bluuebunny/crossref_metadata_2025 huggingface dataset:
Polycarbonate microspheres containing tumor necrosis factor‐α genes and magnetic powder as potential cancer therapeutics
Authors: Hu Bin , Yan Guo‐Ping , Zhuo Ren‐Xi , Wu Yuan , Fan Chang‐Lie
Published: November 2007

Amphiphilic polycarbonate copolymers including methoxy‐terminated poly(ethylene glycol)‐co‐poly (5,5‐dimethyl trimethylene carbonate) [Poly(PEG‐b‐TMC)] and poly(ethylene glycol)‐co‐poly(trimethylene carbonate) [Poly(PEG‐b‐DTC)] were synthesized. The water‐in‐oil‐in‐water (W/O/W) solvent evaporation technique was adopted to produce anticancer magnetic Poly(PEG‐b‐DTC) microspheres containing tumor necrosis factor‐α (TNF‐α) genes and Fe3O4 magnetic ultrafine powder. Drug release studies showed that the microspheres can sustain a steady release rate of TNF‐α genes in 0.1M phosphate buffer saline solution in vitro for up to 60 h. In vitro cytotoxicity assays demonstrated that the microspheres have high inhibition and antitumor action to human hepatocellular carcinoma (Bel‐7204) cells in vitro. In vivo inhibition on the growth of hepatic carcinomas and histopathologic observation indicated that the microspheres possess a markedly high antitumor activity to human hepatocellular carcinoma (Bel‐7204). © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Endothelial progenitor cell therapy for the treatment of coronary disease, acute MI, and pulmonary arterial hypertension: Current perspectives
Authors: Ward Michael R. , Stewart Duncan J. , Kutryk Michael J.B.
Published: November 2007

Since their identification in 1997, bone marrow derived endothelial progenitor cells (EPCs) have been studied for their role in the endogenous maintenance and repair of endothelium and their potential regenerative capacity beyond the endothelium. In particular, EPCs have been tested in cell therapy approaches with the aim of developing novel therapies for conditions currently lacking effective treatment options. In this review, we discuss the scientific background and clinical experience using EPC delivery or mobilization for the treatment of post‐angioplasty restenosis, acute myocardial infarction and pulmonary arterial hypertension. Although these approaches are safe, efficacy has yet to be proven in large randomized clinical trials. Unfortunately, the biology of EPCs is still poorly understood. The success of future clinical trials depends on a better understanding of EPC biology and intelligent design. © 2007 Wiley‐Liss, Inc.
A Tabu search heuristic for the vehicle routing problem with two‐dimensional loading constraints
Authors: Gendreau Michel , Iori Manuel , Laporte Gilbert , Martello Silvaro
Published: November 2007

This article addresses the well‐known Capacitated Vehicle Routing Problem (CVRP), in the special case where the demand of a customer consists of a certain number of two‐dimensional weighted items. The problem calls for the minimization of the cost of transportation needed for the delivery of the goods demanded by the customers, and carried out by a fleet of vehicles based at a central depot. In order to accommodate all items on the vehicles, a feasibility check of the two‐dimensional packing (2L) must be executed on each vehicle. The overall problem, denoted as 2L‐CVRP, is NP‐hard and particularly difficult to solve in practice. We propose a Tabu Search algorithm, in which the loading component of the problem is solved through heuristics, lower bounds, and a truncated branch‐and‐bound procedure. The effectiveness of the algorithm is demonstrated through extensive computational experiments. © 2007 Wiley Periodicals, Inc. NETWORKS, 2008
Deletion of PSCA increases metastasis of TRAMP‐Induced prostate tumors without altering primary tumor formation
Authors: Moore Miranda L. , Teitell Michael A. , Kim Yoon , Watabe Tetsuro , Reiter Robert E. , Witte Owen N. , Dubey Purnima
Published: November 2007

BACKGROUND

Prostate stem cell antigen (PSCA) is expressed in normal epithelium of various tissues, in embryos and adult animals. PSCA expression is upregulated in up to 70% of prostate tumors and metastases, and a subset of bladder and pancreatic cancers. However, its function is unknown. We studied the effect of targeted gene deletion of PSCA on normal organ development and prostate carcinogenesis.

METHODS

PSCA +/+, PSCA +/−, and PSCA −/− mice were bred and aged to 22 months. A cohort of animals was treated with γ‐irradiation at 2 and 6 months of age. PSCA knockout mice were crossed to TRAMP mice and TRAMP+ PSCA +/+, TRAMP+ PSCA +/−, and TRAMP+ PSCA −/− mice and offspring aged to 10 months of age. Tissues were analyzed by RT‐PCR, histology, and immunohistochemistry for markers of proliferation, apoptosis, angiogenesis, and tumor progression.

RESULTS

PSCA knockout animals were viable, fertile and indistinguishable from wild‐type littermates. Spontaneous or radiation‐induced primary epithelial tumor formation was also similar in wild‐type and PSCA knockout mice. We observed an increased frequency of metastasis in TRAMP+ PSCA heterozygous and knockout mice, compared to TRAMP+ wild‐type mice. Metastases were largely negative for PSCA and androgen receptor. Cleaved‐caspase 3 and CD31 staining was similar in all genotypes. Aurora‐A and Aurora‐B kinases were detected in the cytoplasm of PSCA heterozygous and knockout tumors, suggesting aberrant kinase function.

CONCLUSION

These data suggest that PSCA may play a role in limiting tumor progression in certain contexts, and deletion of PSCA may promote tumor migration and metastasis. Prostate 68: 139–151, 2008. © 2007 Wiley‐Liss, Inc.
Comparison of Low Fat and Low Carbohydrate Diets on Circulating Fatty Acid Composition and Markers of Inflammation
Authors: Forsythe Cassandra E. , Phinney Stephen D. , Fernandez Maria Luz , Quann Erin E. , Wood Richard J. , Bibus Doug M. , Kraemer William J. , Feinman Richard D. , Volek Jeff S.
Published: November 2007

Abnormal distribution of plasma fatty acids and increased inflammation are prominent features of metabolic syndrome. We tested whether these components of metabolic syndrome, like dyslipidemia and glycemia, are responsive to carbohydrate restriction. Overweight men and women with atherogenic dyslipidemia consumed ad libitum diets very low in carbohydrate (VLCKD) (1504 kcal:%CHO:fat:protein = 12:59:28) or low in fat (LFD) (1478 kcal:%CHO:fat:protein = 56:24:20) for 12 weeks. In comparison to the LFD, the VLCKD resulted in an increased proportion of serum total n‐6 PUFA, mainly attributed to a marked increase in arachidonate (20:4n‐6), while its biosynthetic metabolic intermediates were decreased. The n‐6/n‐3 and arachidonic/eicosapentaenoic acid ratio also increased sharply. Total saturated fatty acids and 16:1n‐7 were consistently decreased following the VLCKD. Both diets significantly decreased the concentration of several serum inflammatory markers, but there was an overall greater anti‐inflammatory effect associated with the VLCKD, as evidenced by greater decreases in TNF‐α, IL‐6, IL‐8, MCP‐1, E‐selectin, I‐CAM, and PAI‐1. Increased 20:4n‐6 and the ratios of 20:4n‐6/20:5n‐3 and n‐6/n‐3 are commonly viewed as pro‐inflammatory, but unexpectedly were consistently inversely associated with responses in inflammatory proteins. In summary, a very low carbohydrate diet resulted in profound alterations in fatty acid composition and reduced inflammation compared to a low fat diet.
Reply to Botros
Authors: Mounce H.O.
Published: November 2007

Sophie Botros's criticism of my review depends in part on certain misprints which appear in the review as printed. In particular, words are omitted from my summary of her position. What I wrote was as follows.
A density matrix-based method for the linear-scaling calculation of dynamic second- and third-order properties at the Hartree-Fock and Kohn-Sham density functional theory levels
Authors: Kussmann Jörg , Ochsenfeld Christian
Published: November 2007

A density matrix-based time-dependent self-consistent field (D-TDSCF) method for the calculation of dynamic polarizabilities and first hyperpolarizabilities using the Hartree-Fock and Kohn-Sham density functional theory approaches is presented. The D-TDSCF method allows us to reduce the asymptotic scaling behavior of the computational effort from cubic to linear for systems with a nonvanishing band gap. The linear scaling is achieved by combining a density matrix-based reformulation of the TDSCF equations with linear-scaling schemes for the formation of Fock- or Kohn-Sham-type matrices. In our reformulation only potentially linear-scaling matrices enter the formulation and efficient sparse algebra routines can be employed. Furthermore, the corresponding formulas for the first hyperpolarizabilities are given in terms of zeroth- and first-order one-particle reduced density matrices according to Wigner’s (2n+1) rule. The scaling behavior of our method is illustrated for first exemplary calculations with systems of up to 1011 atoms and 8899 basis functions.
The effect of the inductive electric field on ion poloidal rotation in all collisionality regimes for the primary ions in tokamaks
Authors: Pan Chengkang , Wang Shaojie
Published: November 2007

The expression for the poloidal rotation velocity of the primary ions that is caused by the parallel inductive electric field in tokamaks and valid in all collisionality regimes is derived via the Hirshman-Sigmar moment approach. Also the expression of the collisional impurity ions poloidal rotation velocity that is caused by the parallel inductive electric field in tokamaks is derived. The poloidal rotation velocities of the primary ions and the impurity ions are sensitive to the primary ion collisionality parameter and the impurity strength parameter. The poloidal rotation velocities of the primary ions and the impurity ions decrease with the primary ion collisionality parameter and decrease with the impurity strength parameter.
A simple model of molecular electronic devices and its analytical solution
Authors: Ernzerhof Matthias
Published: November 2007

I present an analytically solvable model for molecular electronic devices (MEDs). The model contains all the essential components: semi-infinite contacts, molecule-contact interface, and of course, the molecule. I obtain explicit expression for the reflection coefficient r(E), as well as for the transmission probability T(E) [T(E)=1−∣r(E)∣2]. r(E) exhibits a surprisingly simple structure if studied as a function of a complex energy variable E. In this case, r(E) can be expressed in terms of a finite number of eigenvalues of a non-Hermitian Hamiltonian. This Hamiltonian also yields the molecular part of the MED wave function. Considering various MEDs, it is illustrated that the theory presented allows for a transparent interpretation of molecular conductance in terms of discrete eigenstates.
Characterization and analysis of a pulse power system based on Marx generator and Blumlein
Authors: Durga Praveen Kumar D. , Mitra S. , Senthil K. , Sharma Archana , Nagesh K. V. , Singh S. K. , Mondal J. , Roy Amitava , Chakravarthy D. P.
Published: November 2007

A pulse power system (1MV, 50kA, and 100ns) based on Marx generator and Blumlein pulse forming line has been studied for characterization of a general system. Total erected Marx inductance and series resistance are calculated from modular testing of Marx generator and testing of Marx generator with Blumlein. The complete pulse power system has been tested with the termination of a liquid resistor load for finding the Blumlein characteristic impedance. Equivalent electrical circuits during the charging and discharging of the Blumlein are constructed from the characterized parameters of the system. These equivalent circuits can be used in the analysis of prepulse voltage and droop in the flat top of the main pulse in the pulse power systems based on Marx generator and Blumlein.
An electron cyclotron resonance plasma configuration for increasing the efficiency in the yield of nitrogen endohedral fullerenes
Authors: Kaneko T. , Abe S. , Ishida H. , Hatakeyama R.
Published: November 2007

Efficiently yielding a nitrogen-atom endohedral fullerene (N@C60) is demonstrated for the first time using an electron cyclotron resonance (ECR) plasma source with a minimum-B mirror configuration realized by hexapole permanent magnets. Since electrons are effectively confined around a bottom of the minimum-B mirror in the ECR region, the high-temperature electrons can be generated there, and as a result, the dissociation degree of the nitrogen molecules increases drastically. This highly dissociated nitrogen plasma has a number of nitrogen-atom radicals and ions, thus permitting an enhancement of N@C60 yield.
Wetting kinetics of a thin film evaporating in air
Authors: Saritha S. , Neogi P.
Published: November 2007

The conservation equation and the equations of motion are solved for a case where a thin liquid film moves out of a slot onto a horizontal surface. The liquid is allowed to evaporate into air. The evaporation process is taken to be isothermal. Lubrication theory approximation is used where only the tangential velocity and its dependence only in the normal direction are considered. The dynamics of thin films includes the use of disjoining pressure for a pure liquid and where there is a dissolved polymer. The results show that evaporation is quicker than film thinning such that a spreading regime dominated by the effects of disjoining pressure is never achieved. However, unlike the cases of pinning studied so far, there is no singularity in the evaporative flux near the contact line because of the use of disjoining pressure on evaporation. It is also observed that a balance between the rate of viscous dissipation and surface work is able to quantify the steady state contact angle. Consequently, a more macroscopic (and quantitative) description of contact line can be found that avoids the singularities discussed earlier and also the detailed calculations shown here. However, the detailed calculations are necessary to make the above point.
Nitrogen-doped carbon nanotube structure tailoring and time-resolved transport measurements in a transmission electron microscope
Authors: Costa Pedro MFJ , Golberg Dmitri , Mitome Masanori , Bando Yoshio
Published: November 2007

A dynamical response of the current-voltage characteristics of ropes and individual structures of multiwalled nitrogen-doped carbon nanotubes has been observed inside a transmission electron microscope. The drastic change of the current transport properties is thought to be due to purging of contaminating gaseous surface adsorbed species. In addition, an in situ methodology was developed to obtain individually pure and length-tailored nanotubes. By carefully controlling the current flow across the nanotubes, residual surface-decorating and encapsulated catalyst particles were eliminated, and short sections of the nanotubes (200to500nm) were cut.
The effects of obstacle size on periodic travelling waves in oscillatory reaction–diffusion equations
Authors: Smith Matthew J , Sherratt Jonathan A , Armstrong Nicola J
Published: November 2007

Many natural populations undergo multi-year cycles, and field studies have shown that these can be organized into periodic travelling waves (PTWs). Mathematical studies have shown that large-scale landscape obstacles represent a natural mechanism for wave generation. Here, we investigate how the amplitude and wavelength of the selected waves depend on the obstacle size. We firstly consider a large circular obstacle in an infinite domain for a reaction–diffusion system of ‘
λ
–
ω
’ type. We use perturbation theory to derive a leading order approximation to the wave generated by the obstacle. This shows the dependence of the wave properties on both parameter values and obstacle size. We find that the limiting values of the amplitude and wavelength are approached algebraically with distance from the obstacle edge, rather than exponentially in the case of a flat boundary. We use our results to predict the properties of waves generated by a large circular obstacle for an oscillatory predator–prey system, via a reduction of the predator–prey model to normal form close to Hopf bifurcation. Our predictions compare well with numerical simulations. We also discuss the implications of these results for wave stability and briefly investigate the effects of obstacles with elliptical geometries.
Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5
Authors: Mosyak Lidia , Georgiadis Katy , Shane Tania , Svenson Kristine , Hebert Tracy , McDonagh Thomas , Mackie Stewart , Olland Stephane , Lin Laura , Zhong Xiaotian , Kriz Ronald , Reifenberg Erica L. , Collins‐Racie Lisa A. , Corcoran Christopher , Freeman Bethany , Zollner Richard , Marvell Tod , Vera Matthew , Sum Phaik‐Eng , Lavallie Edward R. , Stahl Mark , Somers William
Published: November 2007

Aggrecanases are now believed to be the principal proteinases responsible for aggrecan degradation in osteoarthritis. Given their potential as a drug target, we solved crystal structures of the two most active human aggrecanase isoforms, ADAMTS4 and ADAMTS5, each in complex with bound inhibitor and one wherein the enzyme is in apo form. These structures show that the unliganded and inhibitor‐bound enzymes exhibit two essentially different catalytic‐site configurations: an autoinhibited, nonbinding, closed form and an open, binding form. On this basis, we propose that mature aggrecanases exist as an ensemble of at least two isomers, only one of which is proteolytically active.
Anchoring TRP to the INAD macromolecular complex requires the last 14 residues in its carboxyl terminus
Authors: Peng Li , Popescu Daniela C. , Wang Ning , Shieh Bih‐Hwa
Published: November 2007

J. Neurochem. (2008) 104, 1526–1535.

Drosophila transient‐receptor‐potential (TRP) is a Ca2+ channel responsible for the light‐dependent depolarization of photoreceptors. TRP is anchored to a macromolecular complex by tethering to inactivation‐no‐afterpotential D (INAD). We previously reported that INAD associated with the carboxyl tail of TRP via its third post‐synaptic density protein 95, discs‐large, zonular occludens‐1 domain. In this paper, we further explored the molecular basis of the INAD interaction and demonstrated the requirement of the last 14 residues of TRP, with the critical contribution of Gly1262, Val1266, Trp1274, and Leu1275. We also revealed by pull‐down assays that the last 14 residues of TRP comprised the minimal sequence that competes with the endogenous TRP from fly extracts, leading to the co‐purification of a partial INAD complex containing INAD, no‐receptor‐potential A, and eye‐protein kinase C (PKC). Eye‐PKC is critical for the negative regulation of the visual signaling and was shown to phosphorylate TRP in vivo. To uncover the substrates of eye‐PKC in the INAD complex, we designed a complex‐dependent eye‐PKC assay, which utilized endogenous INAD complexes isolated from flies. We demonstrate that activated eye‐PKC phosphorylates INAD, TRP but not no‐receptor‐potential A. Moreover, phosphorylation of TRP is dependent on the presence of both eye‐PKC and INAD. Together, these findings indicate that stable kinase‐containing protein complexes may be isolated by pull‐down assays, and used in this modified kinase assay to investigate phosphorylation of the proteins in the complex. We conclude that TRP associates with INAD via its last 14 residues to facilitate its regulation by eye‐PKC that fine‐tunes the visual signaling.
Breeding success of Spotted Flycatchers Muscicapa striata in southern England – is woodland a good habitat for this species?
Authors: STEVENS DANAË K. , ANDERSON GUY Q. A. , GRICE PHIL V. , NORRIS KEN
Published: November 2007

The UK population of the Spotted Flycatcher Muscicapa striata has declined markedly in the last 30 years but there have been few recent studies of the species. This study examined the relationship between nest success and the predominant habitat type around Spotted Flycatcher nests in two contrasting areas of England. A breeding population in eastern England, a region where numbers of Spotted Flycatchers are known to have decreased dramatically in recent decades, was compared with another in southwest England, where numbers have remained stable or even increased. Whilst there was no difference in breeding success between the two study areas, there were significant differences between habitats, with garden nests more successful than those in farmland or woodland, at both egg and chick stages. Estimates of productivity per nesting attempt were also lower in farmland and woodland, with nests in gardens fledging twice as many chicks as those in either woodland or farmland. The proximate cause of lower success in farmland and woodland was higher nest predation rates during both egg and chick stages. In terms of nesting success, farmland and woodland appear to be similar in quality for this species, but both appear to be suboptimal habitats when compared with gardens, providing evidence of a problem on the breeding grounds for this species, in at least these two habitats.
Effect of Partial Oxygen Supply on Mitochondrial Electron Transport System During Complete Cardiac Ischemia
Authors: Konuralp Cuneyt , Guner Saadettin , Cakatay Ufuk , Konuralp Zeynep , Yapici Nihan , Maçika Hüseyin , Aydo˘an Hakki , Aykut‐Aka Serap , Alhan Cem , Gultepe Mustafa , Eren Ergin E.
Published: November 2007

Abstract During complete ischemia we assessed myocardial utilization of the small amount of oxygen available. We also determined whether blood cardioplegia has any advantage over crystalloid cardioplegia in this setting. Patients with preserved left ventricular myocardial function and without anterolateral wall infarct or aneurysm were included to the study. Intermittent cold blood and crystalloid cardioplegia were used in 10 patients (group BC) and 9 patients (group CC), respectively. From myocardial biopsies, obtained before and after ischemia, complete electron transport system (ETS) enzyme activities (NDH, SDH, NCCR, SCCR, and COX) and lactate content were analyzed. Biochemical and hemodynamic analyses also were done. Myocardial and blood temperatures were monitored.

Ischemic time was longer in group CC (p < 0.05). There were no important differences in biochemical and hemodynamic variables between the two groups. In addition, there was no difference in NDH and SDH activities as well as COX/SCCR and COX/RS‐NCCR ratios between the two groups before and after ischemia. After Ischemia, RS‐NCCR in group CC and SCCR and COX activities in both groups were lower than the control. For all enzymes, activity change ratios were not different between groups. Myocardial lactate content was increased in both groups after ischemia. However, the increase in group BC was less (p < 0.01).

Based on our findings, we believe that the superiority of blood cardioplegia over crystalloid cardioplegia does not depend on oxygen content, but on other factors such as buffering and free oxygen radical scavenger effects among others. However, with the warm and continuous blood cardioplegia technique, oxygen content might be more important.
Is It Possible to Become Happier? (And If So, How?)
Authors: Sheldon Kennon M. , Lyubomirsky Sonja
Published: November 2007

Although some theory suggests that it is impossible to increase one's subjective well‐being (SWB), our ‘sustainable happiness model’ (Lyubomirsky, Sheldon, & Schkade, 2005) specifies conditions under which this may be accomplished. To illustrate the three classes of predictor in the model, we first review research on the demographic/circumstantial, temperament/personality, and intentional/experiential correlates of SWB. We then introduce the sustainable happiness model, which suggests that changing one's goals and activities in life is the best route to sustainable new SWB. However, the goals and activities must be of certain positive types, must fit one's personality and needs, must be practiced diligently and successfully, must be varied in their timing and enactment, and must provide a continued stream of fresh positive experiences. Research supporting the model is reviewed, including new research suggesting that happiness intervention effects are not just placebo effects.
Specificity of iron transport in iron-stressed sugar beet plants: evidence for preferential accumulation of cobalt in the presence of iron
Authors: Young Terry F. , Terry Norman
Published: November 2007

Cobalt treatment of iron-stressed sugar beet plants resulted in leaf cobalt concentrations nearly three times as high as in cobalt-treated control plants. When iron-stressed plants were treated with cobalt and iron together, cobalt was transported into leaves in preference to iron. The transport system in iron-stressed sugar beet appears to be relatively specific for iron and cobalt because iron-stressed plants supplied with manganese, zinc, and copper did not transport these elements in similarly enhanced amounts. Measurements of metal contents of chloroplasts isolated nonaqueously showed that both cobalt and iron were readily transported into chloroplasts (and therefore the leaf symplast) within 48 h. The implications of these results on the mechanism of iron transport across the root plasmalemma are discussed.
A canopy porometer for photosynthesis studies in field crops
Authors: Daley Paul F. , Cloutier Conrad F. , McNeil Jeremy N.
Published: November 2007

A portable, modular porometer for whole-plant or canopy photosynthetic and respiratory gas exchange estimation is described. The system features within-chamber light and temperature measurement and in its present configuration permits analysis of carbon dioxide and water vapour exchange by an extension of the syringe-based "CO2 depletion" technique. Operating characteristics of the system and potential modifications are discussed, along with limitations and applications.
A COMPOUNDING ALGORITHM FOR 1-FAULT TOLERANT BROADCAST NETWORKS
Authors: RIEKSTS BRIAN Q. , VENTURA JOSÉ A.
Published: November 2007

This theoretical paper presents a new construction algorithm for sparse 1-fault tolerant minimal broadcast networks (1-FTMBNs). To construct a large 1-FTMBN with the algorithm, identical nodes in copies of a broadcast network that is not fault tolerant are connected according to the edge structures of two known 1-FTMBNs with a special property. In most cases, computational results with this algorithm produce the best-known bounds on the cardinalities of the edge sets of the sparsest 1-FTMBNs with an odd number of nodes.
A Neural Network Model of the Eriksen Task: Reduction, Analysis, and Data Fitting
Authors: Liu Yuan Sophie , Holmes Philip , Cohen Jonathan D.
Published: November 2007

We analyze a neural network model of the Eriksen task: a two-alternative forced-choice task in which subjects must correctly identify a central stimulus and disregard flankers that may or may not be compatible with it. We linearize and decouple the model, deriving a reduced drift-diffusion process with variable drift rate that describes the accumulation of net evidence in favor of either alternative, and we use this to analytically describe how accuracy and response time data depend on model parameters. Such analyses both assist parameter tuning in network models and suggest explanations of changing drift rates in terms of attention. We compare our results with numerical simulations of the full nonlinear model and with empirical data and show good fits to both with fewer parameters.
Implications of Noise and Neural Heterogeneity for Vestibulo-Ocular Reflex Fidelity
Authors: Hospedales Timothy M. , van Rossum Mark C. W. , Graham Bruce P. , Dutia Mayank B.
Published: November 2007

The vestibulo-ocular reflex (VOR) is characterized by a short-latency, high-fidelity eye movement response to head rotations at frequencies up to 20 Hz. Electrophysiological studies of medial vestibular nucleus (MVN) neurons, however, show that their response to sinusoidal currents above 10 to 12 Hz is highly nonlinear and distorted by aliasing for all but very small current amplitudes. How can this system function in vivo when single cell response cannot explain its operation? Here we show that the necessary wide VOR frequency response may be achieved not by firing rate encoding of head velocity in single neurons, but in the integrated population response of asynchronously firing, intrinsically active neurons. Diffusive synaptic noise and the pacemaker-driven, intrinsic firing of MVN cells synergistically maintain asynchronous, spontaneous spiking in a population of model MVN neurons over a wide range of input signal amplitudes and frequencies. Response fidelity is further improved by a reciprocal inhibitory link between two MVN populations, mimicking the vestibular commissural system in vivo, but only if asynchrony is maintained by noise and pacemaker inputs. These results provide a previously missing explanation for the full range of VOR function and a novel account of the role of the intrinsic pacemaker conductances in MVN cells. The values of diffusive noise and pacemaker currents that give optimal response fidelity yield firing statistics similar to those in vivo, suggesting that the in vivo network is tuned to optimal performance. While theoretical studies have argued that noise and population heterogeneity can improve coding, to our knowledge this is the first evidence indicating that these parameters are indeed tuned to optimize coding fidelity in a neural control system in vivo.
The LMP1 oncogene of EBV activates PERK and the unfolded protein response to drive its own synthesis
Authors: Lee Dong Yun , Sugden Bill
Published: November 2007

The oncogene latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) without a ligand drives proliferation of EBV-infected B cells. Its levels vary in cells of clonal populations by more than 100-fold, which leads to multiple distinct activities of the oncogene. At intermediate levels it drives proliferation, and at high levels it inhibits general protein synthesis by inducing phosphorylation of eukaryotic initiation factor 2α (eIF2α). We have found that LMP1 activates PERK to induce phosphorylation of eIF2α, which upregulates activating transcription factor 4 (ATF4) expression. ATF4, in turn, transactivates LMP1's own promoter. LMP1 activates not only PERK but also inositol requiring kinase 1 (IRE1) and ATF6, 3 pathways of the unfolded protein response (UPR). Increasing expression levels of LMP1 induced a dose-dependent increase in IRE1 activity, as measured by its “splicing” of XBP-1. These infected B cells secrete immunoglobins independent of the levels of LMP1, indicating that only a threshold level of XBP-1 is required for the secretion. These findings indicate that LMP1's activation of the UPR is a normal event in a continuum of LMP1's expression that leads both to stimulatory and inhibitory functions and regulates the physiology of EBV-infected B cells in multiple, unexpected modes.
Mystery of the Toxic Flea Dip: An Interactive Approach to Teaching Aerobic Cellular Respiration
Authors: Baines A. T. , McVey M. , Rybarczyk B. , Thompson J. T. , Wilkins H. R.
Published: November 2007

We designed an interrupted case study to teach aerobic cellular respiration to major and nonmajor biology students. The case is based loosely on a real-life incident of rotenone poisoning. It places students in the role of a coroner who must determine the cause of death of the victim. The case is presented to the students in four parts. Each part is followed by discussion questions that the students answer in small groups prior to a classwide discussion. Successive parts of the case provide additional clues to the mystery and help the students focus on the physiological processes involved in aerobic respiration. Students learn the information required to solve the mystery by reading the course textbook prior to class, listening to short lectures interspersed throughout the case, and discussing the case in small groups. The case ends with small group discussions in which the students are given the names and specific molecular targets of other poisons of aerobic respiration and asked to determine which process (i.e., glycolysis, citric acid cycle, or the electron transport chain) the toxin disrupts.
Th1/Th2 Cytokines: An Easy Model to Study Gene Expression in Immune Cells
Authors: Morán José M. , González-Polo Rosa A. , Soler Germán , Fuentes José M.
Published: November 2007

This report describes a laboratory exercise that was incorporated into a Cell Biology and Molecular Biology advanced course. The exercise was made for a class size with eight students and was designed to reinforce the understanding of basic molecular biology techniques. Students used the techniques of reverse transcription and arginase activity measurement as well as nitric oxide determination to discover whether two specific genes were expressed by cytokine-stimulated dendritic cells. The experiment served as the basis for discussing the importance of differential gene expression inside the eukaryotic cell and the importance of cytokines in the immune system.
Using the Web to Encourage Student-generated Questions in Large-Format Introductory Biology Classes
Authors: Colbert James T. , Olson Joanne K. , Clough Michael P.
Published: November 2007

Students rarely ask questions related to course content in large-format introductory classes. The use of a Web-based forum devoted to student-generated questions was explored in a second-semester introductory biology course. Approximately 80% of the enrolled students asked at least one question about course content during each of three semesters during which this approach was implemented. About 95% of the students who posted questions reported reading the instructor's response to their questions. Although doing so did not contribute to their grade in the course, approximately 75% of the students reported reading questions posted by other students in the class. Approximately 60% of the students reported that the Web-based question-asking activity contributed to their learning of biology.
High School Biology Today: What the Committee of Ten Actually Said
Authors: Sheppard Keith , Robbins Dennis M.
Published: November 2007

This essay describes how in the 1890s the Committee of Ten arrived at their recommendations about the organization of the high school biological sciences and seeks to correct the frequently held, but erroneous view that the Committee of Ten was the initiator of the Biology-Chemistry-Physics order of teaching sciences prevalent in high schools today. The essay details the factors underlying the changing views of high school biology from its “natural history” origins, through its “zoology, botany, physiology” disciplinary phase to its eventual integration into a “general biology” course. The simultaneous parallel development of the “Carnegie Unit” for measuring coursework is highlighted as a significant contributor in the evolution of the present day high school biology course. The essay concludes with a discussion of the implications of the grade placement of the sciences for the future development of high school biology.
Teaching without a Textbook: Strategies to Focus Learning on Fundamental Concepts and Scientific Process
Authors: Klymkowsky M. W.
Published: November 2007

Note from the Editor

Textbooks are ubiquitous. They are available for almost every conceivable subdiscipline of biology, and few of us would consider teaching a course without using a textbook. Over the years, they have become more colorful, more encyclopedic, and accompanied by more ancillary materials such as CD-ROMs, study guides, and websites. With all these tools to assist our students, it seems reasonable that they are able to learn more and better than ever. Thus, the question most instructors ask themselves is most likely which textbook to use, not whether to use a textbook. But does the use of textbooks really help students learn better? In this Point of View, I invited a commentary on this question from a faculty member who has decided to abandon the use of a textbook in an introductory level cell and molecular biology course. —Gary Reiness
A Bayesian Sensitivity Analysis of Out‐of‐hospital 12‐lead Electrocardiograms: Implications for Regionalization of Cardiac Care
Authors: Youngquist Scott T. , Kaji Amy H. , Lipsky Ari M. , Koenig William J. , Niemann James T.
Published: November 2007

Background The effectiveness of out‐of‐hospital regionalization of ST‐elevation myocardial infarction (STEMI) patients to hospitals providing primary percutaneous coronary intervention depends on the accuracy of the out‐of‐hospital 12‐lead electrocardiogram (PHTL). Although estimates of sensitivity and specificity of PHTL for STEMI have been reported, the impact of out‐of‐hospital STEMI prevalence on positive predictive value (PPV) has not been evaluated.

Objectives To describe the relationship between varying population STEMI prevalences and PHTL predictive values, using ranges of PHTL sensitivity and specificity.

Methods The authors performed a Bayesian analysis using PHTL, where values for sensitivities (60%–70%), specificities (98%), and two prevalence ranges (0.5%–5% and 5%–20%) were derived from a literature review. PPV prediction intervals were compared with three months of prospective data from the Los Angeles County Emergency Medical Services Agency STEMI regionalization program.

Results When the estimated prevalence of STEMI in the out‐of‐hospital population is 5%–20%, the median PPV of the PHTL is 83% (95% credible interval [CrI] = 53% to 97%). However, if the population prevalence of STEMI is between 0.5% and 5%, the median PPV is 43% (95% CrI = 12% to 86%). When the PPV prediction intervals were incorporated with the Los Angeles County Emergency Medical Services Agency data, the PPV was 66%.

Conclusions Even when assuming high specificity for PHTL, the false‐positive rate will be considerable if applied to a population at low risk for STEMI. Before broadening application of PHTL to low‐risk patients, the implications of a high false‐positive rate should be considered.
Digital Collections, Digital Libraries & the Digitization of Cultural Heritage Information
Authors: Lynch Clifford
Published: November 2007

This paper is based on the transcript of a largely extemporaneous keynote address given at the Web-Wise 2002 Conference on March 20, 2002 at Johns Hopkins University. It has been edited, but it preserves the character of an informal talk rather than a formal paper. I have taken the opportunity to expand upon or clarify a few points, and have also added a few footnotes and pointers to additional information on some of the topics discussed. Parts of the question and answer segment that were captured as part of the transcript have also been included, though I've had the advantage of being able to reconsider some of my answers while the questioners have not had that opportunity; my apologies to them.
Business Model Issues in Digitizing Cultural Content
Authors: Wall Gerry
Published: November 2007

This paper examines business model aspects of digitizing cultural content. It is based in large part on a study conducted by the author and his colleagues for the Department of Canadian Heritage. Based on data collected from several cultural institutions regarding their efforts to digitize content, the study found that implications for the cost side have been significant, leading to explorations of facilities and content sharing programs, formalized budgeting, the need for better copyright expertise and improved mid to long term planning. On the revenue (funding) side, a clear need for more rigorous assessments of user demand emerged. In addition, the possibility of revisiting organizational mandates was identified, as well as various revenuegenerating opportunities including sponsorship, user-fees and private/public sector partnerships.
Copyright Issues Relevant to the Creation of a Digital Archive
Authors: Besek June M.
Published: November 2007

The collection and long-term preservation of digital content pose challenges to the intellectual property regime within which libraries and archives are accustomed to working. How to achieve an appropriate balance between copyright owners and users is a topic of ongoing debate in legal and policy circles. This paper describes copyright rights and exceptions and highlights issues potentially involved in the creation of a nonprofit digital archive. The paper is necessarily very general, since many decisions concerning the proposed archive's scope and operation have not yet been made. The purpose of an archive (e.g., to ensure preservation or to provide an easy and convenient means of access), its subject matter, and the manner in which it will acquire copies, as well as who will have access to the archive, from where, and under what conditions, are all factors critical to determining the copyright implications for works to be included in it. The goal of this paper is to provide basic information about the copyright law for those developing such an archive and thereby enable them to recognize areas in which it could impinge on copyright rights and to plan accordingly. After initial decisions have been made, a more detailed analysis will be possible. As the paper indicates, there are a number of areas that would benefit from further research. Such research may not yield definitive legal answers, but could narrow the issues and suggest strategies for proceeding.
Papers Past: Browse Access for Online New Zealand Newspapers
Authors: Adams David
Published: November 2007

The project to provide access to 19
Memory and the Other
Authors: Motzkin Gabriel
Published: November 2007

I Three Duals

There are two competing loci for our interchange with the past, and two positions that we adopt vis-à-vis that past. These loci are history and memory, the one being the sum of what has happened up to now and the other comprising the sum of what we remember about all that has happened. Seen in this way, the set of historical events is much greater than the set of memorial events. Yet the set of all events often appears to be smaller than that of all remembered events because this latter always seems to be full, or certainly much fuller than the set of all events. So little of the sum total of what has happened is accessible that there seem to be far fewer members of the set of all past events than there are members of the set of all remembered events. Nonetheless, both positions are formally possible. The question is whether we begin our discussion of the relation between history and memory from the position of history or from the position of memory. If we commence from the first position, we seek to know all that happened and then ask what do we remember about what happened, whereas if we start from the latter position, we seek to know what we remember about what happened and ask about what happened only as we have gained access to it from what we remember about it.
The Theopolitical Foundations of Strauss's Criticism of Modernity
Authors: Oram Matan
Published: November 2007

I Philosophers and Prophets

The tradition of the Falasifa (medieval Platonic-Aristotelian Muslim philosophers) tends to refute Plato's ideal of the “philosopher-king”, in which the philosopher is distinguished as the highest human type. In contrast to the philosopher, whose knowledge is incomplete and indirect, the prophet, through revelation, attains profound knowledge and truth. According to the Falasifa version of Platonic politics, the prophet, who represents the highest form of human wisdom conditioned by divine providence, is a founder of political community and a lawgiver.
Die Hannah Arendt-Rezeption im russischsprachigen Raum. Michael Hefetz: Hannah Arendt – eine Beurteilung des 20. Jahrhunderts
Authors: Matveev Julia
Published: November 2007

Die gegenwärtige Popularität Arendts, die man in West-Europa als „Wiederentdeckung einer […] Klassikerin durch eine neue Generation von jüngeren Intellektuellen“ bzw. als Arendt-Renaissance definiert, hat das Interesse an Arendt in Russland und in den russischsprachigen intellektuellen Kreisen in Israel geweckt. Dieser Umstand kann zweifellos mit dem Ende des Kommunismus in Russland in Verbindung gebracht werden, weil gerade dort „vieles, was [Arendt] über Politik gesagt hat, durch die Ereignisse erhärtet worden ist“. Die Anerkennung von Arendts hinlänglich bekannter Konzeption des Politischen verweist auf das Interesse der russischsprachigen Intellektuellen nicht nur an Vergangenem, sondern auch an dem, was in die Gegenwart reicht und als Orientierungshilfe für die Zukunft dienen kann.
Top-Down Control of Multimodal Sensitivity in the Barn Owl Optic Tectum
Authors: Winkowski Daniel E. , Knudsen Eric I.
Published: November 2007

We studied the effects of electrically microstimulating a gaze-control area in the owl's forebrain, the arcopallial gaze fields (AGFs), on the responsiveness of neurons in the optic tectum (OT) to visual and auditory stimuli. Microstimulation of the AGF enhanced the visual and auditory responsiveness and stimulus discriminability of OT neurons representing the same location in space as that represented at the microstimulation site in the AGF. At such OT sites, AGF microstimulation also sharpened auditory receptive fields and shifted them toward the location represented at the AGF stimulation site. At the same time, AGF microstimulation suppressed the responsiveness of OT neurons that represented visual or auditory stimuli at other locations in space. The top-down influences of this forebrain gaze-control area on sensory responsiveness in the owl OT are strikingly similar to the space-specific regulation of visual responsiveness in the monkey visual cortex produced by voluntary attention as well as by microstimulation of the frontal eye fields. This experimental approach provides a means for discovering mechanisms that underlie the top-down regulation of sensory responses.
Size stabilization of nanoparticles by polysaccharides: Effectiveness in the wet and curing steps
Authors: Callone Emanuela , Carturan Giovanni , Ischia Marco , Sicurelli Adriana
Published: November 2007

Starch suspension proves to be a useful matrix for the hydrolytic route to metal oxide nanoparticles, due to its size-stabilization effect, which works also at high temperatures. To understand the type of interaction between the organic part and the oxide particles, various parameters, such as viscosity, temperature, degree of polymerization, and organic/inorganic kinds of dispersant, are tested through x-ray diffraction (XRD), transmission electron microscopy (TEM), solid-state nuclear magnetic resonance (NMR), and thermogravimetric mass spectra (TG–MS) analyses of the obtained SnO2nanopowders. Results highlight the unique role of starch compared with other hydrophilic dispersants that do not ensure effective size stabilization on curing up to 600 °C. The proof comes from the study of pyrolysis of the residual organic groups surrounding the particles. They are chelating carboxylic species that prevent the coalescence among metal oxide nanoparticles.
Effects of amphiphilic surfactants on electrolyte distribution in polymer electrolyte fuel-cell electrode
Authors: Hong Suk-Gi , Lee Eun Sung , Bae Jin-Young , Lee Myung-Jin , Chang Hyuk , Seung Do Young
Published: November 2007

To enhance Pt utilization in the fuel-cell electrode by microscopically controlling the distribution of liquid electrolytes around Pt catalysts, the amphiphilic surfactant tergitol phosphate was synthesized and introduced into the fuel-cell electrode. The chemical structure of the surfactant was determined by 1H-nuclear magnetic resonance, and its adsorption property on Pt–C catalyst was ascertained by Fourier transform infrared analysis. The electrode into which the amphiphilic surfactants were incorporated showed improved performance, and especially the amphiphilic surfactant with polyethylene oxide, NPE10-OPO(OH)2, produced higher cell performance.