bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ovarian Adenocarcinomas in the Laying Hen and Women Share Similar Alterations in p53, ras, and HER-2/neu
Authors: Hakim Amy A. , Barry Catherine P. , Barnes H. John , Anderson Kenneth E. , Petitte James , Whitaker Regina , Lancaster Jonathan M. , Wenham Robert M. , Carver Donna K. , Turbov Jane , Berchuck Andrew , Kopelovich Levy , Rodriguez Gustavo C. 
Published: January 2009

Abstract
We examined alterations in the p53 tumor suppressor gene and the ras and HER-2/neu oncogenes in chicken ovarian cancers to determine if these tumors have genetic alterations similar to those in human ovarian adenocarcinomas. Mutations in the p53 tumor suppressor gene and the H-ras and K-ras oncogenes were assessed by direct sequencing in 172 ovarian cancers obtained from 4-year-old birds enrolled at age 2 in two separate 2-year chemoprevention trials. Birds in trial B had approximately twice as many lifetime ovulations as those in trial A. Immunohistochemical staining for the HER-2/neu oncogene was done on a subset of avian ovarian and oviductal adenocarcinomas. Alterations in p53 were detected in 48% of chicken ovarian cancers. Incidence of p53 alterations varied according to the number of lifetime ovulations, ranging from 14% in trial A to 96% in trial B (P &lt; 0.01). No mutations were seen in H-ras, and only 2 of 172 (1.2%) tumors had K-ras mutations. Significant HER-2/neu staining was noted in 10 of 19 ovarian adenocarcinomas but in only 1 of 17 oviductal adenocarcinomas. Similar to human ovarian cancers, p53 alterations are common in chicken ovarian adenocarcinomas and correlate with the number of lifetime ovulations. Ras mutations are rare, similar to high-grade human ovarian cancers. HER-2/neu overexpression is common and may represent a marker to exclude an oviductal origin in cancers involving both the ovary and oviduct.
The Size Distribution and Mass-Weighted Terminal Velocity of Low-Latitude Tropopause Cirrus Crystal Populations
Authors: Schmitt C. G. , Heymsfield A. J. 
Published: January 2009

Abstract
Ice crystal terminal velocities govern the lifetime of radiatively complex, climatologically important, low-latitude tropopause cirrus clouds. To better understand cloud lifetimes, the terminal velocities of low-latitude tropopause cirrus cloud particles have been estimated using data from aircraft field campaigns. Data used in this study were collected during the Cirrus Regional Study of Tropical Anvils and Cirrus Layers–Florida Area Cirrus Experiment (CRYSTAL-FACE) and the Pre-Aura Validation Experiment (Pre-AVE). Particle properties were measured with the NCAR video ice particle sampler (VIPS) probe, thus providing information about particles in a poorly understood size range. Data used in this study were limited to high-altitude nonconvective thin clouds with temperatures between −56° and −86°C.
Realistic particle terminal velocity estimates require accurate values of particle projected area and mass. Exponential functions were used to predict the dimensional properties of ice particles smaller than 200 microns and were found to predict ice water content measurements well when compared to power-law representations. The shapes of the particle size distributions were found to be monomodal and were well represented by exponential or gamma functions. Incorporating these findings into terminal velocity calculations led to lower values of mass-weighted terminal velocities for particle populations than are currently predicted for low-latitude ice clouds. New parameterizations for individual particle properties as well as particle size distribution properties are presented and compared to commonly used parameterizations. Results from this study are appropriate for use in estimating the properties of low-latitude thin and subvisible cirrus at temperatures lower than −56°C.
Anisotropic Response of Surface Currents to the Wind in a Coastal Region
Authors: Kim Sung Yong , Cornuelle Bruce D. , Terrill Eric J. 
Published: January 2009

AbstractAnalysis of coastal surface currents measured off the coast of San Diego for two years suggests an anisotropic and asymmetric response to the wind, probably as a result of bottom/coastline boundary effects, including pressure gradients. In a linear regression, the statistically estimated anisotropic response explains approximately 20% more surface current variance than an isotropic wind–ocean response model. After steady wind forcing for three days, the isotropic surface current response veers 42° ± 2° to the right of the wind regardless of wind direction, whereas the anisotropic analysis suggests that the upcoast (onshore) wind stress generates surface currents with 10° ± 4° (71° ± 3°) to the right of the wind direction. The anisotropic response thus reflects the dominance of alongshore currents in this coastal region. Both analyses yield wind-driven currents with 3%–5% of the wind speed, as expected. In addition, nonlinear isotropic and anisotropic response functions are considered, and the asymmetric current responses to the wind are examined. These results provide a comprehensive statistical model of the wind-driven currents in the coastal region, which has not been well identified in previous field studies, but is qualitatively consistent with descriptions of the current response in coastal ocean models.
Pacific Hindcast Performance of Three Numerical Wave Models
Authors: Hanson Jeffrey L. , Tracy Barbara A. , Tolman Hendrik L. , Scott R. Douglas 
Published: January 2009

Abstract
Although mean or integral properties of wave spectra are typically used to evaluate numerical wave model performance, one must look into the spectral details to identify sources of model deficiencies. This creates a significant problem, as basin-scale wave models can generate millions of independent spectral values. To facilitate selection of a wave modeling technology for producing a multidecade Pacific hindcast, a new approach was developed to reduce the spectral content contained in detailed wave hindcasts to a convenient set of performance indicators. The method employs efficient image processing tools to extract windsea and swell wave components from monthly series of nondirectional and directional wave spectra. Using buoy observations as ground truth, both temporal correlation (TC) and quantile–quantile (QQ) statistical analyses are used to quantify hindcast skill in reproducing measured wave component height, period, and direction attributes. An integrated performance analysis synthesizes the TC and QQ results into a robust assessment of prediction skill and yields distinctive diagnostics on model inputs and source term behavior. The method is applied to a set of Pacific basin hindcasts computed using the WAM, WAVEWATCH III, and WAVAD numerical wave models. The results provide a unique assessment of model performance and have guided the selection of WAVEWATCH III for use in Pacific hindcast production runs for the U.S. Army Corps of Engineers Wave Information Studies Program.
Biceps Activity during Windmill Softball Pitching
Authors: Rojas Idubijes L. , Provencher Matthew T. , Bhatia Sanjeev , Foucher Kharma C. , Bach Bernard R. , Romeo Anthony A. , Wimmer Markus A. , Verma Nikhil N. 
Published: January 2009

Background Windmill pitching produces high forces and torques at the shoulder and elbow, making the biceps labrum complex susceptible to overuse injury. Little is known about the muscle firing patterns during a windmill pitch. Hypothesis Biceps muscle activity is greater during a windmill pitch than during an overhand throw. Study Design Descriptive laboratory study. Methods Seven female windmill pitchers underwent motion analysis and surface electromyography evaluation of their biceps muscles during windmill and overhand throwing. Marker motion analysis, muscle activity, and ball release were captured simultaneously. Surface electromyography trials were collected and related to the athletes’ phases of pitching and throwing, identified based on predefined softball and baseball pitching mechanics. Results Throws were of similar velocity (24 m/s, 53 mph, P =. 71), but peak biceps brachii muscle activation during the windmill pitch was significantly greater than during the overhand throw when normalized (38% vs 19% manual muscle test, P =. 02). The highest muscle activity occurred at the 9-o'clock phase of the windmill pitch, during which the biceps brachii undergoes eccentric contraction. In the overhand throw, the highest level of biceps activity occurred during arm cocking. Conclusion In female athletes, biceps brachii activity during the windmill pitch is higher than during an overhand throw and is most active during the 9-o'clock and follow-through phases of the pitch. Clinical Relevance Repetitive eccentric biceps contractions may help explain the high incidence of anterior shoulder pain clinically observed in elite windmill pitchers. Injury prevention and treatment mechanisms should focus on the phases with the highest muscle activity.
Three-year follow-up after a two-year comprehensive pulmonary rehabilitation program
Authors: Steinsbekk A , Lomundal BK 
Published: January 2009

The main objective of this study is to investigate the long-term effects, 3 years after the end of a 2-year pulmonary rehabilitation program with three weekly 1-h exercise sessions and 32 h of education in patients with chronic obstructive pulmonary disease. The method consists of open prospective observational study with 30 patients. Outcome measures were quality of life (QoL) (St George’s Respiratory Questionnaire, SGRQ), physical exercise performance (6-min walking test, 6MWT), self-management abilities, lung function, hospitalization, and self-reported exercise. FEV1 at baseline was 40.1% of predicted. The participants had statistical and clinical significant decrease in SGRQ (improved QoL) and increase in 6MWT during the program. They maintained the level of health they achieved during the program in the next 3 years, with a stable SGRQ score (−0.5 points, 95% CI −3.8 to 2.6 P = 1.000) and 6MWT (+10 m 95% CI 28 to −4, P = 0.273). Eighty percent of the participants had exercised at least 30 min three times a week from the end of the program to year 5. In conclusion, the participants had maintained their achieved level of health, improved their lung function slightly, and continued to exercise regularly 3 years after the end of the program.
Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myeloma
Authors: Hose Dirk , Rème Thierry , Meissner Tobias , Moreaux Jérôme , Seckinger Anja , Lewis Joe , Benes Vladimir , Benner Axel , Hundemer Michael , Hielscher Thomas , Shaughnessy John D. , Barlogie Bart , Neben Kai , Krämer Alwin , Hillengass Jens , Bertsch Uta , Jauch Anna , De Vos John , Rossi Jean-François , Möhler Thomas , Blake Jonathon , Zimmermann Jürgen , Klein Bernard , Goldschmidt Hartmut 
Published: January 2009

AbstractGenetic instability and cellular proliferation have been associated with aurora kinase expression in several cancer entities, including multiple myeloma. Therefore, the expression of aurora-A, -B, and -C was determined by Affymetrix DNA microarrays in 784 samples including 2 independent sets of 233 and 345 CD138-purified myeloma cells from previously untreated patients. Chromosomal aberrations were assessed by comprehensive interphase fluorescence in situ hybridization and proliferation of primary myeloma cells by propidium iodine staining. We found aurora-A and -B to be expressed at varying frequencies in primary myeloma cells of different patient cohorts, but aurora-C in testis cell samples only. Myeloma cell samples with detectable versus absent aurora-A expression show a significantly higher proliferation rate, but neither a higher absolute number of chromosomal aberrations (aneuploidy), nor of subclonal aberrations (chromosomal instability). The clinical aurora kinase inhibitor VX680 induced apoptosis in 20 of 20 myeloma cell lines and 5 of 5 primary myeloma cell samples. Presence of aurora-A expression delineates significantly inferior event-free and overall survival in 2 independent cohorts of patients undergoing high-dose chemotherapy, independent from conventional prognostic factors. Using gene expression profiling, aurora kinase inhibitors as a promising therapeutic option in myeloma can be tailoredly given to patients expressing aurora-A, who in turn have an adverse prognosis.
Infection and genotype remodel the entire soybean transcriptome
Authors: Zhou Lecong , Mideros Santiago X , Bao Lei , Hanlon Regina , Arredondo Felipe D , Tripathy Sucheta , Krampis Konstantinos , Jerauld Adam , Evans Clive , St Martin Steven K , Maroof MA Saghai , Hoeschele Ina , Dorrance Anne E , Tyler Brett M 
Published: January 2009

AbstractBackgroundHigh throughput methods, such as high density oligonucleotide microarray measurements of mRNA levels, are popular and critical to genome scale analysis and systems biology. However understanding the results of these analyses and in particular understanding the very wide range of levels of transcriptional changes observed is still a significant challenge. Many researchers still use an arbitrary cut off such as two-fold in order to identify changes that may be biologically significant. We have used a very large-scale microarray experiment involving 72 biological replicates to analyze the response of soybean plants to infection by the pathogenPhytophthora sojaeand to analyze transcriptional modulation as a result of genotypic variation.ResultsWith the unprecedented level of statistical sensitivity provided by the high degree of replication, we show unambiguously that almost the entire plant genome (97 to 99% of all detectable genes) undergoes transcriptional modulation in response to infection and genetic variation. The majority of the transcriptional differences are less than two-fold in magnitude. We show that low amplitude modulation of gene expression (less than two-fold changes) is highly statistically significant and consistent across biological replicates, even for modulations of less than 20%. Our results are consistent through two different normalization methods and two different statistical analysis procedures.ConclusionOur findings demonstrate that the entire plant genome undergoes transcriptional modulation in response to infection and genetic variation. The pervasive low-magnitude remodeling of the transcriptome may be an integral component of physiological adaptation in soybean, and in all eukaryotes.
Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer
Authors: Khaled Hussein M , Bahnassy Abeer A , Raafat Amira A , Zekri Abdel-Rahman N , Madboul Maha S , Mokhtar Nadia M 
Published: January 2009

Abstract

Background
Clinical characterization of bladder carcinomas is still inadequate using the standard clinico-pathological prognostic markers. We assessed the correlation between nm23-H1, Rb, EGFR and p53 in relation to the clinical outcome of patients with muscle invasive bilharzial bladder cancer (MI-BBC).

Methods

nm23-H1, Rb, EGFR and p53 expression was assessed in 59 MI-BBC patients using immunohistochemistry and reverse transcription (RT-PCR) and was correlated to the standard clinico-pathological prognostic factors, patient's outcome and the overall survival (OS) rate.

Results
Overexpression of EGFR and p53 proteins was detected in 66.1% and 35.6%; respectively. Loss of nm23-H1and Rb proteins was detected in 42.4% and 57.6%; respectively. Increased EGFR and loss of nm23-H1 RNA were detected in 61.5% and 36.5%; respectively. There was a statistically significant correlation between p53 and EGFR overexpression (p < 0.0001), nm23 loss (protein and RNA), lymph node status (p < 0.0001); between the incidence of local recurrence and EGFR RNA overexpression (p= 0.003) as well as between the incidence of metastasis and altered Rb expression (p = 0.026), p53 overexpression (p < 0.0001) and mutation (p = 0.04). Advanced disease stage correlated significantly with increased EGFR (protein and RNA) (p = 0.003 & 0.01), reduced nm23-H1 RNA (p = 0.02), altered Rb (p = 0.023), and p53 overexpression (p = 0.004). OS rates correlated significantly, in univariate analysis, with p53 overexpression (p = 0.011), increased EGFR (protein and RNA, p = 0.034&0.031), nm23-H1 RNA loss (p = 0.021) and aberrations of ≥ 2 genes. However, multivariate analysis showed that only high EGFR overexpression, metastatic recurrence, high tumor grade and the combination of ≥ 2 affected markers were independent prognostic factors.

Conclusion

nm23-H1, EGFR and p53 could be used as prognostic biomarkers in MI-BBC patients. In addition to the standard pathological prognostic factors, a combination of these markers (≥ 2) has synergistic effects in stratifying patients into variable risk groups. The higher is the number of altered biomarkers, the higher will be the risk of disease progression and death.
A glycosylated recombinant human granulocyte colony stimulating factor produced in a novel protein production system (AVI-014) in healthy subjects: a first-in human, single dose, controlled study
Authors: Varki Roslyn , Pequignot Ed , Leavitt Mark C , Ferber Andres , Kraft Walter K 
Published: January 2009

Abstract

Background
AVI-014 is an egg white-derived, recombinant, human granulocyte colony-stimulating factor (G-CSF). This healthy volunteer study is the first human investigation of AVI-014.

Methods
24 male and female subjects received a single subcutaneous injection of AVI-014 at 4 or 8 mcg/kg. 16 control subjects received 4 or 8 mcg/kg of filgrastim (Neupogen, Amgen) in a partially blinded, parallel fashion.

Results
The Geometric Mean Ratio (GMR) (90% CI) of 4 mcg/kg AVI-014/filgrastim AUC(0–72 hr) was 1.00 (0.76, 1.31) and Cmax was 0.86 (0.66, 1.13). At the 8 mcg/kg dose, the AUC(0–72) GMR was 0.89 (0.69, 1.14) and Cmax was 0.76 (0.58, 0.98). A priori pharmacokinetic bioequivalence was defined as the 90% CI of the GMR bounded by 0.8–1.25. Both the white blood cell and absolute neutrophil count area under the % increase curve AUC(0–9 days) and Cmax (maximal % increase from baseline)GMR at 4 and 8 mcg/kg fell within the 0.5–2.0 a priori bound set for pharmacodynamic bioequivalence. The CD 34+ % increase curve AUC(0–9 days) and Cmax GMR for both doses was ~1, but 90% confidence intervals were large due to inherent variance, and this measure did not meet pharmacodynamic bioequivalence. AVI-014 demonstrated a side effect profile similar to that of filgrastim.

Conclusion
AVI-014 has safety, pharmacokinetic, and pharmacodynamic properties comparable to filgrastim at an equal dose in healthy volunteers. These findings support further investigation in AVI-014.
Use of folding modulators to improve heterologous protein production in Escherichia coli
Authors: Kolaj Olga , Spada Stefania , Robin Sylvain , Wall J Gerard 
Published: January 2009

AbstractDespite the fundamental importance ofE. coliin the manufacture of a wide range of biotechnological and biomedical products, extensive process and/or target optimisation is routinely required in order to achieve functional yields in excess of low mg/l levels. Molecular chaperones and folding catalysts appear to present a panacea for problems of heterologous protein folding in the organism, due largely to their broad substrate range compared with,e.g., protein-specific mutagenesis approaches. Painstaking investigation of chaperone overproduction has, however, met with mixed – and largely unpredictable – results to date. The past 5 years have nevertheless seen an explosion in interest in exploiting the native folding modulators ofE. coli, and particularly cocktails thereof, driven largely by the availability of plasmid systems that facilitate simultaneous, non-rational screening of multiple chaperones during recombinant protein expression. As interest in usingE. colito produce recombinant membrane proteins and even glycoproteins grows, approaches to reduce aggregation, delay host cell lysis and optimise expression of difficult-to-express recombinant proteins will become even more critical over the coming years. In this review, we critically evaluate the performance of molecular chaperones and folding catalysts native toE. coliin improving functional production of heterologous proteins in the bacterium and we discuss how they might best be exploited to provide increased amounts of correctly-folded, active protein for biochemical and biophysical studies.
Primary hepatic carcinoid tumor: a case report and review of the literature
Authors: Lin Chih-Wen , Lai Chung-Hsu , Hsu Chia-Chang , Hsu Chao-Tien , Hsieh Pei-Min , Hung Kuo-Chen , Chen Yaw-Sen 
Published: January 2009

AbstractBackgroundPrimary hepatic carcinoid tumor (PHCT) is very rare and difficult to diagnose before biopsy or operation. We report a patient with a small PHCT and review cases in the literature.Case presentationA 48-year-old Chinese female with underlying hepatitis B virus (HBV) infection was found to have a low echoic hepatic nodule by abdominal ultrasound. Tumor markers were negative. Dynamic liver computed tomography scans showed enhancement of the nodule in the arterial phase and early washout in the portal phase. Hepatocellular carcinoma (HCC) was considered based on the image findings and underlying HBV infection. However, the tumor biopsy revealed a malignant neoplasm that originating from neuroendocrine cells. Pre-operative and intra-operative investigations for the possible other origin of carcinoid tumor were negative, so PHCT was confirmed.ConclusionA small and asymptomatic PHCT is extremely rare. PHCT should be one of the differential diagnoses in patients with small hepatic tumor, even in regions with high prevalence of HBV infection and HCC. Pre-operative biopsy is necessary to avoid misdiagnosis even when HCC is highly suspected clinically.
The retinoic acid binding protein CRABP2 is increased in murine models of degenerative joint disease
Authors: Welch Ian D , Cowan Matthew F , Beier Frank , Underhill Tully M 
Published: January 2009

Abstract
Introduction
Osteoarthritis (OA) is a debilitating disease with poorly defined aetiology. Multiple signals are involved in directing the formation of cartilage during development and the vitamin A derivatives, the retinoids, figure prominently in embryonic cartilage formation. In the present study, we examined the expression of a retinoid-regulated gene in murine models of OA.

Methods
Mild and moderate forms of an OA-like degenerative disease were created in the mouse stifle joint by meniscotibial transection (MTX) and partial meniscectomy (PMX), respectively. Joint histopathology was scored using an Osteoarthritis Research Society International (OARSI) system and gene expression (Col1a1, Col10a1, Sox9 and Crabp2) in individual joints was determined using TaqMan quantitative PCR on RNA from microdissected articular knee cartilage.

Results
For MTX, there was a significant increase in the joint score at 10 weeks (n = 4, p < 0.001) in comparison to sham surgeries. PMX surgery was slightly more severe and produced significant changes in joint score at six (n = 4, p < 0.01), eight (n = 4, p < 0.001) and 10 (n = 4, p < 0.001) weeks. The expression of Col1a1 was increased in both surgical models at two, four and six weeks post-surgery. In contrast, Col10a1 and Sox9 for the most part showed no significant difference in expression from two to six weeks post-surgery. Crabp2 expression is induced upon activation of the retinoid signalling pathway. At two weeks after surgery in the MTX and PMX animals, Crabp2 expression was increased about 18-fold and about 10-fold over the sham control, respectively. By 10 weeks, Crabp2 expression was increased about three-fold (n = 7, not significant) in the MTX animals and about five-fold (n = 7, p < 0.05) in the PMX animals in comparison to the contralateral control joint.

Conclusions
Together, these findings suggest that the retinoid signalling pathway is activated early in the osteoarthritic process and is sustained during the course of the disease.