bluuebunny/crossref_metadata_2025 huggingface dataset:
BAFF and innate immunity: new therapeutic targets for systemic lupus erythematosus
Authors: Vincent Fabien B , Morand Eric F , Mackay Fabienne
Published: January 2012

Recently, the B cell has emerged as a cornerstone of systemic lupus erythematosus (SLE) pathogenesis. This has been highlighted by studies of the cytokine B‐cell‐activating factor of the tumour necrosis factor (TNF) family (BAFF), a crucial factor regulating B‐cell maturation, survival and function. Overexpression of BAFF in mice leads to the development of an SLE‐like disease, independent of T cells but instead relying on innate immunity mechanisms. Moreover, BAFF has been shown to be elevated in the serum of patients suffering from autoimmune conditions, especially SLE, and may correlate with disease activity. These findings challenge the previous notion that T:B‐cell collaboration is the sole driver of SLE. In recent years, controlled trials have for the first time tested targeted therapeutics for SLE. However, agents designed to target B cells failed to meet primary endpoints in clinical trials in SLE, suggesting that a more complex role for B cells in SLE awaited elucidation. By contrast, on 9 March 2011, the US Food and Drug Administration approved belimumab, a fully human anti‐BAFF monoclonal antibody, as a new B‐cell‐specific treatment for SLE. This article will review over 10 years of research on the BAFF system, key findings that led to this recent positive clinical outcome and propose a model potentially explaining why this B‐cell‐specific therapy has yielded positive results in clinical trials. We will also review promising therapies presently in clinical trials targeting innate immunity, which are likely to revolutionize SLE management towards a personalized and targeted therapy approach.
Isoglitter
Authors: Bucknum Michael , Castro Eduardo , Wen Bin
Published: January 2012

Described herein is a novel crystalline pattern in space group Ammm, that is a model of a C allotrope. This so-called isoglitter structure-type is an analogue to the graphite-diamond hybrids. A DFT geometry optimization and band structure calculation indicates that the lattice is metallic in a C realization.
Enhancement in Informational Masking
Authors: Cao Xiang , Richards Virginia M.
Published: January 2012

Purpose

The ability to detect a tone added to a random masker improves when a preview of the masker is provided. In 2 experiments, the authors explored the role that perceptual organization plays in this release from masking.

Method

Detection thresholds were measured in informational masking studies. The maskers were drawn at random prior to each trial. Masker or signal-plus-masker precursors preceded the detection interval, and the time between the precursor and the detection interval was systematically altered. In
Experiment 1
, the signal frequency was either fixed or random. In
Experiment 2
, the random masker was composed of harmonics of a common fundamental frequency (F
0
), and the randomly chosen signal frequency was either harmonically related to, or mistuned from, the masker’s F
0
.

Results

For a masker precursor, the release from informational masking withstood longer precursor-detection interval delays (a) when the signal frequency was fixed versus random and (b) when the signal was mistuned relative to a harmonic of the masker’s F
0
.

Conclusion

These results suggest that listeners' ability to attend to the signal may contribute to the long-lived release from masking with a masker precursor.
Syntactic Structural Assignment in Brazilian Portuguese-Speaking Children With Specific Language Impairment
Authors: Fortunato-Tavares Talita , de Andrade Claudia R. F. , Befi-Lopes Debora M. , Hestvik Arild , Epstein Baila , Tornyova Lidiya , Schwartz Richard G.
Published: January 2012

Purpose

In this study, the authors examined the comprehension of sentences with predicates and reflexives that are linked to a nonadjacent noun as a test of the hierarchical ordering deficit (HOD) hypothesis. That hypothesis and more modern versions posit that children with specific language impairment (SLI) have difficulty in establishing nonadjacent (hierarchical) relations among elements of a sentence. The authors also tested whether additional working memory demands in constructions containing reflexives affected the extent to which children with SLI incorrectly structure sentences as indicated by their picture-pointing comprehension responses.

Method

Sixteen Brazilian Portuguese-speaking children (8;4–10;6 [years;months]) with SLI and 16 children with typical language development (TLD) matched for age (±3 months), gender, and socioeconomic status participated in 2 experiments (predicate and reflexive interpretation). In the reflexive experiment, the authors also manipulated working memory demands. Each experiment involved a 4-choice picture selection sentence comprehension task.

Results

Children with SLI were significantly less accurate on all conditions. Both groups made more hierarchical syntactic construction errors in the long working memory condition than in the short working memory condition.

Conclusion

The HOD hypothesis was not confirmed. For both groups, syntactic factors (structural assignment) were more vulnerable than lexical factors (prepositions) to working memory effects in sentence miscomprehension.
Longitudinal Stability in Genetic Effects on Children's Conversational Language Productivity
Authors: DeThorne Laura Segebart , Harlaar Nicole , Petrill Stephen A. , Deater-Deckard Kirby
Published: January 2012

Purpose

The authors examined the longitudinal stability of genetic and environmental influences on children's productive language sample measures during the early school-age years.

Method

Twin study methodology with structural equation modeling was used to derive univariate estimates of additive genetic (A), shared environmental (C), and nonshared environmental (E) effects on language measures at each of 2 time points, based on 487 twins at the 1st-grade time point and 387 twins at the 2nd-grade time point. To address questions of stability over time, the authors used longitudinal latent factor analysis.

Results

Stability in the Conversational Language factor was accounted for almost entirely by shared genetic effects between 1st and 2nd grade, meaning no new genetic effects were observed at the 2nd time point. In contrast, nonshared environmental effects were entirely time point specific, meaning whatever nonshared environmental influences were operating at the first time point were not influencing individual variation in the language factor at the second time point.

Conclusion

The discussion in this article centers on possible candidates for both genetic and nonshared environmental effects as well as implications for clinical practice and future research.
Tackling the Combined Effects of Reverberation and Masking Noise Using Ideal Channel Selection
Authors: Hazrati Oldooz , Loizou Philipos C.
Published: January 2012

Purpose

In this article, a new signal-processing algorithm is proposed and evaluated for the suppression of the combined effects of reverberation and noise.

Method

The proposed algorithm decomposes, on a short-term basis (every 20 ms), the reverberant stimuli into a number of channels and retains only a subset of the channels satisfying a signal-to-reverberant ratio (SRR) criterion. The construction of this criterion assumes access to a priori knowledge of the target (anechoic) signal, and the aim of this study was to assess the full potential of the proposed channel-selection algorithm, assuming that this criterion could be estimated accurately. Listening tests with normal-hearing listeners were conducted to assess the performance of the proposed algorithm in highly reverberant conditions (
T
60
= 1.0 s), which included additive noise at 0 and 5 dB signal-to-noise ratios (SNRs).

Results

A substantial gain in intelligibility was obtained in both reverberant and combined reverberant and noise conditions. The mean intelligibility scores improved by 44 and 33 percentage points at 0 and 5 dB SNR reverberation + noise conditions. Feature analysis of the consonant confusion matrices revealed that the transmission of voicing information was most negatively affected, followed by manner and place of articulation.

Conclusions

The proposed algorithm produced substantial gains in intelligibility, and this benefit was attributed to the ability of the proposed SRR criterion to detect accurately voiced or unvoiced boundaries. It was postulated that detection of those boundaries is critical for better perception of voicing information and manner of articulation.
Effects of Sampling Context on Spontaneous Expressive Language in Males With Fragile X Syndrome or Down Syndrome
Authors: Kover Sara T. , McDuffie Andrea , Abbeduto Leonard , Brown W. Ted
Published: January 2012

Purpose

In this study, the authors examined the impact of sampling context on multiple aspects of expressive language in male participants with fragile X syndrome in comparison to male participants with Down syndrome or typical development.

Method

Participants with fragile X syndrome (n= 27), ages 10–17 years, were matched groupwise on nonverbal mental age to adolescents with Down syndrome (n= 15) and typically developing 3- to 6-year-olds (n= 15). Language sampling contexts were an interview-style conversation and narration of a wordless book, with scripted examiner behavior. Language was assessed in terms of amount of talk, mean length of communication unit (MLCU), lexical diversity, fluency, and intelligibility.

Results

Participants with fragile X syndrome had lower MLCU and lexical diversity than did participants with typical development. Participants with Down syndrome produced yet lower MLCU. A differential effect of context among those with fragile X syndrome, Down syndrome, and typical development emerged for the number of attempts per minute, MLCU, and fluency. For participants with fragile X syndrome, autism symptom severity related to the number of utterances produced in conversation. Aspects of examiner behavior related to participant performance.

Conclusion

Sampling context characteristics should be considered when assessing expressive language in individuals with neurodevelopmental disabilities.
Fundamental Approaches in Molecular Biology for Communication Sciences and Disorders
Authors: Bartlett Rebecca S. , Jetté Marie E. , King Suzanne N. , Schaser Allison , Thibeault Susan L.
Published: January 2012

Purpose

This contemporary tutorial will introduce general principles of molecular biology, common deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein assays and their relevance in the field of communication sciences and disorders.

Method

Over the past 2 decades, knowledge of the molecular pathophysiology of human disease has increased at a remarkable pace. Most of this progress can be attributed to concomitant advances in basic molecular biology and, specifically, the development of an ever-expanding armamentarium of technologies for analysis of DNA, RNA, and protein structure and function. Details of these methodologies, their limitations, and examples from the communication sciences and disorders literature are presented.

Results/Conclusions

The use of molecular biology techniques in the fields of speech, language, and hearing sciences is increasing, facilitating the need for an understanding of molecular biology fundamentals and common experimental assays.
Aging and the 4-kHz Air–Bone Gap
Authors: Nondahl David M. , Tweed Ted S. , Cruickshanks Karen J. , Wiley Terry L. , Dalton Dayna S.
Published: January 2012

Purpose

In this study, the authors assessed age- and sex-related patterns in the prevalence and 10-year incidence of 4-kHz air–bone gaps and associated factors.

Method

Data were obtained as part of the longitudinal, population-based Epidemiology of Hearing Loss Study (Cruickshanks et al., 1998). An air–bone gap at 4 kHz was defined as an air-conduction threshold ≥ 15 dB higher than the bone-conduction threshold in the right ear.

Results

Among 3,553 participants ages 48–92 years at baseline (1993–1995), 3.4% had a 4-kHz air–bone gap in the right ear. The prevalence increased with age. Among the 120 participants with an air–bone gap, 60.0% did not have a flat tympanogram or an air–bone gap at 0.5 kHz. Ten years later, the authors assessed 2,093 participants who did not have a 4-kHz air–bone gap at baseline; 9.2% had developed a 4-kHz air–bone gap in the right ear. The incidence increased with age. Among the 192 participants who had developed an air–bone gap, 60.9% did not have a flat tympanogram or air–bone gaps at other frequencies.

Conclusion

These results suggest that a finding of a 4-kHz air–bone gap may reflect a combination of aging and other factors and not necessarily exclusively abnormal middle-ear function.
Surface Electromyography for Speech and Swallowing Systems: Measurement, Analysis, and Interpretation
Authors: Stepp Cara E.
Published: January 2012

Purpose

Applying surface electromyography (sEMG) to the study of voice, speech, and swallowing is becoming increasingly popular. An improved understanding of sEMG and building a consensus as to appropriate methodology will improve future research and clinical applications.

Method

An updated review of the theory behind recording sEMG for the speech and swallowing systems is provided. Several factors that are known to affect the content of the sEMG signal are discussed, and practical guidelines for sEMG recording and analysis are presented, focusing on special considerations within the context of the speech and swallowing anatomy.

Results

Unique challenges are seen in application of sEMG to the speech and swallowing musculature owing to the small size of the muscles in relation to the sEMG detection volume and the present lack of knowledge about innervation zone locations.

Conclusions

Despite the challenges discussed, application of sEMG to speech and swallowing has potential as a clinical and research tool when used correctly and is specifically suited to noninvasive clinical studies using between-condition or between-group comparisons for which detection of specific isolated muscle activities is not necessary.
Teaching AAC in the Online Environment: Methods and Challenges
Authors: Zangari Carole
Published: January 2012

The evolution of online education has some parallels with the development of the field of augmentative and alternative communication (AAC). It has taken some time for professionals in the broader fields of education, higher education, and speech-language pathology to seriously consider its potential contribution. Like AAC, online education was initially viewed with skepticism, but is now almost commonplace. In the face of data that affirm the effectiveness of online instruction, clinical educators are increasingly turning their attention to identifying and employing best practices to improve the learning outcomes of their students. The purpose of this article is to explore some of the common features of online education that hold promise for the AAC field. We also will discuss challenges faced by online instructors and strategies for addressing them.
The role of metrology in the field of medical devices
Authors: do Céu Ferreira M.
Published: January 2012

Medical measurements are present in the everyday life of people and are fundamental processes in prevention, diagnosis and treatment of disease. Therefore, a growing interest lies in the role of metrological decisions and conformity assessment, namely where measurements are in support of health. This paper focuses on the use of medical devices looking to enhance its metrological traceability, highlighting the specific role of metrology in the field of health care and the impact of legal control in the framework of the medical devices regulation with a measuring function. It is proposed a new regulatory approach for medical devices in use, facing the convergence between European policy enforcement and Metrological regulations.
Electronic structure calculations in arbitrary electrostatic environments
Authors: Watson Mark A. , Rappoport Dmitrij , Lee Elizabeth M. Y. , Olivares-Amaya Roberto , Aspuru-Guzik Alán
Published: January 2012

Modeling of electronic structure of molecules in electrostatic environments is of considerable relevance for surface-enhanced spectroscopy and molecular electronics. We have developed and implemented a novel approach to the molecular electronic structure in arbitrary electrostatic environments that is compatible with standard quantum chemical methods and can be applied to medium-sized and large molecules. The scheme denoted CheESE (chemistry in electrostatic environments) is based on the description of molecular electronic structure subject to a boundary condition on the system/environment interface. Thus, it is particularly suited to study molecules on metallic surfaces. The proposed model is capable of describing both electrostatic effects near nanostructured metallic surfaces and image-charge effects. We present an implementation of the CheESE model as a library module and show example applications to neutral and negatively charged molecules.
Time evolution of filamentation and self-generated fields in the coronae of directly driven inertial-confinement fusion capsules
Authors: Séguin F. H. , Li C. K. , Manuel M. J.-E. , Rinderknecht H. G. , Sinenian N. , Frenje J. A. , Rygg J. R. , Hicks D. G. , Petrasso R. D. , Delettrez J. , Betti R. , Marshall F. J. , Smalyuk V. A.
Published: January 2012

Time-gated radiography with monoenergetic 15-MeV protons, 3-MeV protons, and 4-MeV alpha particles has revealed a rich and complex evolution of electromagnetic field structures in and around imploding, directly driven inertial-confinement fusion (ICF) targets at the OMEGA laser facility. Plastic-shell capsules and solid plastic spheres were imaged during and after irradiation with ICF-relevant laser drive (up to 6 × 1014 W/cm2). Radial filaments appeared while the laser was on; they filled, and were frozen into, the out-flowing corona, persisting until well after the end of the laser drive. Data from specially designed experiments indicate that the filaments were not generated by two-plasmon-decay instabilities or by Rayleigh-Taylor instabilities associated with shell acceleration. Before the onset of visible filamentation, quasi-spherical field structures appeared outside the capsule in the images in a form that suggests outgoing shells of net positive charge. We conjecture that these discrete shells are related to multiple peaks seen previously in the spectra of protons ablated from the targets.
Singly and doubly lithium doped silicon clusters: Geometrical and electronic structures and ionization energies
Authors: Tam Nguyen Minh , Ngan Vu Thi , de Haeck Jorg , Bhattacharyya Soumen , Thuy Le Hai , Janssens Ewald , Lievens Peter , Tho Nguyen Minh
Published: January 2012

The geometric structures of neutral and cationic SinLim0/+ clusters with n = 2–11 and m = 1, 2 are investigated using combined experimental and computational methods. The adiabatic ionization energy and vertical ionization energy (VIE) of SinLim clusters are determined using quantum chemical methods (B3LYP/6-311+G(d), G3B3, and CCSD(T)/aug-cc-pVxZ with x = D,T), whereas experimental values are derived from threshold photoionization experiments in the 4.68–6.24 eV range. Among the investigated cluster sizes, only Si6Li2, Si7Li, Si10Li, and Si11Li have ionization thresholds below 6.24 eV and could be measured accurately. The ionization threshold and VIE obtained from the experimental photoionization efficiency curves agree well with the computed values. The growth mechanism of the lithium doped silicon clusters follows some simple rules: (1) neutral singly doped SinLi clusters favor the Li atom addition on an edge or a face of the structure of the corresponding Sin− anion, while the cationic SinLi+ binds with one Si atom of the bare Sin cluster or adds on one of its edges, and (2) for doubly doped SinLi20/+ clusters, the neutrals have the shape of the Sin+1 counterparts with an additional Li atom added on an edge or a face of it, while the cations have both Li atoms added on edges or faces of the Sin− clusters.
Symmetry breaking effects of density gradient on parallel momentum transport: A new ρs* effect
Authors: Singh Rameswar , Singh R. , Kaw P. , Gürcan Ö. D. , Diamond P. H. , Nordman H.
Published: January 2012

Symmetry breaking effects of density gradient on parallel momentum transport is studied via quasilinear theory. It is shown that finite ρs*(≡ρs/Ln), where ρs is ion sound radius and Ln is density scale length, leads to symmetry breaking of the ion temperature gradient (ITG) eigenfunction. This broken symmetry persists even in the absence of mean poloidal (from radial electric field shear) and toroidal flows. This effect, as explained in the text, originates from the divergence of polarization particle current in the ion continuity equation. The form of the eigenfunction allows the microturbulence to generate parallel residual stress via 〈k‖〉 symmetry breaking. Comparison with the E→×B→ shear driven parallel residual stress, parallel polarization stress and turbulence intensity gradient driven parallel residual stress are discussed. It is shown that this ρs* driven parallel residual stress may become comparable to E→×B→ shear driven parallel residual stress in small Ln region. In the regular drift wave ordering, where ρs*≪1, this effect is found to be of the same order as the parallel polarization stress. This ρs* driven parallel residual stress can also overtake the turbulence intensity gradient driven parallel residual stress in strong density gradient region whereas the later one is dominant in the strong profile curvature region. The parallel momentum diffusivity is found to remain undisturbed by this ρs* effect as long as the turbulence intensity inhomogenity is not important.
Frequency dependent dynamical electromechanical response of mixed ionic-electronic conductors
Authors: Morozovska A. N. , Eliseev E. A. , Bravina S. L. , Ciucci Francesco , Svechnikov G. S. , Chen Long-Qing , Kalinin S. V.
Published: January 2012

Frequency dependent dynamic electromechanical response of the mixed ionic-electronic conductor film to a periodic electric bias is analyzed for different electronic and ionic boundary conditions. Dynamic effects of mobile ions concentration (stoichiometry contribution), charge state of acceptors (donors), electron concentration (electron-phonon coupling via the deformation potential), and flexoelectric effect contribution are discussed. A variety of possible nonlinear dynamic electromechanical responses of mixed electronic ionic conductors (MIEC) films including quasi-elliptic curves, asymmetric hysteresis-like loops with pronounced memory window, and butterfly-like curves are calculated. The electromechanical response of ionic semiconductor is predicted to be a powerful descriptor of local valence states, band structure and electron-phonon correlations thatcan be readily measured in the nanoscale volumes and in the presence of strong electronic conductivity.
Elastic, anelastic, and piezoelectric coefficients of GaN
Authors: Nakamura N. , Ogi H. , Hirao M.
Published: January 2012

We report elastic, anelastic, and piezoelectric coefficients of wurtzite GaN measured by resonant-ultrasound spectroscopy coupled with laser-Doppler interferometry. Five rectangular parallelepiped specimens, measuring 6.5 × 2.0 × 4.0 mm3, cut from two single crystals were used. Our values of elastic and piezoelectric coefficients were C11 = 359.4 GPa, C12 = 129.2 GPa, C13 = 92.0 GPa, C33 = 389.9 GPa, C44 = 98.0 GPa, e15 = 0.10 C/m2, e31 = 0.17 C/m2, and e33 = 0.29 C/m2. In anelastic coefficients, anisotropy was observed between Q11−1 and Q33−1.
Electric field induced magnetization rotation in patterned Ni ring/Pb(Mg1/3Nb2/3)O3](1−0.32)-[PbTiO3]0.32 heterostructures
Authors: Hockel Joshua L. , Bur Alexandre , Wu Tao , Wetzlar Kyle P. , Carman Gregory P.
Published: January 2012

Electric field induced magnetoelastic anisotropy is shown to rotate the magnetization of a ring-shaped magnet by 90° in a Ni ring/(011) Pb(Mg1/3Nb2/3)O3](1−0.32)-[PbTiO3]0.32 heterostructure. The 2000 nm diameter ring is initially field annealed forming the “onion” magnetization state. A 0.8 MV/m electric field is applied to the substrate creating anisotropic piezostrain and a perpendicular in-plane easy axis. Magnetic force microscopy confirms the 90° rotation of the vortex-type domain walls from the field annealing direction. Rotations are stable without electric field due to remnant strains induced during the poling process, supporting the viability of strain-based magnetic recording methods.
All-oxide system for spin pumping
Authors: Qiu Z. , Kajiwara Y. , Ando K. , Fujikawa Y. , Uchida K. , Tashiro T. , Harii K. , Yoshino T. , Saitoh E.
Published: January 2012

In a simple all-oxide system, spin pumping driven by spin wave resonances have been investigated by using the inverse spin-Hall effect (ISHE). In a lanthanum doped yttrium iron garnet (La:YIG)/indium tin oxide (ITO) bilayer film, the spin pumping generates and injects a spin current into the ITO layer, and an electromotive force signal is observed via the ISHE. The electromotive forces were measured depend on the out-of-plane magnetic-field-angle and the microwave excitation power, which were consistent with the theoretical prediction of the ISHE. The realization of the all-oxide spin pumping system extends possibilities for the oxide spintronics.
High-performance short channel organic transistors using densely aligned carbon nanotube array electrodes
Authors: Sarker Biddut K. , Khondaker Saiful I.
Published: January 2012

We report high-performance short channel pentacene field effect transistor (FET) using carbon nanotube aligned array electrodes. The devices show field effect mobility of up to 0.65 cm2/Vs and current on-off ratio of up to 1.7 × 106, which is the best for sub-micron pentacene FETs. The calculated cutoff frequency (fc) of the devices is up to 211 MHz which is among the best reported fc for organic transistors. The high performance of our short channel FET is attributed to improved charge injections from the aligned array carbon nanotube electrodes into the pentacene.
Pentacene-based metal-insulator-semiconductor memory structures utilizing single walled carbon nanotubes as a nanofloating gate
Authors: Sleiman A. , Rosamond M. C. , Alba Martin M. , Ayesh A. , Al Ghaferi A. , Gallant A. J. , Mabrook M. F. , Zeze D. A.
Published: January 2012

A pentacene-based organic metal-insulator-semiconductor memory device, utilizing single walled carbon nanotubes (SWCNTs) for charge storage is reported. SWCNTs were embedded, between SU8 and polymethylmethacrylate to achieve an efficient encapsulation. The devices exhibit capacitance-voltage clockwise hysteresis with a 6 V memory window at ± 30 V sweep voltage, attributed to charging and discharging of SWCNTs. As the applied gate voltage exceeds the SU8 breakdown voltage, charge leakage is induced in SU8 to allow more charges to be stored in the SWCNT nodes. The devices exhibited high storage density (∼9.15 × 1011 cm−2) and demonstrated 94% charge retention due to the superior encapsulation.
Optical-resolution photoacoustic microscopy based on two-dimensional scanning galvanometer
Authors: Yuan Yi , Yang Sihua , Xing Da
Published: January 2012

An optical-resolution photoacoustic microscopy system was designed and fabricated by integration of a two-dimensional scanning galvanometer, an objective lens, an unfocused ultrasound transducer, and a sample stage. The lateral resolution of the system was measured to be ∼500 nm. Ex vivo erythrocytes were used to test the imaging capability of the system, and a single erythrocyte was mapped with high contrast. Furthermore, invivo blood vessels of a mouse ear were clearly shown, and the injured blood vessels were also monitored. The experimental results demonstrate that galvanometer-based photoacoustic microscopy holds clinical potential in detecting lesion of erythrocyte and blood vessel.
Tuning the Kapitza resistance in pillared-graphene nanostructures
Authors: Loh G. C. , Teo E. H. T. , Tay B. K.
Published: January 2012

The pillared-graphene architecture is a conceivable way of conjoining graphene nanoribbons and carbon nanotubes (CNTs) in nanoelectronics. Especially promising is its capability to dissipate thermal energy in thermal management applications. However, the thermal boundary resistance (Kapitza resistance) at the graphene nanoribbon-CNT interface is a phonon barricade and a bottleneck for efficacious heat extraction. Parallel to strain studies on thermal conductance, this work is a first report on the effects of mechanical strain on the interfacial phonon dynamics in the pillared-graphene nanostructure (PGN). Molecular dynamics simulations are employed to derive the changes in phononics as axial, torsional, and compound strains of various degrees are applied on the PGN. The pillar lattice structure behaves dissimilarly to the different types of strains. In-plane transverse optical mode softening as induced by torsional strain is more effective than LO softening (triggered by tension) in minimizing the thermal boundary resistance. Essentially, it is shown that there is a strong relationship between strained PGN pillar lattice structure, interfacial phononics, and thermal boundary resistance.
Preliminary estimates of genetic parameters for carcass and meat quality traits in Australian sheep
Authors: Mortimer S. I. , van der Werf J. H. J. , Jacob R. H. , Pethick D. W. , Pearce K. L. , Warner R. D. , Geesink G. H. , Hocking Edwards J. E. , Gardner G. E. , Ponnampalam E. N. , Kitessa S. M. , Ball A. J. , Hopkins D. L.
Published: January 2012

Using performance from progeny born in 2007 and 2008 generated by the Information Nucleus program of the Cooperative Research Centre for Sheep Industry Innovation, preliminary estimates of heritability were obtained for a range of novel carcass and meat attributes of lamb relevant to consumers, including carcass characteristics, meat quality and nutritional value of lamb. Phenotypic and genetic correlations of live animal traits with carcass composition and meat quality traits were also estimated. The data were from progeny located at eight sites, sired by 183 rams from Merino, maternal and terminal meat breeds and were representative of the Merino, Border Leicester × Merino, Terminal × Merino and Terminal × Border Leicester-Merino production types of the Australian sheep industry. Data were available from 7176 lambs for weaning weight, 6771 lambs for ultrasound scanning and 4110 lambs for slaughter traits. For the novel meat quality traits, generally moderate to high heritability estimates were obtained for meat quality measures of shear force (0.27 aged 1 day, 0.38 aged 5 days), intramuscular fat (0.39), retail meat colour (range of 0.09 to 0.44) and myoglobin content (0.22). The nutritional value traits of omega-3 fatty acids and iron and zinc contents tended to have low to moderate heritabilities (0.11–0.37), although these were based on fewer records. Fresh meat colour traits were of low to moderate heritability (0.06–0.21) whereas measures of meat pH were of low heritability (~0.10). For the carcass traits, estimates of heritability were moderate to high for the various measures of carcass fat (0.18–0.50), muscle weight (0.22–0.35), meat yield (0.24–0.35), carcass muscle dimensions (0.25–0.34) and bone weight (0.27). Results indicate that for most lamb carcass and meat quality traits there is sufficient genetic variation for selection to alter successfully these characteristics. Additionally, most genetic correlations of live animal assessments of bodyweight, muscle and subcutaneous fat with the carcass and meat quality traits were favourable. Appropriate definition of breeding objectives and design of selection indexes should be able to account for the small unfavourable relationships that exist and achieve the desired outcomes from breeding programs.
Quality of lamb meat from the Information Nucleus Flock
Authors: Warner R. D. , Jacob R. H. , Edwards J. E. Hocking , McDonagh M. , Pearce K. , Geesink G. , Kearney G. , Allingham P. , Hopkins D. L. , Pethick D. W.
Published: January 2012

The effects of production and processing factors on tenderness, and colour of lamb meat produced from 7 locations as part of the Australian Sheep Industry CRC’s Information Nucleus flock were investigated, using data from 2052 lambs slaughtered in 2007. At 24 h post-slaughter, samples of m. longissimus lumborum (LL) and m. semimembranosus (SM) were collected for measurement of intramuscular fat (IMF), myoglobin, iron and copper and fresh meat colour (L*, a*, b*) and pH at 24 h measured on the LL. pH and temperature measurements made pre-rigor were used to calculate the pH at 18°C. Tenderness was measured by LL shear force at days 1 (SF1) and 5 (SF5) post-slaughter, the shear force difference (SF-diff) and SM compression and collagen concentration were determined. Retail colour stability was assessed using over-wrapped LL under simulated retail display for 3 days, according to the change in the oxymyoglobin/metmyoglobin ratio. All traits were affected by flock and date of slaughter (P < 0.001). After 4 days of ageing, 70–95% of the LL samples from all flocks, except for one, had acceptable tenderness for consumers based on their shear force. Low IMF, high LL pH at 18°C and high pH at 24 h increased SF1 and SF5 and also had an effect on SF-diff (P < 0.001). The retail colour of 44.8% of the samples on day 3 of retail display were lower than acceptable. Retail colour was influenced by IMF, pH18 and the concentration of iron and copper (P < 0.001). In conclusion, breeding and management practices that increase muscle IMF levels and reduce ultimate pH values and processing practices that result in moderate rates of pH fall post-slaughter, improve the tenderness of lamb. Extension of retail colour stability may be antagonistic to traits associated with tenderness and nutritional traits, particularly IMF and mineral levels.
Regulation of XFGF8 gene expression through SRY (sex-determining region Y)-box 2 in developing Xenopus embryos
Authors: Kim Yong Hwan , Shin Jee Yoon , Na Wonho , Kim Jungho , Ju Bong-Gun , Kim Won-Sun
Published: January 2012

Fibroblast growth factors (FGFs) function as mitogens and morphogens during vertebrate development. In the present study, to characterise the regulatory mechanism of FGF8 gene expression in developing Xenopus embryos the upstream region of the Xenopus FGF8 (XFGF8) gene was isolated. The upstream region of the XFGF8 gene contains two putative binding sites for the SRY (sex-determining region Y)-box 2 (SOX2) transcription factor. A reporter assay with serially deleted constructs revealed that the putative SOX2-binding motif may be a critical cis-element for XFGF8 gene activation in developing Xenopus embryos. Furthermore, Xenopus SOX2 (XSOX2) physically interacted with the SOX2-binding motif within the upstream region of the XFGF8 gene in vitro and in vivo. Depletion of endogenous XSOX2 resulted in loss of XFGF8 gene expression in midbrain–hindbrain junction, auditory placode, lens placode and forebrain in developing Xenopus embryos. Collectively, our results suggest that XSOX2 directly upregulates XFGF8 gene expression in the early embryonic development of Xenopus.
Collective and single cell behavior in epithelial contact inhibition
Authors: Puliafito Alberto , Hufnagel Lars , Neveu Pierre , Streichan Sebastian , Sigal Alex , Fygenson D. Kuchnir , Shraiman Boris I.
Published: January 2012

Control of cell proliferation is a fundamental aspect of tissue physiology central to morphogenesis, wound healing, and cancer. Although many of the molecular genetic factors are now known, the system level regulation of growth is still poorly understood. A simple form of inhibition of cell proliferation is encountered in vitro in normally differentiating epithelial cell cultures and is known as “contact inhibition.” The study presented here provides a quantitative characterization of contact inhibition dynamics on tissue-wide and single cell levels. Using long-term tracking of cultured Madin-Darby canine kidney cells we demonstrate that inhibition of cell division in a confluent monolayer follows inhibition of cell motility and sets in when mechanical constraint on local expansion causes divisions to reduce cell area. We quantify cell motility and cell cycle statistics in the low density confluent regime and their change across the transition to epithelial morphology which occurs with increasing cell density. We then study the dynamics of cell area distribution arising through reductive division, determine the average mitotic rate as a function of cell size, and demonstrate that complete arrest of mitosis occurs when cell area falls below a critical value. We also present a simple computational model of growth mechanics which captures all aspects of the observed behavior. Our measurements and analysis show that contact inhibition is a consequence of mechanical interaction and constraint rather than interfacial contact alone, and define quantitative phenotypes that can guide future studies of molecular mechanisms underlying contact inhibition.
Extensive chromosomal variation in a recently formed natural allopolyploid species,Tragopogon miscellus(Asteraceae)
Authors: Chester Michael , Gallagher Joseph P. , Symonds V. Vaughan , Cruz da Silva Ana Veruska , Mavrodiev Evgeny V. , Leitch Andrew R. , Soltis Pamela S. , Soltis Douglas E.
Published: January 2012

Polyploidy, or whole genome duplication, has played a major role in the evolution of many eukaryotic lineages. Although the prevalence of polyploidy in plants is well documented, the molecular and cytological consequences are understood largely from newly formed polyploids (neopolyploids) that have been grown experimentally. Classical cytological and molecular cytogenetic studies both have shown that experimental neoallopolyploids often have meiotic irregularities, producing chromosomally variable gametes and progeny; however, little is known about the extent or duration of chromosomal variation in natural neoallopolyploid populations. We report the results of a molecular cytogenetic study on natural populations of a neoallopolyploid,Tragopogon miscellus, which formed multiple times in the past 80 y. Using genomic and fluorescence in situ hybridization, we uncovered massive and repeated patterns of chromosomal variation in all populations. No population was fixed for a particular karyotype; 76% of the individuals showed intergenomic translocations, and 69% were aneuploid for one or more chromosomes. Importantly, 85% of plants exhibiting aneuploidy still had the expected chromosome number, mostly through reciprocal monosomy-trisomy of homeologous chromosomes (1:3 copies) or nullisomy-tetrasomy (0:4 copies). The extensive chromosomal variation still present afterca. 40 generations in this biennial species suggests that substantial and prolonged chromosomal instability might be common in natural populations after whole genome duplication. A protracted period of genome instability in neoallopolyploids may increase opportunities for alterations to genome structure, losses of coding and noncoding DNA, and changes in gene expression.
CD14 cooperates with complement receptor 3 to mediate MyD88-independent phagocytosis ofBorrelia burgdorferi
Authors: Hawley Kelly L. , Olson Chris M. , Iglesias-Pedraz Juan M. , Navasa Nicolás , Cervantes Jorge L. , Caimano Melissa J. , Izadi Hooman , Ingalls Robin R. , Pal Utpal , Salazar Juan C. , Radolf Justin D. , Anguita Juan
Published: January 2012

Phagocytosis ofBorrelia burgdorferi, the causative agent of Lyme disease, is a poorly understood process, despite its importance during the host immune response to infection.B. burgdorferihas been shown to bind to different receptors on the surface of phagocytic cells, including the β2integrin, complement receptor 3 (CR3). However, whether these receptors mediate the phagocytosis of the spirochete remains unknown. We now demonstrate that CR3 mediates the phagocytosis of the spirochete by murine macrophages and human monocytes. Interaction ofB. burgdorferiwith the integrin is not sufficient, however, to internalize the spirochete; phagocytosis requires the interaction of CR3 with the GPI-anchored protein, CD14, independently of TLR/MyD88-induced or inside-out signals. Interestingly, the absence of CR3 leads to marked increases in the production of TNF in vitro and in vivo, despite reduced spirochetal uptake. Furthermore, the absence of CR3 during infection withB. burgdorferiresults in the inefficient control of bacterial burdens in the heart and increased Lyme carditis. Overall, our data identify CR3 as a MyD88-independent phagocytic receptor forB. burgdorferithat also participates in the modulation of the proinflammatory output of macrophages. These data also establish a unique mechanism of CR3-mediated phagocytosis that requires the direct cooperation of GPI-anchored proteins.
Telomere length in early life predicts lifespan
Authors: Heidinger Britt J. , Blount Jonathan D. , Boner Winnie , Griffiths Kate , Metcalfe Neil B. , Monaghan Pat
Published: January 2012

The attrition of telomeres, the ends of eukaryote chromosomes, is thought to play an important role in cell deterioration with advancing age. The observed variation in telomere length among individuals of the same age is therefore thought to be related to variation in potential longevity. Studies of this relationship are hampered by the time scale over which individuals need to be followed, particularly in long-lived species where lifespan variation is greatest. So far, data are based either on simple comparisons of telomere length among different age classes or on individuals whose telomere length is measured at most twice and whose subsequent survival is monitored for only a short proportion of the typical lifespan. Both approaches are subject to bias. Key studies, in which telomere length is tracked from early in life, and actual lifespan recorded, have been lacking. We measured telomere length in zebra finches (n= 99) from the nestling stage and at various points thereafter, and recorded their natural lifespan (which varied from less than 1 to almost 9 y). We found telomere length at 25 d to be a very strong predictor of realized lifespan (P< 0.001); those individuals living longest had relatively long telomeres at all points at which they were measured. Reproduction increased adult telomere loss, but this effect appeared transient and did not influence survival. Our results provide the strongest evidence available of the relationship between telomere length and lifespan and emphasize the importance of understanding factors that determine early life telomere length.
Distinct conformations of the protein complex p97-Ufd1-Npl4 revealed by electron cryomicroscopy
Authors: Bebeacua Cecilia , Förster Andreas , McKeown Ciarán , Meyer Hemmo H. , Zhang Xiaodong , Freemont Paul S.
Published: January 2012

p97 is a key regulator of numerous cellular pathways and associates with ubiquitin-binding adaptors to remodel ubiquitin-modified substrate proteins. How adaptor binding to p97 is coordinated and how adaptors contribute to substrate remodeling is unclear. Here we present the 3D electron cryomicroscopy reconstructions of the major Ufd1-Npl4 adaptor in complex with p97. Our reconstructions show that p97-Ufd1-Npl4 is highly dynamic and that Ufd1-Npl4 assumes distinct positions relative to the p97 ring upon addition of nucleotide. Our results suggest a model for substrate remodeling by p97 and also explains how p97-Ufd1-Npl4 could form other complexes in a hierarchical model of p97-cofactor assembly.
Mechanism of proton/substrate coupling in the heptahelical lysosomal transporter cystinosin
Authors: Ruivo Raquel , Bellenchi Gian Carlo , Chen Xiong , Zifarelli Giovanni , Sagné Corinne , Debacker Cécile , Pusch Michael , Supplisson Stéphane , Gasnier Bruno
Published: January 2012

Secondary active transporters use electrochemical gradients provided by primary ion pumps to translocate metabolites or drugs “uphill” across membranes. Here we report the ion-coupling mechanism of cystinosin, an unusual eukaryotic, proton-driven transporter distantly related to the proton pump bacteriorhodopsin. In humans, cystinosin exports the proteolysis-derived dimeric amino acid cystine from lysosomes and is impaired in cystinosis. Using voltage-dependence analysis of steady-state and transient currents elicited by cystine and neutralization-scanning mutagenesis of conserved protonatable residues, we show that cystine binding is coupled to protonation of a clinically relevant aspartate buried in the membrane. Deuterium isotope substitution experiments are consistent with an access of this aspartate from the lysosomal lumen through a deep proton channel. This aspartate lies in one of the two PQ-loop motifs shared by cystinosin with a set of eukaryotic membrane proteins of unknown function and is conserved in about half of them, thus suggesting that other PQ-loop proteins may translocate protons.
Epigenetic regulation of hypoxic sensing disrupts cardiorespiratory homeostasis
Authors: Nanduri Jayasri , Makarenko Vladislav , Reddy Vaddi Damodara , Yuan Guoxiang , Pawar Anita , Wang Ning , Khan Shakil A. , Zhang Xin , Kinsman Brian , Peng Ying-Jie , Kumar Ganesh K. , Fox Aaron P. , Godley Lucy A. , Semenza Gregg L. , Prabhakar Nanduri R.
Published: January 2012

Recurrent apnea with intermittent hypoxia is a major clinical problem in preterm infants. Recent studies, although limited, showed that adults who were born preterm exhibit increased incidence of sleep-disordered breathing and hypertension, suggesting that apnea of prematurity predisposes to autonomic dysfunction in adulthood. Here, we demonstrate that adult rats that were exposed to intermittent hypoxia as neonates exhibit exaggerated responses to hypoxia by the carotid body and adrenal chromaffin cells, which regulate cardio-respiratory function, resulting in irregular breathing with apneas and hypertension. The enhanced hypoxic sensitivity was associated with elevated oxidative stress, decreased expression of genes encoding antioxidant enzymes, and increased expression of pro-oxidant enzymes. Decreased expression of the
Sod2
gene, which encodes the antioxidant enzyme superoxide dismutase 2, was associated with DNA hypermethylation of a single CpG dinucleotide close to the transcription start site. Treating neonatal rats with decitabine, an inhibitor of DNA methylation, during intermittent hypoxia exposure prevented oxidative stress, enhanced hypoxic sensitivity, and autonomic dysfunction. These findings implicate a hitherto uncharacterized role for DNA methylation in mediating neonatal programming of hypoxic sensitivity and the ensuing autonomic dysfunction in adulthood.
TheArabidopsisNitrate Transporter NRT2.4 Plays a Double Role in Roots and Shoots of Nitrogen-Starved Plants
Authors: Kiba Takatoshi , Feria-Bourrellier Ana-Belen , Lafouge Florence , Lezhneva Lina , Boutet-Mercey Stéphanie , Orsel Mathilde , Bréhaut Virginie , Miller Anthony , Daniel-Vedele Françoise , Sakakibara Hitoshi , Krapp Anne
Published: January 2012

Plants have evolved a variety of mechanisms to adapt to N starvation. NITRATE TRANSPORTER2.4 (NRT2.4) is one of seven NRT2 family genes in Arabidopsis thaliana, and NRT2.4 expression is induced under N starvation. Green fluorescent protein and β-glucuronidase reporter analyses revealed that NRT2.4 is a plasma membrane transporter expressed in the epidermis of lateral roots and in or close to the shoot phloem. The spatiotemporal expression pattern of NRT2.4 in roots is complementary with that of the major high-affinity nitrate transporter NTR2.1. Functional analysis in Xenopus laevis oocytes and in planta showed that NRT2.4 is a nitrate transporter functioning in the high-affinity range. In N-starved nrt2.4 mutants, nitrate uptake under low external supply and nitrate content in shoot phloem exudates was decreased. In the absence of NRT2.1 and NRT2.2, loss of function of NRT2.4 (triple mutants) has an impact on biomass production under low nitrate supply. Together, our results demonstrate that NRT2.4 is a nitrate transporter that has a role in both roots and shoots under N starvation.