bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plant pharming of a full‐sized, tumour‐targeting antibody using different expression strategies
Authors: Villani Maria Elena , Morgun Bogdan , Brunetti Patrizia , Marusic Carla , Lombardi Raffaele , Pisoni Ivan , Bacci Camilla , Desiderio Angiola , Benvenuto Eugenio , Donini Marcello 
Published: September 2008

SummaryThe aims of this work were to obtain a human antibody against the tumour‐associated antigen tenascin‐C (TNC) and to compare the yield and quality of plant‐produced antibody in either stable transgenics or using a transient expression system. To this end, the characterization of a full‐sized human immunoglobulin G (IgG) [monoclonal antibody H10 (mAb H10)], derived from a selected single‐chain variable fragment (scFv) and produced in plants, is presented. The human mAb gene was engineered for plant expression, and Nicotiana tabacum transgenic lines expressing both heavy (HC) and light (LC) chain were obtained and evaluated for antibody expression levels, in vivo assembly and functionality. Affinity‐purified H10 from transgenics (yield, 0.6–1.1 mg/kg fresh weight) revealed that more than 90% of HC was specifically degraded, leading to the formation of functional antigen‐binding fragments (Fab). Consequently, H10 was transiently expressed in Nicotiana benthamiana plants through an Agrobacterium‐mediated gene‐transfer system. Moreover, the use of the p19 silencing suppressor gene from artichoke mottled crinkle virus raised antibody expression levels by an order of magnitude (yields of purified H10, 50–100 mg/kg fresh weight). Approximately 75% of purified protein consisted of full‐sized antibody functionally binding to TNC (KD = 14 nm), and immunohistochemical analysis on tumour tissues revealed specific accumulation around tumour blood vessels. The data indicate that the purification yields of mAb H10, using a transient expression system boosted by the p19 silencing suppressor, are exceptionally high when compared with the results reported previously, providing a technique for the over‐expression of anticancer mAbs by a rapid, cost‐effective, molecular farming approach.
Life Cycle and Cohort Productivity in Economic Research: The Case of Germany
Authors: Rauber Michael , Ursprung Heinrich W. 
Published: September 2008

Abstract
We examine the research productivity of German academic economists over their life cycles. It turns out that the career patterns of research productivity as measured by journal publications are characterized by marked cohort effects. Moreover, the life cycles of younger German economists are hump shaped and resemble the life cycles identified for US economists, whereas the life cycles of older German economists are much flatter. Finally, we find that not only productivity, but also research quality follows distinct life cycles. Our study employs econometric techniques that are likely to produce estimates that are more trustworthy than previous estimates.
Publish or Perish? The Increasing Importance of Publications for Prospective Economics Professors in Austria, Germany and Switzerland
Authors: Graber Michael , Wälde Klaus 
Published: September 2008

Abstract
Tenure decisions depend, among other factors, on a candidate’s career age and publication record.We associate publications with journal articles indexed in EconLit and measure publication output in equivalents of both top-five journal articles and European Economic Review (EER) articles. We find that the average age of a professor in the year of his/her first appointment is 38, i.e. he or she is appointed approximately eight years after completing the PhD. Between 1970 and 2006, the average publication record at the time of the first appointment is equivalent to 1.5 standardized top-five articles or 2.3 standardized EER articles. Publication records vary across subfields and have become more substantial over time.We predict that someone aspiring to a tenured position after 2011 should aim at an equivalent of four standardized top-five articles or six standardized EER articles.
What's the Risk? A Simple Approach for Estimating Adjusted Risk Measures from Nonlinear Models Including Logistic Regression
Authors: Kleinman Lawrence C. , Norton Edward C. 
Published: September 2008

Objective. To develop and validate a general method (called regression risk analysis) to estimate adjusted risk measures from logistic and other nonlinear multiple regression models. We show how to estimate standard errors for these estimates. These measures could supplant various approximations (e.g., adjusted odds ratio [AOR]) that may diverge, especially when outcomes are common.Study Design. Regression risk analysis estimates were compared with internal standards as well as with Mantel–Haenszel estimates, Poisson and log‐binomial regressions, and a widely used (but flawed) equation to calculate adjusted risk ratios (ARR) from AOR.Data Collection. Data sets produced using Monte Carlo simulations.Principal Findings. Regression risk analysis accurately estimates ARR and differences directly from multiple regression models, even when confounders are continuous, distributions are skewed, outcomes are common, and effect size is large. It is statistically sound and intuitive, and has properties favoring it over other methods in many cases.Conclusions. Regression risk analysis should be the new standard for presenting findings from multiple regression analysis of dichotomous outcomes for cross‐sectional, cohort, and population‐based case–control studies, particularly when outcomes are common or effect size is large.
A Nationwide Population‐Based Study of Tension‐Type Headache in Brazil
Authors: Queiroz Luiz P. , Peres Mario F.P. , Piovesan Elcio J. , Kowacs Fernando , Ciciarelli Marcello C. , Souza Jano A. , Zukerman Eliova 
Published: September 2008

Objectives.— To estimate the 1‐year prevalence of tension‐type headache (TTH) and the degree of the association of TTH with some sociodemographic characteristics of a representative sample of the adult population of Brazil.Methods.— This was an observational, cross‐sectional, population‐based study. We conducted telephone interviews on 3848 people, aged 18‐79 years, randomly selected from the 27 states of Brazil. Trained lay interviewers administered the structured questionnaire. It included questions about the sociodemographic characteristics of the population, as well as questions about headache. The degree of the association was calculated through prevalence ratios, adjusted with Poisson regression by gender, age, years of education, marital status, household income, job status, body mass index (BMI), and physical exercise.Results.— The estimated 1‐year gender‐ and‐age‐adjusted prevalence of TTH was 13.0% (95% CI: 11.8‐14.2%); 15.4% in males and 9.5% in females. The prevalence of probable TTH was 22.6% (95% CI: 21.1‐24.1%). Most (86.2%) subjects reported episodic TTH; 6.4% had chronic TTH. The prevalence was higher at 18‐29 years of age (16.2%). TTH was 1.6 times more prevalent in men, and 1.54 times more in subjects with more than 11 years of education. There was no significant association of TTH with marital or job status, household income, BMI, and physical activity.Conclusion.— This is the first nationwide epidemiological study of TTH in Brazil. The overall prevalence of TTH in Brazil is low, at 13%. TTH is significantly more prevalent in males and subjects with higher education level.
The Mode of Action of Migraine Triggers: A Hypothesis
Authors: Lambert Geoffrey A. , Zagami Alessandro S. 
Published: September 2008

Objectives.—To review conjectured modes of action of migraine triggers and to present a new hypothesis about them.Background.—Migraine attacks are initiated in many migraineurs by a variety of “triggers,” although in some patients no external trigger can be identified. Many triggers provoke attacks with such a short latency that only some kind of neural mechanism can explain the triggering.Results.—We present here a hypothesis that the pain of migraine has its ultimate origin in the cortex, but that the immediate generator is in the brainstem. Our hypothesis is that most migraines have triggers that produce excitation of cortical neurons and that this directly causes withdrawal of descending sensory inhibition originating in the brainstem. A wide range of evidence from the literature that cortical activation induced by a number of different mechanisms often produces headache is presented to support this notion. Several nuclei in the brainstem appear to participate in the selective control of trigeminovascular sensation through descending inhibitory mechanisms that arise in the cortex. In this review we focus on 2 of them, the periaqueductal gray matter and nucleus raphe magnus. Our own past results and those of others show that this inhibition is specific for craniovascular sensation and involves the neurotransmitter 5‐hydroxytryptamine. Finally, we summarize our own recent experiments, which show that cortical activation by migraine triggers (including cortical spreading depression) inhibits neuronal discharge in the brainstem and facilitates trigeminovascular sensation.Conclusion.—If the hypothesis can be proven and the neurotransmitters involved in the hypothetical trigger pathway can be identified, it may be possible to develop novel migraine preventative therapies.
STATE TRANSITIONS AND NONPHOTOCHEMICAL QUENCHING DURING A NUTRIENT‐INDUCED FLUORESCENCE TRANSIENT IN PHOSPHORUS‐STARVED DUNALIELLA TERTIOLECTA1
Authors: Petrou K. , Doblin M. A. , Smith R. A. , Ralph P. J. , Shelly K. , Beardall J. 
Published: September 2008

Assessments of nutrient‐limitation in microalgae using chl a fluorescence have revealed that nitrogen and phosphorus depletion can be detected as a change in chl a fluorescence signal when nutrient‐starved algae are resupplied with the limiting nutrient. This photokinetic phenomenon is known as a nutrient‐induced fluorescence transient, or NIFT. Cultures of the unicellular marine chlorophyte Dunaliella tertiolecta Butcher were grown under phosphate starvation to investigate the photophysiological mechanism behind the NIFT response. A combination of low temperature (77 K) fluorescence, photosynthetic inhibitors, and nonphotochemical quenching analyses were used to determine that the NIFT response is associated with changes in energy distribution between PSI and PSII and light‐stress‐induced nonphotochemical quenching (NPQ). Previous studies point to state transitions as the likely mechanism behind the NIFT response; however, our results show that state transitions are not solely responsible for this phenomenon. This study shows that an interaction of at least two physiological processes is involved in the rapid quenching of chl a fluorescence observed in P‐starved D. tertiolecta: (1) state transitions to provide the nutrient‐deficient cell with metabolic energy for inorganic phosphate (Pi)‐uptake and (2) energy‐dependent quenching to allow the nutrient‐stressed cell to avoid photodamage from excess light energy during nutrient uptake.
The effects of infant media usage: what do we know and what should we learn?
Authors: Christakis Dimitri A 
Published: September 2008

AbstractThe rise of infant TV viewing began in the late 1990s and has become an increasingly common occurrence. Today, over 90% of children begin watching TV regularly before the age of 2 years in spite of recommendations to the contrary. This article reviews what is known about the effects of infant TV viewing on multiple domains of child development including language, cognition and attentional capacity as well as directions for future research.Conclusion: No studies to date have demonstrated benefits associated with early infant TV viewing. The preponderance of existing evidence suggests the potential for harm. Parents should exercise due caution in exposing infants to excessive media.
Development of an Electronic Seepage Chamber for Extended Use in a River
Authors: Fritz Brad G. , Mendoza Donaldo P. , Gilmore Tyler J 
Published: September 2008

AbstractSeepage chambers have been used to characterize the flux of water across the water‐sediment interface in a variety of settings. In this work, an electronic seepage chamber was developed specifically for long‐term use in a large river where hydraulic gradient reversals occur frequently with river‐stage variations. A bidirectional electronic flowmeter coupled with a seepage chamber was used to measure temporal changes in the magnitude and direction of water flux across the water‐sediment interface over an 8‐week period. The specific discharge measured from the seepage chamber compared favorably with measurements of vertical hydraulic gradient and previous specific discharge calculations. This, as well as other supporting data, demonstrates the effectiveness of the electronic seepage chamber to accurately quantify water flux in two directions over a multimonth period in this setting. The ability to conduct multimonth measurements of water flux at a subhourly frequency in a river system is a critical capability for a seepage chamber in a system where hydraulic gradients change on a daily and seasonal basis.
Biochemical Indicators for the Bioavailability of Organic Carbon in Ground Water
Authors: Chapelle Francis H. , Bradley Paul M. , Goode Dan J. , Tiedeman Claire , Lacombe Pierre J. , Kaiser Karl , Benner Ronald 
Published: September 2008

AbstractThe bioavailability of total organic carbon (TOC) was examined in ground water from two hydrologically distinct aquifers using biochemical indicators widely employed in chemical oceanography. Concentrations of total hydrolyzable neutral sugars (THNS), total hydrolyzable amino acids (THAA), and carbon‐normalized percentages of TOC present as THNS and THAA (referred to as “yields”) were assessed as indicators of bioavailability. A shallow coastal plain aquifer in Kings Bay, Georgia, was characterized by relatively high concentrations (425 to 1492 μM; 5.1 to 17.9 mg/L) of TOC but relatively low THNS and THAA yields (∼0.2%–1.0%). These low yields are consistent with the highly biodegraded nature of TOC mobilized from relatively ancient (Pleistocene) sediments overlying the aquifer. In contrast, a shallow fractured rock aquifer in West Trenton, New Jersey, exhibited lower TOC concentrations (47 to 325 μM; 0.6 to 3.9 mg/L) but higher THNS and THAA yields (∼1% to 4%). These higher yields were consistent with the younger, and thus more bioavailable, TOC being mobilized from modern soils overlying the aquifer. Consistent with these apparent differences in TOC bioavailability, no significant correlation between TOC and dissolved inorganic carbon (DIC), a product of organic carbon mineralization, was observed at Kings Bay, whereas a strong correlation was observed at West Trenton. In contrast to TOC, THNS and THAA concentrations were observed to correlate with DIC at the Kings Bay site. These observations suggest that biochemical indicators such as THNS and THAA may provide information concerning the bioavailability of organic carbon present in ground water that is not available from TOC measurements alone.
Opinions of Finnish small animal owners about surgery and pain management in small animals
Authors: Väisänen M. A.‐M. , Tuomikoski‐Alin S. K. , Brodbelt D. C. , Vainio O. M. 
Published: September 2008

Objectives:To examine the opinions among small animal owners regarding the management of pain and surgery in small animals.Methods:A questionnaire was presented to 800 owners of dogs or cats who visited one of the four participating clinics in Finland in February 2006.Results:A total of 482 owners completed the questionnaire (60·3 per cent response rate); 90 per cent of the respondents were female. Owners classified surgical procedures (for example, fracture repair, skin tumour removal and neutering) as more painful than medical conditions (otitis externa and lameness). In addition, owners disagreed most with statements that they had received sufficient information on the appropriate methods of management of animal pain and that the recognition of animal pain is easy. With respect to surgical procedures, owners expressed greatest concern in relation to the animal experiencing fear or anxiety during hospitalisation and the presence of postoperative pain.ClinicalSignificance:The animal owners had concerns about the presence and management of animal pain, fear and anxiety. Knowledge of these animal owner opinions could aid veterinary practitioners when communicating with their clients on medical and surgical patient management. Furthermore, studies are merited to clearly define how best to successfully respond to these owner attitudes.
Platelet distribution width and mean platelet volume in the interpretation of thrombocytopenia in dogs
Authors: Bommer N. X. , Shaw D. J. , Milne E. M. , Ridyard A. E. 
Published: September 2008

Objectives:To investigate the use of platelet volume indices in the interpretation of thrombocytopenia in dogs with systemic disease.Methods:Case records of 80 control dogs and 159 thrombocytopenic dogs with systemic disease were reviewed retrospectively. The relationships between mean platelet volume, platelet distribution width and platelet count in systemically well dogs were established. Knowledge of these relationships was used to interpret thrombocytopenia in terms of the underlying disease process.Results:There was a positive relationship between platelet distribution width and mean platelet volume. Both platelet distribution width and mean platelet volume varied in a negative relationship with platelet count, which was unaffected by signalment, underlying disease, variations in haematological parameters or serum proteins.ClinicalSignificance:The interpretation of mean platelet volume and platelet distribution width in dogs requires simultaneous reference to the platelet count. Platelet volume indices did not aid interpretation of thrombocytopenia in terms of underlying pathological processes in the population studied.
Applications of Shuttle Radar Topography Mission Elevation Data
Authors: Zandbergen Paul 
Published: September 2008

AbstractThe Shuttle Radar Topography Mission (SRTM) was flown in February 2000 and collected the first ever high‐resolution near‐global digital elevation data. The final SRTM data have become widely available at 1 arc‐second resolution for the United States and 3 arc‐second resolution for other areas. This article reviews the background of the SRTM mission, the data quality characteristics of the SRTM elevation data, and the many applications of SRTM elevation data that have emerged in recent years, including forest ecology, volcanology, glaciology, geomorphology, and hydrology. SRTM data have been particularly useful for areas where previously limited topographic data were available, but results from STRM data also compare reasonably well with those obtained from other high‐resolution digital elevation models.
Complete DNA Sequences of Two Oka Strain Varicella-Zoster Virus Genomes
Authors: Tillieux Sueli L. , Halsey Wendy S. , Thomas Elizabeth S. , Voycik John J. , Sathe Ganesh M. , Vassilev Ventzislav 
Published: September 2008

ABSTRACT

Varicella-zoster virus (VZV) is a herpesvirus and is the causative agent of chicken pox (varicella) and shingles (herpes zoster). Active immunization against varicella became possible with the development of live attenuated varicella vaccine. The Oka vaccine strain was isolated in Japan from a child who had typical varicella, and it was then attenuated by serial passages in cell culture. Several manufacturers have obtained this attenuated Oka strain and, following additional passages, have developed their own vaccine strains. Notably, the vaccines Varilrix and Varivax are produced by GlaxoSmithKline Biologicals and Merck & Co., Inc., respectively. Both vaccines have been well studied in terms of safety and immunogenicity. In this study, we report the complete nucleotide sequence of the Varilrix (Oka-V
GSK
) and Varivax (Oka-V
Merck
) vaccine strain genomes. Their genomes are composed of 124,821 and 124,815 bp, respectively. Full genome annotations covering the features of Oka-derived vaccine genomes have been established for the first time. Sequence analysis indicates 36 nucleotide differences between the two vaccine strains throughout the entire genome, among which only 14 are involved in unique amino acid substitutions. These results demonstrate that, although Oka-V
GSK
and Oka-V
Merck
vaccine strains are not identical, they are very similar, which supports the clinical data showing that both vaccines are well tolerated and elicit strong immune responses against varicella.
Incorporation of Membrane-Anchored Flagellin into Influenza Virus-Like Particles Enhances the Breadth of Immune Responses
Authors: Wang Bao-Zhong , Quan Fu-Shi , Kang Sang-Moo , Bozja Jadranka , Skountzou Ioanna , Compans Richard W. 
Published: September 2008

ABSTRACT

We have designed a membrane-anchored form of the Toll-like receptor 5 ligand flagellin, the major proinflammatory determinant of enteropathogenic
Salmonella
, which was found to be glycosylated and expressed on cell surfaces. A chimeric influenza virus-like particle (cVLP) vaccine candidate containing A/PR8/34 (H
1
N
1
) hemagglutinin (HA), matrix protein (M1), and the modified flagellin as a molecular adjuvant was produced. The immunogenicity, including the serum antibody levels and cellular immune responses, and the protective efficacy against homologous and heterologous live virus challenge of the resulting VLPs were tested after intramuscular administration in a mouse model. The results demonstrated that flagellin-containing VLPs elicited higher specific immunoglobulin G (IgG) responses than standard HA and M1 VLPs, indicating the adjuvant effect of flagellin. Enhanced IgG2a and IgG2b but not IgG1 responses were observed with flagellin-containing VLPs, illuminating the activation of Th1 class immunity. The adjuvant effects of flagellin were also reflected by enhanced specific cellular responses revealed by the secretion of cytokines by freshly isolated splenocyte cultures when stimulated with pools of major histocompatibility complex class I or II peptides. When immunized mice were challenged with homologous live PR8 virus, complete protection was observed for both the standard and cVLP groups. However, when a heterosubtypic A/Philippines (H
3
N
2
) virus was used for challenge, all of the standard VLP group lost at least 25% of body weight, reaching the experimental endpoint. In contrast, for the cVLP group, 67% of mice survived the challenge infection. These results reveal that cVLPs designed by incorporating flagellin as a membrane-anchored adjuvant induce enhanced cross-protective heterosubtypic immune responses. They also indicate that such cVLP vaccines are a promising new approach for protection against pandemic influenza viruses.