bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of image quality for real‐time target tracking using simultaneous kV‐MV imaging
Authors: Luo W. , Yoo S. , Wu Q. J. , Wang Z. , Yin F.‐F.
Published: December 2008

Real‐time tracking can provide high accuracy localization for a moving target and minimize the effect of motion. Simultaneous kV‐MV imaging has been proposed as a real‐time tracking technique by utilizing the existing kV on‐board imager (OBI) and the MV electronic portal device (EPID) mounted on the linear accelerator. The orthogonal pair of kV‐MV images acquired simultaneously can provide 3‐D localization in real‐time. However, the kV and MV beams cross shooting the target interfere with each other with beam scattering, which affects the quality of images. The success of this modality heavily relies on the image quality, especially the visibility of the target, which was investigated in this study. The kV and MV images were acquired for a gold implant marker that was used as a surrogate of the target and placed in an IMRT thorax phantom, a dynamic phantom, and a pelvis phantom to test the image quality in different situations. Contrast‐to‐noise ration (CNR) was used to quantitatively describe the visibility of the target in the image. CNR can be obtained by statistical calculation from image processing and physics analysis with ion chamber measurement. The difference is described by contrast detection efficiency (CDE). By comparing the ratio of CNR with and without the MV beam on, the MV beam scatter was found to have dramatically reduced the target visibility in the kV images , which was supported by an independent physics analysis that treats beam scatter as a noise. In contrast, the kV scatter effect on the MV images was minor . The effect of tumor motion was visible but tolerable for the target tracking purpose. CNR varied with different tumor sites and was lower for the pelvis than the thorax. Different kV imaging parameters such as kVp, mAs, and exposure time ms were tested for different cases. Considering a threshold of 1.0 CNR as a measure for the target visibility, a range of CNR from 1.3 to 4.2 was reached with appropriate tuning of those imaging parameters. This study has shown that CNR is a key parameter that can be used for assessing the visibility of the target in digital imaging and the quality of kV/MV images. It has also been shown that reasonable target visibility can be obtained using simultaneous kV‐MV imaging for real‐time target tracking.
Monte Carlo dosimetry for and eye plaque brachytherapy
Authors: Thomson R. M. , Taylor R. E. P. , Rogers D. W. O.
Published: December 2008

A Monte Carlo study of dosimetry for eye plaque brachytherapy is performed. BrachyDose, an EGSnrc user code which makes use of Yegin's multi‐geometry package, is used to fully model (model 6711) and (model 200) brachytherapy seeds and the standardized plaques of the Collaborative Ocular Melanoma Study (COMS). Three‐dimensional dose distributions in the eye region are obtained. In general, dose to water is scored; however, the implications of replacing water with eye tissues are explored. The effect of the gold alloy (Modulay) backing is investigated and the dose is found to be sensitive to the elemental composition of the backing. The presence of the silicone polymer (Silastic) seed carrier results in substantial dose decreases relative to water, particularly for . For a plaque with a Modulay backing and Silastic insert, fully loaded with 24 seeds, the dose decrease relative to water is of the order of 14% for and 20% for at a distance of from the inner sclera along the plaque's central axis. For the configurations of seeds used in COMS plaques, interseed attenuation is a small effect within the eye region. The introduction of an air interface results in a dose reduction in its vicinity which depends on the plaque's position within the eye and the radionuclide. Introducing bone in the eye's vicinity also causes dose reductions. The dose distributions in the eye for the two different radionuclides are compared and, for the same prescription dose, generally offers a lower dose to critical normal structures. BrachyDose is sufficiently fast to allow full Monte Carlo dose calculations for routine clinical treatment planning.
An international dosimetry exchange for BNCT Part II: Computational dosimetry normalizations
Authors: Riley K. J. , Binns P. J. , Harling O. K. , Albritton J. R. , Kiger W. S. , Rezaei A. , Sköld K. , Seppälä T. , Savolainen S. , Auterinen I. , Marek M. , Viererbl L. , Nievaart V. A. , Moss R. L.
Published: December 2008

The meaningful sharing and combining of clinical results from different centers in the world performing boron neutron capture therapy (BNCT) requires improved precision in dose specification between programs. To this end absorbed dose normalizations were performed for the European clinical centers at the Joint Research Centre of the European Commission, Petten (The Netherlands), Nuclear Research Institute, Rez (Czech Republic), VTT, Espoo (Finland), and Studsvik, Nyköping (Sweden). Each European group prepared a treatment plan calculation that was benchmarked against Massachusetts Institute of Technology (MIT) dosimetry performed in a large, water‐filled phantom to uniformly evaluate dose specifications with an estimated precision of . These normalizations were compared with those derived from an earlier exchange between Brookhaven National Laboratory (BNL) and MIT in the USA. Neglecting the uncertainties related to biological weighting factors, large variations between calculated and measured dose are apparent that depend upon the uptake in tissue. Assuming a boron concentration of in normal tissue, differences in the evaluated maximum dose to brain for the same nominal specification of at the different facilities range between 7.6 and in the trials using boronophenylalanine (BPA) as the boron delivery compound and between 8.9 and in the two boron sulfhydryl (BSH) studies. Most notably, the value for the same specified dose of determined at the different participating centers using BPA is significantly higher than at BNL by 32% (MIT), 43% (VTT), 49% (JRC), and 74% (Studsvik). Conversion of dose specification is now possible between all active participants and should be incorporated into future multi‐center patient analyses.
Quality and accuracy of cone beam computed tomography gated by active breathing control
Authors: Thompson Bria P. , Hugo Geoffrey D.
Published: December 2008

The purpose of this study was to evaluate the quality and accuracy of cone beam computed tomography (CBCT) gated by active breathing control (ABC), which may be useful for image guidance in the presence of respiration. Comparisons were made between conventional ABC‐CBCT (stop and go), fast ABC‐CBCT (a method to speed up the acquisition by slowing the gantry instead of stopping during free breathing), and free breathing respiration correlated CBCT. Image quality was assessed in phantom. Accuracy of reconstructed voxel intensity, uniformity, and root mean square error were evaluated. Registration accuracy (bony and soft tissue) was quantified with both an anthropomorphic and a quality assurance phantom. Gantry angle accuracy was measured with respect to gantry speed modulation. Conventional ABC‐CBCT scan time ranged from . Fast ABC‐CBCT scan time ranged from , and respiratory correlated CBCT scans took to complete. Voxel intensity value for ABC gated scans was accurate relative to a normal clinical scan with all projections. Uniformity and root mean square error performance degraded as the number of projections used in the reconstruction of the fast ABC‐CBCT scans decreased (shortest breath hold, longest free breathing segment). Registration accuracy for small, large, and rotational corrections was within and 1°. Gantry angle accuracy was within 1° for all scans. For high‐contrast targets, performance for image‐guidance purposes was similar for fast and conventional ABC‐CBCT scans and respiration correlated CBCT.
Science Books for Fun and Learning--Some Recommendations from 2008
Authors: Malcomson Heather , Jasny Barbara , Suter Sherman
Published: December 2008

To aid those seeking gifts for younger readers, we present the 19 finalists for the four 2009 Science Books and Films Prizes for Excellence in Science Books.
A Comparison of Møller-Plesset and Coupled Cluster Linear Response Theory Methods for the Calculation of Dipole Oscillator Strength Sum Rules and C6 Dispersion Coefficients
Authors: Paidarová Ivana , Sauer Stephan P. A.
Published: December 2008

Four correlated linear response theory methods - the second order polarization propagator approximation (SOPPA), the second order polarization propagator approximation with coupled cluster singles and doubles amplitudes, SOPPA(CCSD), the CC2 and coupled cluster singles doubles (CCSD) linear response theory - were used to determine the dipole oscillator strength sum rules of the hydrogen halides HX (with X = F, Cl, Br and I) and the C6 dispersion coefficient for all pairs of interacting HX molecules via numerical integration of the Casimir-Polder formula. The dependence of the polarizabilities, their frequency dependence and the C6 coefficients on the level of correlation and the dependence of the C6 coefficients on the two intramolecular bond lengths were studied.
Rethinking the placebo effect
Authors: Louhiala P , Puustinen R
Published: December 2008

There is a rather wide range of meanings forplaceboandplacebo effect, and some of the controversy has arisen when the proponents of various positions have ignored each other. An attempt is made to clarify some of the conceptual issues related to these concepts. Five uses of placebos as inert substances or treatments are listed. The problem of the placebo effect and the discussion of its existence are examined, and other terms that could cover the phenomenon are suggested. It is suggested that the conceptplacebois appropriate only to the research context and that the termcare effectbe introduced to replace it in clinical contexts.
A portrait of a female body: Rubens and Helena’s legs
Authors: Abastado P , Chemla D
Published: December 2008

For a long time the Western world was in a state of denial about the human body. There were conventions governing its representation and it could be regarded as an element of discourse. Between 1636 and 1638, Peter Paul Rubens painted a portrait of his second wife, Helena Fourment, entitledThe little fur. This may be a turning-point in the perception of the body. We see in this work that the skin of this 22-year-old woman has lost its elasticity, her breasts are not symmetrical and her ankles are pink, contrasting with the pearly white of the rest of her body. The inside of her left thigh shows signs of a varicose saphenous vein. While today’s doctors can suggest the possibility of venous insufficiency and benign familial hyperelasticity, and talk of the consequences of breast-feeding, what this canvas is doing above all is showing the body of a real, named individual, “warts and all”. This may be one of the first portraits of a body in the history of European painting.
DATA ACCESS CHARACTERISTICS AND OPTIMIZATIONS FOR SUN ULTRASPARC T2 AND T2+ SYSTEMS
Authors: HAGER GEORG , ZEISER THOMAS , WELLEIN GERHARD
Published: December 2008

Processor and system architectures that feature multiple memory controllers and/or ccNUMA characteristics are prone to show bottlenecks and erratic performance numbers on scientific codes. Although cache thrashing, aliasing conflicts, and ccNUMA locality and contention problems are well known for many types of systems, they take on peculiar forms on the new Sun UltraSPARC T2 and T2+ processors, which we use here as prototypical multi-core designs. We analyze performance patterns in low-level and application benchmarks and put some emphasis on a comparison of performance features between T2 and its successor. Furthermore we show ways to circumvent bottlenecks by careful data layout, placement and padding.
Electroacupuncture Promotes Insulin-Like Growth Factors System in Ovariectomized Osteoporosis Rats
Authors: Feng Yi , Lin Huagang , Zhang Ying , Li Lierong , Wu Xuping , Wang Tienpei , Liu Youxiang , Tan Yilun
Published: December 2008

Postmenopausal Osteoporosis (PMOP) is induced by the deficiency of estrogen in postmenopausal women. Electroacupuncture (EA) has been confirmed to be effective in clinic. We adopted ovariectomized osteoporosis model of rats to observe the role of EA in PMOP. Fifty female SD rats were divided randomly into 5 groups: intact (INT, n = 10), sham operation (Sham, n = 10), model ( n = 10), estrogen (E, n = 10) and electroacupuncture (EA, n = 10). The bone mineral content (BMC) and the bone mineral density (BMD) were examined in lumbar1–6 and right thigh-bone, respectively, and estrodiol (E2), insulin-like growth factor I (IGF-I) and insulin-like growth factor binding proteins (IGF-BPs) were tested by RIA or ELISA. The results showed that BMC and BMD of lumbar 1–6 and right thigh-bone in PMOP model rats decreased markedly, while the level of serum E2, IGF-I and IGF-BP1 were lower than in INT and Sham. However, EA could upgrade the contents of IGF-I and IGF-BP1 to increase BMD in PMOP rats, while no significant difference was seen in E group. Therefore, EA may promote IGF system to improve PMOP.
Saponins Isolated from the Root of Panax notoginseng Showed Significant Anti-Diabetic Effects in KK-Ay Mice
Authors: Chen Zhong-Hua , Li Jie , Liu Jie , Zhao Yuan , Zhang Pu , Zhang Meng-Xue , Zhang Liu
Published: December 2008

Panax notoginseng, a well-known and commonly used traditional Chinese herb, has been used in China for six hundred years. Panax notoginseng Saponins (PNS) were extracted from the root of the plant. This is the first study on anti-hyperglycemic and anti-obese effects of PNS in genetic model mice. Additionally, the preventive effect on diabetic nephropathy was investigated. Animals received intraperitoneal injections of PNS 50 or 200 mg/kg daily. On day 12, 22 and 30, PNS-treated groups had significantly lower fasting blood glucose levels and smaller body weight incremental percentage. After a 12-day treatment, glucose tolerance of PNS groups were significantly improved; these indices in PNS-treated mice exhibited a dose-dependent improvement. Furthermore, on day 30, the serum insulin resistance index and triglyceride levels of PNS-treated groups decreased significantly, and the development of the mice glomerular lesions was prevented significantly. The results in this present paper indicate that PNS possesses anti-diabetes and anti-obese activities and may prove to be of clinical importance in improving the management of type 2 diabetes.
Alternative Medicine Products as a Novel Treatment Strategy for Inflammatory Bowel Disease
Authors: Jackson Lindsey N. , Zhou Yuning , Qiu Suimin , Wang Qingding , Mark Evers B.
Published: December 2008

Inflammatory bowel disease (IBD) affects the mucosal lining of the gastrointestinal tract; the etiology is unknown and treatment is directed at systemic immunosuppression. Natural products, including medicinal herbs, have provided approximately half of the drugs developed for clinical use over the past 20 years. The purpose of our current study was to determine the effects of a novel combination of herbal extracts on intestinal inflammation using a murine model of IBD. Female Swiss-Webster mice were randomized to receive normal water or 5% dextran sulfate sodium (DSS) drinking water to induce colitis. Mice were treated with either a novel combination of herbal aqueous extracts or vehicle control per os (po) or per rectum (pr) every 24 hours for 7–8 days. Disease activity index score (DAI) was determined daily; mice were sacrificed and colons were analyzed by H & E staining, MPO assay, and cytokine (TNF-α, IL-6) ELISAs. Mice treated with the combination of herbal extracts, either po or pr, had significantly less rectal bleeding and lower DAI scores compared to the vehicle-treated group. Moreover, colonic ulceration, leukocytic infiltration, and cytokine levels (TNF-α and IL-6) were also decreased in the colons of herbal-treated mice, reflected by H & E staining, MPO assay, and cytokine ELISA. Treatment with the combination of medicinal herbs decreases leukocyte infiltration and mucosal ulceration, ameliorating the course of acute colonic inflammation. This herbal remedy may prove to be a novel and safe therapeutic alternative in the treatment of IBD.
Salvia miltiorrhiza Depresses Plasminogen Activator Inhibitor-1 Production Through Inhibition of Angiotensin II
Authors: Yuan Jun , Wang Xiaoqin , Chen Taohou , Chen Gang , Lu Yanfang
Published: December 2008

The purpose of this study was to investigate the effect of Salvia miltiorrhiza on the production of plasminogen activator inhibitor-1(PAI-1) induced by angiotensin II (Ang II) in renal mesangial cells. Rat mesangial cells were exposed to 100 nM Ang II. Meanwhile, different concentrations of Salvia miltiorrhiza injection were added to Mesangial Cells. PAI-1 mRNA was measured by semi-quantification reverse transcriptase polymerase chain reaction (RT-PCR) and PAI-1 protein by Western blotting. ELISA was used to detect the expression of transforming growth factor β1(TGF-β1) in serum free MEM medium. The level of cellular reactive oxygen species (ROS) was measured by confocal laser scanning microscopy. Salvia miltiorrhiza notably attenuated expression of PAI-1 induced by Ang II in a concentration-dependent manner. Meanwhile, it suppressed the production of TGF-β1and cellular ROS in mesangial cells. These effects were due to Salvia miltiorrhiza's ability of inhibiting the activities of angiotensin II. Therefore, Salvia miltiorrhiza can be used to retard progression of glomerular sclerosis.
Changes of Aerobic Capacity, Fat Ratio and Flexibility in Older TCC Practitioners: A Five-Year Follow-Up
Authors: Lan Ching , Chen Ssu-Yuan , Lai Jin-Shin
Published: December 2008

The objective of this study was to evaluate the 5-year changes of aerobic capacity, fat ratio and flexibility in older Tai Chi Chuan (TCC) practitioners and sedentary controls. Sixty-nine community-dwelling elderly individuals (mean age: 68.6 ± 6.3 years) completed this study. The TCC group (18 M; 17 F) had been practicing TCC regularly for 6.3 ± 3.7 years at baseline and continued training in the study interval. The control group (16 M; 18 F) did not participate in any regular exercise program. A graded bicycle exercise testing was conducted at the baseline and at 5-year to evaluate the age-related decline in aerobic capacity. Triceps and subscapular skinfolds, and thoracolumbar flexibility were also measured. At baseline, the TCC group displayed higher peak oxygen uptake [Formula: see text] and thoraolumbar flexibility, and lower fat ratio than the control group. At the 5-year follow-up, the TCC group displayed a smaller decrease in [Formula: see text] than the sedentary group. The annual decrease of [Formula: see text] in TCC men and women was 0.32 and 0.22 ml · kg-1 · min-1, respectively. In the control group, the annual decrease of [Formula: see text] was 0.50 and 0.36 ml · kg-1 · min-1 in men and women, respectively. The TCC group also showed a smaller increase of body fat ratio, and a less decrease of flexibility than the control group. In conclusion, long-term practice of TCC attenuates the age-related decline of aerobic capacity, and it also reduces the increase of body fat ratio in older individuals. TCC may be prescribed as a conditioning exercise for the elderly to maintain their health fitness.
Towards Customer Knowledge Relationship Management: Integrating Knowledge Management and Customer Relationship Management Process
Authors: Alryalat Haroun , Al Hawari Samer
Published: December 2008

Due to the strong competition that exists among organisations and the rapid change in the business environment, knowledge has turned out to become a key source for organisations to enhance the competitive advantage. Integrating Knowledge Management (KM) and Customer Relationship Management (CRM) process is a new research area, therefore, scientific research and literature around it remain limited. In addition, the impact of KM process on customer acquisition, retention, and expansion to improve customer satisfaction remains under study and report. The aim of this paper is to present a conceptual framework of KM integrated with CRM called Customer Knowledge Relationship Management (CKRM) Process depending on analysis of various models presented in KM and CRM. The main highlighting is laid upon the concepts of the concept of customer knowledge (knowledge about customer, knowledge for customer, knowledge from customer). Therefore, this paper contributes to the development of KM process (Knowledge Process about Customer, Knowledge Process for Customer, and Knowledge Process from Customer). The paper investigated how the companies in Jordan developed KM process to improvement the CRM process. Based on data collected from the company, results from analysis indicated that the KM process had a positive effect on CRM process.
From Rhetoric to Reality: An Enquiry into KM Initiatives in an Organisation of Higher Learning
Authors: Pillai Sumit , Gupta Rajen K. , Saxena K. B. C.
Published: December 2008

The expression "knowledge is power" has become a convenient soundbyte for all and sundry. Boardrooms and corporate luncheons are abuzz with sweeping remarks such as "we need to effectively manage our knowledge" or "harnessing the power of knowledge is the way forward." Despite an abundance of literature on the subject of knowledge management, many firms struggle to manage their knowledge assets. Of all contemporary management techniques, knowledge management demonstrates the biggest gap between promise and results realised. Why do some organisations benefit from the implementation of KM systems while other organisations do not? Can this intangible entity called "knowledge" be managed and harnessed at all, or is it merely a matter of throwing the dice and hoping for the best? Can the rhetoric be translated into a reality? This paper presents a thorough literature review followed by a case study approach. The authors have delved deep into the realities of an educational institute as a study of an organisation. Some propositions that can be helpful in translating the knowledge management "rhetoric" into a "practical reality" have been proposed. The authors have attempted to identify the causes of failure/success of any KM initiative.
Case Studies of Knowledge Modeling for Knowledge Preservation and Sharing in the US Nuclear Power Industry
Authors: Coffey John W. , Eskridge Thomas
Published: December 2008

As populations age and large numbers of skilled workers progress toward retirement, the importance of preserving and sharing expert knowledge is becoming an increasing concern for organisations worldwide. This article contains descriptions of two case studies involving initiatives to elicit, preserve, and share expert knowledge in the nuclear power industry using a knowledge modeling toolkit named CmapTools and knowledge elicitation techniques that were originated at the Institute for Human and Machine Cognition, Pensacola, FL., USA. Along with an account of preparations for the work including the selection of the experts, the course of the sessions, results and impacts of the studies, missed opportunities, and lessons learned are described. Some similarities and some interesting differences between the case studies are discussed.
Empirical Investigation of the Efficacy and Efficiency of Tools for Transferring Software Engineering Knowledge
Authors: Ardimento Pasquale , Caivano Danilo , Cimitile Marta , Visaggio Giuseppe
Published: December 2008

Continuous pressure on behalf of enterprises leads to a constant need for innovation. This involves exchanging results of knowledge and innovation among research groups and enterprises in accordance to the Open Innovation paradigm. The technologies that seem to be apparently attractive for exchanging knowledge are the Internet and its search engines. Literature provides many discordant opinions on their efficacy, and no empirical evidence on the topic. This work starts from the definition of a Knowledge Acquisition Process, and presents a rigorous empirical investigation that evaluates the efficacy of the previous technologies within the Exploratory Search of Knowledge and of Relevant Knowledge according to specific knowledge requirements. The investigation has pointed out that these technologies are not effective for Explorative Search. The paper concludes with a brief analysis of other technologies to develop and analyse in order to overcome the weaknesses that this investigation has pointed out within the Knowledge Acquisition Process.
Portably solving file races with hardness amplification
Authors: Tsafrir Dan , Hertz Tomer , Wagner David , Silva Dilma Da
Published: December 2008

The file-system API of contemporary systems makes programs vulnerable to TOCTTOU (time-of-check-to-time-of-use) race conditions. Existing solutions either help users to detect these problems (by pinpointing their locations in the code), or prevent the problem altogether (by modifying the kernel or its API). But the latter alternative is not prevalent, and the former is just the first step: Programmers must still address TOCTTOU flaws within the limits of the existing API with which several important tasks cannot be accomplished in a portable straightforward manner. Recently, Dean and Hu [2004] addressed this problem and suggested a probabilistic hardness amplification approach that alleviated the matter. Alas, shortly after, Borisov et al. [2005] responded with an attack termed “filesystem maze” that defeated the new approach.

We begin by noting that mazes constitute a generic way to deterministically win many TOCTTOU races (gone are the days when the probability was small). In the face of this threat, we: (1) develop a new user-level defense that can withstand mazes; and (2) show that our method is undefeated even by much stronger hypothetical attacks that provide the adversary program with ideal conditions to win the race (enjoying complete and instantaneous knowledge about the defending program's actions and being able to perfectly synchronize accordingly). The fact that our approach is immune to these unrealistic attacks suggests it can be used as a simple and portable solution to a large class of TOCTTOU vulnerabilities, without requiring modifications to the underlying operating system.
Collaborative group testing benefits high- and low-performing students
Authors: Giuliodori Mauricio J. , Lujan Heidi L. , DiCarlo Stephen E.
Published: December 2008

We used collaborative group testing in a veterinary physiology course (65 students) to test the hypothesis that all students (e.g., high-performing and low-performing students of each group) benefit from collaborative group testing. In this format, students answered questions in the traditional format as individuals. Immediately after completing the exam as individuals, students answered the same questions in groups of two, and, finally, the same questions were discussed by the instructor and students. We measured two learning outcomes for every student: individual and group test scores. Based on individual test scores, students were categorized as “high performing” (students with higher individual scores) or “low performing” (students with lower individual scores). Finally, student evaluations of the format were collected. Collaborative group testing enhanced student performance. Specifically, group scores were higher than individual scores ( P < 0.001). Importantly, the size of the collaborative testing effect was large for the population and for the low-performing students; however, the collaborative testing effect was small for the high-performing students. Finally, student evaluations of this testing format were very positive. In conclusion, collaborative group testing was beneficial for all students; however, collaborative testing was significantly more beneficial for low-performing students.
How the story unfolds: exploring ways faculty develop open-ended and closed-ended case designs
Authors: Nesbitt Leslie M. , Cliff William H.
Published: December 2008

Open-ended or closed-ended case study design schemes offer different educational advantages. Anatomy and physiology faculty members who participated in a conference workshop were given an identical case about blood doping and asked to build either an open-ended study or a closed-ended study. The workshop participants created a rich array of case questions. Participant-written learning objectives and case questions were compared, and the questions were examined to determine whether they satisfied criteria for open or closed endedness. Many of the participant-written learning objectives were not well matched with the case questions, and participants had differing success writing suitable case questions. Workshop participants were more successful in creating closed-ended questions than open-ended ones. Eighty-eight percent of the questions produced by participants assigned to write closed-ended questions were considered closed ended, whereas only 43% of the questions produced by participants assigned to write open-ended questions were deemed open ended. Our findings indicate that, despite the fact that instructors of anatomy and physiology recognize the value of open-ended questions, they have greater difficulty in creating them. We conclude that faculty should pay careful attention to learning outcomes as they craft open-ended case questions if they wish to ensure that students are prompted to use and improve their higher-order thinking skills.
Is formative assessment an effective way to improve learning? A symposium at Experimental Biology 2008
Authors: Cliff William , Freeman Scott , Hansen Penelope A. , Kibble Jonathan D. , Peat Mary , Wenderoth Mary Pat
Published: December 2008

Formative assessment is designed to provide information about students' learning to help them and their teachers to identify deficiencies and misconceptions. It differs from summative assessment, which aims to rank students according to their achievements to determine which students pass or fail or to assign grades to students. This article reports on a symposium concerned with evidence for the effectiveness of formative assessment in improving learning. It was presented by the Teaching of Physiology Section of the American Physiological Society at the Experimental Biology Meeting of 2008.
Epidermal growth factor receptor is involved in enterocyte anoikis through the dismantling of E-cadherin-mediated junctions
Authors: Lugo-Martínez Verónica-Haydée , Petit Constance S. , Fouquet Stéphane , Le Beyec Johanne , Chambaz Jean , Pinçon-Raymond Martine , Cardot Philippe , Thenet Sophie
Published: December 2008

Enterocytes of the intestinal epithelium are continually regenerated. They arise from precursor cells in crypts, migrate along villi, and finally die, 3–4 days later, when they reach the villus apex. Their death is thought to occur by anoikis, a form of apoptosis induced by cell detachment, but the mechanism of this process remains poorly understood. We have previously shown that a key event in the onset of anoikis in normal enterocytes detached from the basal lamina is the disruption of adherens junctions mediated by E-cadherin (Fouquet S, Lugo-Martinez VH, Faussat AM, Renaud F, Cardot P, Chambaz J, Pincon-Raymond M, Thenet S. J Biol Chem 279: 43061–43069, 2004). Here we have further investigated the mechanisms underlying this disassembly of the adherens junctions. We show that disruption of the junctions occurs through endocytosis of E-cadherin and that this process depends on the tyrosine-kinase activity of the epidermal growth factor receptor (EGFR). Activation of EGFR was detected in detached enterocytes before E-cadherin disappearance. Specific inhibition of EGFR by tyrphostin AG-1478 maintained E-cadherin and its cytoplasmic partners β- and α-catenin at cell-cell contacts and decreased anoikis. Finally, EGFR activation was evidenced in the intestinal epithelium in vivo, in rare individual cells, which were shown to lose their interactions with the basal lamina. We conclude that EGFR is activated as enterocytes become detached from the basal lamina, and that this mechanism contributes to the disruption of E-cadherin-dependent junctions leading to anoikis. This suggests that EGFR participates in the physiological elimination of the enterocytes.
Synchrotron X-ray powder diffraction data of atorvastatin
Authors: Antonio Selma Gutierrez , Benini Fernanda Ribeiro , Ferreira Fabio Furlan , Rosa Paulo César Pires , de Oliveira Paiva-Santos Carlos
Published: December 2008

X-ray powder diffraction data collected in transmission and high-throughput geometries were used to analyze form I of atorvastatin. The X-ray wavelength of the synchrotron radiation used in this study was determined to be λ=1.3771 Å. Form I of atorvastatin was found to be triclinic with space group P1 and unit cell parameters a=5.4568(2) Å, b=9.8887(4) Å, c=30.3091(9) Å, α=76.801(3)°, β=99.177(5)°, γ=105.318(5)°, V=1527.1(1) Å3, Z=1, and M=1209.41 g mol−1 Alternatively, another unit cell dimension can be used to describe the same P1 crystal with a=5.4564(2) Å, b=9.8883(4) Å, c=29.6555(8) Å, α=95.745(3)°, β=94.297(5)°, γ=105.327(5)°, and V=1526.8(1) Å3.
New powder diffraction data of some derivatives of N-alkyl (aryl)-2,4-dichlorophenoxyacetamide—New potential pesticides
Authors: Olszewska E. , Pikus S. , Tarasiuk B.
Published: December 2008

Four new derivatives of N-aryl-2,4-dichlorophenoxyacetamide, 2-(2,4-dichlorophenoxy)-N-(4-fluorophenyl)acetamide, N-(4-bromophenyl)-2-(2,4-dichlorophenoxy)acetamide, N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(2,4-dichlorophenoxy)acetamide, and N-(3-chloro-4-fluorophenyl)-2-(2,4-dichlorophenoxy)acetamide, and two of N-alkyl-2,4-dichlorophenoxyacetamide, N-dodecyl-2,4-dichlorophenoxy-acetamide and 2-(2,4-dichlorophenoxy)-N-hexadecylacetamide, have been characterized by X-ray powder diffraction. These organic compounds are potential pesticides. Experimental 2θ peaks positions, relative peak intensities, values of d and Miller indices, and unit cell parameters are presented.
Improvement in determining the crystal structure of inorganic compounds using powder diffraction data
Authors: Reinaudi Luis , Leiva Ezequiel P.M. , Carbonio Raúl E.
Published: December 2008

A new way of incorporating powder diffraction data into a cost function to predict the crystalline structure of inorganic solids is proposed. This approach was applied to the following series of compounds: cubic
SrTiO3, tetragonal NaNbO3, TiO2 (anatase), tetragonal
CaTiO3, and hexagonal BaTiO3. A tremendous increase in the efficiency of obtaining the correct structure is achieved when a cost function based upon this new approach is applied to these problems.
Epigenetic Enhancement of Antigen Processing and Presentation Promotes Immune Recognition of Tumors
Authors: Setiadi A. Francesca , Omilusik Kyla , David Muriel D. , Seipp Robyn P. , Hartikainen Jennifer , Gopaul Rayshad , Choi Kyung Bok , Jefferies Wilfred A.
Published: December 2008

Histone deacetylase inhibitors (HDACi) have been hailed as a powerful new class of anticancer drugs. The HDACi, trichostatin A (TSA), is thought to interfere with epigenetic control of cell cycle progression in G1 and G2-M phase, resulting in growth arrest, differentiation, or apoptosis. Here, we describe a novel mechanism of action of HDACis in promoting immune responses against tumors. We report that treatment of carcinoma cells with TSA increases the expression of many components of the antigen processing machinery, including TAP-1, TAP-2, LMP-2, and Tapasin. Consistent with this result, we found that treatment of metastatic carcinoma cells with TSA also results in an increase in MHC class I expression on the cell surface that functionally translates into an enhanced susceptibility to killing by antigen-specific CTLs. Finally, we observed that TSA treatment suppresses tumor growth and increases tap-1 promoter activity in TAP-deficient tumor cells in vivo. Intriguingly, this in vivo anti-tumoral effect of TSA is entirely mediated by an increase in immunogenicity of the tumor cells, as it does not occur in immunodeficient mice. These novel insights into the molecular mechanisms controlling tumor immune escape may help revise immunotherapeutic modalities for eradicating cancers. [Cancer Res 2008;68(23):9601–7]
HPV-16 E7 Reveals a Link between DNA Replication Stress, Fanconi Anemia D2 Protein, and Alternative Lengthening of Telomere–Associated Promyelocytic Leukemia Bodies
Authors: Spardy Nicole , Duensing Anette , Hoskins Elizabeth E. , Wells Susanne I. , Duensing Stefan
Published: December 2008

Expression of the high-risk human papillomavirus (HPV-16) E7 oncoprotein extends the life span of primary human keratinocytes and partially restores telomere length in the absence of telomerase. The molecular basis of this activity is incompletely understood. Here, we show that HPV-16 E7 induces an increased formation of alternative lengthening of telomeres (ALT)–associated promyelocytic leukemia bodies (APBs) in early passage primary human keratinocytes as well as HPV-negative tumor cells. This activity was found to require sequences of HPV-16 E7 involved in degradation of the retinoblastoma tumor suppressor protein as well as regions in the COOH terminus. HPV-16 E7–induced APBs contained ssDNA and several proteins that are involved in the response to DNA replication stress, most notably the Fanconi anemia D2 protein (FANCD2) as well as BRCA2 and MUS81. In line with these results, we found that FANCD2-containing APBs form in an ATR-dependent manner in HPV-16 E7–expressing cells. To directly show a role of FANCD2 in ALT, we provide evidence that knockdown of FANCD2 rapidly causes telomere dysfunction in cells that rely on ALT to maintain telomeres. Taken together, our results suggest a novel link between replication stress and recombination-based telomere maintenance that may play a role in HPV-16 E7–mediated extension of host cell life span and immortalization. [Cancer Res 2008;68(23):9954–63]
Gene Therapy Using TRAIL-Secreting Human Umbilical Cord Blood–Derived Mesenchymal Stem Cells against Intracranial Glioma
Authors: Kim Seong Muk , Lim Jung Yeon , Park Sang In , Jeong Chang Hyun , Oh Ji Hyeon , Jeong Moonsup , Oh Wonil , Park Sang-Hoon , Sung Young-Chul , Jeun Sin-Soo
Published: December 2008

Adenovirus-mediated gene therapies against brain tumors have been limited by the difficulty in tracking glioma cells infiltrating the brain parenchyma. Human umbilical cord blood–derived mesenchymal stem cells (UCB-MSC) are particularly attractive cells for clinical use in cell-based therapies. In the present study, we evaluated the tumor targeting properties and antitumor effects of UCB-MSCs as gene delivery vehicles for glioma therapy. We efficiently engineered UCB-MSCs to deliver a secretable trimeric form of tumor necrosis factor-related apoptosis-inducing ligand (stTRAIL) via adenoviral transduction mediated by cell-permeable peptides. We then confirmed the migratory capacity of engineered UCB-MSCs toward tumor cells by an in vitro migration assay and by in vivo injection of UCB-MSCs into the tumor mass or the opposite hemisphere of established human glioma in nude mice. Moreover, in vitro coculture, experiments on Transwell plates, and in vivo survival experiments showed that MSC-based stTRAIL gene delivery has more therapeutic efficacy compared with direct injection of adenovirus encoding the stTRAIL gene into a tumor mass. In vivo efficacy experiments showed that intratumoral injection of engineered UCB-MSCs (MSCs-stTRAIL) significantly inhibited tumor growth and prolonged the survival of glioma-bearing mice compared with controls. These results suggest that human UCB-MSCs have potential use as effective delivery vehicles for therapeutic genes in the treatment of intracranial glioma. [Cancer Res 2008;68(23):9614–23]
Chromatin Immunoprecipitation–on-Chip Reveals Stress-Dependent p53 Occupancy in Primary Normal Cells but Not in Established Cell Lines
Authors: Shaked Helena , Shiff Idit , Kott-Gutkowski Miriam , Siegfried Zahava , Haupt Ygal , Simon Itamar
Published: December 2008

The p53 tumor suppressor protein is a transcription factor that plays a key role in the cellular response to stress and cancer prevention. Upon activation, p53 regulates a large variety of genes causing cell cycle arrest, apoptosis, or senescence. We have developed a p53-focused array, which allows us to investigate, simultaneously, p53 interactions with most of its known target sequences using the chromatin immunoprecipitation (ChIP)-on-chip methodology. Applying this technique to multiple cell types under various growth conditions revealed a profound difference in p53 activity between primary cells and established cell lines. We found that, in peripheral blood mononuclear cells, p53 exists in a form that binds only a small subset of its target regions. Upon exposure to genotoxic stress, the extent of targets bound by p53 significantly increased. By contrast, in established cell lines, p53 binds to essentially all of its targets irrespective of stress and cellular fate (apoptosis or arrest). Analysis of gene expression in these established lines revealed little correlation between DNA binding and the induction of gene expression. Our results suggest that nonactivated p53 has limited binding activity, whereas upon activation it binds to essentially all its targets. Additional triggers are most likely required to activate the transcriptional program of p53. [Cancer Res 2008;68(23):9671–7]
Opposite Effects of Notch-1 and Notch-2 on Mesothelioma Cell Survival under Hypoxia Are Exerted through the Akt Pathway
Authors: Graziani Irene , Eliasz Sandra , De Marco Melissa A. , Chen Yuanbin , Pass Harvey I. , De May Richard M. , Strack Peter R. , Miele Lucio , Bocchetta Maurizio
Published: December 2008

Malignant mesothelioma (MM) is a cancer of the lining of the lungs, heart, and intestine and is known to respond poorly to chemotherapy. Here we show that malignant mesothelial cells have an elevated Notch signaling pathway compared with normal human mesothelial cells. We studied the role of Notch in MM under normoxic and hypoxic conditions, the latter condition best recapitulating the MM microenvironment. Genetic and chemical modulation of the Notch pathway indicated that MM cells are dependent on Notch signaling. More specifically, this signaling was Notch-1 dependent as the result of its negative transcriptional regulation on phosphatase and tensin homologue (PTEN), which led to activation of the prosurvival phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. Our study also provides evidence that whereas Notch-1 is elevated in the malignant setting, Notch-2 is diminished. This differential expression of the two Notch isoforms benefits cancer cell survival because reexpression of Notch-2 was toxic to MM cells. The mechanism of Notch-2 toxicity to MM cells countered that of Notch-1, as it was the result of positive transcriptional regulation of PTEN and inhibition of the PI3K/Akt/mTOR signaling pathway. These results provide new insight into the role of Notch in MM and suggest that Notch pathway inhibitors may be useful in the treatment of this deadly disease. [Cancer Res 2008;68(23):9678–85]
Degradation of BRCA2 in Alkyltransferase-Mediated DNA Repair and Its Clinical Implications
Authors: Philip Subha , Swaminathan Srividya , Kuznetsov Sergey G. , Kanugula Sreenivas , Biswas Kajal , Chang Suhwan , Loktionova Natalia A. , Haines Diana C. , Kaldis Philipp , Pegg Anthony E. , Sharan Shyam K.
Published: December 2008

Germ-line mutations in BRCA2 have been linked to early-onset familial breast cancer. BRCA2 is known to play a key role in repairing double-strand breaks. Here, we describe the involvement of BRCA2 in O6-alkylguanine DNA alkyltransferase (AGT)–mediated repair of O6-methylguanine adducts. We show that BRCA2 physically associates and undergoes repair-mediated degradation with AGT. In contrast, BRCA2 with a 29-amino-acid deletion in an evolutionarily conserved domain does not bind to alkylated AGT; the two proteins are not degraded; and mouse embryonic fibroblasts are specifically sensitive to alkylating agents that result in O6-methylguanine adducts. We show that O6-benzylguanine (O6BG), a nontoxic inhibitor of AGT, can also induce BRCA2 degradation. BRCA2 is a viable target for cancer therapy because BRCA2-deficient cells are hypersensitive to chemotherapeutic DNA-damaging agents. We show a marked effect of O6BG pretreatment on cell sensitivity to cisplatin. We also show the efficacy of this approach on a wide range of human tumor cell lines, which suggests that chemosensitization of tumors by targeted degradation of BRCA2 may be an important consideration when devising cancer therapeutics. [Cancer Res 2008;68(23):9973–81]
A Range of Cancers Is Associated with the rs6983267 Marker on Chromosome 8
Authors: Wokołorczyk Dominika , Gliniewicz Bartłomiej , Sikorski Andrzej , Złowocka Elżbieta , Masojć Bartłomiej , Dębniak Tadeusz , Matyjasik Joanna , Mierzejewski Marek , Mędrek Krzysztof , Oszutowska Dorota , Suchy Janina , Gronwald Jacek , Teodorczyk Urszula , Huzarski Tomasz , Byrski Tomasz , Jakubowska Anna , Górski Bohdan , van de Wetering Thierry , Walczak Swietłana , Narod Steven A. , Lubiński Jan , Cybulski Cezary
Published: December 2008

Several genome-wide searches for common cancers have lead to the identification of a small number of loci that harbor low-risk cancer susceptibility markers. One marker, rs6983267 on chromosome 8q24, has been linked to both colon and prostate cancer, and is therefore a good candidate for a multicancer susceptibility marker. To determine the range of cancer sites associated with rs6983267, we genotyped 7,665 cases of cancer, representing 11 common cancer sites, and 1,910 controls. A significant odds ratio (OR) was observed for prostate cancer for carriers of genotype GG [OR, 1.77; 95% confidence interval (CI), 1.47–2.13]. The homozygote OR was higher for tumors with Gleason score 8 to 10 (OR, 1.94; 95% CI, 1.18–3.20) than for tumors with Gleason score 7 and below (OR, 1.65; 95% CI, 1.31–2.08). Significantly elevated (homozygote) ORs were observed for 4 other cancer sites, including colon (OR, 1.36; 95% CI, 1.08–1.72), kidney (OR, 1.52; 95% CI, 1.12–2.05), thyroid (OR, 1.37; 95% CI, 1.02–1.82), and larynx (OR, 1.39; 95% CI, 1.02–1.90). Information was available on family histories of cancer for eight sites. For six of the eight sites (prostate, breast, bladder, larynx, lung, and kidney), the homozygote ORs were higher for cases with a positive family history (at least one first-degree with any cancer) than for cases with unaffected first-degree relatives. Our results suggest that the range of cancers associated with the rs6983267 marker might be larger than previously thought. [Cancer Res 2008;68(23):9982–6]