bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol Outlets, Youth Drinking, and Self‐Reported Ease of Access to Alcohol: A Constraints and Opportunities Approach
Authors: Treno Andrew J. , Ponicki William R. , Remer Lillian G. , Gruenewald Paul J.
Published: June 2008

Background:  Despite recent research examining youth access to alcohol, the extent to which relative ease of access to alcohol from various sources translates into the use of these sources is not known.

Methods:  Patterns of adolescent alcohol access in California were studied using a hierarchical analysis of self‐reported and archival measures. A survey of 30 youths age 14 to 16 in each of 50 zip codes selected to maximize variability in median household income and off‐premise outlet densities was conducted.

Results:  (1) Both actual use of and perceived ease of access to formal sources were positively associated with off‐premise outlet density (a measure of formal access). (2) Actual use of informal sources was negatively associated with outlet densities. (3) Perceived and realized informal access were associated positively with deviance and negatively with conventionality. (4) Deviance was associated with increased perceived and realized access from both formal and social sources, whereas conventionality was only associated with realized and perceived informal access.

Conclusions:  Correlates of perceived and actual alcohol access differ somewhat, and the differences between informal and formal access (both perceived and actual) are many, creating a complex picture of the patterns of underage access to alcohol. Youth drinking is affected by opportunities and constraints. Specifically, as one form of access becomes constrained, youth appear to circumvent restrictions by relying on other modes of access. Thus interventions targeting formal alcohol access by youth may result in a shift to reliance on social sources. This complex problem requires a multi‐faceted intervention approach.
Differential Dietary Ethanol Intake and Blood Ethanol Levels in Adolescent and Adult Rats: Effects on Anxiety‐Like Behavior and Seizure Thresholds
Authors: Wills Tiffany A. , Knapp Darin J. , Overstreet David H. , Breese George R.
Published: June 2008

Background:  Adult rats exhibit increased anxiety‐like behavior after exposure to repeated cycles of chronic ethanol and withdrawal. While adolescent rats have differential responses to both acute and chronic ethanol treatments, the potential differences in the effects of repeated withdrawals in this population have yet to be determined.

Methods:  Male adult and adolescent rats received three 5‐day cycles of either a 4.5% or 7% ethanol diet (ED) separated by two 2‐day withdrawal periods. Five hours into the final withdrawal, rats were tested for social interaction (SI) deficits (an index of anxiety‐like behavior) and then assessed for seizure thresholds (audiogenic and bicuculline‐induced). Ethanol intake was monitored throughout, and blood ethanol concentrations (BEC) were obtained from a separate group of rats.

Results:  Adolescent rats have reduced SI during the final withdrawal from either ED and exhibit a greater reduction in SI compared to adult rats when exposed to a 7%ED. Audiogenic seizures were not increased during withdrawal from either ED in adult rats, but adolescent rats that received 7%ED displayed increased seizures. The bicuculline seizure thresholds were decreased in both ages exposed to a 7%ED, but only adolescent rats showed this decreased threshold after 4.5%ED. Ethanol intakes and BECs were higher in adolescent rats compared to similarly treated adults. However, ethanol intakes and BECs were comparable between 4.5%ED‐treated adolescent and 7%ED‐treated adult rats.

Conclusions:  Behavioral results from the 7%ED‐treated groups suggested that adolescent rats may be more vulnerable to repeated withdrawals from ethanol than adults; however, differences in ethanol intake and BECs may be at least in part responsible. When ethanol intakes and BECs were similar between 4.5%ED‐treated adolescent and 7%ED‐treated adult rats, behavioral effects were not different. Importantly, these data illustrated that adolescent rats can exhibit anxiety and reduced seizure thresholds following this repeated withdrawal paradigm.
Development and Validation of the AmpFℓSTR® MiniFilerTM PCR Amplification Kit: A MiniSTR Multiplex for the Analysis of Degraded and/or PCR Inhibited DNA*
Authors: Mulero Julio J. , Chang Chien Wei , Lagacé Robert E. , Wang Dennis Y. , Bas Jennifer L. , McMahon Timothy P. , Hennessy Lori K.
Published: June 2008

Abstract:  DNA typing of degraded DNA samples can be a challenging task when using the current commercially available multiplex short tandem repeat (STR) analysis kits. However, the ability to type degraded DNA specimens improves by redesigning current STR marker amplicons such that smaller sized polymerase chain reaction (PCR) products are generated. In an effort to increase the amount of information derived from these types of DNA samples, the AmpFℓSTR® MiniFiler™ PCR Amplification Kit has been developed. The kit contains reagents for the amplification of eight miniSTRs which are the largest sized loci in the AmpFℓSTR® Identifiler® PCR Amplification Kit (D7S820, D13S317, D16S539, D21S11, D2S1338, D18S51, CSF1PO, and FGA). Five of these STR loci (D16S539, D21S11, D2S1338, D18S51, and FGA) also are some of the largest loci in the AmpFℓSTR® SGM Plus® kit. This informative nine‐locus multiplex, which includes the gender‐identification locus Amelogenin, has been validated according to the FBI/National Standards and SWGDAM guidelines. Our results demonstrate significant performance improvements in models of DNA degradation, PCR inhibition, and nonprobative samples when compared to the AmpFℓSTR® Identifiler® and SGM Plus® kits. These data support that the MiniFiler™ kit will increase the likelihood of obtaining additional STR information from forensic samples in situations in which standard STR chemistries fail to produce complete profiles.
Forensic Evaluation of Sudden Death Due to Tuberculosis
Authors: Törő Klára , Mészáros Árpád , Keller Éva
Published: June 2008

Abstract:  The emergence of drug‐resistant tuberculosis (TB) poses a major threat to TB control efforts. We report a case of a 50‐year‐old man with pulmonary TB. The scene investigation had initially suspected for homicide; however, the result of medico‐legal autopsy demonstrated natural cause of death. Statistical data suggest that the rates of national mortality by respiratory TB decreased in the last decades in Hungary; however, an increasing TB mortality was detected in the capital Budapest. Facing a new mortality trend in TB, the forensic scene investigation and determination of manner of death represent new challenges for practitioners.
Translation to Practice: A Randomised, Controlled Study of an Evidence‐Based Booklet for Breast‐Care Nurses in the United Kingdom
Authors: Kirshbaum Marilyn
Published: June 2008

Background: In the United Kingdom (UK), it was documented that a problem of knowledge transfer existed within the speciality of breast‐cancer care, thus depriving patients of receiving optimal care. Despite increasingly robust research evidence indicating recommendation of whole body exercise for people affected by breast cancer, commensurate changes to practice were not noted amongst breast‐care nurses (BCNs).

Aim: To evaluate the effect of a targeted booklet, Exercise and Breast Cancer: A Booklet for Breast‐Care Nurses, on changes in knowledge, reported practice, and attitudes of BCNs in the UK.

Method: A prospective, experimental approach was used for designing a pre‐ and post‐test randomised controlled study. Comparisons of knowledge, reported practice, and attitudes based on responses to a questionnaire were made at two time‐points in two groups of BCNs (control and experimental). The unit of randomisation and analysis was hospital clusters of BCNs. The sample comprised 92 nurses from 62 hospitals. Analysis consisted of descriptive statistics and clustered regression techniques: clustered logistic regression for knowledge items, clustered linear regression for knowledge scores, ologit for attitude and reported practice items, and clustered multiple regression for paired and multiple variable analysis.

Results: A statistically significant increase in knowledge and changes in reported practice and attitudes were found. Robust variables affecting knowledge acquisition were: promotion of health, promotion of exercise, and understanding how exercise can reduce cancer‐related fatigue.

Discussion: The study has shown that evidence‐based printed material, such as an information booklet, can be used as an effective research dissemination method when developed for needs, values, and context of a target audience.

Conclusions: This practical approach to research dissemination could be replicated and applied to other groups of nurses.
Effects of diets high in whey, soy, red meat and milk protein on body weight maintenance in diet‐induced obesity in mice
Authors: HUANG Xu‐Feng , LIU Yingxu , RAHARDJO Gita L. , MCLENNAN Peter L. , TAPSELL Linda C. , BUTTEMER William A.
Published: June 2008

This study examined the effects of different food sources of protein on energy intake, body weight maintenance, and on the responses of plasma leptin, insulin and adiponectin in chronic high‐fat diet‐induced obese mice. Obesity was induced in 47 mice with a high‐fat diet for 20 weeks. They were divided into five diet groups to test the effects of a higher protein proportion (30% energy), achieved at the expense of carbohydrate. For the next eight weeks, four of the groups were fed diets of chow formulated with whey, soy, red meat or milk while the control group continued on their high‐fat diet. The results showed that: (i) increasing the protein : carbohydrate ratio (both at 30% energy) in a high‐fat diet did not reduce the level of obesity; (ii) the type of protein added, however, did have a significant effect on the level of obesity attained; (iii) whey protein stabilised weight gain the most, had the strongest satiety effects and also stimulated the highest production of adiponectin; and (iv) whey protein also was associated with the lowest insulin values among all proteins tested. Plasma leptin levels were not affected by any of the diets. Dietary fat remains a potent factor in weight management, but the type and amount of protein may also be important through its effects on food intake. In particular, the apparent decreased appetite associated with increased adiponectin in the whey‐based high‐protein diet may contribute to stabilised body mass in chronic high‐fat diet‐induced obesity.
Role of protein and carbohydrate sources on acute appetite responses in lean and overweight men
Authors: BOWEN Jane , NOAKES Manny , CLIFTON Peter
Published: June 2008

Dietary protein induces greater satiety compared with carbohydrate in lean subjects, which may involve appetite‐regulatory gut hormones. Little is known about the duration of effect, influence of protein and carbohydrate source and relevance to non‐lean individuals. We compared the effect of various dietary proteins and carbohydrates on post‐prandial appetite ratings, ad libitum energy intake (EI) and appetite hormones in lean and overweight men. Three randomised double‐blinded cross‐over studies examined appetite response (appetite ratings, ghrelin, glucagon‐like peptide‐1 (GLP‐1) and cholecystokinin) to liquid preloads over three to four hours followed by a buffet meal to assess ad libitum EI. The 1‐MJ preloads contained ∼55 g of protein (whey, casein, soy and gluten), carbohydrate (glucose, lactose and fructose) or combined whey/fructose. EI was 10% higher following glucose preloads compared with protein preloads, observed at three hours but not four hours. Protein ingestion was followed by prolonged elevation of cholecystokinin and GLP‐1 (two hours) and suppression of ghrelin (three to four hours) compared with glucose and independent of protein type. Replacing some whey with fructose attenuated the effect of protein on these hormones. Treatment effects on EI and appetite hormones were independent of bodyweight status, despite higher GLP‐1 and lower ghrelin in overweight subjects. Protein‐rich liquid preloads reduce EI over three hours in overweight men compared with glucose. These findings suggest a potential application for protein‐rich drinks and/or foods to facilitate reduced EI. Future studies should explore additional dietary manipulations that may enhance this relationship, and confirm these effects within the context of energy‐restricted dietary patterns.
Industry syndicates in functional foods: Evaluating existing models for the development of future projects
Authors: PROBST Yasmine
Published: June 2008

The syndicate model developed by the National Centre of Excellence in Functional Foods enables a number of companies to work together in a pre‐competitive space, leveraging their investment. Companies have access to a wide range of research knowledge and skills for a portion of what it would cost to complete the entire project as a single entity. By 2007, the Centre had run three separate syndicate projects each with different models. Both food and pharmaceutical companies have participated in the projects. This paper reports on an evaluation of the Functional Foods for Healthy Ageing and Functional Foods for Appetite Control projects conducted during 2007 with the aim of re‐developing the syndicate model for future projects. The evaluations were conducted with an external interviewer and followed a structured interview approach via telephone. The companies participating in these syndicate projects were favourable to the model being used for future projects due to the ability to interact with other companies, value for their research dollar and the access to research and development resources. Regular communications and a company‐driven approach were favoured though a dedicated staff member was identified as needed for these projects. A new model for the syndicate projects was developed utilising the feedback. The primary modifications were a change from group ideation to individualised company ideation as well as the management and planning for the projects. The Centre will incorporate these changes in two future syndicate projects: Functional Foods for Cognitive Health and Functional Foods for Gut Health.
Comment on "Intermittent Plate Tectonics?"
Authors: Korenaga Jun
Published: June 2008

Silver and Behn (Reports, 4 January 2008, p. 85) proposed that intermittent plate tectonics may resolve a long-standing paradox in Earth's thermal evolution. However, their analysis misses one important term, which subsequently brings their main conclusion into question. In addition, the Phanerozoic eustasy record indicates that the claimed effect of intermittency is probably weak.
A Transient Radio Jet in an Erupting Dwarf Nova
Authors: Körding Elmar , Rupen Michael , Knigge Christian , Fender Rob , Dhawan Vivek , Templeton Matthew , Muxlow Tom
Published: June 2008

Astrophysical jets seem to occur in nearly all types of accreting objects, from supermassive black holes to young stellar objects. On the basis of x-ray binaries, a unified scenario describing the disc/jet coupling has evolved and been extended to many accreting objects. The only major exceptions are thought to be cataclysmic variables: Dwarf novae, weakly accreting white dwarfs, show similar outburst behavior to x-ray binaries, but no jet has yet been detected. Here we present radio observations of a dwarf nova in outburst showing variable flat-spectrum radio emission that is best explained as synchrotron emission originating in a transient jet. Both the inferred jet power and the relation to the outburst cycle are analogous to those seen in x-ray binaries, suggesting that the disc/jet coupling mechanism is ubiquitous.
Serotonin Modulates Behavioral Reactions to Unfairness
Authors: Crockett Molly J. , Clark Luke , Tabibnia Golnaz , Lieberman Matthew D. , Robbins Trevor W.
Published: June 2008

Serotonin (5-HT) has long been implicated in social behavior and impulsivity, but the mechanisms through which it modulates self-control remain unclear. We observed the effects of manipulating 5-HT function on behavior in the ultimatum game, where players must decide whether to accept or reject fair or unfair monetary offers from another player. Participants with depleted 5-HT levels rejected a greater proportion of unfair offers, but not fair offers, without showing changes in mood, fairness judgment, basic reward processing, or response inhibition. Our results suggest that 5-HT plays a critical role in regulating emotion during social decision-making.
Identification of Non-Precious Metal Alloy Catalysts for Selective Hydrogenation of Acetylene
Authors: Studt Felix , Abild-Pedersen Frank , Bligaard Thomas , Sørensen Rasmus Z. , Christensen Claus H. , Nørskov Jens K.
Published: June 2008

The removal of trace acetylene from ethylene is performed industrially by palladium hydrogenation catalysts (often modified with silver) that avoid the hydrogenation of ethylene to ethane. In an effort to identify catalysts based on less expensive and more available metals, density functional calculations were performed that identified relations in heats of adsorption of hydrocarbon molecules and fragments on metal surfaces. This analysis not only verified the facility of known catalysts but identified nickel-zinc alloys as alternatives. Experimental studies demonstrated that these alloys dispersed on an oxide support were selective for acetylene hydrogenation at low pressures.
Signifying Little
Authors: Porter Theodore M.
Published: June 2008

The Cult of Statistical Significance
. How the Standard Error Costs Us Jobs, Justice, and Lives.
By Stephen T. Ziliak and Deirdre N. McCloskey
. University of Michigan Press, Ann Arbor, 2008. 348 pp. $75, £48.95. ISBN 9780472070077. Paper, $24.95, £16.50. ISBN 9780472050079. Economics, Cognition, and Society.

Through their consideration of a wide range of fields (including their home discipline of economics, psychology, epidemiology, and biomedical science), the authors argue that statistical significance is far too often mistakenly applied--to the detriment of science and society.
Angiogenic Effects of the Extracts from Chinese Herbs: Angelica and ChuanXiong
Authors: Meng Hua , Guo Jun , Sun Ji-Yuan , Pei Jian-Ming , Wang Yue-Min , Zhu Miao-Zhang , Huang Chen
Published: June 2008

Angelica and ChuanXiong are used to cure ischemic heart disease in China. Previous studies found that these two herbs could increase myocardial blood flow, oxygen-supply and keep myocardial oxygen balance, etc. However, the mechanisms of angiogenic effects of these two herbs are not well-known. The purpose of this study was to assess the effects of Angelica and ChuanXiong on vascular endothelial growth factor (VEGF) expression in rat myocardial infarction, on endothelial cell proliferation and quantity of vessels on chick embryo chorioallantoic membrane (CAM). In this study, rats were divided randomly into either pre-treatment or acute-treatment group and sacrificed at the end of the treatments. VEGF expression using Western blot analysis was significantly increased in the groups pre-treated with ChuanXiong and Angelica when compared to the control group ( p < 0.05). There was significant increase in VEGF expression in the rats treated acutely with Angelica ( p < 0.05). In the contrary, the rats treated with ChuanXiong showed a decrease in VEGF expression when compared to the acute-treatment control group ( p < 0.05). Similar results were observed in immunohistochemistry of VEGF expression in the myocardia. Our study also demonstrated that these two herbs significantly enhanced endothelial cell proliferation ( p < 0.05) and revascularity in CAM ( p < 0.05). The data showed that Angelica and ChuanXiong could affect VEGF expression in rat myocardial infarction, promote endothelial cell proliferation and stimulate quantity of vessels on CAM model. The results suggest that Angelica and ChuanXiong have angiogenic effects, and may provide some mechanisms for the treatment of myocardial infarction and peripheral ischemia.
SCATTERING OF A SPIN-POLARIZED NEUTRAL FERMION WITH THE ANOMALOUS MAGNETIC MOMENT IN AN AHARONOV–CASHER CONFIGURATION
Authors: KHALILOV V. R.
Published: June 2008

The scattering of a nonrelativistic neutral massive fermion having the anomalous magnetic moment (AMM) in an electric field of a uniformly charged long conducting thread aligned perpendicularly to the fermion motion is considered to study the so-called Aharonov–Casher (AC) effect by taking into account the particle spin. For this solution, the nonrelativistic Dirac–Pauli equation for a neutral massive fermion with AMM in (3+1) dimensions is found, which takes into account explicitly the particle spin and interaction between AMM of moving fermion and the electric field. Expressions for the scattering amplitude and the cross-section are obtained for spin-polarized massive neutral fermion scattered off the above conducting thread. We conclude that the scattering amplitude and cross-section of spin-polarized massive neutral fermions are influenced by the interaction of AMM of moving neutral fermions with the electric field as well as by the polarization of fermion beam in the initial state.
BLACK-BODY PHOTON CLUSTERING BY SEMICLASSICAL MEANS
Authors: LESTONE J. P.
Published: June 2008

If stimulated emission could be turned off, then only uncorrelated photons would be emitted from black bodies and the photon counting statistics would be Poissonian. Through the process of stimulated emission, some fraction of the photons emitted from a black body are correlated and thus emitted in clusters. This photon clustering can be calculated by semiclassical means. The corresponding results are in agreement with quantum theory.
CONSIDERING TESTING EFFICIENCY AND TESTING RESOURCE CONSUMPTION VARIATIONS IN ESTIMATING SOFTWARE RELIABILITY
Authors: GUPTA ANSHU , KAPUR REECHA , JHA P. C.
Published: June 2008

Advances in software technologies have promoted the growth of computer-related applications to a great extent. Building quality in terms of reliability of the software has become one of the main issues for software developers. Software testing is necessary to build highly reliable software. Monitoring and controlling the resource utilization, measuring and controlling the progress of testing, efficiency of testing and debugging personals and reliability growth are important for effective management the testing phase and meeting the quality objectives. Over the past 35 years many Software reliability growth models (SRGM) are proposed to accomplish the above-mentioned activities related to the software testing. From the literature it appears that most of the SRGM do not account the changes in the testing effort consumption. During the testing process especially in the beginning and towards the end of the testing frequent changes are observed in testing resource consumption due to changes in testing strategy, team constitution, schedule pressures etc. Apart from this testing efficiency plays a major role determining the progress of the testing process. In this paper we incorporate the important concept of testing resource consumption variations for Weibull type testing effort functions and testing efficiency in software reliability growth modeling. The performance of the proposed models is demonstrated through two real life data sets existing in literature. The experimental result shows fairly accurate estimating capabilities of the proposed models.
INSPECTION FREQUENCY OPTIMIZATION MODEL FOR DEGRADING FLOWLINES ON AN OFFSHORE PLATFORM
Authors: KUMAR SAURABH , DANDOTIYA RAJIV , KUMAR RAJESH , KUMAR UDAY
Published: June 2008

Many offshore oil and gas installations in the North Sea are approaching the end of their designed lifetimes. Technological improvements and higher oil prices have developed favorable conditions for more oil recovery from these existing installations. However, in most cases, an extended oil production period does not justify investment in new installations. Therefore cost-effective maintenance of the existing platform infrastructure is becoming very important.

In this paper, an inspection frequency optimization model has been developed which can be used effectively by the inspection and maintenance personnel in the industry to estimate the number of inspections/optimum preventive maintenance time required for a degrading component at any age or interval in its lifecycle at a minimum total maintenance cost. The model can help in planning inspections and maintenance intervals for different components of the platform infrastructure. The model has been validated by a case study performed on flowlines installed on the top side of an offshore oil and gas platform in the North Sea. Reliability analysis has been carried out to arrive at the best inspection frequency for the flowline segments under study.
Bistability, Epigenetics, and Bet-Hedging in Bacteria
Authors: Veening Jan-Willem , Smits Wiep Klaas , Kuipers Oscar P.
Published: June 2008

Clonal populations of microbial cells often show a high degree of phenotypic variability under homogeneous conditions. Stochastic fluctuations in the cellular components that determine cellular states can cause two distinct subpopulations, a property called bistability. Phenotypic heterogeneity can be readily obtained by interlinking multiple gene regulatory pathways, effectively resulting in a genetic logic-AND gate. Although switching between states can occur within the cells' lifetime, cells can also pass their cellular state over to the next generation by a mechanism known as epigenetic inheritance and thus perpetuate the phenotypic state. Importantly, heterogeneous populations can demonstrate increased fitness compared with homogeneous populations. This suggests that microbial cells employ bet-hedging strategies to maximize survival. Here, we discuss the possible roles of interlinked bistable networks, epigenetic inheritance, and bet-hedging in bacteria.
An endocrinology laboratory exercise demonstrating the effect of confinement stress on the immune system of mice
Authors: Brehe Jacqueline , Way Amy L.
Published: June 2008

This article describes a simple laboratory exercise for examining the effect of stress on the immune system in mice. Mice are subjected to confinement stress for 1 h, after which a sample of blood is collected via the caudal vein. Blood samples are smeared onto microscope slides, air dried, and stained with Wright's Giemsa stain. When differential white blood cell counts are performed, there are noticeable differences between the neutrophil and lymphocyte counts of stressed versus control mice. The protocol is simple enough for students to perform, and the entire experiment can be completed within 3 h. Examples of ways in which the basic protocol can be modified to accommodate a shorter laboratory class are provided. This hands-on laboratory experiment provides students with experience using the scientific method to investigate the interaction between the endocrine and immune systems in response to stress.
Self-expression assignment as a teaching approach to enhance the interest of Kuwaiti women in biological sciences
Authors: El-Sabban Farouk
Published: June 2008

Stimulating the interest of students in biological sciences necessitates the use of new teaching methods and motivating approaches. The idea of the self-expression assignment (SEA) has evolved from the prevalent environment at the College for Women of Kuwait University (Safat, State of Kuwait), a newly established college where the number of students is low and where students have varied backgrounds and interests and are being instructed biological sciences in English for the first time. This SEA requires each student to choose a topic among a long list of topics and interact with it in any way to produce a finished product without the interference of the course instructor. Students are told that the SEA will be graded based on their commitment, creative thinking, innovation in developing the idea, and finishing up of the chosen assignment. The SEA has been implemented in three introductory courses, namely, Biology, Introduction to Human Nutrition and Food Science, and The Human Body. Many interesting projects resulted from the SEA, and, based on an administered survey, students assessed this assignment very favorably. Students expressed their pleasure of experiencing freedom in choosing their own topics, interacting with such topics, learning more about them, and finishing up their projects. Students appreciated this type of exposure to biological sciences and expressed that such an experience enhanced their interest in such sciences.
Channels active in the excitability of nerves and skeletal muscles across the neuromuscular junction: basic function and pathophysiology
Authors: Goodman Barbara E.
Published: June 2008

Ion channels are essential for the basic physiological function of excitable cells such as nerve, skeletal, cardiac, and smooth muscle cells. Mutations in genes that encode ion channels have been identified to cause various diseases and disorders known as channelopathies. An understanding of how individual ion channels are involved in the activation of motoneurons and their corresponding muscle cells is essential for interpreting basic neurophysiology in nerves, the heart, and skeletal and smooth muscle. This review article is intended to clarify how channels work in nerves, neuromuscular junctions, and muscle function and what happens when these channels are defective. Highlighting the human diseases that result from defective ion channels is likely to be interesting to students in helping them choose to learn about channel physiology.
Using truncated lectures, conceptual exercises, and manipulatives to improve learning in the neuroanatomy classroom
Authors: Krontiris-Litowitz Johanna
Published: June 2008

Functional Neuroanatomy is a course designed to help students learn the function and anatomy of the human nervous system. Historically, students have had difficulty with the spinal tract curricular unit and frequently resorted to memorization to “learn” the material. They performed poorly on exams and failed to demonstrate competence in the functional application of their knowledge. In an effort to improve learning and promote critical thinking in this course, the instructor revised the curriculum to include 1) shorter, less detailed lectures; 2) a set of practice problems that presented the spinal tracts in an applied context; and 3) a manipulative, which was composed of a magnetic bulletin board and a kit of magnets representing structures of the nervous system. Student learning, as assessed by summative exams, improved under the revised curriculum. Scores on knowledge, analytical, and synthesis questions were significantly higher than scores from previous classes using the traditional lecture curriculum ( P < 0.05). This curricular protocol could potentially be applied to other topics where students resort to memorization and fail to comprehend concepts and processes.
Integrating research and education at research-extensive universities with research-intensive communities
Authors: Desai Ketaki V. , Gatson Sarah N. , Stiles Thomas W. , Stewart Randolph H. , Laine Glen A. , Quick Christopher M.
Published: June 2008

Although the Boyer Commission (1998) lamented the lack of research opportunities for all undergraduates at research-extensive universities, it did not provide a feasible solution consistent with the mandate for faculty to maintain sustainable physiology research programs. The costs associated with one-on-one mentoring, and the lack of a sufficient number of faculty members to give intensive attention to undergraduate researchers, make one-on-one mentoring impractical. We therefore developed and implemented the “research-intensive community” model with the aim of aligning diverse goals of participants while simultaneously optimizing research productivity. The fundamental organizational unit is a team consisting of one graduate student and three undergraduates from different majors, supervised by a faculty member. Undergraduate workshops, Graduate Leadership Forums, and computer-mediated communication provide an infrastructure to optimize programmatic efficiency and sustain a multilevel, interdisciplinary community of scholars dedicated to research. While the model radically increases the number of undergraduates that can be supported by a single faculty member, the inherent resilience and scalability of the resulting complex adaptive system enables a research-intensive community program to evolve and grow.
Effects of extracellular matrixes and growth factors on the hepatic differentiation of human embryonic stem cells
Authors: Ishii Takamichi , Fukumitsu Ken , Yasuchika Kentaro , Adachi Keiko , Kawase Eihachiro , Suemori Hirofumi , Nakatsuji Norio , Ikai Iwao , Uemoto Shinji
Published: June 2008

Hepatocytes derived from human embryonic stem cells (hESCs) are a potential cell source for regenerative medicine. However, the definitive factors that are responsible for hepatic differentiation of hESCs remain unclear. We aimed to evaluate the effects of various extracellular matrixes and growth factors on endodermal differentiation and to optimize the culture conditions to induce hepatic differentiation of hESCs. The transgene vector that contained enhanced green fluorescent protein (EGFP) under the control of human α-fetoprotein (AFP) enhancer/promoter was transfected into hESC lines. The transgenic hESCs were cultured on extracellular matrixes (collagen type I, laminin, and Matrigel) in the presence or absence of growth factors including hepatocyte growth factor (HGF), bone morphogenetic protein 4, fibroblast growth factor 4, all- trans-retinoic acid, and activin A. The expression of AFP-EGFP was measured by flow cytometry. The culture on Matrigel-coated dishes with 100 ng/ml activin A showed 19.5% of EGFP-positive proportions. Moreover, the sequential addition of 100 ng/ml activin A and 20 ng/ml HGF resulted in 21.7% and produced a higher yield of EGFP-positive cells than the group stimulated by activin A alone. RT-PCR and immunocytochemical staining revealed these EGFP-positive cells to differentiate into mesendoderm-like cells by use of activin A and then into hepatic endoderm cells by use of HGF. Two other hESC lines also differentiated into endoderm on the hepatic lineage by our method. In conclusion, we therefore found this protocol to effectively differentiate multiple hESC lines to early hepatocytes using activin A and HGF on Matrigel.
Optimized adeno-associated virus 8 produces hepatocyte-specific Cre-mediated recombination without toxicity or affecting liver regeneration
Authors: Ho Karen J. , Bass Caroline E. , Kroemer Alexander H. K. , Ma Chunyan , Terwilliger Ernest , Karp Seth J.
Published: June 2008

Engineering viral vectors to produce liver-specific protein expression may help advance understanding of hepatic regeneration and disease states. In addition to introducing genes of interest to the liver, these vectors can be adapted for gene deletion when designed to express Cre recombinase. The ability to use this system requires high, liver-restricted expression, low toxicity, and no effect on the process of interest. We developed an adeno-associated virus 8 (AAV8) with a codon-optimized Cre recombinase under a hepatocyte-specific major urinary protein (MUP) promoter (MUP-iCre-AAV8) that fulfills these requirements. A single intravenous injection of ROSA26R reporter mice, which express lacZ after Cre-mediated recombination, demonstrated homogeneous β-galactosidase expression limited to hepatocytes after only 7 days. Cre protein expression remained strong for at least 31 days. Serum liver function tests and histology demonstrated minimal liver toxicity. The presence of MUP-iCre-AAV8 did not affect hepatocyte proliferation after partial hepatectomy as measured by Ki67 staining. Conclusion: AAV8 with the MUP promoter, by virtue of its lack of hepatic toxicity or effect on liver regeneration, may be an efficient alternative to complex transgenic methodologies for studies of the mouse liver.
Bone marrow-derived stromal cells home to and remain in the infarcted rat heart but fail to improve function: an in vivo cine-MRI study
Authors: Carr Carolyn A. , Stuckey Daniel J. , Tatton Louise , Tyler Damian J. , Hale Sarah J. M. , Sweeney Dominic , Schneider Jürgen E. , Martin-Rendon Enca , Radda George K. , Harding Sian E. , Watt Suzanne M. , Clarke Kieran
Published: June 2008

Basic and clinical studies have shown that bone marrow cell therapy can improve cardiac function following infarction. In experimental animals, reported stem cell-mediated changes range from no measurable improvement to the complete restoration of function. In the clinic, however, the average improvement in left ventricular ejection fraction is around 2% to 3%. A possible explanation for the discrepancy between basic and clinical results is that few basic studies have used the magnetic resonance (MR) imaging (MRI) methods that were used in clinical trials for measuring cardiac function. Consequently, we employed cine-MR to determine the effect of bone marrow stromal cells (BMSCs) on cardiac function in rats. Cultured rat BMSCs were characterized using flow cytometry and labeled with iron oxide particles and a fluorescent marker to allow in vivo cell tracking and ex vivo cell identification, respectively. Neither label affected in vitro cell proliferation or differentiation. Rat hearts were infarcted, and BMSCs or control media were injected into the infarct periphery ( n = 34) or infused systemically ( n = 30). MRI was used to measure cardiac morphology and function and to determine cell distribution for 10 wk after infarction and cell therapy. In vivo MRI, histology, and cell reisolation confirmed successful BMSC delivery and retention within the myocardium throughout the experiment. However, no significant improvement in any measure of cardiac function was observed at any time. We conclude that cultured BMSCs are not the optimal cell population to treat the infarcted heart.
Flutamide protects against trauma-hemorrhage-induced liver injury via attenuation of the inflammatory response, oxidative stress, and apopotosis
Authors: Kan Wen-Hong , Hsieh Chi-Hsun , Schwacha Martin G. , Choudhry Mashkoor A. , Raju Raghavan , Bland Kirby I. , Chaudry Irshad H.
Published: June 2008

Although studies have shown that administration of testosterone receptor antagonist, flutamide, following trauma-hemorrhage, improves hepatic, cardiovascular, and immune functions, the precise cellular/molecular mechanisms responsible for producing these salutary effects remain largely unknown. To study this, male C3H/HeN mice were subjected to a midline laparotomy and hemorrhagic shock (35 ± 5 mmHg for ∼90 min), followed by resuscitation with Ringer lactate. Flutamide (25 mg/kg) or vehicle was administered subcutaneously at the onset of resuscitation, and animals were killed 2 h thereafter. Hepatic injury was assessed by plasma α-glutathione S-transferase concentration, liver myeloperoxidase activity, and nitrotyrosine formation. Hepatic malondialdehyde and 4-hydroxyalkenals (lipid peroxidation indicators), cellular DNA fragmentation, and the expression of inducible nitric oxide synthase and hypoxia-inducible factor-1α were also evaluated. Cytokines (TNF-α, IL-6) and chemokines (keratinocyte-derived chemokine and monocyte chemoattractant protein-1) levels were determined by cytometric bead array. The results indicate that flutamide administration after trauma-hemorrhage reduced liver injury, which was associated with decreased levels of α-glutathione S-transferase, myeloperoxidase activity, nitrotyrosine formation, lipid peroxidation, and cytokines/chemokines (systemic, liver tissue, and intracellular cytokines/chemokines). Cellular apoptosis, hepatocyte hypoxia-inducible factor-1α, and inducible nitric oxide synthase expression were also decreased under such conditions. Thus administration of flutamide following trauma-hemorrhage protects against liver injury via reduced inflammation, cellular oxidative stress, and apoptosis.
Differential effect of recruitment maneuvres on pulmonary blood flow and oxygenation during HFOV in preterm lambs
Authors: Polglase Graeme R. , Moss Timothy J. M. , Nitsos Ilias , Allison Beth J. , Pillow J. Jane , Hooper Stuart B.
Published: June 2008

The effects of lung volume recruitment manouvres on pulmonary blood flow (PBF) during high-frequency oscillatory ventilation (HFOV) in preterm neonates are unknown. Since increased airway pressure adversely affects PBF, we compared the effects of two HFOV recruitment strategies on PBF and oxygenation index (OI). Preterm lambs (128 ± 1 day gestation; term ∼150 days) were anesthetized and ventilated using HFOV (10 Hz, 33% tI) with a mean airway pressure (Pao) of 15 cmH2O. Lung volume was recruited by either increasing Pao to 25 cmH2O for 1 min, repeated five times at 5-min intervals (Sigh group; n = 5) or stepwise (5 cmH2O) changes in Pao at 5-min intervals incrementing up to 30 cmH2O then decrementing back to 15 cmH2O (Ramp group; n = 6). Controls ( n = 5) received constant HFOV at 15 cmH2O. PBF progressively decreased (by 45 ± 4%) and OI increased (by 15 ± 6%, indicating reduced oxygenation) in controls during HFOV, which was similar to the changes observed in the Sigh group of lambs. In the Ramp group, PBF fell (by 54 ± 10%) as airway pressure increased ( r2= 0.99), although the PBF did not increase again as the Pao was subsequently reduced. The OI decreased (by 47 ± 9%), reflecting improved oxygenation at high Pao levels during HFOV in the Ramp group. However, high Pao restored retrograde PBF during diastole in four of six lambs, indicating the restoration of right-to-left shunting through the ductus arteriosus. Thus the choice of volume recruitment maneuvre influences the magnitude of change in OI and PBF that occurs during HFOV. Despite significantly improving OI, the ramp recruitment approach causes sustained changes in PBF.
Head Accelerations during Particle Repositioning Manoeuvres
Authors: Faldon M.E. , Bronstein A.M.
Published: June 2008

Benign paroxysmal positional vertigo (BPPV) due to canalithiasis can be treated with particle repositioning manoeuvres, which aim to evacuate trapped particles from the semicircular canals (SCC). The movement of particles within the SCC is affected by gravity as well as by the accelerations of the head during the manoeuvres. Moreover, as experienced by the particles, gravity is indistinguishable from an upward acceleration of the SCC in free space. We used a set of three orthogonal linear accelerometers to measure the net three-dimensional linear acceleration vector acting on the head during the Hallpike manoeuvre and Epley and Semont particle repositioning manoeuvres (which are used to treat posterior canal BPPV). The projection of the net acceleration vector onto the SCC planes showed that both the Epley and Semont manoeuvres approximated to stepwise, 360°, backward rotations in the plane of the targeted posterior canal. Angular velocity measurements however showed that the rotational component during the central stages of these two manoeuvres is opposite in direction. A simple model of head rotations during particle repositioning manoeuvres was created which showed good agreement to the linear acceleration measurements. Analysis of modelled and measured data identified that speed of movement during the Semont manoeuvre should be critical to its clinical success.
Stroke among Siblings in a Biethnic Community
Authors: Lisabeth Lynda D. , Peyser Patricia A. , Long Jeffrey C. , Majerisk Jennifer J. , Smith Melinda A. , Morgenstern Lewis B.
Published: June 2008

Background: Mexican Americans (MAs) have an increased risk of stroke compared with non-Hispanic whites (NHWs), especially at younger ages. Little is known regarding patterns of familial aggregation of stroke and whether familial risk assessment might prove a potentially useful tool in assessing stroke risk in this population. This study’s objective was to estimate the sibling recurrence risk ratio (λs) for stroke and to compare this ratio between MAs and NHWs. Methods: Stroke and transient ischemic attack (TIA) cases (n = 181) between the ages of 45 and 64 years were identified by a population-based stroke study in a biethnic Texas community. λs was calculated overall and by ethnicity. Results: Siblings of ischemic stroke/TIA cases had a doubling in stroke risk compared to what would be expected based on national stroke prevalence estimates (λs = 1.92; 95% CI: 1.39–2.61). λs was 2.0 (95% CI: 1.39–2.81) among MA stroke/TIA cases and 1.66 (95% CI: 0.82–3.10) among NHW stroke/TIA cases. Conclusion: The sibling recurrence risk for stroke was elevated in MA stroke/TIA cases suggesting that further ischemic stroke genetic studies across ethnicities may be warranted. In addition, a positive family history could prove a useful factor in the clinical setting for identifying MAs at increased stroke risk.
Polarization of Natural Killer T Cells towards an NKT2 Subpopulation Occurs after Stimulation with α-Galactosylceramide and rhG-CSF in Aplastic Anemia
Authors: Wang Yingxue , Hu Xiaojing , Guo Chengshan , Zhang Qi , Peng Jun , Zhang Jianhua , Li Lizhen , Zhang Ti , Xu Conggao
Published: June 2008

Natural killer T (NKT) cells play an important role in the regulation of immune responses in a broad range of diseases, including autoimmune disorders, infectious diseases and cancer. So far, few studies have evaluated the roles of NKT cells in the pathogenesis of aplastic anemia (AA), an autoimmune disease. In this study, we investigated the quantitative and qualitative changes in NKT cells in bone marrow (BM) mononuclear cells of AA patients in response to in vitro stimulation with α-galactosylceramide. Compared to healthy controls, BM from AA patients had reduced fraction of NKT cells, which possessed a decreased potential to expand in vitro in response to α-galactosylceramide stimulation, producing more IFNγ+ NKT1 cells. In the presence of rhG-CSF, the expansion capacity of NKT cells stimulated by α-galactosylceramide was significantly reduced in both AA and control groups, with the majority of the activated NKT cells expressing intracellular IL-4, and the fractions of IFNγ+ NKT cells were significantly reduced. In summary, our results indicate that polarization of NKT cells towards the NKT2 subpopulation occurs after co-stimulation with α-galactosylceramide and rhG-CSF in AA.
Effect of the PPAR-Alpha L162V Polymorphism on the Cardiovascular Disease Risk Factor in Response to n–3 Polyunsaturated Fatty Acids
Authors: Caron-Dorval Dominique , Paquet Pascale , Paradis Ann-Marie , Rudkowska Iwona , Lemieux Simone , Couture Patrick , Vohl Marie-Claude
Published: June 2008

Background: Dietary n–3 polyunsaturated fatty acids (PUFAs) decrease the risk of cardiovascular disease (CVD). Yet, genetic variations of the gene encoding the peroxisome proliferator-activated receptor-α (PPARα) can also modulate CVD risk factors. Since fatty acids, including n–3 PUFAs, are natural ligands of PPARα, a gene-diet interaction effect could be observed. Aims: To examine whether n–3 PUFA- induced changes in CVD risk factors are influenced by the PPARα L162V polymorphism. Methods: Fourteen men, carriers of the V162 allele and 14 L162 homozygotes, were matched according to age and body mass index. Subjects followed, for 8 weeks, a low-fat diet and then were supplemented daily with 5 g of fish oil for 6 weeks. Results: Baseline characteristics were similar for both genotype groups. Independently of the genotype, the supplementation was associated with a significant decrease in plasma triacylglycerol and fasting glucose concentrations, diastolic blood pressure, and with an increase in total apolipoprotein B concentrations. The extent of the decrease in plasma triacylglycerol concentrations was comparable for both genotype groups (p < 0.03). A significant genotype-by-diet interaction effect was observed for plasma C-reactive protein concentrations (p = 0.01). Conclusions: The PPARα L162V polymorphism may contribute to the interindividual variability in the CVD risk factor response to n–3 PUFAs.