bluuebunny/crossref_metadata_2025 huggingface dataset:
Replication of the ERES:Golgi junction in bloodstream‐form African trypanosomes
Authors: Bangs James D.
Published: October 2011

The biogenesis of the ER Exit Site/Golgi Junction (EGJ) in bloodstream‐form African trypanosomes is investigated using tagged markers for ER Exit Sites, the Golgi and the bilobe structure. The typical pattern is two EGJ in G1 phase (1 kinetoplast/1 nucleus, 1K1N) through S‐phase (2K1N), duplication to four EGJ in post‐mitotic cells (2K2N) and segregation of two EGJ to each daughter. Lesser cell percentages have elevated EGJ copy numbers in all stages, and blocking cell cycle progression results in even higher copy numbers. EGJs are closely aligned with the flagellar attachment zone (FAZ) indicating nucleation on the FAZ‐associated ER (FAZ:ER). Only the most posterior EGJ in each cell is in proximity to the bilobe, which is located at the base of the FAZ filament near the mouth of the flagellar pocket. These results indicate that EGJ replication in bloodstream trypanosomes is not tightly coupled to the cell cycle. Furthermore, segregation of EGJ is not obligately mediated by the bilobe, rather assembly of the EGJ on the FAZ:ER, which is coupled to the flagellar cytoskeleton, apparently ensures segregation with fidelity during cytokinesis. These findings differ markedly from procyclic‐form trypanosomes, and models highlighting these stage‐specific differences in EGJ biogenesis are proposed.
Proteomic plasticity of two Eucalyptus genotypes under contrasted water regimes in the field
Authors: BEDON FRANK , VILLAR EMILIE , VINCENT DELPHINE , DUPUY JEAN‐WILLIAM , LOMENECH ANNE‐MARIE , MABIALANGOMA ANDRÉ , CHAUMEIL PHILIPPE , BARRÉ AURÉLIEN , PLOMION CHRISTOPHE , GION JEAN‐MARC
Published: October 2011

Water deficit affects tree growth and limits wood production. In an attempt to identify the molecular triggers of adaptation mechanisms to water deficit in Eucalyptus, we investigated protein expression patterns of two ecophysiologically contrasted Eucalyptus genotypes. They were grown in the field in either natural conditions or irrigated for 7 weeks during the dry season in the Republic of Congo. At the phenotypic level, genotype (G), treatment (T) and/or G × T interaction effects were observed for above‐ and below‐ground biomass‐related traits. At the molecular level, changes in protein abundance were recorded in leaves (acidic pH 4–7, and basic pH 7–11, proteomes) and stems (acidic proteome) using two‐dimensional gel electrophoresis (2‐DE). One third of the detected protein spots displayed significant G, T and/or G × T effects, and 158 of them were identified by tandem mass spectrometry (LC‐MS/MS) analysis. Thus, several proteins whose molecular plasticity was genetically controlled (i.e. G × T effect) were revealed, highlighting adaptive mechanisms to water deficit specific to each genotype, namely cell wall modification, cell detoxification and osmoregulation. Transcript abundances corresponding to G × T proteins were also investigated by quantitative RT‐PCR. These proteins represent relevant targets to improve drought resistance in this ecologically and economically important forest tree genus.
Brain correlates of craving for online gaming under cue exposure in subjects with Internet gaming addiction and in remitted subjects
Authors: Ko Chih‐Hung , Liu Gin‐Chung , Yen Ju‐Yu , Chen Chiao‐Yun , Yen Cheng‐Fang , Chen Cheng‐Sheng
Published: October 2011

This study aimed to evaluate brain correlates of cue‐induced craving to play online games in subjects with Internet gaming addiction (IGA), subjects in remission from IGA and controls. The craving response was assessed by event‐related design of functional magnetic resonance images (fMRIs). Fifteen subjects with IGA, 15 in remission from IGA and 15 controls were recruited in this study. The subjects were arranged to view the gaming screenshots and neutral images under investigation of fMRIs. The results showed that bilateral dorsolateral prefrontal cortex (DLPFC), precuneus, left parahippocampus, posterior cingulate and right anterior cingulate were activated in response to gaming cues in the IGA group and their activation was stronger in the IGA group than those in the control group. Their region‐of‐interest was also positively correlated with subjective gaming urge under cue exposure. These activated brain areas represent the brain circuit corresponding to the mechanism of substance use disorder. Thus, it would suggest that the mechanism of IGA is similar to substance use disorder. Furthermore, the IGA group had stronger activation over right DLPFC and left parahippocampus than did the remission group. The two areas would be candidate markers for current addiction to online gaming and should be investigated in future studies.
Nutrient‐associated elongation and asymmetric division of the cyanobacterium Synechococcus PCC 7942
Authors: Goclaw‐Binder Hagit , Sendersky Eleonora , Shimoni Eyal , Kiss Vladimir , Reich Ziv , Perelman Alexander , Schwarz Rakefet
Published: October 2011

While tightly regulated, bacterial cell morphology may change substantially in response to environmental cues. Here we describe such changes in the cyanobacterium Synechococcus sp. strain PCC7942. Once maintained in stationary phase, these rod‐shaped organisms stop dividing and elongate up to 50‐fold. Increase in cell length of a thymidine‐auxotroph strain upon thymidine starvation implies that inhibition of DNA replication underlies cell elongation. Elongation occurs under conditions of limiting phosphorus but sufficient nitrogen levels. Once proliferative conditions are restored, elongated cells divide asymmetrically instead of exhibiting the typical fission characterized by mid‐cell constriction. The progeny are of length characteristic of exponentially growing cells and are proficient of further proliferation. We propose that the ability to elongate under conditions of cytokinesis arrest together with the rapid induction of cell division upon nutrient repletion represents a beneficial cellular mechanism operating under specific nutritional conditions.
Do Tax Reforms Affect Firm Performance and Executive Remuneration? Evidence from a Compressed Wage Environment
Authors: Dale‐Olsen Harald
Published: October 2011

The agency framework predicts a strong positive relationship between executive effort, pay and firm performance. We study how changes in Norwegian payroll tax legislation and earnings tax (which influenceCEOs’ return on effort), affect firm performance and executive earnings for over 11,800 firms. Both reduced payroll tax and reduced marginal earnings tax increase firm performance measured by firms’ operating margins. In the latter case total pay increases, but contingent on the return on firm performance, the fixed wage drops. The sensitivity of the remuneration scheme to the earnings tax depends onCEOproductivity and effort costs.
Pharmacological modulation of GITRL/GITR system: therapeutic perspectives
Authors: Nocentini Giuseppe , Ronchetti Simona , Petrillo Maria Grazia , Riccardi Carlo
Published: October 2011

Glucocorticoid‐induced TNFR‐related (gitr) is a gene coding for a member of the TNF receptor superfamily. GITR activation by its ligand (GITRL) influences the activity of effector and regulatory T cells, thus participating in the development of immune response against tumours and infectious agents, as well as in autoimmune and inflammatory diseases. Notably, treating animals with GITR‐Fc fusion protein ameliorates autoimmune/inflammatory diseases while GITR triggering, by treatment with anti‐GITR mAb, is effective in treating viral, bacterial and parasitic infections, as well in boosting immune response against tumours. GITR modulation has been indicated as one of the top 25 most promising research areas by the American National Cancer Institute, and a clinical trial testing the efficacy of an anti‐GITR mAb in melanoma patients has been started. In this review, we summarize results regarding: (i) the mechanisms by which GITRL/GITR system modulates immune response; (ii) the structural and functional studies clearly demonstrating differences between GITRL/GITR systems of mice and humans; (iii) the molecules with pharmacological activities including anti‐GITR mAbs, GITR‐Fc and GITRL‐Fc fusion proteins, GITRL in monomer or multimer conformation; and (iv) the possible risks deriving from GITRL/GITR system pharmacological modulation. In conclusion, GITR triggering and inhibition could be useful in treating tumours, infectious diseases, as well as autoimmune and inflammatory diseases. However, differences between mouse and human GITRL/GITR systems suggest that further preclinical studies are needed to better understand how safe therapeutic results can be obtained and to design appropriate clinical trials.
Agonists at GPR119 mediate secretion of GLP‐1 from mouse enteroendocrine cells through glucose‐independent pathways
Authors: Lan H , Lin HV , Wang CF , Wright MJ , Xu S , Kang L , Juhl K , Hedrick JA , Kowalski TJ
Published: October 2011

BACKGROUND AND PURPOSE The G protein‐coupled receptor 119 (GPR119) mediates insulin secretion from pancreatic β cells and glucagon‐like peptide 1 (GLP‐1) release from intestinal L cells. While GPR119‐mediated insulin secretion is glucose dependent, it is not clear whether or not GPR119‐mediated GLP‐1 secretion similarly requires glucose. This study was designed to address the glucose‐dependence of GPR119‐mediated GLP‐1 secretion, and to explore the cellular mechanisms of hormone secretion in L cells versus those in β cells.

EXPERIMENTAL APPROACH GLP‐1 secretion in response to GPR119 agonists and ion channel modulators, with and without glucose, was analysed in the intestinal L cell line GLUTag, in primary intestinal cell cultures and in vivo. Insulin secretion from Min6 cells, a pancreatic β cell line, was analysed for comparison.

KEY RESULTS In GLUTag cells, GPR119 agonists stimulated GLP‐1 secretion both in the presence and in the absence of glucose. In primary mouse colon cultures, GPR119 agonists stimulated GLP‐1 secretion under glucose‐free conditions. Moreover, a GPR119 agonist increased plasma GLP‐1 in mice without a glucose load. However, in Min6 cells, GPR119‐mediated insulin secretion was glucose‐dependent. Among the pharmacological agents tested in this study, nitrendipine, an L‐type voltage‐dependent calcium channel blocker, dose‐dependently reduced GLP‐1 secretion from GLUTag cells, but had no effect in Min6 cells in the absence of glucose.

CONCLUSIONS AND IMPLICATIONS Unlike that in pancreatic β cells, GPR119‐mediated GLP‐1 secretion from intestinal L cells was glucose‐independent in vitro and in vivo, probably because of a higher basal calcium tone in the L cells.
Centralized Research Recruitment—Evolving a Local Clinical Research Recruitment Web Application to Better Meet User Needs
Authors: Dwyer‐White Molly , Doshi Aalap , Hill Mary , Pienta Kenneth J.
Published: October 2011

Recruiting volunteers into clinical research remains a significant challenge for many clinical research study teams, thus the Michigan Institute for Clinical and Health Research (MICHR) at the University of Michigan developed UMClinicalStudies (http://www.UMClinicalStudies.org)—a Web application that links the community to a single gateway for clinical research. UMClinicalStudies (formerly named “Engage”) is an integral piece of MICHR’s efforts to increase clinical research participation in order to advance medical discoveries. Despite the initial success of the application, barriers to research participation remain, including the applications accessibility for potential research volunteers and study team members. In response, new initiatives were instigated to identify user needs, in order to broaden the ability to simultaneously assist researchers in recruitment activities, while also aiding potential volunteers in the exploration of and participation in clinical research opportunities. To do this, improvements to the interface and functionality were identified and implemented for both the public and the research audiences through extensive system analysis, and through the application of human computer interactivity processes, resulting in significant improvements in usability and ultimately research volunteerism, indicating that utilizing such technology is pivotal in reaching broader audiences for clinical trial participation. Clin Trans Sci 2011; Volume 4: 363–368
Assessment of LMNA Copy Number Variation in 58 Probands with Dilated Cardiomyopathy
Authors: Norton Nadine , Siegfried Jill D. , Li Duanxiang , Hershberger Ray E.
Published: October 2011

The contribution of copy number variation (CNV) to dilated cardiomyopathy (DCM) is unknown. However, estimates have suggested that CNVs could constitute 15% of mutations underlying Mendelian disease. This is of particular relevance to DCM, where only approximately 35% of genetic cause has been identified. We have previously reported 19 point mutations in LMNA, the gene encoding Lamin A/C, in a cohort of 324 unrelated DCM probands (5.9%), making it the most common genetic cause of DCM. Recently a large deletion was reported in LMNA in 1 of 25 DCM probands. To further assess the contribution of CNVs in LMNA cardiomyopathy, we used Multiplex Ligation Probe Amplification (MLPA) to screen for large deletions and duplications in 58 DCM probands negative for point mutations in LMNA. Despite excellent quality control and robust MLPA results, our study failed to identify any deletions or duplications. We conclude that at least for LMNA, point mutations are the major source of DCM causation. Clin Trans Sci 2011; Volume 4: 351–352
CTSA‐IP: A Solution to Identifying and Aggregating Intellectual Property across the NIH Clinical Translational Science Award (CTSA) Consortium of Biomedical Research Institutes
Authors: Hazard Mike , Steele Scott , Wang Dongwen , Pearson Thomas , Scheideler Mark , Dewhurst Steve
Published: October 2011

One of the objectives of the Consortium of Institutions with Clinical and Translational Science Awards (CTSAs) is to enhance technology transfer among the CTSAs and with public and private sector partners. Clinical and Translational Sciences Award Intellectual Property (CTSA‐IP; http://www.CTSAIP.org) is a web‐based, open access IP search tool that aggregates and promotes technologies from member institutions of the National Institutes of Health’s (NIH) CTSAs consortium. Its ultimate aim is to stimulate collaborative research activity by encouraging the formation of public‐private partnerships with CTSA institutions and the NIH. First launched in 2009, CTSA‐IP has grown rapidly and met its first objectives of developing wide member institution participation and site usage. This communication will discuss the strategy employed in the initiative of aggregating IP across institutional boundaries, the promise that lies therein, as well as the challenges encountered and lessons learned in promoting CTSA‐wide engagement. Clin Trans Sci 2011; Volume 4: 328–331
Cellular Proliferative Response to Cardiac Troponin‐I in Patients with Idiopathic Dilated Cardiomyopathy
Authors: Lappé Jason M. , Pelfrey Clara M. , Cotleur Anne , Tang Wai Hong Wilson
Published: October 2011

Background: Approximately 20% of patients with idiopathic dilated cardiomyopathy (iDCM) have autoantibodies (AAbs) specific to cardiac troponin‐I (cTnI). However, there has been no work evaluating active cellular autoimmunity. We aimed to identify a cTnI‐stimulated cellular autoimmune response and to correlate our findings with cTnI AAb production.

Methods: Samples were obtained from stable ambulatory iDCM patients and healthy controls. Peripheral blood monocytes were incubated with cTnI, and cellular proliferation was measured using flow cytometry. AAbs against cTnI were detected by enzyme‐linked immunosorbent assay.

Results: A positive cellular proliferative response to cTnI was identified in 20.5% (9/44) patients with iDCM and 5.7% (2/35) of healthy controls (p < 0.05). Positive cTnI AAbs were identified in 20% (7/35) of healthy controls and 13.6% (6/44) of patients with iDCM (p = NS). The presence of cTnI AAbs did not correlate with a positive cellular proliferative response. However, patients with iDCM who had an AAb response to cTnI were less likely to be taking a statin (p < 0.05).

Conclusions: A cellular autoimmune response to cTnI is demonstrated in a subset of patients with iDCM. However, the presence of a cellular response did not correlate with the presence of AAbs to the same antigen. Clin Trans Sci 2011; Volume 4: 317–322
Evaluating Research Mentors Working in the Area of Clinical Translational Science: A Review of the Literature
Authors: Meagher Emma , Taylor Lauren , Probsfield Jeff , Fleming Mike
Published: October 2011

The goal of this paper is to review the evaluation of mentors with a focus on training new investigators in clinical translational science. These scholars include physicians and Ph.D. scientists who are generally assistant professors in clinical departments. This white paper is one of a series of articles focused on the programmatic elements of effective mentoring practices and the “current state of the art.” Evaluating mentor performance and providing formative feedback can lead to stronger mentoring and ultimately lead to increased success of new clinical and translational investigators. While there is general agreement that mentor evaluation can be helpful, the process is difficult. Trainees are reluctant to share negative experiences and to rate their mentors. Mentors are not sure they want to be evaluated. Program leaders are not sure how to effectively use the information. This white paper provides mentees, mentors, and program leaders with new perspectives on mentor evaluation and ideas for future research. Clin Trans Sci 2011; Volume 4: 353–358
Expression of Neuropeptide Y, Substance P, and Their Receptors in the Right Atrium of Diabetic Patients
Authors: Ejaz Asma , LoGerfo Frank W. , Khabbaz Kamal , Pradhan Leena
Published: October 2011

Objective: To investigate the expression of neuropeptides and their receptors that play a role in cardiac homeostasis in the right atrium of nondiabetic and diabetic patients undergoing coronary artery bypass graft surgery.

Background: The cardioactive neuropeptides and their receptors investigated in this study were Neuropeptide Y (NPY), and its receptors, NPY Receptor1 (NPY1R), NPY Receptor2 (NPY2R), NPY Receptor5 (NPY5R) and Substance P (SP) and its receptor, Neurokinin1R (NK1R).

Methods: The gene and protein expression of NPY, NPY1R, NPY2R, NPY5R, SP and NK1R from the atrial tissue of 10 nondiabetic and diabetic patients undergoing coronary artery bypass grafting (CABG) was assessed by Q‐RTPCR, immunohistochemistry, Western blot, and ELISA.

Results: Gene expression of NPY2R, NPY5R, preproTachykinin A (SP gene), and NK1R and their respective protein expression were significantly reduced whereas that of NPY and NPY1R were unchanged in the right atrium of diabetic patients compared to nondiabetic patients.

Conclusions: These results demonstrate that the expression of neuropeptides and their receptors in the diabetic heart is significantly impaired, and may be the link between neuropathy and cardiac complications. Further studies are warranted to delineate pathophysiologic mechanisms associated with dysregulation of the cardiac neuropeptide system and the relationship to cardiac complications in diabetes. Clin Trans Sci 2011; Volume 4: 346–350
Navigation-assisted Debridement Arthroplasty for Osteoarthritis of the Elbow: A Preliminary Report
Authors: Ikeda Masayoshi , Kobayashi Yuka , Saito Ikuo , Ishii Takayuki , Shimizu Ayuko , Oka Yoshinori
Published: October 2011

Background

Debridement arthroplasty is a widely accepted operative treatment for elbow osteoarthritis. However, it is sometimes difficult to define the extent of appropriate osteophyte resection. In the present study, a navigation system was used to resect the osteophytes.

Methods

Eight male patients (mean age, 62 years) were enrolled in the present study. When the osteophytes around the olecranon, coronoid and radial fossae of the distal humerus were removed, the operation was monitored using a navigation system. Pre- and postoperative clinical and radiographical assessments were performed with a mean follow-up of 29 months.

Results

There were no major complications during the operations. Postoperative computed tomography showed that the osteophytes were properly removed. The mean range of motion of the elbow improved from –21° to 110° pre-operatively to –13° to 130° at the time of follow-up ( p < 0.05). The mean Mayo Elbow Performance Score improved from 75 points to 98 points ( p < 0.05) and the mean Disabilities of the Arm, Shoulder and Hand score improved from 24.2 points to 8.7 points ( p < 0.05).

Conclusions

The findings of the present study demonstrate that the osteophytes formed at the distal humerus could be precisely visualized using a navigation system. This system effectively defined the region and depth of the morphological configuration for resection.
Evaluation of the cost of therapy for the treatment of sexually transmitted infections in a Nigerian teaching hospital
Authors: Suleiman Ismail A , Tayo Fola
Published: October 2011

Objective

To determine the cost of therapy to patients of sexually transmitted infections in a Nigerian teaching hospital.

Methods

A retrospective drug-utilization evaluation in conjunction with cost-of-illness analysis was used. Two hundred and twenty seven case notes containing 310 prescriptions of patients with sexually transmitted infections were examined over a 1-year period between 2005 and 2006. Relevant data including demographics, diagnosis, prescribed drugs and dosages were extracted and the associated costs, direct and indirect, were evaluated.

Key findings

Disease occurrence was higher among the most productive work force group of 21–40 years (59.0%), which had 82.0% of the prescriptions. The overall average cost of antibacterial agents for sexually transmitted infection per patient (n = 227) was NGN977.85 (US$7.52) while the overall average cost per prescription (n = 310) was NGN716.04 ($5.51). The highest average cost of antibacterial agents of NGN2028.00 ($15.60) was obtained for chlamydial infection. The overall average of cost of therapy per patient (n = 227) was NGN2610.65 ($20.08). Chlamydial infection had the highest overall average cost of therapy, at NGN5408.92 ($41.60). The discounted average total cost of therapy for the year 2010 was $48.23 for chlamydial infection. Antibacterial agents constituted the highest cost component (37.5%) followed by indirect costs (26.5%). The average cost of therapy per patient of NGN2610.65 ($20.04) gave a 2010 discounted value of $23.23.

Conclusion

The cost of therapy for these infections to patients and the nation as a whole is huge.
The Single‐Party Dictator's Dilemma: Information in Elections without Opposition
Authors: MALESKY EDMUND , SCHULER PAUL
Published: October 2011

The literature on authoritarian institutions points to nationwide elections as a mechanism for learning about the preferences of citizens. In using elections in this way, however, authoritarians face a trade‐off between gathering reliable information and guaranteeing electoral victory. In this article, we explore how single‐party regimes manage this trade‐off and the particular types of information available to them. Using candidate‐level data from Vietnam, we demonstrate that single‐party regimes, in particular, forsake information on overall regime support and strength of opposition in favor of information on the popularity of local notables and the compliance of local officials with central mandates. In addition, we show that ex ante electioneering is less risky than ex post fraud at achieving these goals.
Using Cosponsorship to Estimate Ideal Points
Authors: DESPOSATO SCOTT W. , KEARNEY MATTHEW C. , CRISP BRIAN F.
Published: October 2011

Ideal point estimates based on roll‐call vote results have provided leverage for a variety of theory testing efforts. Recently, scholars have suggested using cosponsorship data as a proxy for roll‐call votes. Conceptually similar to roll‐call votes, cosponsorship data are appealing for a variety of reasons. However, the data‐generating process for cosponsorship is untheorized and little studied. We examine the properties of ideal point estimates from cosponsorship data. We find that the ability to estimate ideal points from cosponsorship data is contingent on the underlying data‐generating process; reliance on such measures requires strong and often unrealistic assumptions.
The Influence of Lobbying Activityin State Legislatures: Evidence from Wisconsin
Authors: GRASSE NATHAN , HEIDBREDER BRIANNE
Published: October 2011

This study attempts to assess the degree of influence interest groups can exert on the state policy process, specifically via their lobbying activities. The analysis uses data from the 2005–06 Wisconsin Legislative Session to assess the association between lobbying activity and legislative outcomes in one state legislature. The study finds a direct association between lobbying activities and bill outcomes, while also exploring the potential influences of both key political actors and public attention. Public attention is found to reduce the effects of lobbying efforts, suggesting that lobbying is most effective when focused on less salient issues.
It's Not You, It's Me: Determinants of Voluntary Legislative Turnover in Canada
Authors: KERBY MATTHEW , BLIDOOK KELLY
Published: October 2011

The Canadian federal parliament is unique among Westminster parliamentary democracies due to the unusually high level of voluntary and involuntary MP turnover that occurs at each general election. This article builds on existing research to test the hypothesis that the MP career duration is related to MPs' expectations about parliamentary roles, insofar as voluntary turnover is concerned. Data on MPs drawn from historical records collected by the Library of Parliament and from surveys conducted in 1993 and 20011 are used to develop an event history model which estimates the hazard of voluntary career termination when different parliamentary roles are taken into consideration. Findings suggest that a number of individual factors play a role in voluntary turnover, most notably that MPs who enter Parliament hoping to affect policy are the most likely to move on.
Evaluation of fluorine additive effect on cationic UV-nanoimprint resin
Authors: Okada Makoto , Haruyama Yuichi , Matsui Shinji , Miyake Hiroto , Iyoshi Shuso , Yukawa Takao , Takeuchi Hidekazu
Published: October 2011

Ultraviolet (UV) nanoimprint lithography is used to fabricate nanostructured devices with high-throughput, low cost, and high resolution. The nanoimprint mold is coated with an antisticking layer to enable easy separation of the mold from the UV nanoimprint resins. An important issue is finding a way to prevent the deterioration of the antisticking layer which results from repeated UV nanoimprinting. To do this, a UV nanoimprint resin with release properties is required. The authors evaluated the effect of a fluorine additive on a cationic UV-curable resin by x-ray photoelectron spectroscopy (XPS), scanning probe microscopy, and contact angle measurement. The authors confirmed from the XPS results that fluorine was present on the surface of the cured UV-curable resin with the fluorine additive. Furthermore, the adhesion and frictional forces of the UV-curable resin with the fluorine additive were lower than those of the UV-curable resin without the additive.
Large-area suspended graphene on GaN nanopillars
Authors: Lee Chongmin , Kim Byung-Jae , Ren Fan , Pearton S. J. , Kim Jihyun
Published: October 2011

The authors have demonstrated large-area suspended graphene on GaN nanopillars predefined by nanosphere lithography and inductively coupled plasma etching. The graphene was successfully suspended over large areas without ripples and corrugations. Scanning electron microscopy, atomic force microscopy and micro-Raman spectroscopy were used to characterize the properties of the suspended graphene on nanopillars. The thermal properties of the suspended and supported graphene were investigated by varying the underlying GaN nanopilllar geometries from flat-top to sharp-cone morphologies and heating the resulting structures via irradiation with laser powers of 1.53 mW, 8.03 mW, and 16.19 mW. The heat transfer was effective even when the contact area between the suspended graphene and the supporting substrate was small, due to the high thermal conductivities of graphene and GaN. The extremely high thermal conductivity of the graphene can improve the thermal management in GaN-based high power electronic and optoelectronics devices, a critical factor for their long-term reliability.
Etching characteristics and mechanisms of SiC thin films in inductively-coupled HBr-Ar, N2, O2 plasmas
Authors: Efremov Alexander , Kang Sungchil , Kwon Kwang-Ho , Seok Choi Won
Published: October 2011

Etch characteristics and mechanisms of SiC thin films in HBr-Ar, HBr-N2, and HBr-O2 inductively-coupled plasmas were studied using a combination of experimental and modeling methods. The etch rates of SiC thin films were measured as functions of the additive gas fraction in the range of 0–100% for Ar, N2, and O2 at a fixed gas pressure (6 mTorr), input power (700 W), bias power (200 W), and total gas flow rate (40 sccm). The plasma chemistry was analyzed using Langmuir probe diagnostics and a global (zero-dimensional) plasma model. The good agreement between the behaviors of the SiC etch rate and the H atom flux could suggest that a chemical etch pathway is rather controlled by the gasification of carbon through the CHx or CHxBry compounds.
Evaluation of the curing process of UV resins in a 1,1,1,3,3-pentafluoropropane gas environment by photo differential scanning calorimetry and Fourier transform infrared spectroscopy
Authors: Sawada Yohei , Haruyama Yuichi , Kanda Kazuhiro , Matsui Shinji , Okada Makoto , Miyake Hiroto , Ohsaki Takeshi , Hirai Yoshihiko , Hiroshima Hiroshi
Published: October 2011

The formation of bubble defects during UV-nanoimprinting can be prevented by carrying out the process in a 1,1,1,3,3-pentafluoropropane (PFP) gas environment. The authors therefore evaluated the curing time and the calorific value of UV-curable resins in a PFP gas environment by photo differential scanning calorimetry and their polymerization degree by Fourier transform infrared spectroscopy. The authors found that UV-curable resins polymerized more efficiently in PFP than in air because PFP dissolves in the resins.
Fabrication of a seamless roll mold using inorganic electron beam resist with postexposure bake
Authors: Unno Noriyuki , Taniguchi Jun , Ishikawa Kiyoshi
Published: October 2011

The fabrication of next-generation devices via roll-to-roll (RTR) nanoimprinting has received considerable attention due to the high throughput and resolution associated with the process. In particular, RTR nanoimprinting with ultraviolet (UV)-curable resin is expected to be useful for the fabrication of large-area devices such as nonreflective films, transparent conductive sheets, and organic solar cells. In order to improve the resolution of such devices, the roll mold must be able to produce seamless fine patterns. Generally, a roll mold for nanoimprinting is made by attaching a planar mold replicated from the master mold via a nickel electroforming technique. However, this method produces seams, which reduces the product yield. In order to resolve these issues, the authors have developed a direct writing method using electron beam (EB) lithography on a rotating cylindrical substrate. In this study, the authors examined the potential for fabricating a seamless roll mold using high-resolution inorganic EB resist and the pattern shrink effect from postexposure bake (PEB). The authors used the dip-and-pull method to form the EB resist layer on the roll mold substrate (32 mm diameter, made of brass). The cleaned roll mold was dipped in the inorganic EB resist and then pulled out at a constant speed. The resulting sample was cured at 300 °C for 1 h. Next, the sample was mounted on rotating equipment and placed in a scanning electron microscope (SEM) equipped with an EB writing system, and the roll substrate was exposed to 10 kV EB while rotating at a constant speed. The revolution speed was set to ten turns per line pattern. Subsequently, PEB was carried out at 200 °C for 10 min in air. After the sample was cooled to room temperature, the EB-exposed area of the EB resist layer was developed using buffered HF. The obtained pattern on the roll mold was examined with the same SEM used for writing. Finally, RTR nanoimprinting using the obtained roll mold was carried out using UV-photocurable resin. At that time, the sample was coated with an antisticking layer of fluorinated silane coupling agent. As a result, a seamless line pattern 190 nm wide was obtained on a polyethylene terephthalate film over a length of 10 cm.
Auto‐segmentation of normal and target structures in head and neck CT images: A feature‐driven model‐based approach
Authors: Qazi Arish A. , Pekar Vladimir , Kim John , Xie Jason , Breen Stephen L. , Jaffray David A.
Published: October 2011

Purpose:

Intensity modulated radiation therapy (IMRT) allows greater control over dose distribution, which leads to a decrease in radiation related toxicity. IMRT, however, requires precise and accurate delineation of the organs at risk and target volumes. Manual delineation is tedious and suffers from both interobserver and intraobserver variability. State of the art auto‐segmentation methods are either atlas‐based, model‐based or hybrid however, robust fully automated segmentation is often difficult due to the insufficient discriminative information provided by standard medical imaging modalities for certain tissue types. In this paper, the authors present a fully automated hybrid approach which combines deformable registration with the model‐based approach to accurately segment normal and target tissues from head and neck CT images.

Methods:

The segmentation process starts by using an average atlas to reliably identify salient landmarks in the patient image. The relationship between these landmarks and the reference dataset serves to guide a deformable registration algorithm, which allows for a close initialization of a set of organ‐specific deformable models in the patient image, ensuring their robust adaptation to the boundaries of the structures. Finally, the models are automatically fine adjusted by our boundary refinement approach which attempts to model the uncertainty in model adaptation using a probabilistic mask. This uncertainty is subsequently resolved by voxel classification based on local low‐level organ‐specific features.

Results:

To quantitatively evaluate the method, they auto‐segment several organs at risk and target tissues from 10 head and neck CT images. They compare the segmentations to the manual delineations outlined by the expert. The evaluation is carried out by estimating two common quantitative measures on 10 datasets: volume overlap fraction or the Dice similarity coefficient (DSC), and a geometrical metric, the median symmetric Hausdorff distance (HD), which is evaluated slice‐wise. They achieve an average overlap of 93% for the mandible, 91% for the brainstem, 83% for the parotids, 83% for the submandibular glands, and 74% for the lymph node levels.

Conclusions:

Our automated segmentation framework is able to segment anatomy in the head and neck region with high accuracy within a clinically‐acceptable segmentation time.
Radiochromic EBT2 film dosimetry for low‐energy protontherapy
Authors: Angellier G. , Gautier M. , Hérault J.
Published: October 2011

Purpose:

In protontherapy, accessories are used in order to adapt the beam to the surface and to the depth of the target. They are positioned close to the patient in order to avoid perturbation effects related to proton scattering. The level of contamination of the beam caused by these accessories may be assessed by examining the dose maps in parallel planes to the beam incidence. The EBT2 radiochromic film is a suitable tool for this task, as it can be cut into small pieces and immersed in water. Prior to use the EBT2 film for dose measurements, its response when exposed to a proton beam must be analysed.

Methods:

The measurements were performed at the Centre Antoine Lacassagne, using the hospital‐based MEDICYC isochronous cyclotron which provides 65 MeV protons. Monoenergetic as well as polyenergetic beams were used. Small pieces of EBT2 films were irradiated with proton beams in a small water phantom. Films were exposed at various angles close to the beam incidence and received doses ranging from 0.25 to 500 Gy. The optical density (OD) was studied as a function of angle, dose and linear energy transfer (LET).

Results:

The effective atomic number of the active layer of the film is close to that of water which prevents disturbances of the measurement. However, the high density and the significant thickness of the Mylar substrate surrounding the active layer affect the use of the film in a parallel orientation to the beam. Therefore, the substrate layer may totally or partially slow down the protons. The measurement is then no longer representative to what happens in water. The measurement errors can be corrected by applying a tilt angle of at least 5° between the film and the beam. The dose analysis reveals that the green channel is the most sensitive in the dose range from 1 to 100 Gy. The OD is accurately described by a Weibull function of the dose with four free parameters. The Weibull function is valid for both monoenergetic and polyenergetic beams if the LET is limited to values below 15 MeV g− 1 cm2. When using a film orientation close to the beam incidence angle, increasing LET values are encountered throughout the film axis gradually with the protons slowing down in water. The EBT2 films show an underestimated response for higher LET values. The comparison of data from the present study to data obtained by other authors for EBT films allows modelling the underestimated response as a function of the LET. The definition improvement of the link between OD and LET requires to integrate more closely the beam energy characteristics.

Conclusions:

The EBT2 film is a suitable dosimeter for analysing dose plans in planes nearly parallel to the beam orientation by compensating the underestimated dose response due to LET.
Assessment of three methods for detection of ultrasound artifacts
Authors: King Deirdre M. , Hangiandreou Nicholas J. , Tradup Donald J. , Stekel Scott F.
Published: October 2011

Purpose:

The purpose of this work is to measure the performance (sensitivity and specificity) of three different visually based methods of detecting ultrasound artifacts using dynamic clips obtained with a liquid phantom. It is important to detect the presence of these non uniformities as early as possible, so they can be assessed, tracked, and addressed well before clinical image quality is impacted.

Methods:

A total of 28 transducers of varying models containing a single artificial artifact created by stretching thin filaments across the transducer face were prepared. A second set of 28 matching transducers contained no artifacts. A 10 s clip was recorded of a dynamic speckle pattern from a custom liquid phantom (“dynamic clip”). A single‐frame image was obtained by computing the median values at each pixel location over all frames of the clip (“median image”). This single‐frame median image was then subtracted from a baseline image previously obtained with no induced artifact (“subtracted median”). All images were evaluated by six observers. The mean sensitivity and specificity with 95% exact binomial confidence intervals for the three artifact detection methods were estimated. Evaluation time and observer confidence were recorded.

Results:

Both single‐frame median and subtracted median images had a higher sensitivity than the dynamic clip. Overall the subtracted median images had the highest sensitivity of 97%, while maintaining a high specificity of 92%. Observers identified artifacts in the shortest time and with the highest confidence with this method. The subtracted median method removed the original structural variations and non‐uniformities, and reduced the likelihood of false‐positives.

Conclusions:

From the three methods assessed in this study, subtracted median images allow detection of artifacts with very good sensitivity and specificity, low image evaluation times, and a high degree of observer confidence, making these ideal for routine QC. For acceptance testing, where there are no previous baseline images available for subtraction, the use of median images is useful, although comparison with median images from different transducers of the same model and/or comparison of impressions from multiple observers should be made to decrease the incidence of false‐positive findings. If median and subtracted median images are not available, direct inspection of the dynamic B‐mode clips is useful for acceptance testing and quality control, but with lower sensitivity and somewhat longer evaluation time.
A New Kind of Ancestor:
Ardipithecus
Unveiled
Authors: Gibbons Ann
Published: October 2011

In this special issue of
Science
, the oldest known hominin skeleton,
Ardipithecus ramidus
, reveals the upright origins of humankind
Preclinical and Clinical Evaluation of Intraductally Administered Agents in Early Breast Cancer
Authors: Stearns Vered , Mori Tsuyoshi , Jacobs Lisa K. , Khouri Nagi F. , Gabrielson Edward , Yoshida Takahiro , Kominsky Scott L. , Huso David L. , Jeter Stacie , Powers Penny , Tarpinian Karineh , Brown Regina J. , Lange Julie R. , Rudek Michelle A. , Zhang Zhe , Tsangaris Theodore N. , Sukumar Saraswati
Published: October 2011

Intraductal administration of chemotherapeutic agents may reduce new breast cancer formation and offer a less toxic treatment regimen than intravenous therapy.
Splicing-Directed Therapy in a New Mouse Model of Human Accelerated Aging
Authors: Osorio Fernando G. , Navarro Claire L. , Cadiñanos Juan , López-Mejía Isabel C. , Quirós Pedro M. , Bartoli Catherine , Rivera José , Tazi Jamal , Guzmán Gabriela , Varela Ignacio , Depetris Danielle , de Carlos Félix , Cobo Juan , Andrés Vicente , De Sandre-Giovannoli Annachiara , Freije José M. P. , Lévy Nicolas , López-Otín Carlos
Published: October 2011

Antisense oligonucleotides reverse premature aging and extend life span in mutant mice that mimic aberrant splicing in progeria patients.
Unraveling How Probiotic Yogurt Works
Authors: Bisanz Jordan E. , Reid Gregor
Published: October 2011

A study investigating the effects of a probiotic yogurt on the mouse and human gut microbiota provides a strategy for understanding how probiotic foods affect the mammalian gut.
Science Translational Medicine
Podcast: 26 October 2011
Authors: Gordon Jeffrey I. , Smith Orla
Published: October 2011

A conversation with Jeffrey I. Gordon about how probiotic bacteria in yogurt affect the human and mouse gut microbiota.
Refreshing Your Memory
Authors: Shum Anthony K.
Published: October 2011

A subset of human memory T cells with stem cell-like properties may provide a durable antitumor response.
Novel Vaginal Microflora Colonization Model Providing New Insight into Microbicide Mechanism of Action
Authors: Fichorova Raina N. , Yamamoto Hidemi S. , Delaney Mary L. , Onderdonk Andrew B. , Doncel Gustavo F.
Published: October 2011

Several broad-spectrum microbicides, including cellulose sulfate (CS), have passed conventional preclinical and phase I clinical safety evaluation and yet have failed to protect women from acquiring HIV-1 in phase II/III trials. Concerns have been raised that current preclinical algorithms are deficient in addressing the complexity of the microflora-regulated vaginal mucosal barrier. We applied a novel microflora-colonized model to evaluate CS and hydroxyethylcellulose (HEC), which is used as a “universal placebo” in microbicide trials. Cervicovaginal epithelial cultures were colonized with normal vaginal microflora isolates representing commonLactobacillusspecies used as probiotics (L. acidophilusandL. crispatus) orPrevotella biviaandAtopobium vaginae, most prevalent in the disturbed microflora of bacterial vaginosis (BV). At baseline, all strains maintained constant epithelium-associated CFUs without inducing cytotoxicity and apoptosis. CS selectively reduced epithelium-associated CFUs and (to a lesser extent) planktonic CFUs, most significantly affectingL. crispatus. Inducing only minor changes in sterile epithelial cultures, CS induced expression of innate immunity mediators (RANTES, interleukin-8 [IL-8], and secretory leukocyte protease inhibitor [SLPI]) in microflora-colonized epithelia, most significantly potentiating effects of bacteria causing BV. In the absence of CS, all bacterial strains exceptL. acidophilusactivated NF-κB, although IL-8 and RANTES levels were increased by the presence of BV-causing bacteria only. CS enhanced NF-κB activation in a dose-dependent manner under all conditions, includingL. acidophiluscolonization. HEC remained inert. These results offer insights into possible mechanisms of CS clinical failure. The bacterially colonized cervicovaginal model reveals unique aspects of microflora-epithelium-drug interactions and innate immunity in the female genital tract and should become an integral part of preclinical safety evaluation of anti-HIV microbicides and other vaginal formulations.

IMPORTANCEThis report provides experimental evidence supporting the concept that the vaginal microflora regulates the epithelial innate immunity in a species- and strain-specific manner and that topically applied microbicides may alter both the bacterial and epithelial components of this homeostatic interaction. Our data also highlight the importance of differentiating the effects of biomedical interventions on epithelium-associated versus conventional planktonic bacterial growth when assessing vaginal mucosal health and immunity.