bluuebunny/crossref_metadata_2025 huggingface dataset:
Implications from Ithaca Chasma for the thermal and orbital history of Tethys
Authors: Chen E. M. A. , Nimmo F.
Published: October 2008

Flexural modeling of Ithaca Chasma on Tethys suggests that the elastic thickness and the surface heat flux were 5–7 km and 18–30 mW/m2 respectively, when the feature formed (∼4 Gyr B.P.). Tidal heating is a plausible heat source, suggesting that Tethys' eccentricity was higher in the past. Depending on Tethys' internal structure, eccentricities in the range 0.001 to 0.02 are sufficient to have generated the inferred heat flux. Because the eccentricity damping timescale is short, <20 Myr, it is unlikely that this eccentricity was primordial. More likely, Tethys' eccentricity increased during passage through a 3:2 resonance with Dione. In equilibrium, this resonance produces ∼2.5 mW/m2 suggesting that non‐equilibrium or periodic heating was important, similar to the case for Enceladus at present.
Global cloud‐system‐resolving simulation of aerosol effect on warm clouds
Authors: Suzuki Kentaroh , Nakajima Teruyuki , Satoh Masaki , Tomita Hirofumi , Takemura Toshihiko , Nakajima Takashi Y. , Stephens Graeme L.
Published: October 2008

We simulated the interactions of aerosols with liquid clouds using an aerosol‐coupled global cloud‐system‐resolving model with horizontal resolution of 7 km, and the results are compared with satellite observations of cloud and aerosols. The result shows detailed spatial structures of cloud droplet effective radii (CDR) realistically simulated especially over tropics. The global correlation statistics of liquid water path (LWP) with aerosol index (AI) are investigated for different cloud types to reveal that the LWP slightly decreases with increasing AI, closely resembling satellite‐observed features. The CDRs for different cloud types are also shown to decrease with increasing AI, and the sensitivities are found to be relatively similar among cloud types although of discrepancy in absolute values between the model and satellite observation. The model also simulates vertical growth patterns of liquid droplets and their interactions with aerosols in a manner similar to satellite observations.
Scaling behavior of auroral luminosity fluctuations observed by Auroral Large Imaging System (ALIS)
Authors: Golovchanskaya I. V. , Kozelov B. V. , Sergienko T. I. , Brändström U. , Nilsson H. , Sandahl I.
Published: October 2008

Auroral images obtained by the Auroral Large Imaging System, an optical facility with extremely low noise level and large dynamical range, have been examined in order to study the scaling properties of spatial variations in auroral luminosity. The images under examination were obtained during substorm conditions and contained active auroral forms of different types. The field of view was ±17° from magnetic zenith, which allowed the investigation of auroral fluctuations at scales from 6.4 to 51.2 km. The narrow field of view is assumed to decrease the contamination from aspect angle broadening which leads to distortions of scaling characteristics in the horizontal plane. We analyzed the logscale diagrams constructed by discrete wavelet transform of the data as well as the standard deviation, kurtosis, and probability density functions of the fluctuations. It is found that the data series for substorm auroral forms often reveal closeness to self‐similarity, the observed scaling exponent varying between 0.6 and 0.7. Auroral fluctuations in different emission lines exhibit a very similar scaling behavior. A comparison is performed with fluctuations in an electric field observed by the Dynamics Explorer 2 satellite under substorm conditions. It is shown that the intermittency features are more pronounced for substorm electric fields than for auroral fluctuations.
Retrieving optical depths of optically thin and mixed‐phase clouds from MFRSR measurements
Authors: Wang Tianhe , Min Qilong
Published: October 2008

A new method has been developed to retrieve cloud optical depths for optically thin clouds (τ < 10) from the Multifilter Rotating Shadowband Radiometer (MFRSR). On the basis of simultaneous measurements of direct and diffuse radiation from MFRSR, this method allows partition of water and ice clouds and thus improves cloud optical depth retrievals. The new retrieval algorithm achieves the high consistency of retrieved cloud optical depth from both direct‐beam and total radiation: the slope of 0.95 between the two with correlation coefficient of 0.90 and RMS of 1.00. A sensitivity study illustrates that the maximum biases (relative errors) of cloud optical depth within the range of effective radius of clouds are 0.16 (4.7%) and 0.36 (8.3%) for retrievals from direct‐beam radiation and from total radiation, respectively. Validation and evaluation from measurements at the Point Reyes site have been conducted, illustrating that the new retrieval algorithm provides not only accurate retrievals of cloud optical depth in terms of radiation closure but also unique mix ratio of cloud water and ice for optically thin clouds under overcast conditions. Because of the climatologic importance of thin clouds, this algorithm with unique mix ratio retrievals is important for the climate study.
Altitudinal variation of midlatitude localized TEC enhancement from ground‐ and space‐based measurements
Authors: Datta‐Barua S. , Mannucci A. J. , Walter T. , Enge P.
Published: October 2008

We present terrestrial and space‐based dual‐frequency observations of a region of enhanced total electron content (TEC) over the southeastern United States at local nighttime during the geomagnetic storm of 29–31 October 2003. The apparently localized, large‐amplitude, and nearly Earth‐fixed midlatitude ionosphere disturbance contained about 10 m higher delay at Global Positioning System (GPS) L1 frequency than the nighttime background ionosphere TEC. Using the dual‐frequency altimeter on board the Jason satellite, we show evidence that nearly all of the electron content was below its orbital altitude of 1300 km at 0000 local time on 31 October 2003. Dual frequency GPS measurements from the receiver on board the SAC‐C satellite indicate that some portion of the electron content existed above the 700 km orbit altitude of SAC‐C. We develop a horizontally piecewise constant regional model of the enhancement. We compare the model prediction of TEC with the SAC‐C satellite GPS data to constrain the altitude of this enhanced TEC region. Our model indicates that the peak density of the anomalous region is at slightly higher altitude and greater in amplitude than that of the background. The TEC enhancement provides a concrete case study of an extreme scenario that both space‐based and ground‐based GPS augmentation systems must take into account in order to offer high‐accuracy, high‐integrity corrections to GPS for safety‐of‐life applications.
The emerging role of splicing factors in cancer
Authors: Grosso Ana Rita , Martins Sandra , Carmo‐Fonseca Maria
Published: October 2008

Recent progress in global sequence and microarray data analysis has revealed the increasing complexity of the human transcriptome. Alternative splicing generates a huge diversity of transcript variants and disruption of splicing regulatory networks is emerging as an important contributor to various diseases, including cancer. Current efforts to establish the dynamic repertoire of transcripts that are generated in health and disease are showing that many cancer‐associated alternative‐splicing events occur in the absence of mutations in the affected genes. A growing body of evidence reveals changes in splicing‐factor expression that correlate with cancer development, progression and response to therapy. Here, we discuss how recent links between cancer and altered expression of proteins implicated in splicing regulation are bringing the splicing machinery to the fore as a potential target for anticancer treatment.
Natural acidophilic biofilm communities reflect distinct organismal and functional organization
Authors: Wilmes Paul , Remis Jonathan P , Hwang Mona , Auer Manfred , Thelen Michael P , Banfield Jillian F
Published: October 2008

Pellicle biofilms colonize the air–solution interface of underground acid mine drainage (AMD) streams and pools within the Richmond Mine (Iron Mountain, Redding, CA, USA). They exhibit relatively low species richness and, consequently, represent good model systems to study natural microbial community structure. Fluorescence in situ hybridization combined with epifluorescent microscopy and transmission electron microscopy revealed spatially and temporally defined microbial assemblages. Leptospirillum group II dominates the earliest developmental stages of stream pellicles. With increasing biofilm maturity, the proportion of archaea increases in conjunction with the appearance of eukaryotes. In contrast, mature pool pellicles are stratified with a densely packed bottom layer of Leptospirillum group II, a less dense top layer composed mainly of archaea and no eukarya. Immunohistochemical detection of Leptospirillum group II cytochrome 579 indicates a high abundance of this protein at the interface of the biofilm with the AMD solution. Consequently, community architecture, which most likely develops in response to chemical gradients across the biofilm, is reflected at the functional gene expression level.
Effects of temperature on growth rate and gross growth efficiency of an Antarctic bacterivorous protist
Authors: Rose Julie M , Vora Neil M , Countway Peter D , Gast Rebecca J , Caron David A
Published: October 2008

The effects of temperature on the growth rate and gross growth efficiency (GGE) of the heterotrophic nanoflagellate, Paraphysomonas imperforata, cultured from the Ross Sea, Antarctica were investigated using five experimental temperatures (range=0–20 °C). This bacterivorous protist exhibited measurable growth over the temperature range examined, although temperature exerted a significant effect on its growth rate. There was no evidence for an effect of temperature on GGE. The growth rates and GGE of our Antarctic P. imperforata isolate were compared to values reported for other cultures of species from this genus. A wide range of growth efficiencies have been reported for different strains of Paraphysomonas spp., but our estimates were comparable to mean/median values reported in the literature. The growth rates of our Antarctic P. imperforata were similar to rates obtained for an Arctic conspecific at low temperatures (0–5 °C), among the highest reported rates for any Paraphysomonas species at intermediate temperatures (10–15 °C) and similar to rates reported for temperate congeners and conspecifics at 20 °C. Q10 values of 15, 2.2, 3.6 and 0.93 were calculated for growth rates at 5 °C intervals between 0 and 20 °C, respectively. Results indicated that our Antarctic P. imperforata grew at rates comparable to other polar isolates at ambient polar temperatures, but these low temperatures may be outside the physiological optimum for the isolate.
Age at Arrival and Risk of Obesity Among US Immigrants
Authors: Roshania Reshma , Narayan K.M. Venkat , Oza‐Frank Reena
Published: October 2008

Although immigrants are a rapidly growing subgroup, little is known about overweight/obesity among the foreign‐born in the United States, especially regarding the effect of age at arrival. This study determined whether overweight/obesity prevalence is associated with age at arrival of immigrants to the United States. We analyzed data on 6,421 adult immigrants from the New Immigrant Survey (NIS), a study that is nationally representative of adult immigrants with newly acquired legal permanent residence (LPR). Multiple regression analyses tested the effects of duration of residence and age at arrival on overweight/obesity, defined by BMI of ≥25 kg/m2, and self‐reported dietary change score. We found the relationship between duration of residence and overweight/obesity prevalence varied by age at arrival (P < 0.001). Immigrants ≤20‐years old at arrival who had resided in the United States ≥15 years were 11 times (95% confidence interval: 5.33, 22.56) more likely to be overweight/obese than immigrants <20‐years old at arrival who had resided in the United States ≤1 year. By comparison, there was no difference in overweight/obesity prevalence by duration among immigrants who arrived at >50 years of age. Higher self‐reported dietary change is also associated with overweight/obesity. In conclusion, immigrants younger than 20 at arrival in the United States may be at higher risk of overweight/obesity with increasing duration of residence than those who arrive at later ages. Obesity prevention among young US immigrants should be a priority.
The Association Between Glycemia and Endothelial Function in Nondiabetic Individuals: The Importance of Body Weight
Authors: Voidonikola Paraskevi T. , Stamatelopoulos Kimon S. , Alevizaki Maria , Kollias George E. , Zakopoulos Nikolaos A. , Lekakis John P. , Anastasiou Eleni , Theodorakis Michael J. , Pittas Anastassios G. , Papamichael Christos M.
Published: October 2008

The aim of this study was to examine the association between glycemia and markers of early atherosclerosis in healthy nondiabetic individuals. In 309 individuals without diabetes or symptomatic cardiovascular disease, we assessed long‐term glycemia by glycosylated hemoglobin (HbA1c) and endothelial function by flow‐mediated dilatation (FMD) in the brachial artery. HbA1c was negatively associated with FMD (r = −0.162, P = 0.004). Multivariate linear regression analysis after adjusting for common risk factors of cardiovascular disease showed that BMI was an effect modifier of the association between HbA1c and FMD (P = 0.034 for the HbA1c × BMI interaction). We stratified the FMD outcome data into two groups separated by the median BMI (group 1: BMI ≤ 26.1 kg/m2 and group 2: BMI > 26.1 kg/m2). In the lower BMI group, HbA1c was an independent predictor of FMD even when adjusted for confounding factors associated with impaired glucose metabolism (r = −0.215, P = 0.009), but in the higher BMI group HbA1c was not associated with FMD (r = −0.051, P = 0.5). In a nondiabetic population, long‐term glycemia was associated with endothelial dysfunction only in lean individuals. In the overweight individuals, this association was not apparent, possibly because some of the mechanisms that mediate the effect of glycemia on vascular function are shared by obesity.
Differences Between the 1993 and 2007 Standards for the Certificate of Clinical Competence in Audiology
Authors: Cosby Janel , Figueroa Christina Marie , Allen Rose L.
Published: October 2008

Individuals applying for their initial American Speech-Language-Hearing Association (ASHA) Certificate of Clinical Competence in Audiology (CCC-A) must now adhere to the 2007 Certification Standards in Audiology (ASHA, 2008). The standards, which took effect on January 1, 2007, require a doctoral degree for persons who apply for certification after December 31, 2011. This article compares the 1993 and 2007 Standards for Certification in Audiology and discusses the major differences, such as length of the practicum experience, assignment of patients/clients, the number and type of clock hours, and supervision requirements.
Relationships Between Students' Self-Perceived Supervisory Needs and End of Semester Outcomes
Authors: Hart Pam , Turner Greg , Duesing Blaine , Galley Deborah , Harlan Carl , Turner Joni , Wilson Jim , Zimmer Beverly Jean , de Jonge Robert
Published: October 2008

According to the 2008 Standards for Accreditation of Graduate Education Programs in Audiology and Speech-Language Pathology (American-Speech-Language-Hearing Association, 2008), pre-professional programs must demonstrate how the nature and amount of clinical supervision are adjusted to reflect the individual needs and skills of student clinicians. The purpose of this study was to analyze predictive relationships among student clinician responses to a modified version of Larson’s Supervisory Needs Rating Scale (1981) and variables including (a) current GPA, (b) whether the student was at the undergraduate or graduate level, (c) number of previous semesters of clinical practicum experience, (d) cumulative number of clinical clock hours obtained, (e) grade received for the clinical practicum experience during this study, and (f) score as calculated from the departmental clinical Knowledge and Skills Acquisition (KASA) form in an attempt to find early identification markers for student clinicians who require extra support in clinical practicum assignments. Based on student clinician responses to survey items, two factors were revealed: Supervisory Instructional Behaviors and Supervisory Communicative Behaviors. Correlations between these factors and the end of semester student variables were calculated. One significant relationship between Supervisory Instructional Behaviors and student Grade Point Average was found. Results and implications of this finding and the need for future research of effective supervisory practices are presented.
Reflections on a Rubric Used to Facilitate Accurate and Informative Assessment
Authors: Lee-Wilkerson Dorian , Chabon Shelly S.
Published: October 2008

This article discusses the reasons for creating a rubric to facilitate and assess student learning and its application in a Communication Sciences and Disorders course. The rationale for using reflection as a method of‘ “informed assessment” is presented, the rubric is described, and a summary of the course and learning activities that provided the framework for the student reflections is provided. An example of how the rubric may be used to guide and structure reflections as a part of experiential learning and informed assessment is also provided.
Benefits and Characteristics of Mentoring Students and Young Professionals
Authors: Mills Kristal
Published: October 2008

Mentoring has long been believed to be an effective means of developing students' clinical, research, and teaching skills to become competent professionals. The American Speech-Language-Hearing Association (ASHA) has developed two online mentoring programs, Student to Empowered Professional (S.T.E.P. 1:1) and Mentoring Academic Research Careers (MARC), to aid in the development of students. This paper provides a review of the literature on mentoring and compares and contrasts mentoring/mentors with clinical supervision/preceptors. Characteristics of effective mentors and mentees are offered. Additionally, the benefits of clinical mentoring such as, teambuilding in the workplace, retention of new staff, leadership development, and improved job satisfaction are discussed.
The Clinician Directed Hierarchy: A Clinical Training Tool
Authors: Duthie Jill K.
Published: October 2008

Clinical supervisors in university based clinical settings are challenged by numerous tasks to promote the development of self-analysis and problem-solving skills of the clinical student (American Speech-Language-Hearing Association, ASHA, 1985). The Clinician Directed Hierarchy is a clinical training tool that assists the clinical teaching process by directing the student clinician’s focus to a specific level of intervention. At each of five levels of intervention, the clinician develops an understanding of the client’s speech/language target behaviors and matches clinical support accordingly. Additionally, principles and activities of generalization are highlighted for each intervention level. Preliminary findings suggest this is a useful training tool for university clinical settings. An essential goal of effective clinical supervision is the provision of support and guidance in the student clinician’s development of independent clinical skills (Larson, 2007). The student clinician is challenged with identifying client behaviors in the therapeutic process and learning to match his or her instructions, models, prompts, reinforcement, and use of stimuli appropriately according to the client’s needs. In addition, the student clinician must be aware of techniques in the intervention process that will promote generalization of new communication behaviors. Throughout the intervention process, clinicians are charged with identifying appropriate target behaviors, quantifying the progress of the client’s acquisition of the targets, and making adjustments within and between sessions as necessary. Central to the development of clinical skills is the feedback provided by the clinical supervisor (Brasseur, 1989; Moss, 2007). Particularly in the early stages of clinical skills development, the supervisor is challenged with addressing numerous aspects of clinical performance and awareness, while ensuring the client’s welfare (Moss). To address the management of clinician and client behaviors while developing an understanding of the clinical intervention process, the University of the Pacific has developed and begun to implement the Clinician Directed Hierarchy.
The Use of Supplementary Podcasting as an Instructional Tool in an Online Classroom Setting
Authors: Friberg Jennifer C.
Published: October 2008

The use of podcasting is incredibly widespread, with experts estimating that 60 million Americans will be using podcasting in some form by 2010. The use of podcasting has grown beyond entertainment to become an educational tool, showing promise as a way to disseminate information and create networks of professional learners. However, despite the growing clinical and educational uses of podcasting in other professional disciplines, podcasting is being used primarily as a continuing education tool for speech-language pathologists and audiologists at this time. This article provides guidelines and examines the potential applications for use of podcasting in teaching and learning in communication sciences and disorders.
Expanding Assessment Needs and State Eligibility Criteria
Authors: Thormann Sheryl
Published: October 2008

Speech and language intervention in the public schools is shaped by factors such as curriculum access, service in the least restrictive environment, service to students in natural settings, and functional outcomes. Given that speech and language intervention is characterized in these expanded contexts, we need to make sure our methods of assessment include procedures to show this. It is also important to look at how this fits into our state's speech and language eligibility criteria. The use of formal testing with norm-referenced tests is not always appropriate or feasible to understanding and determining a student's communication skills. Data from both standardized tests and alternative procedures are essential for the documentation of a child's communication skills.
Cross-Cultural Assessment of Young Children's Language and Literacy Development
Authors: Losardo Angela , Notari-Syverson Angela , Coleman Thalia , Botts Dawn C.
Published: October 2008

Speech-language pathologists are faced with an increasing demand to conduct language and literacy assessments for children who are from cultures different from their own. Cross-cultural assessment is challenging. This article outlines the conditions necessary for successful implementation of culturally appropriate models of assessment. Alternative approaches to assessment are proposed that will guide speech-language pathologists about where, when, and how to assess children. Embedded approaches, authentic approaches, mediated approaches, and comprehensive models offer the speech-language pathologist the option of using assessment activities which can be adapted to match the needs of the child being assessed. And finally, ideas for family-professional collaboration in the assessment of young children's language and literacy development are provided.
Generic Verticalization Strategies in Enterprise System Markets: An Exploratory Framework
Authors: Fink Lior , Markovich Sarit
Published: October 2008

In recent years, enterprise system (ES) software markets have been very dynamic. While contemporary customers are increasingly seeking ES solutions that require less and less customization and implementation effort, it is unclear whether all ES providers should take the ‘vertical’ path of offering functionality tailored to specific industries. Given the lack of conceptualization that explores ES markets’ segmentation, this paper offers a typology of generic verticalization strategies. Building on the resource-based view of the firm and the dynamic capabilities perspective, we match ES providers’ organizational characteristics of size and scope with the most effective verticalization strategy. A dynamic dimension is introduced to this framework by analyzing recommended strategies for market entry and growth. Finally, the applicability of the exploratory framework is illustrated using examples from the customer relationship management (CRM) software market.
Herbivore species richness and feeding complementarity affect community structure and function on a coral reef
Authors: Burkepile Deron E. , Hay Mark E.
Published: October 2008

Consumer effects on prey are well known for cascading through food webs and producing dramatic top-down effects on community structure and ecosystem function. Bottom-up effects of prey (primary producer) biodiversity are also well known. However, the role of consumer diversity in affecting community structure or ecosystem function is not well understood. Here, we show that herbivore species richness can be critical for maintaining the structure and function of coral reefs. In two experiments over 2 years, we constructed large cages enclosing single herbivore species, equal densities of mixed species of herbivores, or excluding herbivores and assessed effects on both seaweeds and corals. When compared with single-herbivore treatments, mixed-herbivore treatments lowered macroalgal abundance by 54–76%, enhanced cover of crustose coralline algae (preferred recruitment sites for corals) by 52–64%, increased coral cover by 22%, and prevented coral mortality. Complementary feeding by herbivorous fishes drove the herbivore richness effects, because macroalgae were unable to effectively deter fishes with different feeding strategies. Maintaining herbivore species richness appears critical for preserving coral reefs, because complementary feeding by diverse herbivores produces positive, but indirect, effects on corals, the foundation species for the ecosystem.
Individual binding pockets of importin-β for FG-nucleoporins have different binding properties and different sensitivities to RanGTP
Authors: Otsuka Shotaro , Iwasaka Shizuka , Yoneda Yoshihiro , Takeyasu Kunio , Yoshimura Shige H.
Published: October 2008

Importin-β mediates protein transport across the nuclear envelope through the nuclear pore complex (NPC) by interacting with components of the NPC, called nucleoporins, and a small G protein, Ran. Although there is accumulated knowledge on the specific interaction between importin-β and the Phe-Gly (FG) motif in the nucleoporins as well as the effect of RanGTP on this interaction, the molecular mechanism by which importin-β shuttles across the nuclear envelope through the NPC is unknown. In this study, we focused on four binding pockets of importin-β for the FG motifs and characterized the interaction using a single-molecule force-measurement technique with atomic-force microscopy. The results from a series of importin-β mutants containing amino acid substitutions within the FG-binding pockets demonstrate that the individual FG-binding pockets have different affinities to FG-Nups (Nup62 and Nup153) and different sensitivities to RanGTP; the binding of RanGTP to the amino-terminal domain of importin-β induces the conformational change of the entire molecule and reduces the affinity of some of the pockets but not others. These heterogeneous characteristics of the multiple FG-binding pockets may play an important role in the behavior of importin-β within the NPC. Single-molecule force measurement using the entire molecule of an NPC from a
Xenopus
oocyte also implies that the reduction of the affinity by RanGTP really occurs at the nucleoplasmic side of the entire NPC.
Regulation of proliferating cell nuclear antigen ubiquitination in mammalian cells
Authors: Niimi Atsuko , Brown Stephanie , Sabbioneda Simone , Kannouche Patricia L. , Scott Andrew , Yasui Akira , Green Catherine M. , Lehmann Alan R.
Published: October 2008

After exposure to DNA-damaging agents that block the progress of the replication fork, monoubiquitination of proliferating cell nuclear antigen (PCNA) mediates the switch from replicative to translesion synthesis DNA polymerases. We show that in human cells, PCNA is monoubiquitinated in response to methyl methanesulfonate and mitomycin C, as well as UV light, albeit with different kinetics, but not in response to bleomycin or camptothecin. Cyclobutane pyrimidine dimers are responsible for most of the PCNA ubiquitination events after UV-irradiation. Failure to ubiquitinate PCNA results in substantial sensitivity to UV and methyl methanesulfonate, but not to camptothecin or bleomycin. PCNA ubiquitination depends on Replication Protein A (RPA), but is independent of ATR-mediated checkpoint activation. After UV-irradiation, there is a temporal correlation between the disappearance of the deubiquitinating enzyme USP1 and the presence of PCNA ubiquitination, but this correlation was not found after chemical mutagen treatment. By using cells expressing photolyases, we are able to remove the UV lesions, and we show that PCNA ubiquitination persists for many hours after the damage has been removed. We present a model of translesion synthesis behind the replication fork to explain the persistence of ubiquitinated PCNA.
Motion processing, directional selectivity, and conscious visual perception in the human brain
Authors: Moutoussis Konstantinos , Zeki Semir
Published: October 2008

Several human and monkey studies have demonstrated a close relationship between motion perception and activation of area V5, leading to the general view that activity in this area correlates with the subjective experience of motion. In the present study, we investigate whether the responses of this area are still governed by the motion percept when the latter is in conflict with the reality of the physical visual stimulation. We simultaneously presented two different, specially designed random-dot kinematograms, one to each eye. These stimuli either both had a single direction of motion and worked in synergy, or had opposite motion directions and thus cancelled each other out perceptually. In this way, we were able to pit the visual stimulus (one vs. two stimulating directions) against the reported perception (directional motion vs. motion noise) of human volunteers during fMRI experiments. We found that a strong motion stimulus that is weakly perceived is more effective in activating V5 (as well as V3) than a weaker motion stimulus, which is nevertheless robustly perceived. Thus, contrary to the prevailing view of perception being the correlate of activity in higher visual areas, we show here that activity is instead dominated by the properties of the physical stimulus, raising the question of whether there is a subpopulation of cells in V5 whose activity is critical for generating the motion percept. In addition, our results provide the first robust evidence for the presence of directionally selective neuronal populations in human prestriate cortex.
Role for proteasome activator PA200 and postglutamyl proteasome activity in genomic stability
Authors: Blickwedehl Jennifer , Agarwal Manjula , Seong Changhyun , Pandita Raj K. , Melendy Thomas , Sung Patrick , Pandita Tej K. , Bangia Naveen
Published: October 2008

Proteasome activator PA200 enhances proteasome-mediated cleavage after acidic residues
in vitro
; however, its role within cells is not known. Here, we show that, in response to ionizing radiation, PA200 forms hybrid proteasomes with 19S caps and 20S core proteasomes that accumulate on chromatin, leading to an increase in proteolytic activity. Unlike many other proteins that respond to DNA damage, the response of PA200 appears to be independent of Ataxia Telangiectasia Mutated and p53, but dependent on DNA-dependent protein kinase activity. Nonetheless, PA200 is critical because PA200-knockdown cells show genomic instability and reduced survival after exposure to ionizing radiation. This phenotype is reproduced by specific inhibition of postglutamyl activity of proteasomes, but combined treatment with PA200 siRNA and postglutamyl inhibitor does not show additive effects on survival. Together, these data suggest a unique role for PA200 in genomic stability that is likely mediated through its ability to enhance postglutamyl cleavage by proteasomes.
Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: Implications for vaccines
Authors: Zhu Qing , Egelston Colt , Vivekanandhan Aravindhan , Uematsu Satoshi , Akira Shizuo , Klinman Dennis M. , Belyakov Igor M. , Berzofsky Jay A.
Published: October 2008

Toll-like receptors (TLRs) may need to cooperate with each other to be effective in detecting imminent infection and trigger immune responses. Understanding is still limited about the intracellular mechanism of this cooperation. We found that when certain TLRs are involved, dendritic cells (DCs) establish unidirectional intracellular cross-talk, in which the MyD88-independent TRIF-dependent pathway amplifies the MyD88-dependent DC function through a JNK-dependent mechanism. The amplified MyD88-dependent DC function determines the induction of the T cell response to a given vaccinein vivo. Therefore, our study revealed an underlying TLR mechanism governing the functional, nonrandom interplay among TLRs for recognition of combinatorial ligands that may be dangerous to the host, providing important guidance for design of novel synergistic molecular vaccine adjuvants.
Rab11a-dependent exocytosis of discoidal/fusiform vesicles in bladder umbrella cells
Authors: Khandelwal Puneet , Ruiz Wily G. , Balestreire-Hawryluk Elena , Weisz Ora A. , Goldenring James R. , Apodaca Gerard
Published: October 2008

The discoidal/fusiform vesicles (DFV) of bladder umbrella cells undergo regulated exocytosis in response to stretch, but little is known about their biogenesis or the molecular machinery that modulates this process. We observed that Rab11a was expressed in umbrella cells (but not Rab11b or Rab25) and was associated with DFV. Using adenovirus-mediated delivery we transduced umbrella cells
in situ
with either dominant active (DA) or dominant negative (DN) mutants of Rab11a. DA-Rab11a stimulated an increase in apical surface area in the absence of stretch, whereas DN-Rab11a inhibited stretch-induced changes. Endocytosed fluid and membrane markers had little access to Rab11a-positive DFV, but virally expressed human growth hormone (hGH), a secretory protein, was packaged into DFV. Whereas expression of DA-Rab11a stimulated release of hGH into the bladder lumen, expression of DN-Rab11a had the opposite effect. Our results indicate that DFV may be biosynthetic in nature and that their exocytosis depends on the activity of the Rab11a GTPase.
The PIDDosome mediates delayed death of hippocampal CA1 neurons after transient global cerebral ischemia in rats
Authors: Niizuma Kuniyasu , Endo Hidenori , Nito Chikako , Myer D. Jeannie , Kim Gab Seok , Chan Pak H.
Published: October 2008

A brief period of global brain ischemia, such as that induced by cardiac arrest or cardiopulmonary bypass surgery, causes cell death in vulnerable hippocampal CA1 pyramidal neurons days after reperfusion. Although numerous factors have been suggested to account for this phenomenon, the mechanisms underlying it are poorly understood. We describe a cell death signal called the PIDDosome, a protein complex of p53-induced protein with a death domain (PIDD), receptor-interacting protein–associated ICH-1/CED-3 homologous protein with a death domain (RAIDD), and procaspase-2. We induced 5 min of transient global cerebral ischemia (tGCI) using bilateral common carotid artery occlusion with hypotension. Western blot analysis showed that expression of twice-cleaved fragment of PIDD (PIDD-CC) increased in the cytosolic fraction of the hippocampal CA1 subregion and preceded procaspase-2 activation after tGCI. Caspase-2 cleaved Bid in brain homogenates. Co-immunoprecipitation and immunofluorescent studies demonstrated that PIDD-CC, RAIDD, and procaspase-2 were co-localized and bound directly, which indicates the formation of the PIDD death domain complex. Furthermore, we tested inhibition of PIDD expression by using small interfering RNA (siRNA) treatment that was initiated 48 h before tGCI. Administration of siRNA against PIDD decreased not only expression of PIDD-CC, but also activation of procaspase-2 and Bid, resulting in a decrease in histological neuronal damage and DNA fragmentation in the hippocampal CA1 subregion after tGCI. These results imply that PIDD plays an important role in procaspase-2 activation and delayed CA1 neuronal death after tGCI. We propose that PIDD is a hypothetical molecular target for therapy against neuronal death after tGCI.
Predicting the sizes of large RNA molecules
Authors: Yoffe Aron M. , Prinsen Peter , Gopal Ajaykumar , Knobler Charles M. , Gelbart William M. , Ben-Shaul Avinoam
Published: October 2008

We present a theory of the dependence on sequence of the three-dimensional size of large single-stranded (ss) RNA molecules. The work is motivated by the fact that the genomes of many viruses are large ssRNA molecules—often several thousand nucleotides long—and that these RNAs are spontaneously packaged into small rigid protein shells. We argue that there has been evolutionary pressure for the genome to have overall spatial properties—including an appropriate radius of gyration,
R
g
—that facilitate this assembly process. For an arbitrary RNA sequence, we introduce the (thermal) average maximum ladder distance (〈MLD〉) and use it as a measure of the “extendedness” of the RNA secondary structure. The 〈MLD〉 values of viral ssRNAs that package into capsids of fixed size are shown to be consistently smaller than those for randomly permuted sequences of the same length and base composition, and also smaller than those of natural ssRNAs that are not under evolutionary pressure to have a compact native form. By mapping these secondary structures onto a linear polymer model and by using 〈MLD〉 as a measure of effective contour length, we predict the
R
g
values of viral ssRNAs are smaller than those of nonviral sequences. More generally, we predict the average 〈MLD〉 values of large nonviral ssRNAs scale as
N
0.67±0.01
, where
N
is the number of nucleotides, and that their
R
g
values vary as 〈MLD〉
0.5
in an ideal solvent, and hence as
N
0.34
. An alternative analysis, which explicitly includes all branches, is introduced and shown to yield consistent results.
Temporal control of the dephosphorylation of Cdk substrates by mitotic exit pathways in budding yeast
Authors: Jin Fengzhi , Liu Hong , Liang Fengshan , Rizkallah Raed , Hurt Myra M. , Wang Yanchang
Published: October 2008

The temporal phosphorylation of cell cycle-related proteins by cyclin-dependent kinases (Cdks) is critical for the correct order of cell cycle events. In budding yeast,
CDC28
encodes the only Cdk and its association with various cyclins governs the temporal phosphorylation of Cdk substrates. S-phase Cdk substrates are phosphorylated earlier than mitotic Cdk substrates, which ensures the sequential order of DNA synthesis and mitosis. However, it remains unclear whether Cdk substrates are dephosphorylated in temporally distinct windows. Cdc14 is a conserved protein phosphatase responsible for the dephosphorylation of Cdk substrates. In budding yeast, FEAR (Cdc14 early anaphase release) and MEN (mitotic exit network) activate phosphatase Cdc14 by promoting its release from the nucleolus in early and late anaphase, respectively. Here, we show that the sequential Cdc14 release and the distinct degradation timing of different cyclins provides the molecular basis for the differential dephosphorylation windows of S-phase and mitotic cyclin substrates. Our data also indicate that FEAR-induced dephosphorylation of S-phase Cdk substrates facilitates anaphase progression, revealing an extra layer of mitotic regulation.
Effect of host cell lipid metabolism on alphavirus replication, virion morphogenesis, and infectivity
Authors: Ng Ching G. , Coppens Isabelle , Govindarajan Dhanasekaran , Pisciotta John , Shulaev Vladimir , Griffin Diane E.
Published: October 2008

The alphavirus Sindbis virus (SINV) causes encephalomyelitis in mice. Lipid-containing membranes, particularly cholesterol and sphingomyelin (SM), play important roles in virus entry, RNA replication, glycoprotein transport, and budding. Levels of SM are regulated by sphingomyelinases (SMases). Acid SMase (ASMase) deficiency results in the lipid storage disease type A Niemann-Pick disease (NPD-A), mimicked in mice by interruption of the ASMase gene. We previously demonstrated that ASMase-deficient mice are more susceptible to fatal SINV encephalomyelitis, with increased viral replication, spread, and neuronal death. To determine the mechanisms by which ASMase deficiency enhances SINV replication, we compared NPD-A fibroblasts (NPAF) to normal human fibroblasts (NHF). NPAF accumulated cholesterol- and sphingolipid-rich late endosomes/lysosomes in the perinuclear region. SINV replication was faster and reached higher titer in NPAF than in NHF, and NPAF died more quickly. SINV RNA and protein synthesis was greater in NHF than in NPAF, but virions budding from NPAF were 26 times more infectious and were regular dense particles whereas virions from NHF were larger particles containing substantial amounts of CD63. Cellular regulation of alphavirus morphogenesis is a previously unrecognized mechanism for control of virus replication and spread.
Phage φ29 protein p56 prevents viral DNA replication impairment caused by uracil excision activity of uracil-DNA glycosylase
Authors: Serrano-Heras Gemma , Bravo Alicia , Salas Margarita
Published: October 2008

Protein p56 encoded by the
Bacillus subtilis
phage φ29 inhibits host uracil-DNA glycosylase (UDG) activity. In previous studies, we suggested that this inhibition is likely a defense mechanism developed by phage φ29 to prevent the action of UDG if uracilation occurs in DNA either from deamination of cytosine or the incorporation of dUMP during viral DNA replication. In this work, we analyzed the ability of φ29 DNA polymerase to insert dUMP into DNA. Primer extension analysis showed that viral DNA polymerase incorporates dU opposite dA with a catalytic efficiency only 2-fold lower than that for dT. Using the φ29 DNA amplification system, we found that φ29 DNA polymerase is also able to carry out the extension of the dA:dUMP pair and replicate past uracil. Additionally, UDG and apurinic-apyrimidinic endonuclease treatment of viral DNA isolated from φ29-infected cells revealed that uracil residues arise in φ29 DNA during replication, probably as a result of misincorporation of dUMP by the φ29 DNA polymerase. On the other hand, the action of UDG on uracil-containing φ29 DNA impaired
in vitro
viral DNA replication, which was prevented by the presence of protein p56. Furthermore, transfection activity of uracil-containing φ29 DNA was significantly higher in cells that constitutively synthesized p56 than in cells lacking this protein. Thus, our data support a model in which protein p56 ensures an efficient viral DNA replication, preventing the deleterious effect caused by UDG when it eliminates uracil residues present in the φ29 genome.
Comparison of 40 and 60 milliliters of contrast in assessment of the carotid artery by computed tomography angiography
Authors: Takeyama N. , Ohgiya Y. , Itokawa H. , Takahashi Y. , Obuchi M. , Shinjyo H. , Matsui S. , Hayashi T. , Kato K. , Fujimoto T. , Kinebuchi Y. , Kitahara T. , Gokan T.
Published: October 2008

Background: Although fast acquisition of multidetector-row computed tomography (MDCT) can make it possible to acquire sufficient early vascular enhancement using small volumes and high concentrations of contrast material (CM), there are still some problems with nephrotoxicity and costs related to CM.

Purpose: To compare the qualitative and quantitative performance in cervicocranial CT angiography (CTA) using two different iodine volumes and concentrations of CM.

Material and Methods: CTA ranging from the aortic arch (AA) to distal to the circle of Willis (cW) was performed on a 32-MDCT system. Fifty-eight patients were randomly divided into two groups: group A (29 patients) received 60 ml of 300 mg I/ml CM, and group B (the other 29 patients) received 40 ml of 370 mg I/ml CM. Time to peak arterial enhancement at cW (Tc) was calculated. As scan speed was 96.9 mm/s and injection rate was 4.0 ml/s, scanning delay was individually decided according to Tc and scan duration between AA and cW. Arterial attenuation along the z-axis at eight points in the carotid-cerebral artery and venous attenuation of the internal jugular vein (IJV) at carotid bifurcation were measured. Mean attenuation values were then quantitatively analyzed. Postprocessing images were qualitatively assessed.

Results: Arterial attenuation profiles revealed maximum attenuation at the distal common carotid artery in both groups. Although there were no significant differences in mean arterial attenuation in group A versus group B (402±70 HU vs. 407±67 HU; P=0.78), venous attenuation of the IJV was lower in group B than in group A (114±57 HU vs. 224±81 HU; P<0.001). Although arterial images demonstrated no difference qualitatively between the two groups, the venous contamination of IVC was less prominent in group B.

Conclusion: Although a different amount of CM was administered in both groups, quantitative and qualitative arterial images did not show significant differences between the two groups.
Reproducibility of sonographic measurements of carotid intima-media thickness
Authors: Velázquez F. , Berná J. D. , Abellán J. L. , Serrano L. , Escribano A. , Canteras M.
Published: October 2008

Background: Carotid intima-media thickness (IMT), measured with B-mode ultrasound, is a marker for atherosclerosis and widely used as an outcome in intervention trials.

Purpose: To evaluate the reproducibility of carotid intima-media thickness measurements using tissue harmonic imaging (THI) sonography between two observers with different levels of experience.

Material and Methods: IMT measurement was performed in 40 patients: 26 males and 14 females, with a mean age of 62.6 years. The measurements were taken on the posterior wall of the right common carotid artery using a standardized protocol. Observer measurement of the IMT was independent and blind. Statistical analysis was done with parametric tests and Pearson's correlation coefficient.

Results: The measurements of the IMT were taken satisfactorily in all cases. IMT measurement time was 5min/study. No significant differences were noted between the means obtained by the two observers. The interobserver correlation of the measurements was very high (97.2%).

Conclusion: The results of this study show that carotid IMT measurement using THI sonography and a standardized protocol is accurate and reproducible.
Effect of Screening for Methicillin-Resistant Staphylococcus aureus Carriage by Polymerase Chain Reaction on the Duration of Unnecessary Preemptive Contact Isolation
Authors: Uçkay Ilker , Sax Hugo , Iten Anne , Camus Véronique , Renzi Gesuele , Schrenzel Jacques , Perrier Arnaud , Pittet Didier
Published: October 2008

A high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage at hospital readmission among previous MRSA carriers warrants screening and preemptive isolation precautions. The replacement of culture on chromogenic agar with rapid quantitative polymerase chain reaction for readmission screening reduces the number of unnecessary preemptive isolation-days by 54% (from 6.88 to 3.14 isolation-days) and related costs by 45% (from US$113.2 to US$62.1) for patients who test negative for MRSA.