bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro induction and differentiation of newborn guinea pig hippocampus neural stem cells into cells resembling inner hair cells, using artificial perilymph
Authors: Wang Y , Dong M-M
Published: June 2011

Objective:

To investigate whether artificial perilymph can induce neural stem cells, derived from the hippocampus of newborn guinea pigs, to differentiate into inner ear hair cells, in vitro.

Methods:

Primary neural stem cells derived from the hippocampus of newborn guinea pigs were incubated in medium containing either 10 per cent fetal bovine serum or 5, 10 or 15 per cent artificial perilymph, for three weeks. Differentiated cells were identified using immunofluorescence, Western blot and scanning electron microscopy.

Results:

Both fetal bovine serum and artificial perilymph induced the neural stem cells to differentiate into cells with hair-cell-specific antibodies.

Conclusion:

Neural stem cells can survive in both fetal bovine serum and artificial perilymph, and within these media can differentiate into cells with hair-cell-specific antibodies. This provides an experimental basis for transplantation of neural stem cells into the inner ear.
Is childhood OCD a risk factor for eating disorders later in life? A longitudinal study
Authors: Micali N. , Hilton K. , Natatani E. , Heyman I. , Turner C. , Mataix-Cols D.
Published: June 2011

Background

It has been suggested that childhood obsessive-compulsive disorder (OCD) may be a risk factor for the development of an eating disorder (ED) later in life, but prospective studies are lacking. We aimed to determine the prevalence of ED at follow-up and clinical predictors in a longitudinal clinical sample of adolescents/young adults diagnosed with OCD in childhood.

Method

All contactable (n=231) young people with OCD assessed over 9 years at a national and specialist paediatric OCD clinic were included in this study. At follow-up, 126 (57%) young people and parents completed the ED section of the Developmental and Well-being Assessment. Predictors for ED were investigated using logistic regression.

Results

In total, 16 participants (12.7%) had a diagnosis of ED at follow-up. Having an ED was associated with female gender and persistent OCD at follow-up. There was a trend for family history of ED being predictive of ED diagnosis. Five (30%) of those who developed an ED at follow-up had ED symptoms or food-related obsessions/compulsions at baseline. A difference in predictors for an EDversusother anxiety disorders at follow-up was identified.

Conclusions

This study provides initial evidence that baseline clinical predictors such as female gender and family history of ED might be specific to the later development of ED in the context of childhood OCD. Clinicians should be alert to ED subthreshold symptoms in young girls presenting with OCD. Future longitudinal studies are needed to clarify the relationship between childhood OCD and later ED.
LOCALLY STATIONARY FACTOR MODELS: IDENTIFICATION AND NONPARAMETRIC ESTIMATION
Authors: Motta Giovanni , Hafner Christian M. , von Sachs Rainer
Published: June 2011

In this paper we propose a new approximate factor model for large cross-section and time dimensions. Factor loadings are assumed to be smooth functions of time, which allows considering the model aslocally stationarywhile permitting empirically observed time-varying second moments. Factor loadings are estimated by the eigenvectors of a nonparametrically estimated covariance matrix. As is well known in the stationary case, this principal components estimator is consistent in approximate factor models if the eigenvalues of the noise covariance matrix are bounded. To show that this carries over to our locally stationary factor model is the main objective of our paper. Under simultaneous asymptotics (cross-section and time dimension go to infinity simultaneously), we give conditions for consistency of our estimators. A simulation study illustrates the performance of these estimators.
High-Integrity GPS/INS Integrated Navigation with Error Detection and Application to LAAS
Authors: Chan Fang-Cheng , Pervan Boris
Published: June 2011

A dynamic state realization for tightly coupling Global Positioning System (GPS) measurements with an Inertial Navigation System (INS) is described. The realization, based on the direct fusion of GPS and INS systems through Kalman filter state dynamics, explicitly accounts for temporal and spatial decorrelation of GPS measurement errors (such as tropospheric, ionospheric, and multipath errors) through state augmentation, thereby ensuring Kalman filter integrity under fault-free error conditions. Predicted system performance for a Local Area Augmentation System (LAAS) aircraft precision approach application is evaluated using covariance analysis and validated with flight data.

Built-in fault detection mechanisms based on the Kalman filter innovations are also evaluated to help provide integrity under certain fault conditions. It is shown that an algorithm based on the integral of Kalman filter innovations outperforms other existing GPS fault detection methods in the detection of slowly developing ranging errors, such as those caused by ionospheric and tropospheric anomalies.
The epidemiology of sporadic human infections with unusual cryptosporidia detected during routine typing in England and Wales, 2000–2008
Authors: ELWIN K. , HADFIELD S. J. , ROBINSON G. , CHALMERS R. M.
Published: June 2011

Routine typing of 14 469 isolates from human cryptosporidiosis cases between 2000 and 2008 revealed that 7439 (51·4%) were Cryptosporidium (C.) hominis, 6372 (44·0%) C. parvum, 51 (0·4%) both C. hominis and C. parvum, 443 (3·1%) were not typable and 164 (1·1%) were other Cryptosporidium species or genotypes. Of the latter, 109 were C. meleagridis, 38 C. felis, 11 C. ubiquitum, one C. canis, two horse, two novel and one skunk genotype. C. hominis monkey genotype and C. cuniculus were identified in a separate study. Patients with unusual infections were older than those with C. hominis (P<0·01) or C. parvum (P<0·01) and were more likely to be immunocompromised (Fisher's exact P<0·01). Forty-one percent of unusual cases had travelled abroad, mainly to the Indian subcontinent. Significant risk factors in those with unusual species were travel abroad (C. meleagridis, P<0·01), being immunocompromised (C. felis, Fisher's exact P=0·02), and contact with cats (C. felis, Fisher's exact P=0·02).
Burden of acute gastroenteritis and healthcare-seeking behaviour in France: a population-based study
Authors: VAN CAUTEREN D. , De VALK H. , VAUX S. , Le STRAT Y. , VAILLANT V.
Published: June 2011

In France surveillance underestimates the true burden of acute gastroenteritis (AG). We conducted a population-based, retrospective cross-sectional telephone survey between May 2009 and April 2010 in order to obtain more accurate estimates of the incidence and the burden of AG and to describe healthcare-seeking behaviour for AG. Of the 10 080 persons included in the survey, 260 respondents reported 263 episodes of AG. The incidence rate of AG was estimated at 0·33 cases/person-year (95% CI 0·28–0·37). It was highest in children aged <5 years and declined with age. Thirty-three percent (95% CI 27–40) of the AG cases consulted a physician and 76% (95% CI 70–82) used medication. Our results indicate that there are more than 21 million episodes of AG each year in France. These results allow a more accurate interpretation of the data derived from existing AG surveillance systems.
Amacrine-to-amacrine cell inhibition: Spatiotemporal properties of GABA and glycine pathways
Authors: CHEN XIN , HSUEH HAIN ANN , WERBLIN FRANK S.
Published: June 2011

We measured the spatial and temporal properties of GABAergic and glycinergic inhibition to amacrine cells in the whole-mount rabbit retina. The amacrine cells were parsed into two morphological classes: narrow-field cells with processes spreading less than 200μm and wide-field cells with processes extending more than 300μm. The inhibition was also parsed into two types: sustained glycine and transient GABA. Narrow-field amacrine cells receive 1) very transient GABAergic inhibition with a fast onset latency of 140 ± 16 ms decaying to 30% of the peak level within 208 ± 27 ms elicited broadly over a lateral distance of up to 1500μm and 2) sustained glycinergic inhibition with a medium onset latency of 286 ± 23 ms that was elicited over a spatial area often broader than the processes of the narrow-field amacrine cells. Wide-field amacrine cells received sustained glycinergic inhibition but no broad transient GABAergic inhibition. Surprisingly, neither of these amacrine cell classes received sustained local GABAergic inhibition, commonly found in an earlier study of ganglion cells.
IDENTITY AND INDISCERNIBILITY
Authors: KETLAND JEFFREY
Published: June 2011

The notion of strict identity is sometimes given an explicit second-order definition: objects with all the same properties are identical. Here, a somewhat different problem is raised:Under what conditions is the identity relation on the domain of a structure first-order definable? A structure may have objects that are distinct, but indiscernible by the strongest means of discerning them given the language (the indiscernibility formula). Here a number of results concerning the indiscernibility formula, and the definability of identity, are collected and a number of applications discussed.
Effects of a Group Program to Increase Cognitive Performance Through Cognitively Stimulating Leisure Activities in Healthy Older Subjects
Authors: Tesky Valentina A. , Thiel Christian , Banzer Winfried , Pantel Johannes
Published: June 2011

To investigate the effects of leisure activities on cognitive performance of healthy older subjects, an innovative intervention program was developed. Frequent participation in cognitively stimulating activities (i.e., reading, playing chess, or playing music) is associated with reduced risk of dementia. AKTIVA (active cognitive stimulation – prevention in the elderly) is an intervention program designed to enhance cognitive stimulation in everyday life by increasing cognitive stimulating leisure activities. The present study determines the effects of AKTIVA on cognitive function, mood and attitude toward aging in a sample of older participants from the general population. Several measurement instruments were used including the Alzheimer’s Disease Assessment Scale (ADAS-Cog), the Trail-Making Test (TMT), and the Memory Complaint Questionnaire (MAC-Q). Initially, the sample consisted of 307 older persons (170 female, 72 ± 7 years). The intervention was evaluated with a randomized, controlled pre-post follow-up design. Participants were randomly assigned to one of three conditions: AKTIVA intervention (n = 126), AKTIVA intervention plus nutrition and exercise counseling (n = 84), no-intervention control group (n = 97). The AKTIVA intervention consisted of 8 weekly sessions and two booster sessions after a break of 4 months. Participation in the group program resulted in positive effects on cognitive function and attitude toward aging for subassembly groups. Older persons (≥ 75 years) showed enhanced speed of information processing (by TMT Version A) (F = 4.17*, p < .05); younger participants (< 75 years) showed an improvement in subjective memory decline (by MAC-Q) (F = 2.55*, p < .05). Additionally, AKTIVA enhanced the frequency of activities for leisure activities for subassembly groups. The results of this study suggest that the AKTIVA program can be used to increase cognitively stimulating leisure activities in the elderly. Further research is necessary to identify the long-term effects of this intervention particularly with respect to the prevention of dementia.
Psychometrische Gütekriterien des Metakognitionsfragebogens (Kurzversion, MKF-30)
Authors: Arndt Antina , Patzelt Julia , Andor Tanja , Hoyer Jürgen , Gerlach Alexander L.
Published: June 2011

Zusammenfassung. Theoretischer Hintergrund: Metakognitionen wird für das Verständnis verschiedener psychischer Störungen eine wichtige Rolle beigemessen. So kann z.B. übermäßiges Sorgen durch Metakognitionen ausgelöst und aufrechterhalten werden. Fragestellung: Ziel dieser Arbeit war die systematische psychometrische Untersuchung der deutschen Kurzform des Metacognition Questionnaire (MKF-30). Methode: Mittels einer Teilstichprobe (N = 1168) wurde explorativ die Faktorenstruktur des MKF-30 ermittelt. Die ermittelte 5-Faktorenstruktur wurde anschließend konfirmiert (Teilstichprobe 2: N = 1155). Zur Konstruktvalidierung wurden Angst- sowie ein Depressionsfragebogen eingesetzt. Ergebnisse: Es ließen sich die fünf Faktoren des englischen Originals replizieren und konfirmieren. Die Analysen der Itemkennwerte sowie der konvergenten Validität lieferten insgesamt gute Ergebnisse. Schlussfolgerungen: Der MKF-30 kann vorläufig als ein reliables, valides und ökonomisches Instrument zur Erfassung von Metakognitionen angesehen werden.
Validierung einer deutschen Version der Self-Compassion Scale (SCS-D)
Authors: Hupfeld Jörg , Ruffieux Nicole
Published: June 2011

Zusammenfassung. Theoretischer Hintergrund: Self-Compassion bezeichnet eine positive Grundeinstellung gegenüber der eigenen Person in schwierigen Lebenssituationen. Dieses Persönlichkeitsmerkmal hat sich als wirksamer Schutzfaktor erwiesen, der die emotionale Resilienz fördert. In letzter Zeit wurden Therapieansätze entwickelt, in denen die Förderung von Self-Compassion eine zentrale Rolle einnimmt. Fragestellung: Wie gut sind die Gütekriterien der deutschen Übersetzung der Self-Compassion Scale (SCS-D)? Methode: Die 26-Item Skala wurde ins Deutsche übersetzt. An zwei Stichproben (396 und 165 Personen) wurden die dimensionale Struktur, Reliabilität und Validität der Skala überprüft. Ergebnisse: In Übereinstimmung mit den Ergebnissen zur Originalfassung zeigten sich für die SCS-D eine sechsfaktorielle Struktur und erwartungsgemäße Zusammenhänge mit psychischer Belastung und subjektivem Wohlbefinden. Schlussfolgerung: Mit der deutschen Übersetzung der SCS liegt ein Inventar vor, mit dem Self-Compassion ökonomisch, reliabel und valide erfasst werden kann.
Toll‐like receptor 2 siRNA suppresses corneal inflammation and attenuates Aspergillus fumigatus keratitis in rats
Authors: Guo Hui , Gao Jianlu , Wu Xinyi
Published: June 2011

Toll‐like receptors (TLRs) are key components of innate immunity that detect microbial infection and trigger host defense responses. However, they are capable of initiating both protective and damaging immune responses, as exaggerated expression of inflammatory components can have devastating effects on the host. We previously reported that TLR2 in corneal epithelium has an important role in the pathogenesis of fungal keratitis, however, how the corneal inflammation is modulated remains to be elucidated. This study aims to investigate the effect of targeting TLR2 on Aspergillus fumigatus keratitis in rats. The control or TLR2 small interfering RNA (siRNA) was applied sub‐conjunctively and topically to the cornea. TLR2 immunostaining was performed to determine the feasibility of TLR2 siRNA delivery. Production of inflammatory cytokines and chemokines were determined by real‐time quantitative PCR. Polymorphonuclear leukocyte (PMN) infiltration was assessed by myeloperoxidase activity. It was found that rat corneas treated with TLR2 siRNA showed a significant reduction of TLR2 expression in corneal epithelium. TLR2 siRNA treatment improved the outcome of keratitis, which was characterized by decreased corneal opacity, less corneal perforation, suppressed PMN infiltration, reduced production of inflammatory cytokines and chemokines, and less fungal burden. In conclusion, TLR2 siRNA treatment attenuated A. fumigatus keratitis by suppressing corneal inflammation and preventing fungal invasion, suggesting a novel avenue to control fungal infection and avert damage caused by excessive inflammation.
Evaluation of a Telephone Speech-Enhancement Algorithm Among Older Adults With Hearing Loss
Authors: Roup Christina M. , Poling Gayla L. , Harhager Kimberly , Krishnamurthy Ashok , Feth Lawrence L.
Published: June 2011

Purpose

In this study, the authors evaluated a processing algorithm aimed at improving speech recognition via the telephone among older adults with sensorineural hearing loss (SNHL).

Method

Thirty older adults with SNHL participated. Speech recognition was measured in quiet using the Modified Rhyme Test (MRT; Kreul et al., 1968) and the Speech Perception in Noise (SPIN; Bilger et al., 1984) sentences, and in noise using the Quick Speech in Noise (QSIN; Killion et al., 2004) test. Each test was presented via the telephone with and without processing.

Results

Significant improvements in recognition performance due to processing were observed for the SPIN and QSIN. The improvement on the QSIN was significantly greater than on the MRT and SPIN, likely because the MRT and SPIN sentences were presented in quiet, whereas the QSIN was presented in noise. Significant improvements in recognition performance were observed for both an offline version and a real-time version of the algorithm relative to the unprocessed condition, although no difference was noted between the 2 versions.

Conclusions

Results indicate that preprocessing the acoustic signal is a viable method of improving speech recognition via the telephone. The algorithm has the potential to benefit older adults with SNHL who struggle to communicate via the telephone with or without hearing aids.
Multi-particle and tetrad statistics in numerical simulations of turbulent relative dispersion
Authors: Hackl J. F. , Yeung P. K. , Sawford B. L.
Published: June 2011

The evolution in size and shape of three and four-particle clusters (triangles and tetrads, respectively) in isotropic turbulence is studied using direct numerical simulations at grid resolution up to 40963 and Taylor-scale Reynolds numbers from 140 to 1000. A key issue is the attainment of inertial range behavior at high Reynolds number, while the small- and large-time limits of ballistic and diffusive regimes, respectively, are also considered in some detail. Tetrad size expressed by the volume (V) and (more appropriately) the gyration radius (R) is shown to display inertial range scaling consistent with a Richardson constant close to 0.56 for two-particle relative dispersion. For tetrads of initial size in a suitable range moments of shape parameters, including the ratio V2/3/R2 and normalized eigenvalues of a moment-of-inertia-like dispersion tensor, show a regime of near-constancy which is identified with inertial-range scaling. Sheet-like structures are dominant in this period, while pancakes and needles are more prevalent at later times. For triangles taken from different faces of each tetrad effects of the initial shape (isosceles right-angled or equilateral) are retained only for about one Batchelor time scale. In the inertial range there is a prevalence of nearly isosceles triangles of two long sides and one short side, representing one particle moving away from the other two which are still close together. In general, measures of shape display asymptotic scaling ranges more readily than measures of size. With some caveats, the simulation results are also compared with the limited literature available for multiparticle cluster dispersion in turbulent flow.
Influence of external traveling-wave magnetic field on trapped field of a high temperature superconducting bulk magnet used in a linear synchronous motor
Authors: Jin Jianxun , Zheng Luhai , Xu Wei , Guo Youguang , Zhu Jianguo
Published: June 2011

A single-sided high temperature superconducting (HTS) linear synchronous motor (HTSLSM) has been developed with a pulse magnetization system to obtain the HTS bulk magnet array with alternating magnetic poles for the motor secondary. In order to identify the trapped field characteristics of the HTS bulk magnet exposed to the external traveling-wave magnetic field generated by the primary of the HTSLSM, a measurement system has been built up and the relevant experiments have been carried out. The relationships between the trapped field attenuation of the HTS bulk magnet and the amplitude, frequency and acting direction of the external traveling-wave magnetic field are experimentally obtained to allow the HTSLSM characteristics to be practically verified.
A state-specific partially internally contracted multireference coupled cluster approach
Authors: Datta Dipayan , Kong Liguo , Nooijen Marcel
Published: June 2011

A state-specific partially internally contracted multireference coupled cluster approach is presented for general complete active spaces with arbitrary number of active electrons. The dominant dynamical correlation is included via an exponential parametrization of internally contracted cluster operators (\documentclass[12pt]{minimal}\begin{document}$\hat{T}$\end{document}T̂) which excite electrons from a multideterminantal reference function. The remaining dynamical correlation and relaxation effects are included via a diagonalization of the transformed Hamiltonian \documentclass[12pt]{minimal}\begin{document}${\smash{\hat{\overline{H}}=e^{-\hat{T}}\hat{H}e^{\hat{T}}}}$\end{document}H¯̂=e−T̂ĤeT̂ in the multireference configuration interaction singles space in an uncontracted fashion. A new set of residual equations for determining the internally contracted cluster amplitudes is proposed. The second quantized matrix elements of \documentclass[12pt]{minimal}\begin{document}${\smash{\hat{\overline{H}}}}$\end{document}H¯̂, expressed using the extended normal ordering of Kutzelnigg and Mukherjee, are used as the residual equations without projection onto the excited configurations. These residual equations, referred to as the many-body residuals, do not have any near-singularity and thus, should allow one to solve all the amplitudes without discarding any. There are some relatively minor remaining convergence issues that may arise from an attempt to solve all the amplitudes and an initial analysis is provided in this paper. Applications to the bond-stretching potential energy surfaces for N2, CO, and the low-lying electronic states of C2 indicate clear improvements of the results using the many-body residuals over the conventional projected residual equations.
Morphological and chemical influences on alumina-supported palladium catalysts active for the gas phase hydrogenation of crotonaldehyde
Authors: McInroy A. R. , Uhl A. , Lear T. , Klapötke T. M. , Shaikhutdinov S. , Schauermann S. , Rupprechter G. , Freund H.-J. , Lennon D.
Published: June 2011

A series of five alumina-supported palladium catalysts have previously been prepared and characterised by a combination of CO chemisorption and infrared spectroscopy. The reactive attributes of these catalysts are examined using the hydrogenation of crotonaldehyde as a test reaction, using a modified infrared gas cell as a batch reactor. Periodic scanning of the infrared spectrum of the gaseous phase present over the Pd/Al2O3 catalysts was used to construct reaction profiles. Four of the catalysts were able to facilitate a 2-stage hydrogenation process (crotonaldehyde → butanal → butanol), whilst one catalyst was totally selective for the first stage hydrogenation process (crotonaldehyde → butanal). Rate coefficients for the first and second stage hydrogenation processes are normalised to the number of surface palladium atoms for the particular catalyst. Correlation of these kinetic parameters as a function of mean particle size indicates the first stage process to be structure insensitive, whilst the second stage hydrogenation is structure sensitive. Chlorine residues associated with the preparative process of one of the catalysts is seen to selectively poison the second stage hydrogenation process for that catalyst. Structure/activity relationships are considered to explain the observed trends.
Thiolene-based microfluidic flow cells for surface plasmon resonance imaging
Authors: Sheppard Gareth , Oseki Takao , Baba Akira , Patton Derek , Kaneko Futao , Mao Leidong , Locklin Jason
Published: June 2011

Thiolene-based microfluidic devices have been coupled with surface plasmon resonance imaging (SPRI) to provide an integrated platform to study interfacial interactions in both aqueous and organic solutions. In this work, we develop a photolithographic method that interfaces commercially available thiolene resin to gold and glass substrates to generate microfluidic channels with excellent adhesion that leave the underlying sensor surface free from contamination and readily available for surface modification through self-assembly. These devices can sustain high flow rates and have excellent solvent compatibility even with several organic solvents. To demonstrate the versatility of these devices, we have conducted nanomolar detection of streptavidin-biotin interactions using in situ SPRI.
Detection of organophosphorus compound based on a sol–gel silica planar waveguide doped with a green fluorescent protein and an organophosphorus hydrolase
Authors: Enami Y. , Tsuchiya K. , Suye S.
Published: June 2011

In this letter, the authors report the real-time detection of an organophosphorus compound using a sol–gel silica planar waveguide doped with a green fluorescent protein and an organophosphorus hydrolase on a yeast-cell surface display. The waveguide was pumped at 488 nm, and it emitted green fluorescence at the far field. The green fluorescent light at 550 nm changed by 50% from the original power 1 min after application of the organophosphorus compound. The results enable the real-time detection of sarin and other biochemicals by using an in-line fiber sensor network.
A graph-theoretical kinetic Monte Carlo framework for on-lattice chemical kinetics
Authors: Stamatakis Michail , Vlachos Dionisios G.
Published: June 2011

Existing kinetic Monte Carlo (KMC) frameworks for the simulation of adsorption, desorption, diffusion, and reaction on a lattice often assume that each participating species occupies a single site and represent elementary events involving a maximum of two sites. However, these assumptions may be inadequate, especially in the case of complex chemistries, involving multidentate species or complex coverage and neighboring patterns between several lattice sites. We have developed a novel approach that employs graph-theoretical ideas to overcome these challenges and treat easily complex chemistries. As a benchmark, the Ziff-Gulari-Barshad system is simulated and comparisons of the computational times of the graph-theoretical KMC and a simpler KMC approach are made. Further, to demonstrate the capabilities of our framework, the water-gas shift chemistry on Pt(111) is simulated.
Ultrafast spectroscopy with a scanning tunneling microscope
Authors: Moult Ian , Herve Marie , Pennec Yan
Published: June 2011

We present a method combining a scanning tunneling microscope and a pulse generator to achieve unprecedented spatiotemporal resolution for spectroscopy at surfaces. Using the so-called pulsed scanning tunneling spectroscopy (P-STS) we identify the stacking schemes at the surface of graphite with a probe time down to 300 ps while conserving atomic resolution. The technique is simple to implement and requires only increasing the signal bandwidth on the bias side of the tunneling junction. We foresee the P-STS as a highly versatile dynamical probe which could be applied to track in time the variation in the sample local density of states induced by any possible excitation.
Phonostat: Thermostatting phonons in molecular dynamics simulations
Authors: Raghunathan Rajamani , Greaney P. Alex , Grossman Jeffrey C.
Published: June 2011

Thermostat algorithms in a molecular dynamics simulation maintain an average temperature of a system by regulating the atomic velocities rather than the internal degrees of freedom. Herein, we present a “phonostat” algorithm that can regulate the total energy in a given internal degree of freedom. In this algorithm, the modal energies are computed at each time step using a mode-tracking scheme and then the system is driven by an external driving force of desired frequency and amplitude. The rate and amount of energy exchange between the phonostat and the system is controlled by two distinct damping parameters. Two different schemes for controlling the external driving force amplitude are also presented. In order to test our algorithm, the method is applied initially to a simple anharmonic oscillator for which the role of various phonostat parameters can be carefully tested. We then apply the phonostat to a more realistic (10,0) carbon nanotube system and show how such an approach can be used to regulate energy of highly anharmonic modes.
Comparing Single and Joint Preferences: A Choice Experiment on Residential Location in Three-Member Households
Authors: Marcucci Edoardo , Stathopoulos Amanda , Rotaris Lucia , Danielis Romeo
Published: June 2011

There is growing evidence indicating that there can be significant differences between choices made by single individuals and those made by the same individuals when choosing collectively. This study investigates the dissimilarities between individual and joint decision making in the context of residential location choice. It is widely recognised that household location choices involve several members of a household with heterogeneous preferences and influence. Nonetheless, little is known about group decision-making processes in practice. In particular, there is only scant evidence on how preferences differ among family members and to what extent individual preferences can be aggregated to achieve an approximation of joint choices. The paper addresses the issue of heterogeneity in single members' preferences, compares ex ante single preferences and ex post joint choice outcomes, and quantifies the implicit bias generated by relying on the representative member approach. A set of hypotheses is tested via a two-stage conjoint choice experiment administered to a sample of seventy-eight Italian families. The main novelty of the paper relates to the extension of the dyadic interaction approach to consider the role of adolescents in household decision making.
Loss of Bardet–Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization, and axon targeting
Authors: Tadenev Abigail L. D. , Kulaga Heather M. , May-Simera Helen L. , Kelley Matthew W. , Katsanis Nicholas , Reed Randall R.
Published: June 2011

Bardet–Biedl syndrome (BBS) is a pleiotropic, heterogeneous human disease whose etiology lies primarily in dysfunctional basal bodies and/or cilia. Both BBS patients and several BBS mouse models exhibit impaired olfactory function. To explore the nature of olfactory defects in BBS, a genetic ablation of the mouse
Bbs8
gene that incorporates a fluorescent reporter protein was created. The endogenous BBS8 protein and reporter are particularly abundant in olfactory sensory neurons (OSNs), and specific BBS8 antibodies reveal staining in the dendritic knob in a shell-like structure that surrounds the basal bodies.
Bbs8
-null mice have reduced olfactory responses to a number of odorants, and immunohistochemical analyses reveal a near-complete loss of cilia from OSNs and mislocalization of proteins normally enriched in cilia. To visualize altered protein localization in OSNs, we generated a

SLP3
eGFP

knock-in mouse and imaged the apical epithelium, including dendritic knobs and proximal cilia, in ex vivo tissue preparations. Additionally, protein reagents that reflect the characteristic neuronal activity of each OSN revealed altered activity in
Bbs8
-null cells. In addition to previously known defects at the ciliary border, we also observed aberrant targeting of OSN axons to the olfactory bulb; axons expressing the same receptor display reduced fasciculation and project to multiple targets in the olfactory bulb. We suggest that loss of BBS8 leads to a dramatic and variable reduction in cilia, the essential signaling platform for olfaction, which alters the uniformity of responses in populations of OSNs expressing the same receptor, thereby contributing to the observed axon-targeting defects.
Preexisting drug-resistance mutations reveal unique barriers to resistance for distinct antivirals
Authors: Robinson Margaret , Tian Yang , Delaney William E. , Greenstein Andrew E.
Published: June 2011

Clinical trials of direct-acting antiviral agents in patients chronically infected with hepatitis C virus (HCV) have demonstrated that viral resistance is detected rapidly during monotherapy. In patients, HCV does not exist as a single, genetically homogenous virus but rather as a population of variants termed “quasispecies.” Preexisting variants resistant to specific antiviral drugs, overlooked in traditional hit-to-lead discovery efforts, may be responsible for these poor clinical outcomes. To enable real-time studies of resistance emergence in live cells, we established fluorescent protein-labeled HCV replicon cell lines. We validated these cell lines by demonstrating that antiviral susceptibility and the selection of signature resistance mutations for various drug classes are similar to traditional replicon cell lines. By quantifying the kinetics and uniformity of replication within colonies of drug-resistant fluorescent replicon cells, we showed that resistance emerged from a single cell and preexisted in a treatment-naive replicon population. Within this population, we determined the relative frequency of preexisting replicons capable of establishing foci during treatment with distinct antivirals. By measuring relative frequency as a function of dose, we quantitatively ranked distinct antiviral molecules on the basis of their distinct barriers to resistance. These insights into RNA virus quasispecies structure provide guidance for selecting clinical drug concentrations and selecting antiviral drug combinations most likely to suppress resistance.
Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations
Authors: Buch Ignasi , Giorgino Toni , De Fabritiis Gianni
Published: June 2011

The understanding of protein–ligand binding is of critical importance for biomedical research, yet the process itself has been very difficult to study because of its intrinsically dynamic character. Here, we have been able to quantitatively reconstruct the complete binding process of the enzyme-inhibitor complex trypsin-benzamidine by performing 495 molecular dynamics simulations of free ligand binding of 100 ns each, 187 of which produced binding events with an rmsd less than 2 Å compared to the crystal structure. The binding paths obtained are able to capture the kinetic pathway of the inhibitor diffusing from solvent (S0) to the bound (S4) state passing through two metastable intermediate states S2 and S3. Rather than directly entering the binding pocket the inhibitor appears to roll on the surface of the protein in its transition between S3 and the final binding pocket, whereas the transition between S2 and the bound pose requires rediffusion to S3. An estimation of the standard free energy of binding gives ΔG° = -5.2 ± 0.4 kcal/mol (cf. the experimental value -6.2 kcal/mol), and a two-states kinetic modelkon = (1.5 ± 0.2) × 108 M-1 s-1andkoff = (9.5 ± 3.3) × 104 s-1for unbound to bound transitions. The ability to reconstruct by simple diffusion the binding pathway of an enzyme-inhibitor binding process demonstrates the predictive power of unconventional high-throughput molecular simulations. Moreover, the methodology is directly applicable to other molecular systems and thus of general interest in biomedical and pharmaceutical research.
Interference by clustered regularly interspaced short palindromic repeat (CRISPR) RNA is governed by a seed sequence
Authors: Semenova Ekaterina , Jore Matthijs M. , Datsenko Kirill A. , Semenova Anna , Westra Edze R. , Wanner Barry , van der Oost John , Brouns Stan J. J. , Severinov Konstantin
Published: June 2011

Prokaryotic clustered regularly interspaced short palindromic repeat (CRISPR)/Cas (CRISPR-associated sequences) systems provide adaptive immunity against viruses when a spacer sequence of small CRISPR RNA (crRNA) matches a protospacer sequence in the viral genome. Viruses that escape CRISPR/Cas resistance carry point mutations in protospacers, though not all protospacer mutations lead to escape. Here, we show that in the case of
Escherichia coli
subtype CRISPR/Cas system, the requirements for crRNA matching are strict only for a seven-nucleotide seed region of a protospacer immediately following the essential protospacer-adjacent motif. Mutations in the seed region abolish CRISPR/Cas mediated immunity by reducing the binding affinity of the crRNA-guided Cascade complex to protospacer DNA. We propose that the crRNA seed sequence plays a role in the initial scanning of invader DNA for a match, before base pairing of the full-length spacer occurs, which may enhance the protospacer locating efficiency of the
E. coli
Cascade complex. In agreement with this proposal, single or multiple mutations within the protospacer but outside the seed region do not lead to escape. The relaxed specificity of the CRISPR/Cas system limits escape possibilities and allows a single crRNA to effectively target numerous related viruses.
Morphology, body proportions, and postcranial hypertrophy of a female Neandertal from the Sima de las Palomas, southeastern Spain
Authors: Walker Michael J. , Ortega Jon , Parmová Klara , López Mariano V. , Trinkaus Erik
Published: June 2011

Considerations of Neandertal geographical variation have been hampered by the dearth of remains from Mediterranean Europe and the absence there of sufficiently complete associated postcrania. The 2006 and 2007 excavation of an articulated partial skeleton of a small adult female Neandertal at the Sima de las Palomas, Murcia, southeastern Spain (Sima de las Palomas 96) provides substantial and secure information on body proportions among southern European Neandertals, as well as further documenting the nature of Neandertal biology in southern Iberia. The remains exhibit a suite of cranial, mandibular, dental, and postcranial features, of both Neandertals and archaicHomogenerally, that distinguish them from contemporary and subsequent early modern humans. Its lower limbs exhibit the robustness of later PleistoceneHomogenerally, and its upper limbs conform to the pattern of elevated robustness of the Neandertals. Its body proportions, including relative clavicular length, distal limb segment lengths, and body mass to stature indicators, conform to the “cold-adapted” pattern of more northern Neandertals. Palomas 96 therefore documents the presence of a suite of “Neandertal” characteristics in southern Iberia and, along with its small body size, the more “Arctic” body proportions of other European Neandertals despite the warmer climate of southern Iberia during marine isotope stage 3.
SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses
Authors: Knosp Camille A. , Carroll Helen P. , Elliott Joanne , Saunders Sean P. , Nel Hendrik J. , Amu Sylvie , Pratt Joanne C. , Spence Shaun , Doran Emma , Cooke Nicola , Jackson Ruaidhri , Swift Jonathan , Fitzgerald Denise C. , Heaney Liam G. , Fallon Padraic G. , Kissenpfennig Adrien , Johnston James A.
Published: June 2011

The incidence of allergy and asthma in developed countries is on the increase and this trend looks likely to continue. CD4+ T helper 2 (Th2) cells are major drivers of these diseases and their commitment is controlled by cytokines such as interleukin 4, which are in turn regulated by the suppressor of cytokine signaling (SOCS) proteins. We report that SOCS2−/− CD4+ T cells show markedly enhanced Th2 differentiation. SOCS2−/− mice, as well as RAG-1−/− mice transferred with SOCS2−/− CD4+ T cells, exhibit elevated type 2 responses after helminth antigen challenge. Moreover, in in vivo models of atopic dermatitis and allergen-induced airway inflammation, SOCS2−/− mice show significantly elevated IgE, eosinophilia, type 2 responses, and inflammatory pathology relative to wild-type mice. Finally, after T cell activation, markedly enhanced STAT6 and STAT5 phosphorylation is observed in SOCS2−/− T cells, whereas STAT3 phosphorylation is blunted. Thus, we provide the first evidence that SOCS2 plays an important role in regulating Th2 cell expansion and development of the type 2 allergic responses.
Ibn Khaldun
Authors: Leezenberg Michael
Published: June 2011

Although Ibn Khaldun (b. 732/1332–d. 808/1406) does not appear to have exerted any constitutive influence on any of the founders of the modern social sciences, he is often described as a precursor or ancestor of sociology. Among others, he is the author of a voluminous world history, the Kitāb al-ʿibar or Book of Examples, part of which is a chronicle of the various local dynasties—many of them of Berber extraction—in North Africa. Another part of this work deals with other Muslim lands, and even with the non-Muslim world, making it one of the first Islamic attempts at world history. By far the most famous part of this book, however, is the Muqaddimah, or introduction, in which Ibn Khaldun formulates the principles of what he himself described as a new science serving as an auxiliary for historiography. This ʿilm al- ʿumran, or “science of civilization” as he called it, attempts to formulate general laws of history, as a principled means of establishing the veracity of historical reports. The most important of these laws is the circular, or pendulum-swing, movement between rural or tribal (badawa) societies and urban civilizations (hadara). Rural societies are bound together and strengthened by a bond of ʿasabiyya (solidarity or group spirit), which also enables them to conquer more refined urban civilizations. Once in power, however, the new dynasty will progressively become weakened by the refinements of urban life, and after several generations it will be overthrown by a new rural group still held together by its ʿasabiyya. Among contemporaries, Ibn Khaldun’s ideas did not generate much interest, but in later centuries he has been read with great interest by both scholars and policymakers, and both inside and outside the Muslim world.
First and Second Chronicles
Authors: Tuell Steven Shawn
Published: June 2011

Although divided into two books in modern Bibles (a division dating to the Septuagint), Chronicles was originally a single book. In Jewish Bibles, Chronicles closes the canon, coming at the end of the Kethubim (Writings) after Ezra-Nehemiah; there, the mention of Adam at the beginning of its genealogies (1 Chr 1:1) provides a neat parallel to Genesis, the first book of the Bible. In Christian Bibles, Chronicles is placed where it appears in the Septuagint: grouped with other “historical” books, following 2 Kings and preceding Ezra and Nehemiah. The content of Chronicles is arranged in four parts. The book begins with a collection of genealogical lists (1 Chr 1–9), spanning from Adam to Anani, seventh son in the seventh generation of David’s line after the Babylonian exile (1 Chr 3:24). Then Chronicles relates the stories of David (1 Chr 10–29), Solomon (2 Chr 1–9), and the kings of Judah in David’s line, from the dissolution of the united monarchy to the fall of Jerusalem (2 Chr 10–36). But the emphasis on David’s line has more to do with religion than with politics. Although Solomon builds the temple and sets its cult in motion, David is architect of the temple and author of its liturgy. David’s descendants, charged with preserving the temple and the worship of the Lord conducted there, are praised for their faithfulness, or cursed for their faithlessness. The destruction of the temple and the fall of Jerusalem are blamed upon the failure to seek the Lord in Scripture and in worship, as David had done. Therefore, the community of Chronicles, living in the days of the second, rebuilt temple, is warned to avoid the mistakes of their forebears and urged to be faithful to their ancient heritage. In recent years, Chronicles scholarship has undergone a renaissance and a considerable shift in emphasis. Until about forty years ago, it was assumed that Chronicles and Ezra-Nehemiah had been composed together, probably in the late fifth or early fourth century bce. This Chronicler’s history was understood to share a common theological perspective and common attitudes regarding what constitutes the people of Israel. However, the work of Japhet and Williamson in particular (see Japhet 1971 [cited under General Overviews], Japhet 1993 and Williamson 1982 [both cited under Commentaries], Japhet 1989 and Williamson 1996 [both cited under Relationship with Ezra-Nehemiah], Williamson 1977 [cited under Theological Perspective]) has effected a shift in the consensus and the reopening of some questions once considered closed. The mainstream of contemporary scholarship now regards Chronicles and Ezra-Nehemiah as separate works, with divergent composition histories and theologies. Chronicles is dated by some as late as the third or second century bce and by others as early as the fifth. As a result, the study of these once-ignored texts has become an exciting and sometimes heated conversation, marked by the convergence of studies in text criticism, ancient historiography, the composition of Scripture, and the history of Israelite religion in the Persian and Hellenistic Periods.
Jeremiah
Authors: Sweeney Marvin A. , Birdsong Shelley
Published: June 2011

The Book of Jeremiah is the second of the major prophetic books of the Hebrew Bible, although Rabbinic tradition sometimes places it first following Kings and prior to Ezekiel due to its thematic focus on destruction (b. Baba Batra 14b–15a). It presents the words of the prophet, Jeremiah son of Hilkiah, who lived in Jerusalem during the reigns of the Judean kings, Josiah (640–609 bce), Jehoahaz (609 bce), Jehoiakim (609–598 bce), Jehoiachin (597 bce), and Zedekiah (597–587 or 586 bce). Jeremiah was a Levitical priest from Anathoth, who resided in Jerusalem during the last years of the kingdom of Judah. Major events during the period ascribed to Jeremiah include the outset of King Josiah’s reforms (c. 628 bce), the death of Josiah (609 bce), the Babylonian subjugation of Judah (605 bce), Nebuchadnezzar’s first deportation of Jews to Babylon (597 bce), the Babylonian destruction of Jerusalem (587–586 bce), and the assassination of Gedaliah (582 bce). Jeremiah interpreted the Babylonian subjugation of Jerusalem in 605 bce and the later destruction of Jerusalem in 587 or 586 bce as acts of punishment by YHWH, the G-d of Israel and Judah, for the people’s alleged failure to observe the divine will. Although the book of Jeremiah is largely concerned with destruction, it also holds out hope for the restoration of Israel and Jerusalem, especially in Jeremiah 30–33. The book appears in two very distinctive forms from antiquity. The Hebrew Masoretic text (MT) is the standard form of Jeremiah in Jewish Bibles, but the Greek Septuagint (LXX) form of the book is approximately one-eighth shorter and displays a very different arrangement of materials (e.g., the oracles concerning the nations in MT Jeremiah 46–51 appear following portions of Jeremiah 25 in the LXX form of the book). The Dead Sea Scrolls likewise include remnants of early Hebrew forms of both of these versions. Scholarly consensus maintains that both versions grew out of a common original text, although the issue is still debated.