bluuebunny/crossref_metadata_2025 huggingface dataset:
Notch-HES1 signaling axis controls hemato-endothelial fate decisions of human embryonic and induced pluripotent stem cells
Authors: Lee Jung Bok , Werbowetski-Ogilvie Tamra E. , Lee Jong-Hee , McIntyre Brendan A. S. , Schnerch Angelique , Hong Seok-Ho , Park In-Hyun , Daley George Q. , Bernstein Irwin D. , Bhatia Mickie
Published: June 2013

Key Points

Notch signaling controls hematopoiesis of human pluripotent stem cells.
Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study
Authors: Mukonzo Jackson K , Okwera Alphonse , Nakasujja Neoline , Luzze Henry , Sebuwufu Deogratious , Ogwal-Okeng Jasper , Waako Paul , Gustafsson Lars L , Aklillu Eleni
Published: June 2013

Background

HIV infection, anti-tuberculosis and efavirenz therapy are associated with neuropsychological effects. We evaluated the influence of rifampicin cotreatment, efavirenz pharmacokinetics and pharmacogenetics on neuropsychiatric disorders in Ugandan HIV patients with or without tuberculosis coinfection.

Methods

197 treatment naïve Ugandan HIV patients, of whom 138 were TB co-infected, enrolled prospectively and received efavirenz based HAART. TB-HIV confected patients received concomitant rifampicin based anti-TB therapy. Genotypes forCYP2B6(*6,*11),CYP3A5(*3,*6,*7), ABCB1 (c.3435C>T and c.4036 A/G rs3842),CYP2A6(*9, *17) andNR1I3rs3003596 T/C were determined. Efavirenz plasma concentrations were serially quantified at 3rd day, 1st, 2nd, 4th, 6th, 8th and 12th weeks during therapy. Efavirenz neuropsychiatric symptoms were evaluated in terms of sleep disorders, hallucinations and cognitive effects at baseline, at two and twelve weeks of efavirenz treatment using a modified Mini Mental State Examination (MMSE) score.

Results

During the first twelve weeks of ART, 73.6% of the patients experienced at least one efavirenz related neuropsychiatric symptom. Commonest symptoms experienced were sleep disorders 60.5% (n=124) and hallucination 30.7% (n=63). Neuropsychiatric symptoms during HAART were significantly predicted by efavirenz plasma concentrations consistently. Rifampicin cotreatment reduced plasma efavirenz concentrations significantly only during the first week but not afterwards. There was no significant difference in the incidence of neuropsychiatric symptoms between patients receiving efavirenz with or without rifampicin cotreatment.CYP2B6*6and ABCB1 c.4036 A/G genotype significantly predicted efavirenz concentrations. The tendency ofCYP2B6*6genotype association with higher incidence of having vivid dream (p=0.05), insomnia (p=0.19) and tactile hallucination (p=0.09) was observed mainly at week-2.

Conclusions

Efavirenz related neuropsychiatric symptoms are common among Ugandan HIV patients receiving ART and is mainly predicted by higher efavirenz plasma concentrations andCYP2B6genotype but not by rifampicin based anti-TB co-treatment.
Association between psychiatric disorders and iron deficiency anemia among children and adolescents: a nationwide population-based study
Authors: Chen Mu-Hong , Su Tung-Ping , Chen Ying-Sheue , Hsu Ju-Wei , Huang Kai-Lin , Chang Wen-Han , Chen Tzeng-Ji , Bai Ya-Mei
Published: June 2013

Background

A great deal of evidence has shown that iron is an important component in cognitive, sensorimotor, and social-emotional development and functioning, because the development of central nervous system processes is highly dependent on iron-containing enzymes and proteins. Deficiency of iron in early life may increase the risk of psychiatric morbidity.

Methods

Utilizing the National Health Insurance Database from 1996 to 2008, children and adolescents with a diagnosis of IDA were identified and compared with age and gender-matched controls (1:4) in an investigation of the increased risk of psychiatric disorders.

Results

A total of 2957 patients with IDA, with an increased risk of unipolar depressive disorder (OR = 2.34, 95% CI = 1.58 ~ 3.46), bipolar disorder (OR = 5.78, 95% CI = 2.23 ~ 15.05), anxiety disorder (OR = 2.17, 95% CI = 1.49 ~ 3.16), autism spectrum disorder (OR = 3.08, 95% CI = 1.79 ~ 5.28), attention deficit hyperactivity disorder (OR = 1.67, 95% CI = 1.29 ~ 2.17), tic disorder (OR = 1.70, 95% CI = 1.03 ~ 2.78), developmental delay (OR = 2.45, 95% CI = 2.00 ~ 3.00), and mental retardation (OR = 2.70, 95% CI = 2.00 ~ 3.65), were identified. A gender effect was noted, in that only female patients with IDA had an increased OR of bipolar disorder (OR = 5.56, 95% CI = 1.98 ~ 15.70) and tic disorder (OR = 2.95, 95% CI = 1.27 ~ 6.86).

Conclusion

Iron deficiency increased the risk of psychiatric disorders, including mood disorders, autism spectrum disorder, attention deficit hyperactivity disorder, and developmental disorders. Further study is required to clarify the mechanism in the association between IDA and psychiatric disorder.
What is different about medical students interested in non-clinical careers?
Authors: Kim Kyong-Jee , Park Jae-Hyun , Lee Young-Ho , Choi Kyusik
Published: June 2013

Background

The proportion of medical school graduates who pursue careers other than full-time clinical practice has increased in some countries as the physician’s role has evolved and diversified with the changing landscape of clinical practice and the advancement of biomedicine. Still, past studies of medical students’ career choices have focused on clinical specialties and little is known about their choice of non-clinical careers. The present study examined backgrounds, motivation and perceptions of medical students who intended non-clinical careers.

Methods

A questionnaire was administered to students at six Korean medical schools distributed across all provinces in the nation. The questionnaire comprised 40 items on respondents’ backgrounds, their motivation for and interest in the study of medicine, their perceptions of medical professions, and their career intentions. Data was analyzed using various descriptive and inferential statistics.

Results

In total, 1,388 students returned the questionnaire (60% response rate), 12.3% of whom intended non-clinical careers (i.e., basic sciences, non-clinical medical fields, and non-medical fields). Those who planned non-clinical careers were comparable with their peers in their motivation for studying medicine and in their views of medical professions, but they were less interested in the study of medicine (P < 0.01). The two groups also differed significantly on their perceptions of what was uninteresting about the study of medicine (P < 0.01). The two groups were comparable in gender and entry-level ratios but their distributions across ages and years of study differed significantly (P < 0.01). A majority of respondents agreed with the statements that “it is necessary for medical school graduates to pursue non-clinical careers” and that “medical schools need to offer programs that provide information on such careers.” Still, our finding indicates that medical school curricula do not address such needs sufficiently.

Conclusions

Our study found some differences in backgrounds and perceptions of the study of medicine in medical students interested in non-clinical careers from their peers. Future studies are suggested to enhance our understanding of medical students” choice of non-clinical careers.
Some common fixed point theorems for a family of non-self mappings in cone metric spaces
Authors: Huang Xianjiu , Zhu Chuanxi , Wen Xi , Lalović Ljubica
Published: June 2013

Some common fixed point theorems for a family of non-self mappings defined on a closed subset of a metrically convex cone metric space (over the cone which is not necessarily normal) are obtained which generalize earlier results due to Imdad et al. and Janković et al.

MSC:47H10, 54H25.
Smoking and alcohol consumption patterns among elderly Canadians with mobility disabilities
Authors: Liu Fang , Woodrow Jennifer , Loucks-Atkinson Angela , Buehler Sharon , West Roy , Wang Peizhong Peter
Published: June 2013

Background

Mobility disability is a major adverse health outcome associated with aging and an impediment to older adults’ well-being and behaviors in social and leisure activities. It has been shown that lifestyle factors, including smoking and alcohol consumption, have been used as coping strategies to deal with the negative impact of disability. The aim of this study was to determine the prevalence of smoking and alcohol consumption among older Canadians with different levels of mobility disabilities and to examine factors associated with these two lifestyle patterns among those with disabilities.

Methods

Secondary data analysis was performed using individuals (n = 6,038) aged 65 years and older from both the 2001 Participation and Activity Limitation Survey and the 2003 Canadian Community Health Survey. Multivariate logistic regressions examined the relationship between disability severity and smoking as well as alcohol consumption while controlling for potential confounding socioeconomic factors.

Results

The proportion of current smokers among seniors with less-severe and more-severe mobility disabilities and those in the general population was comparable with 12.55%, 11.57% and 11.93%, respectively. Forty-eight percent of seniors in the general population consumed alcohol regularly, compared to only 12.85% with more-severe mobility disabilities. No significant association was shown between the severity level of mobility disabilities and smoking (odds ratio = 0.90, 95% confidence interval: 0.75, 1.08). However, seniors having more-severe disability were less likely to consume alcohol regularly (odds ratio = 0.76, 95% confidence interval: 0.65, 0.89). Other variables including age, gender, income, living status, and social participation also impacted these lifestyle patterns among the study population.

Conclusions

Smoking and alcohol patterns present different associations with the severity level of mobility disabilities. Compared with the general population, elderly Canadians with mobility disabilities had similar smoking prevalence but differ significantly in terms of alcohol consumption. Results from this research will be relevant to decision makers involved in program planning, health education, and policy development as it pertains to the prevention and management of age-related disability.
Distinct roles of KAP1, HP1 and G9a/GLP in silencing of the two-cell-specific retrotransposon MERVL in mouse ES cells
Authors: Maksakova Irina A , Thompson Peter J , Goyal Preeti , Jones Steven JM , Singh Prim B , Karimi Mohammad M , Lorincz Matthew C
Published: June 2013

Background

In mouse embryonic stem cells (mESCs), transcriptional silencing of numerous class I and II endogenous retroviruses (ERVs), including IAP, ETn and MMERVK10C, is dependent upon the H3K9 methyltransferase (KMTase) SETDB1/ESET and its binding partner KAP1/TRIM28. In contrast, the H3K9 KMTases G9a and GLP and HP1 proteins are dispensable for this process. Intriguingly, MERVL retroelements are actively transcribed exclusively in the two-cell (2C) embryo, but the molecular basis of silencing of these class III ERVs at later developmental stages has not been systematically addressed.

Results

Here, we characterized the roles of these chromatin factors in MERVL silencing in mESCs. While MMERVK10C and IAP ERVs are bound by SETDB1 and KAP1 and are induced following their deletion, MERVL ERVs show relatively low levels of SETDB1 and KAP1 binding and are upregulated exclusively following KAP1 depletion, indicating that KAP1 influences MERVL expression independent of SETDB1. In contrast to class I and class II ERVs, MERVL and MERVL LTR-driven genic transcripts are also upregulated following depletion of G9a or GLP, and G9a binds directly to these ERVs. Consistent with a direct role for H3K9me2 in MERVL repression, these elements are highly enriched for G9a-dependent H3K9me2, and catalytically active G9a is required for silencing of MERVL LTR-driven transcripts. MERVL is also derepressed in HP1α and HP1β KO ESCs. However, like KAP1, HP1α and HP1β are only modestly enriched at MERVL relative to IAP LTRs. Intriguingly, as recently shown for KAP1, RYBP, LSD1 and G9a-deficient mESCs, many genes normally expressed in the 2C embryo are also induced in HP1 KO mESCs, revealing that aberrant expression of a subset of 2C-specific genes is a common feature in each of these KO lines.

Conclusions

Our results indicate that G9a and GLP, which are not required for silencing of class I and II ERVs, are recruited to MERVL elements and play a direct role in silencing of these class III ERVs, dependent upon G9a catalytic activity. In contrast, induction of MERVL expression in KAP1, HP1α and HP1β KO ESCs may occur predominantly as a consequence of indirect effects, in association with activation of a subset of 2C-specific genes.
Intellectual function evaluation of first generation immigrant children with sickle cell disease: the role of language and sociodemographic factors
Authors: Montanaro Maria , Colombatti Raffaella , Pugliese Marisa , Migliozzi Camilla , Zani Fabiana , Guerzoni Maria Elena , Manoli Sheila , Manara Renzo , Meneghetti Giorgio , Rampazzo Patrizia , Cavalleri Francesca , Giordan Marco , Paolucci Paolo , Basso Giuseppe , Palazzi Giovanni , Sainati Laura
Published: June 2013

Background

Sickle Cell Disease (SCD) is the most common genetic disease worldwide. Neurological events are among the most worrisome clinical complications of SCD and are frequently accompanied by cognitive impairment. Intellectual function in SCD may vary according to genetic and environmental factors. Immigrant children with SCD are increasing at a global level and display specific health care needs. The aim of our multicenter study was to describe the intellectual function of first generation African immigrants with SCD and the influence of sociodemographic factors on its characteristics.

Methods

The Wechsler Intelligence Scales were administered to evaluate broad intellectual functions in children with SCD and in age-matched healthy siblings. Patients’ clinical, socio-demographic, Magnetic Resonance Imaging (MRI) and Angiography (MRA) data were correlated to intellectual function scores.

Results

68 children, mean age 8.95 years were evaluated. 72% spoke three languages, 21% two. FSIQ was <75 in 25% of the children. Mean VIQ was lower than PIQ in 75%. Mean verbal subtest scores were lower than performance scores. Female gender, number of languages spoken at home and mother’s employment were associated with single subtest performances (p < 0.05). MRA was abnormal in 73.4% and MRI in 35.9%. No significant correlation was established between silent lesions and intellectual function, even if patients with lesions performed worse. Fifteen siblings performed better than patients on cognitive domains, including language (p < 0.05).

Conclusions

Immigrant bilingual children with SCD seem to display a rate of cognitive impairment similar to their monolingual counterparts but a more pronounced and precocious onset of language difficulties. Adjunctive tests need to be considered in this group of patients to better define their specific deficits.
Lineages of Streptococcus equi ssp. equi in the Irish equine industry
Authors: Moloney Emma , Kavanagh Kerrie S , Buckley Tom C , Cooney Jakki C
Published: June 2013

Background

Streptococcus equi ssp. equi is the causative agent of ‘Strangles’ in horses. This is a debilitating condition leading to economic loss, yard closures and cancellation of equestrian events. There are multiple genotypes of S. equi ssp. equi which can cause disease, but to date there has been no systematic study of strains which are prevalent in Ireland. This study identified and classified Streptococcus equi ssp. equi strains isolated from within the Irish equine industry.

Results

Two hundred veterinary isolates were subjected to SLST (single locus sequence typing) based on an internal sequence from the seM gene of Streptococcus equi ssp equi. Of the 171 samples which successfully gave an amplicon, 162 samples (137 Irish and 24 UK strains) gave robust DNA sequence information. Analysis of the sequences allowed division of the isolates into 19 groups, 13 of which contain at least 2 isolates and 6 groups containing single isolates. There were 19 positions where a DNA SNP (single nucleotide polymorphism) occurs, and one 3 bp insertion. All groups had multiple (2–8) SNPs. Of the SNPs 17 would result in an amino acid change in the encoded protein. Interestingly, the single isolate EI8, which has 6 SNPs, has the three base pair insertion which is not seen in any other isolate, this would result in the insertion of an Ile residue at position 62 in that protein sequence. Comparison of the relevant region in the determined sequences with the UK Streptococcus equi seM MLST database showed that Group B (15 isolates) and Group I (2 isolates), as well as the individual isolates EI3 and EI8, are unique to Ireland, and some groups are most likely of UK origin (Groups F and M), but many more probably passed back and forth between the two countries.

Conclusions

The strains occurring in Ireland are not clonal and there is a considerable degree of sequence variation seen in the seM gene. There are two major clades causing infection in Ireland and these strains are also common in the UK.
Assessment and clinical course of hypocalcemia in critical illness
Authors: Steele Tom , Kolamunnage-Dona Ruwanthi , Downey Colin , Toh Cheng-Hock , Welters Ingeborg
Published: June 2013

Introduction

Hypocalcemia is common in critically ill patients. However, its clinical course during the early days of admission and the role of calcium supplementation remain uncertain, and the assessment of calcium status is inconsistent. We aimed to establish the course of hypocalcemia during the early days of critical illness in relation to mortality and to assess the impact of calcium supplementation on calcium normalization and mortality.

Methods

Data were collected on 1,038 admissions to the critical care units of a tertiary care hospital. One gram of calcium gluconate was administered intravenously once daily to patients with adjusted calcium (AdjCa) <2.2 mmol/L. Demographic and outcome data were compared in normocalcemic (ionized calcium, iCa, 1.1-1.3 mmol/L) and mildly and severely hypocalcemic patients (iCa 0.9-1.1 mmol/L and <0.9 mmol/L, respectively). The change in iCa concentrations was monitored during the first four days of admission and comparisons between groups were made using Repeated Measures ANOVA. Comparisons of normalization and outcome were made between hypocalcemic patients who did and did not receive calcium replacement according to the local protocol. The suitability of AdjCa to predict low iCa was determined by analyzing sensitivity, specificity and receiver operating characteristic (ROC) curves. Multivariate logistic regression was performed to determine associations of other electrolyte derangements with hypocalcemia.

Results

55.2% of patients were hypocalcemic on admission; 6.2% severely so. Severely hypocalcemic patients required critical care for longer (P = 0.001) compared to normocalcemic or mildly hypocalcemic patients, but there was no difference in mortality between groups (P = 0.48). iCa levels normalized within four days in most, with no difference in normalization between those who died and survived (P = 0.35). Severely hypocalcemic patients who failed to normalize their iCa by day 4 had double the mortality (38% vs. 19%, P = 0.15). Neither iCa normalization nor survival were superior in hypocalcemic patients receiving supplementation on admission. AdjCa <2.2 mmol/L had a sensitivity of 78.2% and specificity of 63.3% for predicting iCa <1.1 mmol/L. Low magnesium, sodium and albumin were independently associated with hypocalcemia on admission.

Conclusions

Hypocalcemia usually normalizes within the first four days after admission to ICU and failure to normalize in severely hypocalcemic patients may be associated with increased mortality. Calcium replacement appears not to improve normalization or mortality. AdjCa is not a good surrogate of iCa in an ICU setting.
Mesenchymal stem cells generate a CD4+CD25+Foxp3+ regulatory T cell population during the differentiation process of Th1 and Th17 cells
Authors: Luz-Crawford Patricia , Kurte Monica , Bravo-Alegría Javiera , Contreras Rafael , Nova-Lamperti Estefania , Tejedor Gautier , Noël Danièle , Jorgensen Christian , Figueroa Fernando , Djouad Farida , Carrión Flavio
Published: June 2013

Introduction

Mesenchymal stem cells (MSCs) are adult, multipotent, stem cells with immunomodulatory properties. The mechanisms involved in the capacity of MSCs to inhibit the proliferation of proinflammatory T lymphocytes, which appear responsible for causing autoimmune disease, have yet to be fully elucidated. One of the underlying mechanisms studied recently is the ability of MSCs to generate T regulatory (Treg) cells in vitro and in vivo from activated peripheral blood mononuclear cells (PBMC), T-CD4+ and also T-CD8+ cells. In the present work we investigated the capacity of MSCs to generate Treg cells using T-CD4+ cells induced to differentiate toward the proinflammatory Th1 and Th17 lineages.

Methods

MSCs were obtained from mouse bone marrow and characterized according to their surface antigen expression and their multilineage differentiation potential. CD4+ T cells isolated from mouse spleens were induced to differentiate into Th1 or Th17 cells and co-cultured with MSCs added at day 0, 2 or 4 of the differentiation processes. After six days, CD25, Foxp3, IL-17 and IFN-γ expression was assessed by flow cytometry and helios and neuropilin 1 mRNA levels were assessed by RT-qPCR. For the functional assays, the ‘conditioned’ subpopulation generated in the presence of MSCs was cultured with concanavalin A-activated CD4+ T cells labeled with carboxyfluorescein succinimidyl ester. Finally, we used the encephalomyelitis autoimmune diseases (EAE) mouse model, in which mice were injected with MSCs at day 18 and 30 after immunization. At day 50, the mice were euthanized and draining lymph nodes were extracted for Th1, Th17 and Treg detection by flow cytometry.

Results

MSCs were able to suppress the proliferation, activation and differentiation of CD4+ T cells induced to differentiate into Th1 and Th17 cells. This substantial suppressive effect was associated with an increase of the percentage of functional induced CD4+CD25+Foxp3+ regulatory T cells and IL-10 secretion. However, using mature Th1 or Th17 cells our results demonstrated that while MSCs suppress the proliferation and phenotype of mature Th1 and Th17 cells they did not generate Treg cells. Finally, we showed that the beneficial effect observed following MSC injection in an EAE mouse model was associated with the suppression of Th17 cells and an increase in the percentage of CD4+CD25+Foxp3+ T lymphocytes when administrated at early stages of the disease.

Conclusions

This study demonstrated that MSCs contribute to the generation of an immunosuppressive environment via the inhibition of proinflammatory T cells and the induction of T cells with a regulatory phenotype. Together, these results might have important clinical implications for inflammatory and autoimmune diseases.
From F = ma to Flying Squirrels: Curricular Change in an Introductory Physics Course
Authors: O’Shea Brian , Terry Laura , Benenson Walter
Published: June 2013

We present outcomes from curricular changes made to an introductory calculus-based physics course whose audience is primarily life sciences majors, the majority of whom plan to pursue postbaccalaureate studies in medical and scientific fields. During the 2011–2012 academic year, we implemented a Physics of the Life Sciences curriculum centered on a draft textbook that takes a novel approach to teaching physics to life sciences majors. In addition, substantial revisions were made to the homework and hands-on components of the course to emphasize the relationship between physics and the life sciences and to help the students learn to apply physical intuition to life sciences–oriented problems. Student learning and attitudinal outcomes were assessed both quantitatively, using standard physics education research instruments, and qualitatively, using student surveys and a series of postsemester interviews. Students experienced high conceptual learning gains, comparable to other active learning–based physics courses. Qualitatively, a substantial fraction of interviewed students reported an increased interest in physics relative to the beginning of the semester. Furthermore, more than half of students self-reported that they could now relate physics topics to their majors and future careers, with interviewed subjects demonstrating a high level of ability to come up with examples of how physics affects living organisms and how it helped them to better understand content presented in courses in their major.
A Framework for Analyzing Interdisciplinary Tasks: Implications for Student Learning and Curricular Design
Authors: Gouvea Julia Svoboda , Sawtelle Vashti , Geller Benjamin D. , Turpen Chandra
Published: June 2013

The national conversation around undergraduate science instruction is calling for increased interdisciplinarity. As these calls increase, there is a need to consider the learning objectives of interdisciplinary science courses and how to design curricula to support those objectives. We present a framework that can help support interdisciplinary design research. We developed this framework in an introductory physics for life sciences majors (IPLS) course for which we designed a series of interdisciplinary tasks that bridge physics and biology. We illustrate how this framework can be used to describe the variation in the nature and degree of interdisciplinary interaction in tasks, to aid in redesigning tasks to better align with interdisciplinary learning objectives, and finally, to articulate design conjectures that posit how different characteristics of these tasks might support or impede interdisciplinary learning objectives. This framework will be useful for both curriculum designers and education researchers seeking to understand, in more concrete terms, what interdisciplinary learning means and how integrated science curricula can be designed to support interdisciplinary learning objectives.
Toward University Modeling Instruction—Biology: Adapting Curricular Frameworks from Physics to Biology
Authors: Manthey Seth , Brewe Eric
Published: June 2013

University Modeling Instruction (UMI) is an approach to curriculum and pedagogy that focuses instruction on engaging students in building, validating, and deploying scientific models. Modeling Instruction has been successfully implemented in both high school and university physics courses. Studies within the physics education research (PER) community have identified UMI's positive impacts on learning gains, equity, attitudinal shifts, and self-efficacy. While the success of this pedagogical approach has been recognized within the physics community, the use of models and modeling practices is still being developed for biology. Drawing from the existing research on UMI in physics, we describe the theoretical foundations of UMI and how UMI can be adapted to include an emphasis on models and modeling for undergraduate introductory biology courses. In particular, we discuss our ongoing work to develop a framework for the first semester of a two-semester introductory biology course sequence by identifying the essential basic models for an introductory biology course sequence.
Developing and Assessing Curriculum on the Physics of Medical Instruments
Authors: Christensen Warren , Johnson James K. , Van Ness Grace R. , Mylott Elliot , Dunlap Justin C. , Anderson Elizabeth A. , Widenhorn Ralf
Published: June 2013

Undergraduate educational settings often struggle to provide students with authentic biologically or medically relevant situations and problems that simultaneously improve their understanding of physics. Through exercises and laboratory activities developed in an elective Physics in Biomedicine course for upper-level biology or pre–health majors at Portland State University, we aim to teach fundamental physical concepts, such as light absorption and emission and atomic energy levels, through analysis of biological systems and medical devices. The activities address the properties of electromagnetic waves as they relate to the interaction with biological tissue and make links between physics and biomedical applications such as microscopy or laser eye surgery. We report on the effect that engaging students in tasks with actual medical equipment has had on their conceptual understanding of light and spectroscopy. These initial assessments indicate that students’ understanding improves in some areas as a result of taking the course, but gains are not uniform and are relatively low for other topics. We also find a promising “nonshift” in student attitudes toward learning science as a result of taking the course. A long-term goal of this work is to develop these materials to the extent that they can eventually be imported into an introductory curriculum for life sciences majors.
Integration of Physics and Biology: Synergistic Undergraduate Education for the 21st Century
Authors: Woodin Terry , Vasaly Helen , McBride Duncan , White Gary
Published: June 2013

This is an exciting time to be a biologist. The advances in our field and the many opportunities to expand our horizons through interaction with other disciplines are intellectually stimulating. This is as true for people tasked with helping the field move forward through support of research and education projects that serve the nation's needs as for those carrying out that research and educating the next generation of biologists. So, it is a pleasure to contribute to this edition of CBE—Life Sciences Education. This column will cover three aspects of the interactions of physics and biology as seen from the viewpoint of four members of the Division of Undergraduate Education of the National Science Foundation. The first section places the material to follow in context. The second reviews some of the many interdisciplinary physics–biology projects we support. The third highlights mechanisms available for supporting new physics–biology undergraduate education projects based on ideas that arise, focusing on those needing and warranting outside support to come to fruition.
A low-frequency passive seismic array experiment over an onshore oil field in Abu Dhabi, United Arab Emirates
Authors: Ali Mohammed Y. , Barkat Braham , Berteussen Karl A. , Small James
Published: June 2013

A low-frequency passive seismic experiment using an array of 49 3C broadband seismometers was conducted over an onshore oil field in the emirate of Abu Dhabi in the United Arab Emirates. The aim of the experiment was to understand the characteristics and origins of the microseism (0.15–0.4 Hz) and microtremor (about 1–6 Hz) signals recorded, the latter having been reported as being a hydrocarbon indicator above several reservoirs in the region. The recorded array data were analyzed for their polarization, apparent velocities, and wavefront azimuths using various techniques, including spectral and time-frequency analyses, particle motion, H/V spectral ratios, and high-resolution frequency-wavenumber (f-k) analyses. In the frequency range of 0.15–0.4 Hz, the dominant feature observed consisted of double-frequency microseisms peaks generated by the nonlinear interactions of ocean waves with the shoreline along the coasts of the Arabian Sea and the Arabian Gulf. The f-k analyses confirmed that microtremor events in the frequency range of 2–3 Hz have an azimuth pointing toward a major oil pipeline and oil plant facilities to the west–southwest of the study area, as well as a motorway to the southeast. This would indicate that the microtremor events are probably caused by local sources, including the continuous movement of oil through the pipeline, the noise from oil plant facilities, as well as nearby traffic noise. This interpretation was confirmed by the polarization analysis performed on the data. The data also indicated that no clear correlation exists between the microtremor signal and local meteorological conditions. Although some body waves with an infinite apparent velocity generated by earthquakes were recorded, no other body waves that could have possibly been generated by hydrocarbon reservoirs were observed using the analyses techniques used in this study. Therefore, our results indicated that for the site under investigation, the microseism and the microtremor signals detected could not be related to the presence of hydrocarbon accumulations in the subsurface, but instead they may be attributed to local anthropogenic sources.
Modeling of pseudoacoustic P-waves in orthorhombic media with a low-rank approximation
Authors: Song Xiaolei , Alkhalifah Tariq
Published: June 2013

Wavefield extrapolation in pseudoacoustic orthorhombic anisotropic media suffers from wave-mode coupling and stability limitations in the parameter range. We use the dispersion relation for scalar wave propagation in pseudoacoustic orthorhombic media to model acoustic wavefields. The wavenumber-domain application of the Laplacian operator allows us to propagate the P-waves exclusively, without imposing any conditions on the parameter range of stability. It also allows us to avoid dispersion artifacts commonly associated with evaluating the Laplacian operator in space domain using practical finite-difference stencils. To handle the corresponding space-wavenumber mixed-domain operator, we apply the low-rank approximation approach. Considering the number of parameters necessary to describe orthorhombic anisotropy, the low-rank approach yields space-wavenumber decomposition of the extrapolator operator that is dependent on space location regardless of the parameters, a feature necessary for orthorhombic anisotropy. Numerical experiments that the proposed wavefield extrapolator is accurate and practically free of dispersion. Furthermore, there is no coupling of qSv and qP waves because we use the analytical dispersion solution corresponding to the P-wave.
On seismic deghosting using integral representation for the wave equation: Use of Green’s functions with Neumann or Dirichlet boundary conditions
Authors: Amundsen Lasse , Weglein Arthur B. , Reitan Arne
Published: June 2013

The recent interest in broadband seismic technology has spurred research into new and improved seismic deghosting solutions. One starting point for deriving deghosting methods is the representation theorem, which is an integral representation for the wave equation. Recent research results show that by using Green’s functions with Dirichlet boundary conditions in the representation theorem, source-side deghosting of already receiver-side deghosted wavefields can be achieved. We found that the choice of Green’s functions with Neumann boundary conditions on the sea surface and the plane that contains the sources leads to an identical but simpler solution with fewer processing steps. In addition, we found that pressure data can be receiver-side deghosted by introducing Green’s functions with Dirichlet boundary conditions on the sea surface and the plane containing the receivers into a modified representation theorem. The deghosting methods derived from the representation theorem are wave-theoretic algorithms defined in the frequency-space domain and can accommodate streamers of any shape (e.g., slanted). Our theoretical analysis of deghosting is performed in the frequency-wavenumber domain where analytical deghosting solutions are well known and thus are available for verifying the solutions. A simple numerical example can be used to show how source-side deghosting can be performed in the space domain by convolving data with Green’s functions.
Randomized Double-Blind Placebo-Controlled Trial of Acetyl-L-Carnitine for the Prevention of Taxane-Induced Neuropathy in Women Undergoing Adjuvant Breast Cancer Therapy
Authors: Hershman Dawn L. , Unger Joseph M. , Crew Katherine D. , Minasian Lori M. , Awad Danielle , Moinpour Carol M. , Hansen Lisa , Lew Danika L. , Greenlee Heather , Fehrenbacher Louis , Wade James L. , Wong Siu-Fun , Hortobagyi Gabriel N. , Meyskens Frank L. , Albain Kathy S.
Published: June 2013

Purpose

Chemotherapy-induced peripheral neuropathy (CIPN) is common and leads to suboptimal treatment. Acetyl-L-carnitine (ALC) is a natural compound involved in neuronal protection. Studies have suggested ALC may be effective for the prevention and treatment of CIPN.

Patients and Methods

A 24-week randomized double-blind trial comparing ALC (3,000 mg per day) with placebo in women undergoing adjuvant taxane-based chemotherapy was conducted. The primary objective was to determine if ALC prevents CIPN as measured by the 11-item neurotoxicity (NTX) component of the Functional Assessment of Cancer Therapy (FACT) –Taxane scale at 12 weeks. Secondary objectives included changes in 24-week end points, functional status (FACT–Trial Outcome Index [TOI]), fatigue (Functional Assessment of Chronic Illness Therapy [FACIT] –Fatigue), and NTX grade.

Results

A total of 409 patients were evaluable (208 received ALC; 201, placebo). In a multivariate linear regression, week-12 scores were 0.9 points lower (more CIPN) with ALC than placebo (95% CI, −2.2 to 0.4; P = .17), whereas week-24 scores were 1.8 points lower with ALC (95% CI, −3.2 to −0.4; P = .01). Patients receiving ALC were more likely to have a > 5-point decrease in FACT-NTX scores (38% v 28%; P = .05), and FACT-TOI scores were 3.5 points lower with ALC (P = .03). Grade 3 to 4 neurotoxicity was more frequent in the ALC arm (eight v one). No differences between arms were observed for FACIT-Fatigue or other toxicities. Serum carnitine level increased with ALC but remained stable with placebo.

Conclusion

There was no evidence that ALC affected CIPN at 12 weeks; however, ALC significantly increased CIPN by 24 weeks. This is the first study to our knowledge showing that a nutritional supplement increased CIPN. Patients should be discouraged from using supplements without proven efficacy.
Population-Based Molecular Screening for Lynch Syndrome: Implications for Personalized Medicine
Authors: Ward Robyn L. , Hicks Sian , Hawkins Nicholas J.
Published: June 2013

Purpose

Molecular screening techniques are available to identify hereditary Lynch syndrome in people with newly diagnosed colorectal cancer (CRC). We aimed to determine whether decisions of patients or clinicians reduced detection of Lynch syndrome.

Patients and Methods

A prospective cohort of 245 consecutive individuals with mismatch repair–deficient CRC recruited from a population-based molecular screening program of all incident patient cases of CRC in a health care region of 1.2 million inhabitants. All incident CRCs were analyzed for mismatch repair protein loss, supported by BRAF mutation and microsatellite instability testing. Advice regarding referral for germline testing was provided to treating surgeons.

Results

The mean age of patients was 72.5 ± standard deviation of 12 years; 64% were women; 65% had BRAF-mutant cancers. Consent for germline testing was received from 194 patients (79%): 120 with low and 74 with high likelihood of Lynch syndrome based on tumor molecular profile. Of patients who consented, 143 provided samples for germline analysis, with 12 of 143 showing a mutation (8.4%; 95% CI, 4.4% to 14.2%). Among the 102 patients who chose not to provide a sample or did not consent, an estimated 5.3 of 102 had germline mutations (5.2%; 95% CI, 2.0% to 17.5%).

Conclusion

A universal screening strategy for Lynch syndrome is potentially effective because the overall estimate of germline mutations was 17.3 of 245 patient cases (7.1%; 95% CI, 2.8% to 18.2%). However, the true value of screening is likely to be greatly limited by the decisions and circumstances of patients in taking up germline testing.
Impact of Age on the Efficacy of Newer Adjuvant Therapies in Patients With Stage II/III Colon Cancer: Findings From the ACCENT Database
Authors: McCleary Nadine J. , Meyerhardt Jeffrey A. , Green Erin , Yothers Greg , de Gramont Aimery , Van Cutsem Eric , O'Connell Michael , Twelves Christopher J. , Saltz Leonard B. , Haller Daniel G. , Sargent Daniel J.
Published: June 2013

Purpose

Prior studies have suggested that patients with stage II/III colon cancer receive similar benefit from intravenous (IV) fluoropyrimidine adjuvant therapy regardless of age. Combination regimens and oral fluorouracil (FU) therapy are now standard. We examined the impact of age on colon cancer recurrence and mortality after adjuvant therapy with these newer options.

Patients and Methods

We analyzed 11,953 patients age < 70 and 2,575 age ≥ 70 years from seven adjuvant therapy trials comparing IV FU with oral fluoropyrimidines (capecitabine, uracil, or tegafur) or combinations of fluoropyrimidines with oxaliplatin or irinotecan in stage II/III colon cancer. End points were disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR).

Results

In three studies comparing oxaliplatin-based chemotherapy with IV FU, statistically significant interactions were not observed between treatment arm and age (P interaction = .09 for DFS, .05 for OS, and .36 for TTR), although the stratified point estimates suggested limited benefit from the addition of oxaliplatin in elderly patients (DFS hazard ratio [HR], 0.94; 95% CI, 0.78 to 1.13; OS HR, 1.04; 95% CI, 0.85 to 1.27). No significant interactions by age were detected with oral fluoropyrimidine therapy compared with IV FU; noninferiority was supported in both age populations.

Conclusion

Patients age ≥ 70 years seemed to experience reduced benefit from adding oxaliplatin to fluoropyrimidines in the adjuvant setting, although statistically, there was not a significant effect modification by age, whereas oral fluoropyrimidines retained their efficacy.
Pro-oxidant activity of dietary chemopreventive agents: an under-appreciated anti-cancer property
Authors: Azmi Asfar S , Sarkar Fazlul H , Hadi SM
Published: June 2013

“Let food be thy medicine and medicine be thy food” was quoted by Hippocrates more than two thousand years ago and since ancient times the health benefits of different natural agents have been exploited. In modern research, the disease preventive benefits of many such natural agents, particularly dietary compounds and their derivatives, has been attributed to their well recognized activity as the regulators of redox state of the cell. Nevertheless, most of these studies have focused on their antioxidant activity. A large body of evidence indicates that a major fraction of these agents can elicit pro-oxidant (radical generating) behavior which has been linked to their anti-cancer effects. This editorial provides an overview of the under-appreciated pro-oxidant activity of natural products, with a special focus on their ability to generate reactive oxygen species in the presence of transition metal ions, and discusses their possible use as cancer chemotherapeutic agents.
Effecting Healthy Lifestyle Changes in Overweight and Obese Young Adults With Intellectual Disability
Authors: Pett Marjorie , Clark Lauren , Eldredge Alison , Cardell Beth , Jordan Kristine , Chambless Cathy , Burley Jeff
Published: June 2013

We evaluated a 12-week recreation center–based healthy lifestyle intervention for 30 obese home-dwelling young adults (YA) with intellectual disabilities. Three cohorts participated: YA only, YA and parents, and parents only. The YA cohorts received a nutrition/exercise intervention; parents focused on modeling healthy lifestyle behaviors. Outcomes included YA blood, nutrition, anthropometric, and fitness measures at pre, post, and 3-month follow-up. Compared with wait-list controls, the YA-only cohort improved immediately postintervention in blood pressure (BP), weight, and balance (p < .05). At 3-month follow-up, no intervention was consistently superior; overall reductions in weight, BP, hip circumference, and exercise barriers were obtained (p < .05). Linear and curvilinear changes from baseline to 3 months after the intervention varied by outcome and participant. Participants with Down syndrome lost less weight.
Assessment of the Tempering Behavior of Grade 91 Steel
Authors: Parker Jonathan , Siefert John , Coleman Kent
Published: June 2013

At any point in the fabrication and installation of Grade 91 components, undesirable metallurgical conditions can develop as a result of incorrect heat treatment. Industry techniques for locating and evaluating these microstructures using nondestructive methods are necessary. Field hardness testing is commonly utilized to characterize Grade 91 steel installed in plants. However, it is apparent that there are numerous variables that can affect the results of field hardness testing. Thus, the results can vary significantly depending on the equipment and procedures used. The present study has been undertaken to identify the accuracy of hardness measurements made under controlled laboratory conditions. Measurements were performed on samples that had been subjected to a range of different tempering conditions. The trend in these data provides information relevant to understanding the metallurgical behavior of this steel. Comparison of the data also indicates how measurements made using different hardness testers and methods can be used to assess component condition.
Estrogen receptor α (ESR1) over-expression mediated apoptosis in Hep3B cells by binding with SP1 proteins
Authors: Tu Chuan-Chou , Kumar V Bharath , Day Cecilia Hsuan , Kuo Wei-Wen , Yeh Su-Peng , Chen Ray-Jade , Liao Chen-Rong , Chen Hsiao-Yu , Tsai Fuu-Jen , Wu Wen-Jun , Huang Chih-Yang
Published: June 2013

Previous studies have reported that estrogen receptors (ERs) are expressed in normal human liver, chronic hepatitis, and benign hepatic tumor tissues. However, decreased expression of ERs can be observed in hepatocellular carcinoma (HCC) and the role of ERs in HCC is not fully understood. Thus, the present study aimed to investigate the molecular mechanism induced by the overexpression of ERα (ERα (ESR1)) in Hep3B cells. We first detected the induction of apoptosis in ER-negative Hep3B cells using DNA fragmentation assay and flow cytometry. We found that ERα and ERα plus 17β-estradiol treatment increased apoptosis in Hep3B cells. Additionally, western blotting showed increased expression of active caspase 3 and tumor necrosis factor α (TNFα (TNF)) inERα-transfected cells. To further understand the importance of SP1-binding sites in theTNFαpromoter, ERα-negative Hep3B cells were co-transfected withERαand a wild-type TNFα plasmid orTNFαwith deleted SP1 regions. Deletion of both distant and primal SP1 sites abolished the activity of ERα, and similar results were observed by blocking the expression of SP1 protein using mithramycin (MA). This result indicates that SP1 protein is essential for ERα-activatedTNFαpromoter activity. Co-immunoprecipitation assay further confirmed the binding interaction between ERα and SP1 in a ligand-dependent manner. In general, we demonstrate that the overexpression of ERα mediates apoptosis in ERα-negative Hep3B cells by the binding of ERα to SP1 protein. Additionally, this ERα–SP1 complex binds to the proximal and distal sites of theTNFαgene promoter and further induces the expression of active caspase 3 in a ligand-dependent manner.