb in primary leukemic cells and in p53wild-type myeloid (OCI, MOLM) and lymphoblastoid (SKW6.4, EHEB) but not in p53mutated (NB4, BJAB, MAVER) or p53deleted (HL-60) leukemic cell lines. The transcriptional repression of B-Myb was also observed in primary normal endothelial cells and fibroblasts. B-Myb downregulation played a critical role in the cell-cycle block in G1 phase induced by Nutlin-3, as shown by transfection experiments with specific siRNA. Moreover, we have provided experimental evidence suggesting that miR-34a is a central mediator in the repression of B-Myb both directly and through E2F1.Conclusions: Owing to the role of B-Myb and E2F1 transcription factors in controlling cell-cycle progression of leukemic cells, the downregulation of these oncogenes by miR-34a suggests the usefulness of therapeutic approaches aimed to modulate the levels of miR-34a. Clin Cancer Res; 17(9); 2712–24. ©2011 AACR.
Targeting the Hedgehog Pathway in Cancer: Can the Spines Be Smoothened?
Authors: Ailles Laurie , Siu Lillian L. 
Published: March 2011

Abstract
Aberrant Hedgehog (Hh) pathway signaling has been suggested to play a role in the development of multiple solid tumors and hematologic malignancies. GDC-0449 is a novel first-in-human, first-in-class smoothened (SMO) inhibitor, which has completed its phase I evaluation and achieved proof of concept in tumors with Hh pathway mutations. Clin Cancer Res; 17(8); 2071–3. ©2011 AACR.
Chemoprevention of Azoxymethane/Dextran Sodium Sulfate–Induced Mouse Colon Carcinogenesis by Freeze-Dried YamSanyakuand Its Constituent Diosgenin
Authors: Miyoshi Noriyuki , Nagasawa Tomoki , Mabuchi Ryota , Yasui Yumiko , Wakabayashi Keiji , Tanaka Takuji , Ohshima Hiroshi 
Published: March 2011

AbstractThe effects of sanyaku, a traditional Chinese medicine [freeze-dried powder of the yam tuber (Dioscorea)], and its major steroidal saponin constituent, diosgenin, on colon carcinogenesis were investigated. Male ICR mice were subjected to a single intraperitoneal injection of azoxymethane (AOM; 10 mg/kg body weight) followed by administration of 1.5% dextran sodium sulfate (DSS) in drinking water for 7 days to establish carcinogenesis. Commercial diosgenin or sanyaku, which contained diosgenin at 63.8 ± 1.2 mg/kg dry weight, was given in the diet at 20, 100, or 500 mg/kg for 17 weeks. Groups of mice that received diosgenin or sanyaku at all doses yielded significantly less number of colon tumors compared with the AOM/DSS-treated mice. Occurrence of colonic mucosal ulcer and dysplastic crypt induced by AOM/DSS treatment was also significantly decreased by the administration of diosgenin and sanyaku, which was in accordance with the significant reduction of AOM/DSS-mediated increases in expression of inflammatory cytokines such as IL-1β by diosgenin and sanyaku. Furthermore, elevated levels of serum triglyceride in the AOM/DSS-treated mice tended to be reduced in mice given diosgenin and sanyaku. Microarray and real-time reverse transcriptase PCR analyses revealed that diosgenin administration increased 12-fold the expression of lipoprotein lipase, which may contribute to reduced serum triglyceride levels. Other genes altered by diosgenin included those associated with antioxidative stress responses and apoptosis, such as heme oxygenase-1, superoxide dismutase-3, and caspase-6. Our results imply that the Chinese medicine sanyaku and the tubers of various yams containing diosgenin as food could be ingested to prevent colon carcinogenesis in humans. Cancer Prev Res; 4(6); 924–34. ©2011 AACR.
Association of Prostate Cancer Risk Loci with Disease Aggressiveness and Prostate Cancer–Specific Mortality
Authors: Pomerantz Mark M. , Werner Lillian , Xie Wanling , Regan Meredith M. , Lee Gwo-Shu Mary , Sun Tong , Evan Carolyn , Petrozziello Gillian , Nakabayashi Mari , Oh William K. , Kantoff Philip W. , Freedman Matthew L. 
Published: March 2011

Abstract
Genome-wide association studies have detected more than 30 inherited prostate cancer risk variants. While clearly associated with risk, their relationship with clinical outcome, particularly prostate cancer–specific mortality, is less well known. We investigated whether the risk variants are associated with various measures of disease aggressiveness and prostate cancer–specific mortality. In a cohort of 3,945 men of European ancestry with prostate cancer, we genotyped 36 single nucleotide polymorphisms (SNP): 35 known prostate cancer risk variants and one SNP (rs4054823) that was recently reported to be associated with prostate cancer aggressiveness. The majority of subjects had a diagnosis of prostate cancer between 1995 and 2004, and the cohort included a total of 580 prostate cancer–specific deaths. We evaluated associations between the 36 polymorphisms and prostate cancer survival, as well as other clinical parameters including age at diagnosis, prostate-specific antigen (PSA) at diagnosis, and Gleason score. Two SNPs, rs2735839 at chromosome 19q13 and rs7679673 at 4q24, were associated with prostate cancer–specific survival (P = 7 × 10−4 and 0.014, respectively). A total of 12 SNPs were associated with other variables (P &lt; 0.05): age at diagnosis, PSA at diagnosis, Gleason score, and/or disease aggressiveness based on D'Amico criteria. Genotype status at rs4054823 was not associated with aggressiveness or outcome. Our results identify two common polymorphisms associated with prostate cancer–specific mortality. Cancer Prev Res; 4(5); 719–28. ©2011 AACR.
A Horizontal Wind and Wind Confidence Algorithm for Doppler Wind Profilers
Authors: Goodrich Robert K. , Morse Corrinne S. , Cornman Larry B. , Cohn Stephen A. 
Published: March 2011

Abstract
Boundary layer wind profilers are increasingly being used in applications that require high-quality, rapidly updated winds. An example of this type of application is an airport wind hazard warning system. Wind shear can be a hazard to flight operations and is also associated with the production of turbulence. A method for calculating wind and wind shear using a linear wind field assumption is presented. This method, applied to four- or five-beam profilers, allows for the explicit accounting of the measurable shear terms. An error analysis demonstrates why some shears are more readily estimated than others, and the expected magnitudes of the variance for the wind and wind shear estimates are given. A method for computing a quality control index, or confidence, for the calculated wind is also presented. This confidence calculation is based on an assessment of the validity of the assumptions made in the calculations. Confidence values can be used as a quality control metric for the calculated wind and can also be used in generating a confidence-weighted average wind value from the rapid update values. Results are presented that show that errors in the wind estimates are reduced after removing values with low confidence. The wind and confidence methods are implemented in the NCAR Wind and Confidence Algorithm (NWCA), and have been used with the NCAR Improved Moments Algorithm (NIMA) method for calculating moments and associated moment confidence from Doppler spectra. However, NWCA may be used with any moment algorithm that also computes a first moment confidence. For example, a very simple confidence algorithm can be defined in terms of the signal-to-noise ratio.
Exploring the Land–Ocean Contrast in Convective Vigor Using Islands
Authors: Robinson F. J. , Sherwood S. C. , Gerstle D. , Liu C. , Kirshbaum D. J. 
Published: March 2011

AbstractMoist convection is well known to be generally more intense over continental than maritime regions, with larger updraft velocities, graupel, and lightning production. This study explores the transition from maritime to continental convection by comparing the trends in Tropical Rainfall Measuring Mission (TRMM) radar and microwave (37 and 85 GHz) observations over islands of increasing size to those simulated by a cloud-resolving model. The observed storms were essentially maritime over islands of &lt;100 km2 and continental over islands &gt;10 000 km2, with a gradual transition in between.Equivalent radar and microwave quantities were simulated from cloud-resolving runs of the Weather Research and Forecasting model via offline radiation codes. The model configuration was idealized, with islands represented by regions of uniform surface heat flux without orography, using a range of initial sounding conditions without strong horizontal winds or aerosols. Simulated storm strength varied with initial sounding, as expected, but also increased sharply with island size in a manner similar to observations. Stronger simulated storms were associated with higher concentrations of large hydrometeors. Although biases varied with different ice microphysical schemes, the trend was similar for all three schemes tested and was also seen in 2D and 3D model configurations. The successful reproduction of the trend with such idealized forcing supports previous suggestions that mesoscale variation in surface heating—rather than any difference in humidity, aerosol, or other aspects of the atmospheric state—is the main reason that convection is more intense over continents and large islands than over oceans.Some dynamical storm aspects, notably the peak rainfall and minimum surface pressure low, were more sensitive to surface forcing than to the atmospheric sounding or ice scheme. Large hydrometeor concentrations and simulated microwave and radar signatures, however, were at least as sensitive to initial humidity levels as to surface forcing and were more sensitive to the ice scheme.Issues with running the TRMM simulator on 2D simulations are discussed, but they appear to be less serious than sensitivities to model microphysics, which were similar in 2D and 3D. This supports the further use of 2D simulations to economically explore modeling uncertainties.
Radar Anomalous Propagation Associated with Foehn Winds Induced by Typhoon Krosa (2007)
Authors: Chang Pao-Liang , Lin Pin-Fang 
Published: March 2011

AbstractIn this study, unusual radar anomalous propagation (AP) phenomena associated with foehn winds induced by Typhoon Krosa (2007) were documented by using observations from radar, surface stations, and soundings. The AP echoes embedded within rainband areas and exhibited inward motions toward the radar site within 2–3 h prior to the occurrences of foehn winds at the radar site, which would interfere with the interpretation of radar data and associated downstream applications. As Typhoon Krosa appeared in the vicinity of the northeastern coast of Taiwan, foehn winds with significant subsidence warming and drying generated by downslope winds were observed in southeastern Taiwan. The foehn winds continuously moved northward within confined areas from the southeastern to eastern–central parts of Taiwan. Before the foehn winds penetrated to the surface, the subsidence warming introduced a temperature inversion layer above the surface and caused the ducting of radar beams. Analyses of refractive index and ray tracing suggested that the occurrence and evolution of the AP echoes during Typhoon Krosa were closely related to the varying inversion heights induced by downslope winds.