bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodynamic variables and mortality in cardiogenic shock: a retrospective cohort study
Authors: Torgersen Christian , Schmittinger Christian A , Wagner Sarah , Ulmer Hanno , Takala Jukka , Jakob Stephan M , Dünser Martin W
Published: October 2009

Introduction

Despite the key role of hemodynamic goals, there are few data addressing the question as to which hemodynamic variables are associated with outcome or should be targeted in cardiogenic shock patients. The aim of this study was to investigate the association between hemodynamic variables and cardiogenic shock mortality.

Methods

Medical records and the patient data management system of a multidisciplinary intensive care unit (ICU) were reviewed for patients admitted because of cardiogenic shock. In all patients, the hourly variable time integral of hemodynamic variables during the first 24 hours after ICU admission was calculated. If hemodynamic variables were associated with 28-day mortality, the hourly variable time integral of drops below clinically relevant threshold levels was computed. Regression models and receiver operator characteristic analyses were calculated. All statistical models were adjusted for age, admission year, mean catecholamine doses and the Simplified Acute Physiology Score II (excluding hemodynamic counts) in order to account for the influence of age, changes in therapies during the observation period, the severity of cardiovascular failure and the severity of the underlying disease on 28-day mortality.

Results

One-hundred and nineteen patients were included. Cardiac index (CI) (P = 0.01) and cardiac power index (CPI) (P = 0.03) were the only hemodynamic variables separately associated with mortality. The hourly time integral of CI drops <3, 2.75 (both P = 0.02) and 2.5 (P = 0.03) L/min/m2 was associated with death but not that of CI drops <2 L/min/m2 or lower thresholds (all P > 0.05). The hourly time integral of CPI drops <0.5-0.8 W/m2 (all P = 0.04) was associated with 28-day mortality but not that of CPI drops <0.4 W/m2 or lower thresholds (all P > 0.05).

Conclusions

During the first 24 hours after intensive care unit admission, CI and CPI are the most important hemodynamic variables separately associated with 28-day mortality in patients with cardiogenic shock. A CI of 3 L/min/m2 and a CPI of 0.8 W/m2 were most predictive of 28-day mortality. Since our results must be considered hypothesis-generating, randomized controlled trials are required to evaluate whether targeting these levels as early resuscitation endpoints can improve mortality in cardiogenic shock.
Facilitative Glucose Transporter 9 Expression Affects Glucose Sensing in Pancreatic β-Cells
Authors: Evans Sarah A. , Doblado Manuel , Chi Maggie M. , Corbett John A. , Moley Kelle H.
Published: October 2009

Facilitative glucose transporters (GLUTs) including GLUT9, accelerate the facilitative diffusion of glucose across the plasma membrane. Studies in GLUT2-deficient mice suggested the existence of another GLUT in the mammalian β-cell responsible for glucose sensing. The objective of this study was to determine the expression and function of GLUT9 in murine and human β-cells. mRNA and protein expression levels were determined for both isoforms of GLUT9 in murine and human isolated islets as well as insulinoma cell lines (MIN6). Immunohistochemistry and subcellular localization were performed to localize the protein within the cell. Small interfering RNA knockdown of GLUT9 was used to determine the effect of this transporter, in the presence of GLUT2, on cell metabolism and insulin secretion in MIN6 and INS cells. In this report we demonstrate that GLUT9a and GLUT9b are expressed in pancreatic islets and that this expression localizes to insulin-containing β-cells. Subcellular localization studies indicate that mGLUT9b is found associated with the plasma membrane as well as in the high-density microsome fraction and low-density microsome fraction, whereas mGLUT9a appears to be located only in the high-density microsome and low-density microsome under basal conditions. Functionally GLUT9 appears to participate in the regulation of glucose-stimulated insulin secretion in addition to GLUT2. small interfering RNA knockdown of GLUT9 results in reduced cellular ATP levels that correlate with reductions in glucose-stimulated insulin secretion in MIN6 and INS cells. These studies confirm the expression of GLUT9a and GLUT9b in murine and human β-cells and suggest that GLUT9 may participate in glucose-sensing in β-cells.
Subclinical Hypothyroidism in Korean Preterm Infants Associated with High Levels of Iodine in Breast Milk
Authors: Chung Hye Rim , Shin Choong Ho , Yang Sei Won , Choi Chang Won , Kim Beyong Il
Published: October 2009

Context: The dietary iodine intake of lactating women has been reported to be high in Korea.

Objectives: The aim of this study was to assess iodine balance and to determine its relationship with thyroid function in preterm infants.

Design: Thyroid functions of preterm infants born at 34 wk gestation or less were evaluated in the first (n = 31) and third (n = 19) weeks. Mothers’ breast milk (BM) and random urine samples of infants were taken on the same days for thyroid function tests.

Results: Iodine concentrations in BM were very high (198–8484 μg/liter), and one third of the infants had an iodine intake of more than 100 μg/kg per day at the third week after birth (excessive iodine intake group). At that time, the levels of TSH were positively correlated with urinary iodine (r = 0.622; P = 0.004). The frequencies of subclinical hypothyroidism were high in the excessive iodine intake group at the third and sixth weeks. The estimated daily iodine intake at the third week (51.2 ± 45.5 vs. 149.0 ± 103.8 μg/kg per day; P = 0.033), urinary iodine at the third week (913.2 ± 1179.7 vs. 1651.3 ± 1135.2 μg/liter; P = 0.051), and estimated daily iodine intake at the sixth week (32.8 ± 35.5 vs. 92.1 ± 51.2 μg/kg per day; P = 0.032) were significantly higher in infants with subclinical hypothyroidism than in controls.

Conclusions: Excessive iodine intake from BM contributed to subclinical hypothyroidism in these preterm Korean infants.

An excessive amount of iodine in breast milk causes subclinical hypothyroidism in preterm infants.
Phantom of the Forever War: Fazul Abdullah Muhammad and the Terrorist Imaginary
Authors: Prestholdt Jeremy
Published: October 2009

This essay addresses myths about al Qaeda operative Fazul Abdullah Muhammad and their implications for American foreign policy. The essay demonstrates how Fazul's legend mirrors broader genealogies of information that shape contemporary perceptions of terrorism. Fazul orchestrated two major al Qaeda attacks in Kenya, including the 1998 bombing of the U.S. Embassy, but he has also become the object of fantastic speculation—the product of a psychology of fear combined with a popular imagination saturated with the layered syntax of the entertainment industry's imagery. Fazul's myth reveals how, in declaring war on terrorism, we have likewise waged a shadow war against the projections of collective paranoia.
“We're Mexican Too”: Publicity and Status at the International Line
Authors: Yeh Rihan
Published: October 2009

A series of ethnographic examples, all related to a demonstration at the International Port of Entry connecting Tijuana, Mexico, to San Diego, California, show the importance for Tijuana's public sphere of the distinction between documented and undocumented status vis-à-vis the United States. They also show how Tijuana's documented public reproduces itself across a range of communicative genres and sites, from a newspaper poll, to face-to-face dialogue, to the local baseball stadium, to the port of entry itself.
Virtual Museums of Forbidden Memories: Hu Jie's Documentary Films on the Cultural Revolution
Authors: Li Jie
Published: October 2009

This essay explores the politics of remembering the Chinese Cultural Revolution through a study of two banned documentaries by Hu Jie that have circulated widely in cyberspace: Though I Am Gone (2006) and In Search of Lin Zhao's Soul (2004). Contextualizing them in discourses on the (still unrealized) Cultural Revolution Museum, I argue that these films manifest an intriguing tension between the traumatic past and the oblivious present, between the intimate confidentiality of interviews and their address of a larger public sphere, and between the courtroom-like “objectivity” of their photographic evidence and the passionate “subjectivity” of testimony.
The Park Pass: Peopling and Civilizing a New Old Beijing
Authors: Farquhar Judith
Published: October 2009

Many mundane practices of city life in public in Beijing converge on public parks. Focusing on the uses, significance, and powers of the annual park pass, an inexpensive identity card that gives residents free access to the city's well-known and historic parks, I demonstrate some ways in which the “routines and rituals” of state articulate in practice with both a spatial and a nationalist politics of the people. This is not a politics of rebellion or resistance; rather, it advances a compliant civilizational nationalism with deep roots in China's revolutionary twentieth century. It displays a particular sensitivity to the history of spaces in the city and to the forms of ownership and control to which such spaces can be subjected. To understand the daily enjoyments of ordinary city residents as a continuation of China's revolutionary century is to acknowledge the voices and the public activism of many whose forms of political communication are usually ignored, or even denounced as passive. But a more generous definition of the political, one that does not presume liberal democracy as its natural setting or emancipation as its aim, can show how even compliance and personal pleasures work on the dispositions of power in public.
Biogenesis of tail-anchored proteins: the beginning for the end?
Authors: Rabu Catherine , Schmid Volker , Schwappach Blanche , High Stephen
Published: October 2009

Tail-anchored proteins are a distinct class of integral membrane proteins located in several eukaryotic organelles, where they perform a diverse range of functions. These proteins have in common the C-terminal location of their transmembrane anchor and the resulting post-translational nature of their membrane insertion, which, unlike the co-translational membrane insertion of most other proteins, is not coupled to ongoing protein synthesis. The study of tail-anchored proteins has provided a paradigm for understanding the components and pathways that mediate post-translational biogenesis of membrane proteins at the endoplasmic reticulum. In this Commentary, we review recent studies that have converged at a consensus regarding the molecular mechanisms that underlie this process – namely, that multiple pathways underlie the biogenesis of tail-anchored proteins at the endoplasmic reticulum.
Myosin-Va-interacting protein, RILPL2, controls cell shape and neuronal morphogenesis via Rac signaling
Authors: Lisé Marie-France , Srivastava Deepak P. , Arstikaitis Pamela , Lett Robyn L. , Sheta Razan , Viswanathan Vijay , Penzes Peter , O'Connor Timothy P. , El-Husseini Alaa
Published: October 2009

Neuronal morphology plays an essential role in neuronal function. The establishment and maintenance of neuronal morphology is intimately linked to the actin cytoskeleton; however, the molecular mechanisms that regulate changes in neuronal morphology are poorly understood. Here we identify a novel myosin-Va (MyoVa)-interacting protein, RILPL2, which regulates cellular morphology. Overexpression of this protein in young or mature hippocampal neurons results in an increase in the number of spine-like protrusions. By contrast, knockdown of endogenous RILPL2 in neurons by short hairpin RNA (shRNA) interference results in reduced spine-like protrusions, a phenotype rescued by overexpression of an shRNA-insensitive RILPL2 mutant, suggesting a role for RILPL2 in both the establishment and maintenance of dendritic spines. Interestingly, we demonstrate that RILPL2 and the Rho GTPase Rac1 form a complex, and that RILPL2 is able to induce activation of Rac1 and its target, p21-activated kinase (Pak). Notably, both RILPL2-mediated morphological changes and activation of Rac1-Pak signaling were blocked by expression of a truncated tail form of MyoVa or MyoVa shRNA, demonstrating that MyoVa is crucial for proper RILPL2 function. This might represent a novel mechanism linking RILPL2, the motor protein MyoVa and Rac1 with neuronal structure and function.
Real-time measurements of cAMP production in liveDictyosteliumcells
Authors: Bagorda Anna , Das Satarupa , Rericha Erin C. , Chen David , Davidson Jean , Parent Carole A.
Published: October 2009

Cyclic AMP has a crucial role during the entire developmental program of the social amoebae Dictyostelium, acting both as an intracellular second messenger and, when secreted, as a directional cue that is relayed to neighboring cells during chemotaxis. Although significant knowledge about cAMP production in chemotaxing cells has been derived from studies performed on cell populations, cAMP dynamics at the single cell level have not been investigated. To examine this, we used a FRET-based cAMP sensor that possesses high cAMP sensitivity and great temporal resolution. We show the transient profile of cAMP accumulation in live Dictyostelium cells and establish that chemoattractants control intracellular cAMP dynamics by regulating synthesis via the adenylyl cyclase ACA. aca– cells show no significant change in FRET response following chemoattractant addition. Furthermore, cells lacking ACB, the other adenylyl cyclase expressed in chemotaxing cells, behave similarly to wild-type cells. We also establish that the RegA is the major phosphodiesterase that degrades intracellular cAMP in chemotaxis-competent cells. Interestingly, we failed to measure intracellular cAMP compartmentalization in actively chemotaxing cells. We conclude that cytosolic cAMP, which is destined to activate PKA, is regulated by ACA and RegA and does not compartmentalize during chemotaxis.
Ubiquitylation of the gap junction protein connexin-43 signals its trafficking from early endosomes to lysosomes in a process mediated by Hrs and Tsg101
Authors: Leithe Edward , Kjenseth Ane , Sirnes Solveig , Stenmark Harald , Brech Andreas , Rivedal Edgar
Published: October 2009

Gap junctions are dynamic plasma membrane domains, and their protein constituents, the connexins, have a high turnover rate in most tissue types. However, the molecular mechanisms involved in degradation of gap junctions have remained largely unknown. Here, we show that ubiquitin is strongly relocalized to connexin-43 (Cx43; also known as Gja1) gap junction plaques in response to activation of protein kinase C. Cx43 remained ubiquitylated during its transition to a Triton X-100-soluble state and along its trafficking to early endosomes. Following internalization, Cx43 partly colocalized with the ubiquitin-binding proteins Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate; also known as Hgs) and Tsg101 (tumor susceptibility gene 101). Depletion of Hrs or Tsg101 by small interfering RNA abrogated trafficking of Cx43 from early endosomes to lysosomes. Under these conditions, Cx43 was able to undergo dephosphorylation and deubiquitylation, locate to the plasma membrane and form functional gap junctions. Simultaneous depletion of Hrs and Tsg101 caused accumulation of a phosphorylated and ubiquitylated subpopulation of Cx43 in early endosomes and in hybrid organelles between partly degraded annular gap junctions and endosomes. Collectively, these data reveal a central role of early endosomes in sorting of ubiquitylated Cx43, and identify Hrs and Tsg101 as crucial regulators of trafficking of Cx43 to lysosomes.
Nuclear localisation is crucial for the proapoptotic activity of the HtrA-like serine protease Nma111p
Authors: Belanger Kenneth D. , Walter David , Henderson Tracey A. , Yelton Allison L. , O'Brien Travis G. , Belanger Karyn G. , Geier Susan J. , Fahrenkrog Birthe
Published: October 2009

Programmed cell death is induced by the activation of a subset of intracellular proteins in response to specific extra- and intracellular signals. In the yeast Saccharomyces cerevisiae, Nma111p functions as a nuclear serine protease that is necessary for apoptosis under cellular stress conditions, such as elevated temperature or treatment of cells with hydrogen peroxide to induce cell death. We have examined the role of nuclear protein import in the function of Nma111p in apoptosis. Nma111p contains two small clusters of basic residues towards its N-terminus, both of which are necessary for efficient translocation into the nucleus. Nma111p does not shuttle between the nucleus and cytoplasm during either normal growth conditions or under environmental stresses that induce apoptosis. The N-terminal half of Nma111p is sufficient to provide the apoptosis-inducing activity of the protein, and the nuclear-localisation signal (NLS) sequences and catalytic serine 235 are both necessary for this function. We provide compelling evidence that intranuclear Nma111p activity is necessary for apoptosis in yeast.
Do Television and Radio Destroy Social Capital? Evidence from Indonesian Villages
Authors: Olken Benjamin A
Published: October 2009

This paper investigates the impact of television and radio on social capital in Indonesia. I use two sources of variation in signal reception—one based on Indonesia's mountainous terrain, and a second based on the differential introduction of private television throughout Indonesia. I find that increased signal reception, which leads to more time watching television and listening to the radio, is associated with less participation in social organizations and with lower self-reported trust. Improved reception does not affect village governance, at least as measured by discussions in village meetings and by corruption in village road projects. (JEL L82, O15, Z13)
Iodine Deficiency and Schooling Attainment in Tanzania
Authors: Field Erica , Robles Omar , Torero Maximo
Published: October 2009

Cognitive damage from iodine deficiency disorders (IDD) has important implications for economic growth through its effect on human capital. To gauge the magnitude of this influence, we evaluate the impact on schooling of reductions in IDD from intensive iodine supplementation in Tanzania. Our findings suggest a large effect of in utero iodine on cognition and human capital: treated children attain an estimated 0.35–0.56 years of additional schooling relative to siblings and older and younger peers. Furthermore, the effect appears to be substantially larger for girls, consistent with laboratory evidence indicating greater cognitive sensitivity of female fetuses to maternal thyroid deprivation. (JEL I12, I21, J16, O15)
In Pursuit of Balance: Randomization in Practice in Development Field Experiments
Authors: Bruhn Miriam , McKenzie David
Published: October 2009

We present new evidence on the randomization methods used in existing experiments, and new simulations comparing these methods. We find that many papers do not describe the randomization in detail, implying that better reporting is needed. Our simulations suggest that in samples of 300 or more, the different methods perform similarly. However, for very persistent outcome variables, and in smaller samples, pair-wise matching and stratification perform best and appear to dominate the rerandomization methods commonly used in practice. The simulations also point to specific recommendations for which variables to balance on, and for which controls to include in the ex post analysis. (JEL C83, C93, O12)
Peer Effects in the Workplace: Evidence from Random Groupings in Professional Golf Tournaments
Authors: Guryan Jonathan , Kroft Kory , Notowidigdo Matthew J
Published: October 2009

This paper uses random assignment in professional golf tournaments to test for peer effects in the workplace. We find no evidence that playing partners' ability affects performance, contrary to recent evidence on peer effects in the workplace from laboratory experiments, grocery scanners, and soft fruit pickers. In our preferred specification, we can rule out peer effects larger than 0.043 strokes for a one stroke increase in playing partners' ability. Our results complement existing studies on workplace peer effects and are useful in explaining how social effects vary across labor markets, across individuals, and with the form of incentives faced. (JEL D83, J44, L83)
Teaching Students and Teaching Each Other: The Importance of Peer Learning for Teachers
Authors: Jackson C. Kirabo , Bruegmann Elias
Published: October 2009

Using longitudinal elementary school teacher and student data, we document that students have larger test score gains when their teachers experience improvements in the observable characteristics of their colleagues. Using within-school and within-teacher variation, we show that a teacher's students have larger achievement gains in math and reading when she has more effective colleagues (based on estimated value-added from an out-of-sample pre-period). Spillovers are strongest for less experienced teachers and persist over time, and historical peer quality explains away about 20 percent of the own-teacher effect, results that suggest peer learning. (JEL I21, J24, J45)
Safety and Efficacy of Quetiapine in Bipolar Depression
Authors: Bogart Gregory T , Chavez Benjamin
Published: October 2009

Objective:

To review the clinical data investigating the efficacy and safety of quetiapine in bipolar depression.

Data Sources:

Searches of MEDLINE and PubMed (1977–July 2009) were conducted using the key words quetiapine and bipolar depression. The references of literature found were cross-referenced. The pharmaceutical company that produces quetiapine was contacted to obtain the posters for the EMBOLDEN I and EMBOLDEN II trials.

Study Selection and Data Extraction:

Only double-blind, placebo-controlled trials were included for review, as well as any subanalyses of the literature that matched this criterion.

Data Synthesis:

There was a total of 5 double-blind, placebo-controlled trials and 5 subanalyses reviewed. The results of these data demonstrated quetiapine's efficacy in the treatment of depressive phases of bipolar disorder, including statistically significant improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS). In the trials reviewed in this article, the change in MADRS scores ranged from -15.4 to -16.94 within the quetiapine groups, and from -10.26 to -11.93 in the placebo groups. There were also statistically significant improvements in the Hamilton Anxiety Rating Scale, the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire, the Pittsburgh Sleep Quality Index, and the Sheehan Disability Scale. All of these trials had a duration of 8 weeks and therefore cannot be applied to the long-term use of quetiapine in bipolar depression. The most common adverse events were sedation, somnolence, and dry mouth. The overall dropout rates for the trials reviewed ranged from 24% to 47%.

Conclusions:

Based on the literature reviewed here, quetiapine appears to be a safe and efficacious short-term treatment option for bipolar depression. Patients with bipolar type I showed greater improvement on the MADRS than those with bipolar type II. Patients with a rapid-cycling disease course showed an improvement in depressive symptoms, regardless of bipolar type.
Comparative Pharmacodynamics of Intermittent and Prolonged Infusions of Piperacillin/Tazobactam Using Monte Carlo Simulations and Steady-State Pharmacokinetic Data from Hospitalized Patients
Authors: Shea Katherine M , Cheatham S Christian , Smith David W , Wack Matthew F , Sowinski Kevin M , Kays Michael B
Published: October 2009

Background:

Prolonging the infusion of a β-lactam antibiotic enhances the time in which unbound drug concentrations remain above the minimum inhibitory concentration (fT>MIC).

Objective:

To compare the pharmacodynamics of several dosing regimens of piperacillin/tazobactam administered by intermittent and prolonged infusion using pharmacokinetic data from hospitalized patients.

Methods:

Steady-state pharmacokinetic data were obtained from 13 patients who received piperacillin/tazobactam 4.5 g every 8 hours, infused over 4 hours. Monte Carlo simulations (10,000 pts.) were performed to calculate pharmacodynamic exposures at 50% fT>MIC for 4 intermittent-infusion regimens (3.375 g every 4 and 6 h, 4.5 g every 6 and 8 h) and 4 prolonged-infusion regimens (2.25 g, 3.375 g. 4.5 g, and 6.75 g every 8 h [4-h infusion]) of piperacillin/tazobactam using pharmacokinetic data for piperacillin. Cumulative fraction of response (CFR) was calculated using MIC data for 6 gram-negative pathogens (Meropenem Yearly Susceptibility Test Information Collection, 2004-2007), and probability of target attainment (PTA) was calculated at MICs ranging from 1 μg/mL to 64 μ/g/mL

Results:

The CFR for 3.375 g every 4 hours (intermittent infusion) and 3.375–4.5 g every 8 hours (prolonged infusion) greater than or equal to 90.3% for Escherichia coli, Serratia marcescens, and Citrobacter spp. Increasing the prolonged-infusion dose to 6.75 g improved the CFR to greater than 90% for Enterobacter spp. For every regimen evaluated, the CFR was less than 90% for Klebsiella pneumoniae and Pseudomonas aeruginosa. At an MIC of 16 μg/mL, PTA was greater than 90% for one intermittent-infusion regimen (3.375 g every 4 h) and 3 prolonged-infusion regimens (≥3.375 g every 8 h). but no regimen achieved a PTA greater than 90% at an MIC of 64 μ/g/mL.

Conclusions:

At doses greater than or equal to 3.375 g every 8 hours, 4-hour infusions of piperacillin/tazobactam achieved excellent target attainment with lower daily doses compared with standard regimens at MICs less than or equal to 16 μg/mL
Bendamustine-Associated Hemolytic Anemia
Authors: Glance Lisa E , Cumpston Aaron , Kanate Abraham , Remick Scot C
Published: October 2009

Objective:

To report a case of probable bendamustine-related hemolytic anemia.

Case Summary:

A 64-year-old white female had recently received treatment with bendamustine for stage III follicular lymphoma. After her fourth cycle, she was admitted to an outside facility with severe right upper quadrant pain across her back and findings consistent with obstructive jaundice. She was found to have pancytopenia and elevations in total bilirubin, alkaline phosphatase, and transaminase levels. A bone marrow biopsy showed no evidence of lymphoma and presence of megakaryocytes on 2 occasions. Upon transfer to West Virginia University Hospitals, her haptoglobin was found to be undetectable, total bilirubin 10.3 mg/dL (unconjugated bilirubin 4.9 mg/dL), reticulocyte count 21.4% (reticulocyte index ≥2%), alkaline phosphatase 1125 U/L, and lactate dehydrogenase 421 U/L. The peripheral smear showed evidence of spherocytes and very rare schistocytes. Based on these findings, the woman was diagnosed with hemolytic anemia secondary to bendamustine exposure. She was started on prednisone 1 mg/kg (60 mg) daily and, soon after, her platelets and hemoglobin stabilized.

Discussion:

Drug-induced hemolytic anemia is an acquired or extrinsic process that results in antibody-mediated red blood cell destruction. The patient was not taking any medications commonly associated with hemolytic anemia; however, her laboratory test results were consistent with hemolytic anemia. Based on bendamustine's structural similarity to fludarabine and fludarabine s association with causing hemolytic anemia, we considered exposure to bendamustine to be the most likely contributory factor for her diagnosis. According to the Naranjo probability scale, a probable likelihood was reflected in bendamustine causing the hemolytic anemia.

Conclusions:

Continued monitoring of postmarketing data is necessary to correlate this occurrence of hemolytic anemia with bendamustine therapy.
Bipolar Disorder Patient Care Opportunities: Let's Answer the Call
Authors: Caley Charles F
Published: October 2009

Bipolar disorder is a brain illness with complexities in its composition and treatment. Results from the National Comorbidity Survey Replication study estimate the lifetime prevalence of bipolar spectrum illnesses to be 4.5%. These patients were also reported to have their illnesses frequently treated suboptimally and to be at risk of suffering extensive disability. Pharmacists are in a key position to deliver important pharmacy care services to patients who have bipolar disorder and receive treatments in need of close monitoring. Described here are the results of this study and opportunities for pharmacists to support this important patient population.
Thermodynamics in an icy world: The atmosphere and internal structure of Saturn's moon Titan
Authors: Heintz Andreas , Bich Eckard
Published: October 2009

Thermodynamic principles can be applied for describing the atmospheres and the internal structure of celestial bodies using Saturn's moon Titan as a most appropriate example. Some basic physical data of Titan such as the measured temperature and pressure on its surface, the atmospheric composition, Titan’s density and diameter, and other information allow us to predict further properties which have not been determined directly by measurements. The existence of a liquid phase covering smaller parts of the surface can be confirmed, and the composition of the liquid can be predicted. The change of temperature with the height over the surface and the appearance of clouds and rainfall in the atmosphere consisting essentially of CH4 + N2 mixtures can also be predicted. By developing a new method of calculation of atmospheric scenarios, the chemical history of Titan’s surface and atmosphere can be roughly reconstructed taking into account the known rate of methane destruction caused by radiative absorption of sunlight. Finally, some estimations concerning the material structure and the pressure behavior of Titan’s interior can be made. Only basic knowledge of thermodynamics and physics is required to understand essential features in a strange world that is more than one billion kilometers away from us.
On the cuspidal cohomology of arithmetic groups
Authors: Li Jian-Shu , Schwermer Joachim
Published: October 2009

It is the main objective of this paper to show a vanishing result
for cuspidal cohomology of arithmetic groups in classical groups~$G$
defined over some number field~$k$.
Our approach relies on the fact that cuspidal automorphic forms are nonsingular
in the sense of Howe. This result puts a strong constraint on the
(archimedean components of) irreducible cuspidal automorphic representations of $G$
that can possibly contribute to the cuspidal cohomology. Combining this with the
classification of Vogan-Zuckerman of unitary representations with nonzero cohomology
provides a constant $r_0(G/k)$, only depending on $G/k$, below which the cuspidal
cohomology vanishes. We will give a formula for this constant for each classical
group of type (I) in the classification scheme due to Weil. We conclude with making
this result explicit for some split classical groups over a totally real algebraic
number field.
J. Walter Thompson and the Creation of the Modern Advertising Agency
Authors: Gennaro Stephen
Published: October 2009

This article traces the J. Walter Thompson Company's rise to prominence in the advertising industry against the backdrop of the growth of the American advertising industry, American big business, and the emergence of a mass consumer society. Furthermore, the article looks into the internal records of the J. Walter Thompson Company to highlight how the advertising agency itself defined "advertising" and explained some of its practices. It begins by providing a historical overview of the emergence of the modern advertising agency. In addition to examining the business history of the early advertising industry and how the J. Walter Thompson Company became the world's largest agency by the middle of the 20th century, the article also explores the economic and social roles of the advertising agency.
Contemporary Hollywood Masculinity and the Double-Protagonist Film
Authors: Greven David
Published: October 2009

In the double-protagonist film, a genre that has emerged in the past two decades, two male protagonists, each played by a film star, vie for narrative dominance. American manhood is depicted as fundamentally split, a split that can be understood as conflict between a narcissistic and a masochistic mode of masculine identity.
Rethinking Copyrights for the Library through Creative Commons Licensing
Authors: Kapitzke Cushla
Published: October 2009

Two recent and related social developments of note for libraries are an upsurge in cultural participation enabled by Web 2.0 media and calls in government policy for enhanced innovation through education. Ironically, these have occurred at the same time that increasingly stringent copyright laws have restricted access to cultural content. Concepts of governmentality are used here to examine these tensions and contradictions. In particular, Foucault’s critique of the author figure and freedom as part of the will to govern within liberal democratic societies is used to argue for better quality copyright education programs in school libraries and library information science education programs. For purposes of teaching and research, copyrights are defined as agglomerations of legal, economic, and educational discourses that enable and constrain what can and cannot be done with text in homes, schools, and library media centers. This article presents some possibilities for renewal of school libraries around copyright education and Creative Commons licensing.
Radical Change Theory, Youth Information Behavior, and School Libraries
Authors: Dresang Eliza T. , Koh Kyungwon
Published: October 2009

School libraries confront significant changes in the digital age, the age of Web 2.0 and of participatory culture. Radical Change theory, based on the digital age principles of interactivity, connectivity, and access, is germane to understanding these transformations. The theory was originally developed to explain changes in digital age books for youth. It is expanded here through the creation of a typology and accompanying characteristics that address how digital age youth think and seek information; perceive themselves and others; and access information and seek community. As a basis for their typology, the authors provide detailed evidence from an extensive interdisciplinary review of research literature concerning youth information behavior. Also proposed is a multistage research agenda that involves applying Radical Change theory in various school library settings for proof of concept followed by an exploration of potential associations between digital age youth information behaviors and twenty-first-century learning skills. This theory development will assist in determining what implications the new information behaviors and resources have for libraries, schools, and other information environments and how information professionals can better help youth become skilled twenty-first-century information seekers.
Gamma-Band Synchronization in the Macaque Hippocampus and Memory Formation
Authors: Jutras Michael J. , Fries Pascal , Buffalo Elizabeth A.
Published: October 2009

Increasing evidence suggests that neuronal synchronization in the gamma band (30–100 Hz) may play an important role in mediating cognitive processes. Gamma-band synchronization provides for the optimal temporal relationship between two signals to produce the long-term synaptic changes that have been theorized to underlie memory formation. Although neuronal populations in the hippocampus oscillate in the gamma range, the role of these oscillations in memory formation is still unclear. To address this issue, we recorded neuronal activity in the hippocampus while macaque monkeys performed a visual recognition memory task. During the encoding phase of this task, hippocampal neurons displayed gamma-band synchronization. Additionally, enhanced gamma-band synchronization during encoding predicted greater subsequent recognition memory performance. These changes in synchronization reflect enhanced coordination among hippocampal neurons and may facilitate synaptic changes necessary for successful memory encoding.
Properties of Piriform Cortex Pyramidal Cell Dendrites: Implications for Olfactory Circuit Design
Authors: Bathellier Brice , Margrie Troy W. , Larkum Matthew E.
Published: October 2009

Unlike the neocortex, sensory input to the piriform cortex is anatomically segregated in layer 1, making it ideal for studying the dendritic integration of synaptic inputs pivotal for sensory information processing. Here we investigated dendritic integration of olfactory bulb inputs in pyramidal cells using dual patch-clamp recordings along the soma–apical dendritic axis. We found that these dendrites are relatively compact with 50% maximal somatic current loss for synaptic inputs arriving at distal dendritic regions. Distal dendrites could generate small and fast local spikes, but they had little impact on the soma, indicating that they are only weakly active. In contrast to the neocortex, we found no evidence for dendritic Ca2+or NMDA spikes though these dendrites actively supported action potential backpropagation with concomitant entry of Ca2+ions. Based on experiments and simulations we suggest that regardless of dendritic location, olfactory bulb inputs have nearly uniform potency and are distributed diffusely over the distal apical tree (layer Ia), thereby minimizing sublinear summation effects. This indicates that any stimulus feature extraction performed by these cells will occur at the soma and is based on the nearly linear sum of olfactory bulb inputs, rather than on explicitly designed clusters of functionally related synapses in the dendritic tree.
Autocrine Activation of Neuronal NMDA Receptors by Aspartate Mediates Dopamine- and cAMP-Induced CREB-Dependent Gene Transcription
Authors: Almeida Luis E. F. , Murray Peter D. , Zielke H. Ronald , Roby Clinton D. , Kingsbury Tami J. , Krueger Bruce K.
Published: October 2009

cAMP can stimulate the transcription of many activity-dependent genes via activation of the transcription factor, cAMP response element-binding protein (CREB). However, in mouse cortical neuron cultures, prior to synaptogenesis, neither cAMP nor dopamine, which acts via cAMP, stimulated CREB-dependent gene transcription when NR2B-containing NMDA receptors (NMDARs) were blocked. Stimulation of transcription by cAMP was potentiated by inhibitors of excitatory amino acid uptake, suggesting a role for extracellular glutamate or aspartate in cAMP-induced transcription. Aspartate was identified as the extracellular messenger: enzymatic scavenging ofl-aspartate, but not glutamate, blocked stimulation of CREB-dependent gene transcription by cAMP; moreover, cAMP induced aspartate but not glutamate release. Together, these results suggest that cAMP acts via an autocrine or paracrine pathway to release aspartate, which activates NR2B-containing NMDARs, leading to Ca2+entry and activation of transcription. This cAMP/aspartate/NMDAR signaling pathway may mediate the effects of transmitters such as dopamine on axon growth and synaptogenesis in developing neurons or on synaptic plasticity in mature neural networks.
A Protein Interaction Node at the Neurotransmitter Release Site: Domains of Aczonin/Piccolo, Bassoon, CAST, and Rim Converge on the N-Terminal Domain of Munc13-1
Authors: Wang Xiaolu , Hu Bin , Zieba Agata , Neumann Nicole G. , Kasper-Sonnenberg Monika , Honsbein Annegret , Hultqvist Greta , Conze Tim , Witt Wolfgang , Limbach Christoph , Geitmann Matthis , Danielson Helena , Kolarow Richard , Niemann Gesa , Lessmann Volkmar , Kilimann Manfred W.
Published: October 2009

Multidomain scaffolding proteins organize the molecular machinery of neurotransmitter vesicle dynamics during synaptogenesis and synaptic activity. We find that domains of five active zone proteins converge on an interaction node that centers on the N-terminal region of Munc13-1 and includes the zinc-finger domain of Rim1, the C-terminal region of Bassoon, a segment of CAST1/ELKS2, and the third coiled-coil domain (CC3) of either Aczonin/Piccolo or Bassoon. This multidomain complex may constitute a center for the physical and functional integration of the protein machinery at the active zone. An additional connection between Aczonin and Bassoon is mediated by the second coiled-coil domain of Aczonin. Recombinant Aczonin-CC3, expressed in cultured neurons as a green fluorescent protein fusion protein, is targeted to synapses and suppresses vesicle turnover, suggesting involvements in synaptic assembly as well as activity. Our findings show that Aczonin, Bassoon, CAST1, Munc13, and Rim are closely and multiply interconnected, they indicate that Aczonin-CC3 can actively participate in neurotransmitter vesicle dynamics, and they highlight the N-terminal region of Munc13-1 as a hub of protein interactions by adding three new binding partners to its mechanistic potential in the control of synaptic vesicle priming.
Rapid Assembly of Functional Presynaptic Boutons Triggered by Adhesive Contacts
Authors: Lucido Anna Lisa , Suarez Sanchez Fernando , Thostrup Peter , Kwiatkowski Adam V. , Leal-Ortiz Sergio , Gopalakrishnan Gopakumar , Liazoghli Dalinda , Belkaid Wiam , Lennox R. Bruce , Grutter Peter , Garner Craig C. , Colman David R.
Published: October 2009

CNS synapse assembly typically follows after stable contacts between “appropriate” axonal and dendritic membranes are made. We show that presynaptic boutons selectively formde novofollowing neuronal fiber adhesion to beads coated with poly-d-lysine (PDL), an artificial cationic polypeptide. As demonstrated by atomic force and live confocal microscopy, functional presynaptic boutons self-assemble as rapidly as 1 h after bead contact, and are found to contain a variety of proteins characteristic of presynaptic endings. Interestingly, presynaptic compartment assembly does not depend on the presence of a biological postsynaptic membrane surface. Rather, heparan sulfate proteoglycans, including syndecan-2, as well as others possibly adsorbed onto the bead matrix or expressed on the axon surface, are required for assembly to proceed by a mechanism dependent on the dynamic reorganization of F-actin. Our results indicate that certain (but not all) nonspecific cationic molecules like PDL, with presumably electrostatically mediated adhesive properties, can effectively bypass cognate and natural postsynaptic ligands to trigger presynaptic assembly in the absence of specific target recognition. In contrast, we find that postsynaptic compartment assembly depends on the prior presence of a mature presynaptic ending.
Involvement of the Thalamocortical Loop in the Spontaneous Switching of Percepts in Auditory Streaming
Authors: Kondo Hirohito M. , Kashino Makio
Published: October 2009

Perceptual grouping of successive frequency components, namely, auditory streaming, is essential for auditory scene analysis. Prolonged listening to an unchanging triplet-tone sequence produces a series of illusory switches between a single coherent stream (S1) and two distinct streams (S2). The predominant percept depends on the frequency difference (Δf) between high and low tones. Here, we combined the use of different Δfs with an event-related fMRI design to identify whether the temporal dynamics of brain activity differs depending on the direction of perceptual switches. The results demonstrated that the activity of the medial geniculate body (MGB) in the thalamus occurred earlier during switching from nonpredominant to predominant percepts, whereas that of the auditory cortex (AC) occurred earlier during switching from predominant to nonpredominant percepts, regardless of Δf. The asymmetry of temporal precedence indicates that the MGB and AC activations play different roles in perceptual switching and depend on perceptual predominance rather than on S1 and S2 percepts per se. Our results suggest that feedforward and feedback processes in the thalamocortical loop are involved in the formation of percepts in auditory streaming.
Long-Term Modifications in Motor Cortical Dynamics Induced by Intensive Practice
Authors: Kilavik Bjørg E. , Roux Sébastien , Ponce-Alvarez Adrián , Confais Joachim , Grün Sonja , Riehle Alexa
Published: October 2009

The planning of goal-directed movements requires sensory, temporal, and contextual information to be combined. Sensorimotor functions are embedded in large neuronal networks, but it is unclear how networks organize their activity in space and time to optimize behavior. Temporal coordination of activity in many neurons within a network, e.g., spike synchrony, might be complementary to a firing rate code, allowing efficient computation with overall less population activity. Here we asked the question whether intensive practice induces long-term modifications in the temporal structure of synchrony and firing rate at the population level. Three monkeys were trained in a delayed pointing task in which the selection of movement direction depended on correct time estimation. The synchronous firing among pairs of simultaneously recorded neurons in motor cortex was analyzed using the “unitary event” technique. The evolution of synchrony in both time, within the trial, and temporal precision was then quantified at the level of an entire population of neurons by using two different quantification techniques and compared with the population firing rate. We find that the task timing was represented in the temporal structure of significant spike synchronization at the population level. During practice, the temporal structure of synchrony was shaped, with synchrony becoming stronger and more localized in time during late experimental sessions, in parallel with an improvement in behavioral performance. Concurrently, the average population firing rate mainly decreased. Performance optimization through practice might therefore be achieved by boosting the computational contribution of spike synchrony, allowing an overall reduction in population activity.
Mouse RIC-3, an Endoplasmic Reticulum Chaperone, Promotes Assembly of the α7 Acetylcholine Receptor through a Cytoplasmic Coiled-Coil Domain
Authors: Wang Ying , Yao Yun , Tang Xiao-Qing , Wang Zuo-Zhong
Published: October 2009

RIC-3 (resistant toinhibitor ofcholinesterase) is a transmembrane protein, found in invertebrates and vertebrates, that modulates the surface expression of a variety of nicotinic acetylcholine receptors (nAChRs) in neurons and other cells. To understand its mechanism of action, we investigated the cellular location, transmembrane topology and cellular mechanism by which RIC-3 facilitates α7 assembly and surface expression in cultured mammalian cells. We show that the mouse protein is targeted to the ER by the first 31 aa which act as a cleavable signal sequence. The mature protein is a single-pass type I transmembrane protein whose N terminus resides in the lumen of the ER with the coiled-coil domain in the cytoplasm. RIC-3, which binds both unfolded and folded α7 subunits, facilitates the surface expression of receptor principally by promoting the folding and assembly of the α7 subunits in the ER into fully polymerized receptor. Functional analysis shows that facilitation of surface expression of α7 in mammalian cells is reduced in RIC-3 mutants lacking the signal peptide, the lumenal segment or the coiled-coil domain, but not in mutants lacking the long C-terminal region downstream of the coiled-coil domain. We show that the coiled-coil domain of mRIC-3 is not required for the interaction of mRIC-3 with α7, but does mediate a homotypic interaction between molecules of mRIC-3. We suggest that efficient assembly of the homomeric α7 nAChR may thus require mRIC-3 self-association through the cytoplasmic coiled-coil domain and suggest a model by which this may occur.