bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of plasma and vacuum-ultraviolet exposure on the mechanical properties of low-k porous organosilicate glass
Authors: Guo X. , Jakes J. E. , Banna S. , Nishi Y. , Shohet J. L.
Published: July 2014

The effects of plasma exposure and vacuum-ultraviolet (VUV) irradiation on the mechanical properties of low-k porous organosilicate glass (SiCOH) dielectric films were investigated. Nanoindentation measurements were made on SiCOH films before and after exposure to an electron-cyclotron-resonance plasma or a monochromatic synchrotron VUV beam, to determine the changes of film hardness, elastic modulus, and crack threshold due to these exposures. This permits the effects of ion bombardment and photon bombardment to be analyzed separately. The role of energetic ions was examined with a variety of inert plasma-exposure conditions. The role of VUV photons was analyzed as a function of synchrotron photon energy. It was found that both energetic ions and VUV photons with energies larger than the bond energy of the Si-O bond cause a significant increase in film hardness along with a smaller increase in elastic modulus and crack threshold. Differential Fourier transform infrared spectra and x-ray photoemission spectroscopy results show that the energetic ions affect the SiCOH properties mainly through physical bombardment, during which the ions transfer their momentum to the Si-O-Si backbone and transform them into more energetically stable Si-O-Si network structures. This results in the Si-O-Si network structures becoming densified. VUV photons assist reaction that increase the number of bridging O3≡Si-O-Si≡O3 bonds and deplete nonbridging O3≡Si-O and C-Si≡O3 bonds. This increased degree of cross linking in porous organosilicate dielectrics can substantially enhance their hardness and elastic modulus while showing no significant film shrinkage or densification.
Experimental observation of standing wave effect in low-pressure very-high-frequency capacitive discharges
Authors: Liu Yong-Xin , Gao Fei , Liu Jia , Wang You-Nian
Published: July 2014

Radial uniformity measurements of plasma density were carried out by using a floating double probe in a cylindrical (21 cm in electrode diameter) capacitive discharge reactor driven over a wide range of frequencies (27–220 MHz). At low rf power, a multiple-node structure of standing wave effect was observed at 130 MHz. The secondary density peak caused by the standing wave effect became pronounced and shifts toward the axis as the driving frequency further to increase, indicative of a much more shortened standing-wave wavelength. With increasing rf power, the secondary density peak shift toward the radial edge, namely, the standing-wave wavelength was increased, in good qualitative agreement with the previous theory and simulation results. At higher pressures and high frequencies, the rf power was primarily deposited at the periphery of the electrode, due to the fact that the waves were strongly damped as they propagated from the discharge edge into the center.
Large area photodetector based on microwave cavity perturbation techniques
Authors: Braggio C. , Carugno G. , Lombardi A. , Ruoso G. , Sirugudu R. K.
Published: July 2014

We present a preliminary study to develop a large area photodetector, based on a semiconductor crystal placed inside a superconducting resonant cavity. Laser pulses are detected through a variation of the cavity impedance, as a consequence of the conductivity change in the semiconductor. A novel method, whereby the designed photodetector is simulated by finite element analysis, makes it possible to perform pulse-height spectroscopy on the reflected microwave signals. We measure an energy sensitivity of 100 fJ in the average mode without the employment of low noise electronics and suggest possible ways to further reduce the single-shot detection threshold, based on the results of the described method.
On plasmon-induced photocurrent and doping of metal-patterned graphene
Authors: Hosseini T. , Kouklin N. A.
Published: July 2014

Patterning graphene with noble metal plasmonic nanostructures to enhance and to manipulate the optical and electronic properties of graphene promises a variety of technological innovations in the field of nano-optoelectronics. In this report, we briefly revisit photoconduction experiments done recently on graphene plasmonic sensors and show that the excess electrical current generated in response to spatially non-uniform optical excitation is primarily induced by a photo-thermo-electric effect in the graphene itself. As this mechanism has nothing to do with the excess free carrier generation common with conventional semiconductors, the plasmonic nanostructures cannot be utilized to regulate the free carrier density and doping of graphene, in contrast to what has been proposed recently.
Leak current estimated from the shot noise in magnetic tunneling junctions
Authors: Tanaka Takahiro , Arakawa Tomonori , Maeda Masahiro , Kobayashi Kensuke , Nishihara Yoshitaka , Ono Teruo , Nozaki Takayuki , Fukushima Akio , Yuasa Shinji
Published: July 2014

We performed the shot noise measurement in epitaxial Fe/MgO/Fe-based magnetic tunneling junctions (MTJs) with various MgO thicknesses between 1.1 nm and 1.625 nm. While the Fano factor to characterize the shot noise is very close to 1 in MTJs with MgO barrier thicker than 1.2 nm, the magnetic configuration-dependent reduction of the Fano factor for MTJs with thin MgO barrier was observed, which is mainly due to the existence of leakage current. By using a simple parallel circuit model, we demonstrated that the contribution of the leak current can be sensitively derived from the shot noise.
Measurement of ionic polarization of SrTiO3 single crystal by far-infrared spectroscopic ellipsometry
Authors: Kanehara Kazuki , Hoshina Takuya , Takeda Hiroaki , Tsurumi Takaaki
Published: July 2014

We developed a far-infrared spectroscopic ellipsometer for measuring the complex permittivity of high-permittivity materials in the terahertz (THz) region and demonstrated the dielectric function of SrTiO3 single crystal at 0.75–21 THz. The responses of the Slater, Last, and O6 displacive modes, which are all optical phonon modes of SrTiO3 at room temperature, were clearly observed. The complex permittivity measured by the ellipsometer agreed with the permittivity simulated by a damped harmonic oscillator model. The far-infrared spectroscopic ellipsometry is useful to analyze the phonon modes of high-permittivity materials, which enable us to understand the contribution of the ionic polarizations to the low-frequency permittivity.
Two-photon polymerization of cylinder microstructures by femtosecond Bessel beams
Authors: Yang Liang , El-Tamer Ayman , Hinze Ulf , Li Jiawen , Hu Yanlei , Huang Wenhao , Chu Jiaru , Chichkov Boris N
Published: July 2014

In this work, we present an approach to modulate femtosecond laser beams into Bessel beams with a spatial light modulator (SLM) for two-photon polymerization applications. Bessel beams with different parameters are generated and annular optical fields are produced at the focal plane of the objective. Uniform cylinder microstructures are fabricated by a single illumination during a few seconds without stage translation. By modulating the holograms encoded on the SLM, the diameters of the fabricated annular structures can be flexibly controlled in a wide range with no need of changing the optical elements and realignment of the optical path.
Electron and hole drift mobility measurements on thin film CdTe solar cells
Authors: Long Qi , Dinca Steluta A. , Schiff E. A. , Yu Ming , Theil Jeremy
Published: July 2014

We report electron and hole drift mobilities in thin film polycrystalline CdTe solar cells based on photocarrier time-of-flight measurements. For a deposition process similar to that used for high-efficiency cells, the electron drift mobilities are in the range of 10−1–100 cm2/V s, and holes are in the range of 100–101 cm2/V s. The electron drift mobilities are about a thousand times smaller than those measured in single crystal CdTe with time-of-flight; the hole mobilities are about ten times smaller. Cells were examined before and after a vapor phase treatment with CdCl2; treatment had little effect on the hole drift mobility, but decreased the electron mobility. We are able to exclude bandtail trapping and dispersion as a mechanism for the small drift mobilities in thin film CdTe, but the actual mechanism reducing the mobilities from the single crystal values is not known.
Ge1−xSnx alloys synthesized by ion implantation and pulsed laser melting
Authors: Gao Kun , Prucnal S. , Huebner R. , Baehtz C. , Skorupa I. , Wang Yutian , Skorupa W. , Helm M. , Zhou Shengqiang
Published: July 2014

The tunable bandgap and the high carrier mobility of Ge1−xSnx alloys stimulate a large effort for bandgap and strain engineering for Ge based materials using silicon compatible technology. In this Letter, we present the fabrication of highly mismatched Ge1−xSnx alloys by ion implantation and pulsed laser melting with Sn concentration ranging from 0.5 at. % up to 1.5 at. %. According to the structural investigations, the formed Ge1−xSnx alloys are monocrystalline with high Sn-incorporation rate. The shrinkage of the bandgap of Ge1−xSnx alloys with increasing Sn content is proven by the red-shift of the E1 and E1 + Δ1 critical points in spectroscopic ellipsometry. Our investigation provides a chip technology compatible route to prepare high quality monocrystalline Ge1−xSnx alloys.
Characterization of CZTSSe photovoltaic device with an atomic layer-deposited passivation layer
Authors: Wu Wei , Cao Yanyan , Caspar Jonathan V. , Guo Qijie , Johnson Lynda K. , Mclean Robert S. , Malajovich Irina , Choudhury Kaushik Roy
Published: July 2014

We describe a CZTSSe (Cu2ZnSn(S1−x,Sex)4) photovoltaic (PV) device with an ALD (atomic layer deposition) coated buffer dielectric layer for CZTSSe surface passivation. An ALD buffer layer, such as TiO2, can be applied in order to reduce the interface recombination and improve the device's open-circuit voltage. Detailed characterization data including current-voltage, admittance spectroscopy, and capacitance profiling are presented in order to compare the performance of PV devices with and without the ALD layer.
Dual-enhancement of ferro-/piezoelectric and photoluminescent performance in Pr3+ doped (K0.5Na0.5)NbO3 lead-free ceramics
Authors: Wei Yongbin , Wu Zheng , Jia Yanmin , Wu Jiang , Shen Yichao , Luo Haosu
Published: July 2014

A mutual enhancement action between the ferro-/piezoelectric polarization and the photoluminescent performance of rare earth Pr3+ doped (K0.5Na0.5)NbO3 (KNN) lead-free ceramics is reported. After Pr3+ doping, the KNN ceramics exhibit the maximum enhancement of ∼1.2 times in the ferroelectric remanent polarization strength and ∼1.25 times in the piezoelectric coefficient d33, respectively. Furthermore, after undergoing a ferro-/piezoelectric polarization treatment, the maximum enhancement of ∼1.3 times in photoluminescence (PL) was observed in the poled 0.3% Pr3+ doped sample. After the trivalent Pr3+ unequivalently substituting the univalent (K0.5Na0.5)+, A-sites ionic vacancies will occur to maintain charge neutrality, which may reduce the inner stress and ease the domain wall motions, yielding to the enhancement in ferro-/piezoelectric performance. The polarization-induced enhancement in PL is attributed to the decrease of crystal symmetry abound the Pr3+ ions after polarization. The dual-enhancement of the ferro-/piezoelectric and photoluminescent performance makes the Pr3+ doped KNN ceramic hopeful for piezoelectric/luminescent multifunctional devices.
EEG Correlates of Perceptual Reversals in Boring's Ambiguous Old/Young Woman Stimulus
Authors: Kornmeier Jürgen , Bach Michael
Published: July 2014

Ambiguous figures attract observers because perception alternates between different interpretations while the sensory information stays unchanged. Understanding the underlying processes is difficult because the precise time instant of this endogenous reversal event needs to be known but is difficult to measure. Presenting ambiguous figures discontinuously and using stimulus onset as estimation of the reversal event increased temporal resolution and provided a series of well-confirmed EEG signatures. In the current EEG study we used this ‘onset paradigm’ for the first time with Boring's old/young woman stimulus. We found an early occipital event-related potential (ERP) correlate of reversals between the perception of the old woman and the perception of the young woman that fits well with previous ERP findings. This component was not followed by the often-reported occipito-parietal Reversal Negativity at 260 ms, but instead by an occipito-temporal N170, that is typically reported with face stimuli. We interpret our results as follows: Ambiguity conflicts take place during processing of stimulus elements in early visual areas roughly 130 ms after stimulus onset. The disambiguation of these elements and their assembly to object ‘gestalts’ result from an interplay between early visual and object-specific brain areas in a temporal window between 130 and 260 ms after stimulus onset. In the particular case of Boring's old/young woman the processes of element disambiguation and gestalt construction are already finished at 170 ms and, thus, 90 ms earlier than in the case of ambiguous geometric figures (eg Necker cube or Schroeder staircase) or of binocular rivalrous gratings.
The effect of anthropogenic volatile organic compound sources on ozone in Boise, Idaho
Authors: Vargas Victor , Chalbot Marie-Cecile , O'Brien Robert , Nikolich George , Dubois David W. , Etyemezian Vic , Kavouras Ilias G.
Published: July 2014

Environmental context
Volatile organic compounds are precursors of ozone, a pollutant with adverse environmental effects. It is important to determine the associations between the various sources of volatile organic compounds and ozone levels because emission controls are based on sources. We estimated the contributions of specific sources of volatile organic compounds on ozone levels using both measurements and statistical models, and found that traffic is the largest source even in events when wildfire smoke is present.

Abstract
Here, we present the application of a tiered approach to apportion the contributions of volatile organic compound (VOC) sources on ozone (O3) concentrations. VOCs from acetylene to n-propylbenzene were measured at two sites at Boise, Idaho, using an online pneumatically focussed gas chromatography system. The mean 24-h concentrations of individual VOCs varied from 0.4ppbC (parts per billion carbon) for 1-butene to 23.2ppbC for m- and p-xylene. The VOC sources at the two monitoring sites were determined by positive matrix factorisation. They were attributed to: (i) liquefied petroleum and natural gas (LPG/NG) emissions; (ii) fugitive emissions of olefins from fuel and solvents; (iii) fugitive emissions of aromatic VOCs from area sources and (iv) vehicular emissions. Vehicle exhausts accounted for 36 to 45% of VOCs followed by LPG/NG and fugitive emissions of aromatic VOCs. Evaluation of photochemical changes showed that the four separate VOC sources were identified by PMF rather than different stages of photochemical processing of fresh emissions. The contributions of VOC sources on daily 8-h maximum O3 concentrations measured at seven locations in the metropolitan urban area were identified by regression analysis. The four VOC sources added, on average, 6.4 to 16.5 parts per billion by volume (ppbv) O3, whereas the unexplained (i.e. intercept) O3 was comparable to non-wildfire policy-relevant background O3 levels in the absence of all anthropogenic emissions of VOC precursors in North America for the region. Traffic was the most significant source influencing O3 levels contributing up to 32ppbv for days with O3 concentrations higher than 75ppbv.
Patients’ experiences of the management of lower back pain in general practice: use of diagnostic imaging, medication and provision of self-management advice
Authors: Carey Mariko , Turon Heidi , Goergen Stacy , Sanson-Fisher Rob , Yoong Sze Lin , Jones Kay
Published: July 2014

Lower back pain is prevalent in the general community. Guidelines recommend against the use of diagnostic imaging unless ‘red flags’ are present that may indicate a potentially serious cause. This paper reports on a cross-sectional electronic survey to investigate self-reported experiences of lower back pain management among Australian general practice patients. Of the 872 participants, 551 (63%) reported that they had experienced lower back pain in the past 12 months. Approximately 40% of patients who had experienced lower back pain reported that they had consulted their general practitioner (GP) regarding this issue. Among those who sought general practice care, 67% reported being referred for diagnostic imaging. Those who received imaging were more likely to have been prescribed medication by their GP, but received self-management advice at the same rate as those who had not been referred. Rates of self-reported referral for diagnostic imaging were higher than expected, given the low prevalence of potentially serious causes for lower back pain reported in the international literature. However, it remains unclear whether this is due to poor guideline adherence by GPs or lack of specificity in the red flags identified in guidelines. Findings suggest the need for improvements in the provision of evidence-based self-management advice.
Recruiting general practitioners as participants for qualitative and experimental primary care studies in Australia
Authors: McKinn Shannon , Bonner Carissa , Jansen Jesse , McCaffery Kirsten
Published: July 2014

Recruiting general practitioners (GPs) for participation in primary care research is vitally important, but it can be very difficult for researchers to engage time-poor GPs. This paper describes six different strategies used by a research team recruiting Australian GPs for three qualitative interview studies and one experimental study, and reports the response rates and costs incurred. Strategies included: (1) mailed invitations via Divisions of General Practice; (2) electronic newsletters; (3) combining mailed invitations and newsletter; (4) in-person recruitment at GP conferences; (5) conference satchel inserts; and (6) combining in-person recruitment and satchel inserts. Response rates ranged from 0 (newsletter) to 30% (in-person recruitment). Recruitment costs per participant ranged from A$83 (in-person recruitment) to A$232 (satchel inserts). Mailed invitations can be viable for qualitative studies, especially when free/low-cost mailing lists are used, if the response rate is less important. In-person recruitment at GP conferences can be effective for short quantitative studies, where a higher response rate is important. Newsletters and conference satchel inserts were expensive and ineffective.
Improving genetic monitoring of the northern hairy-nosed wombat (Lasiorhinus krefftii)
Authors: White Lauren C. , Horsup Alan , Taylor Andrea C. , Austin Jeremy J.
Published: July 2014

The endangered northern hairy-nosed wombat (Lasiorhinus krefftii) has been monitored via remote sampling and genetic techniques since 2000, thus avoiding the detrimental effects on the animals of trapping and increasing the precision of abundance estimates. The currently available dinucleotide microsatellite markers used for this task are prone to stutter and other polymerase chain reaction artefacts, making allele calling difficult, and requiring costly duplication to ensure accuracy. To remedy this we have developed eight new tri- and tetranucleotide microsatellite markers that reduce the problem of stutter in DNA analysis. These new markers, along with three of the existing markers (two microsatellites and the SRY gender marker) were optimised in a single multiplex reaction that will reduce the time and cost of future northern hairy-nosed wombat hair censuses. We tested this new multiplex on 277 non-invasively collected hairs. One locus was rejected due to null-allele issues. The remaining nine microsatellite loci had two or three alleles. Genotype frequencies in the sample of detected individuals did not differ significantly from Hardy–Weinberg equilibrium and there was no evidence of linkage disequilibrium. This new multiplex provides comparable power to distinguish individuals, fewer issues with stutter artefacts and a reduced time and cost of analysis. It will be useful for future population censuses and long-term monitoring of individuals once they have been scored in previously genotyped and assigned samples.
Strand-specific (asymmetric) contribution of phosphodiester linkages on RNA polymerase II transcriptional efficiency and fidelity
Authors: Xu Liang , Zhang Lu , Chong Jenny , Xu Jun , Huang Xuhui , Wang Dong
Published: July 2014

Significance

The nonenzymatic RNA polymerization introduces backbone heterogeneity with a mixture of 2′–5′ and 3′–5′ linkages. RNA polymerase II (pol II) is a key modern enzyme responsible for synthesizing 3′–5′–linked RNA with high fidelity. It is unclear how pol II selectively recognizes the 3′–5′ over 2′–5′ linkage. Here, we systematically investigated how phosphodiester linkages of nucleic acids govern pol II transcriptional efficiency and fidelity. We revealed pol II has an asymmetric (strand-specific) recognition of phosphodiester linkage, which may reflect a universal principle of template-dependent genetic information transfer. Our results elucidate essential contributions of the phosphodiester linkage to pol II transcription and provide important understanding on nucleic acid recognition and genetic information transfer during molecular evolution.
Effective treatment of allergic airway inflammation with
Helicobacter pylori
immunomodulators requires BATF3-dependent dendritic cells and IL-10
Authors: Engler Daniela B. , Reuter Sebastian , van Wijck Yolanda , Urban Sabine , Kyburz Andreas , Maxeiner Joachim , Martin Helen , Yogev Nir , Waisman Ari , Gerhard Markus , Cover Timothy L. , Taube Christian , Müller Anne
Published: July 2014

Significance

Allergic asthma represents an increasingly common public health problem. Here, we provide preclinical evidence for the efficacy of active tolerization using
Helicobacter pylori
components as a viable strategy for asthma prevention. We use a mouse model of allergic asthma to show that regular treatment with
H. pylori
extract effectively alleviates all hallmarks of the disease. Successful treatment depends on the regulatory cytokine IL-10 and on basic leucine zipper ATF-like 3 (BATF3)-dependent dendritic cell lineages.
H. pylori
extracts lacking the γ-glutamyl-transpeptidase GGT or the vacuolating cytotoxin VacA fail to protect against asthma; conversely, both factors can be administered in purified form to achieve protection. In conclusion, the immunomodulatory properties of the common infectious agent
H. pylori
can be exploited for therapeutic purposes in an allergy model.
Targeting PI3Kγ activity decreases vascular trauma-induced intimal hyperplasia through modulation of the Th1 response
Authors: Smirnova Natalia F. , Gayral Stéphanie , Pedros Christophe , Loirand Gervaise , Vaillant Nathalie , Malet Nicole , Kassem Sahar , Calise Denis , Goudounèche Dominique , Wymann Matthias P. , Hirsch Emilio , Gadeau Alain-Pierre , Martinez Laurent O. , Saoudi Abdelhadi , Laffargue Muriel
Published: July 2014

Interventional strategies to treat atherosclerosis, such as transluminal angioplasty and stent implantation, often cause vascular injury. This leads to intimal hyperplasia (IH) formation that induces inflammatory and fibroproliferative processes and ultimately restenosis. We show that phosphoinositide 3-kinase γ (PI3Kγ) is a key player in IH formation and is a valid therapeutic target in its prevention/treatment. PI3Kγ-deficient mice and mice expressing catalytically inactive PI3Kγ (PI3Kγ KD) showed reduced arterial occlusion and accumulation of monocytes and T cells around sites of vascular lesion. The transfer of PI3Kγ KD CD4+ T cells into Rag2-deficient mice greatly reduced vascular occlusion compared with WT cells, clearly demonstrating the involvement of PI3Kγ in CD4+ T cells during IH formation. In addition we found that IH is associated with increased levels of Th1 and Th17 cytokines. A specific decrease in the Th1 response was observed in the absence of PI3Kγ activity, leading to decreased CXCL10 and RANTES production by smooth muscle cells. Finally, we show that treatment with the PI3Kγ inhibitor AS-605240 is sufficient to decrease IH in both mouse and rat models, reinforcing the therapeutic potential of PI3Kγ inhibition. Altogether, these findings demonstrate a new role for PI3Kγ activity in Th1-controlled IH development.
Role of Blimp-1 in programing Th effector cells into IL-10 producers
Authors: Neumann Christian , Heinrich Frederik , Neumann Katrin , Junghans Victoria , Mashreghi Mir-Farzin , Ahlers Jonas , Janke Marko , Rudolph Christine , Mockel-Tenbrinck Nadine , Kühl Anja A. , Heimesaat Markus M. , Esser Charlotte , Im Sin-Hyeog , Radbruch Andreas , Rutz Sascha , Scheffold Alexander
Published: July 2014

Secretion of the immunosuppressive cytokine interleukin (IL) 10 by effector T cells is an essential mechanism of self-limitation during infection. However, the transcriptional regulation of IL-10 expression in proinflammatory T helper (Th) 1 cells is insufficiently understood. We report a crucial role for the transcriptional regulator Blimp-1, induced by IL-12 in a STAT4-dependent manner, in controlling IL-10 expression in Th1 cells. Blimp-1 deficiency led to excessive inflammation during Toxoplasma gondii infection with increased mortality. IL-10 production from Th1 cells was strictly dependent on Blimp-1 but was further enhanced by the synergistic function of c-Maf, a transcriptional regulator of IL-10 induced by multiple factors, such as the Notch pathway. We found Blimp-1 expression, which was also broadly induced by IL-27 in effector T cells, to be antagonized by transforming growth factor (TGF) β. While effectively blocking IL-10 production from Th1 cells, TGF-β shifted IL-10 regulation from a Blimp-1–dependent to a Blimp-1–independent pathway in IL-27–induced Tr1 (T regulatory 1) cells. Our findings further illustrate how IL-10 regulation in Th cells relies on several transcriptional programs that integrate various signals from the environment to fine-tune expression of this critical immunosuppressive cytokine.
Bioenergetic Shifts during Transitions between Stem Cell States (2013 Grover Conference Series)
Authors: Zhang Lianghui , Marsboom Glenn , Glick Danielle , Zhang Yanmin , Toth Peter T. , Jones Nicole , Malik Asrar B. , Rehman Jalees
Published: July 2014

Two defining characteristics of stem cells are their multilineage differentiation potential (multipotency or pluripotency) and their capacity for self‐renewal. Growth factors are well‐established regulators of stem cell differentiation and self renewal, but less is known about the influence of the metabolic state on stem cell function. Recent studies investigating cellular metabolism during the differentiation of adult stem cells, human embryonic stem cells (ESCs), and induced pluripotent stem cells have demonstrated that activation of specific metabolic pathways depends on the type of stem cells as well as the lineage cells are differentiating into and that these metabolic pathways can influence the differentiation process. However, some common patterns have emerged, suggesting that undifferentiated stem cells primarily rely on glycolysis to meet energy demands. Our own data indicate that undifferentiated ESCs not only exhibit a low mitochondrial membrane potential but also express high levels of the mitochondrial uncoupling protein 2 and of glutamine metabolism regulators when compared with differentiated cells. More importantly, interventions that target stem cell metabolism are able to either prevent or enhance differentiation. These findings suggest that the metabolic state of stem cells is not just a marker of their differentiation status but also plays an active role in regulating stem cell function. Regulatory metabolic pathways in stem cells may thus serve as important checkpoints that can be modulated to direct the regenerative capacity of stem cells.
National Osteoporosis Society Vitamin D Guideline Summary
Authors: Aspray Terry J. , Bowring Claire , Fraser William , Gittoes Neil , Javaid M. Kassim , Macdonald Helen , Patel Sanjeev , Selby Peter , Tanna Nuttan , Francis Roger M.
Published: July 2014

The National Osteoporosis Society (NOS) published its document, Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management, in 2013 as a practical clinical guideline on the management of vitamin D deficiency in adult patients with, or at risk of developing, bone disease. There has been no clear consensus in the UK on vitamin D deficiency its assessment and treatment, and clinical practice is inconsistent. This guideline is aimed at clinicians, including doctors, nurses and dieticians. It recommends the measurement of serum 25 (OH) vitamin D (25OHD) to estimate vitamin D status in the following clinical scenarios: bone diseases that may be improved with vitamin D treatment; bone diseases, prior to specific treatment where correcting vitamin D deficiency is appropriate; musculoskeletal symptoms that could be attributed to vitamin D deficiency. The guideline also states that routine vitamin D testing is unnecessary where vitamin D supplementation with an oral antiresorptive treatment is already planned and sets the following serum 25OHD thresholds: <30 nmol/l is deficient; 30–50 nmol/l may be inadequate in some people; >50 nmol/l is sufficient for almost the whole population.

For treatment, oral vitamin D3 is recommended with fixed loading doses of oral vitamin D3 followed by regular maintenance therapy when rapid correction of vitamin D deficiency is required, although loading doses are not necessary where correction of deficiency is less urgent or when co-prescribing with an oral antiresorptive agent. For monitoring, serum calcium (adjusted for albumin) should be checked 1 month after completing a loading regimen, or after starting vitamin D supplementation, in case primary hyperparathyroidism has been unmasked. However, routine monitoring of serum 25OHD is generally unnecessary but may be appropriate in patients with symptomatic vitamin D deficiency or malabsorption and where poor compliance with medication is suspected.

The guideline focuses on bone health as, although there are numerous putative effects of vitamin D on immunity modulation, cancer prevention and the risks of cardiovascular disease and multiple sclerosis, there remains considerable debate about the evaluation of extraskeletal factors and optimal vitamin D status in these circumstances.
FARVAT: a family-based rare variant association test
Authors: Choi Sungkyoung , Lee Sungyoung , Cichon Sven , Nöthen Markus M. , Lange Christoph , Park Taesung , Won Sungho
Published: July 2014

Motivation : Individuals in each family are genetically more homogeneous than unrelated individuals, and family-based designs are often recommended for the analysis of rare variants. However, despite the importance of family-based samples analysis, few statistical methods for rare variant association analysis are available.

Results: In this report, we propose a FA mily-based R are V ariant A ssociation T est ( FARVAT ). FARVAT is based on the quasi-likelihood of whole families, and is statistically and computationally efficient for the extended families. FARVAT assumed that families were ascertained with the disease status of family members, and incorporation of the estimated genetic relationship matrix to the proposed method provided robustness under the presence of the population substructure. Depending on the choice of working matrix, our method could be a burden test or a variance component test, and could be extended to the SKAT-O-type statistic. FARVAT was implemented in C++, and application of the proposed method to schizophrenia data and simulated data for GAW17 illustrated its practical importance.

Availability: The software calculates various statistics for the analysis of related samples, and it is freely downloadable from http://healthstats.snu.ac.kr/software/farvat .

Contact:  won1@snu.ac.kr or tspark@stats.snu.ac.kr

Supplementary information:  supplementary data are available at Bioinformatics online.
NetPathMiner: R/Bioconductor package for network path mining through gene expression
Authors: Mohamed Ahmed , Hancock Timothy , Nguyen Canh Hao , Mamitsuka Hiroshi
Published: July 2014

Summary: NetPathMiner is a general framework for mining, from genome-scale networks, paths that are related to specific experimental conditions. NetPathMiner interfaces with various input formats including KGML, SBML and BioPAX files and allows for manipulation of networks in three different forms: metabolic, reaction and gene representations. NetPathMiner ranks the obtained paths and applies Markov model-based clustering and classification methods to the ranked paths for easy interpretation. NetPathMiner also provides static and interactive visualizations of networks and paths to aid manual investigation.

Availability: The package is available through Bioconductor and from Github at http://github.com/ahmohamed/NetPathMiner

Contact:  mohamed@kuicr.kyoto-u.ac.jp

Supplementary information:  Supplementary data are available at Bioinformatics online.
Greater power and computational efficiency for kernel-based association testing of sets of genetic variants
Authors: Lippert Christoph , Xiang Jing , Horta Danilo , Widmer Christian , Kadie Carl , Heckerman David , Listgarten Jennifer
Published: July 2014

Motivation: Set-based variance component tests have been identified as a way to increase power in association studies by aggregating weak individual effects. However, the choice of test statistic has been largely ignored even though it may play an important role in obtaining optimal power. We compared a standard statistical test—a score test—with a recently developed likelihood ratio (LR) test. Further, when correction for hidden structure is needed, or gene–gene interactions are sought, state-of-the art algorithms for both the score and LR tests can be computationally impractical. Thus we develop new computationally efficient methods.

Results: After reviewing theoretical differences in performance between the score and LR tests, we find empirically on real data that the LR test generally has more power. In particular, on 15 of 17 real datasets, the LR test yielded at least as many associations as the score test—up to 23 more associations—whereas the score test yielded at most one more association than the LR test in the two remaining datasets. On synthetic data, we find that the LR test yielded up to 12% more associations, consistent with our results on real data, but also observe a regime of extremely small signal where the score test yielded up to 25% more associations than the LR test, consistent with theory. Finally, our computational speedups now enable (i) efficient LR testing when the background kernel is full rank, and (ii) efficient score testing when the background kernel changes with each test, as for gene–gene interaction tests. The latter yielded a factor of 2000 speedup on a cohort of size 13 500.

Availability: Software available at http://research.microsoft.com/en-us/um/redmond/projects/MSCompBio/Fastlmm/ .

Contact:  heckerma@microsoft.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Circleator: flexible circular visualization of genome-associated data with BioPerl and SVG
Authors: Crabtree Jonathan , Agrawal Sonia , Mahurkar Anup , Myers Garry S. , Rasko David A. , White Owen
Published: July 2014

Summary: Circleator is a Perl application that generates circular figures of genome-associated data. It leverages BioPerl to support standard annotation and sequence file formats and produces publication-quality SVG output. It is designed to be both flexible and easy to use. It includes a library of circular track types and predefined configuration files for common use-cases, including. (i) visualizing gene annotation and DNA sequence data from a GenBank flat file, (ii) displaying patterns of gene conservation in related microbial strains, (iii) showing Single Nucleotide Polymorphisms (SNPs) and indels relative to a reference genome and gene set and (iv) viewing RNA-Seq plots.

Availability and implementation: Circleator is freely available under the Artistic License 2.0 from http://jonathancrabtree.github.io/Circleator/ and is integrated with the CloVR cloud-based sequence analysis Virtual Machine (VM), which can be downloaded from http://clovr.org or run on Amazon EC2.

Contact:  jcrabtree@som.umaryland.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Metabomxtr: an R package for mixture-model analysis of non-targeted metabolomics data
Authors: Nodzenski Michael , Muehlbauer Michael J. , Bain James R. , Reisetter Anna C. , Lowe William L. , Scholtens Denise M.
Published: July 2014

Summary: Non-targeted metabolomics technologies often yield data in which abundance for any given metabolite is observed and quantified for some samples and reported as missing for other samples. Apparent missingness can be due to true absence of the metabolite in the sample or presence at a level below detectability. Mixture-model analysis can formally account for metabolite ‘missingness’ due to absence or undetectability, but software for this type of analysis in the high-throughput setting is limited. The R package metabomxtr has been developed to facilitate mixture-model analysis of non-targeted metabolomics data in which only a portion of samples have quantifiable abundance for certain metabolites.

Availability and implementation: metabomxtr is available through Bioconductor. It is released under the GPL-2 license.

Contact:  dscholtens@northwestern.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Retro: concept-based clustering of biomedical topical sets
Authors: Yeganova Lana , Kim Won , Kim Sun , Wilbur W. John
Published: July 2014

Motivation: Clustering methods can be useful for automatically grouping documents into meaningful clusters, improving human comprehension of a document collection. Although there are clustering algorithms that can achieve the goal for relatively large document collections, they do not always work well for small and homogenous datasets.

Methods: In this article, we present Retro—a novel clustering algorithm that extracts meaningful clusters along with concise and descriptive titles from small and homogenous document collections. Unlike common clustering approaches, our algorithm predicts cluster titles before clustering. It relies on the hypergeometric distribution model to discover key phrases, and generates candidate clusters by assigning documents to these phrases. Further, the statistical significance of candidate clusters is tested using supervised learning methods, and a multiple testing correction technique is used to control the overall quality of clustering.

Results: We test our system on five disease datasets from OMIM ® and evaluate the results based on MeSH ® term assignments. We further compare our method with several baseline and state-of-the-art methods, including K-means, expectation maximization, latent Dirichlet allocation-based clustering, Lingo, OPTIMSRC and adapted GK-means. The experimental results on the 20-Newsgroup and ODP-239 collections demonstrate that our method is successful at extracting significant clusters and is superior to existing methods in terms of quality of clusters. Finally, we apply our system to a collection of 6248 topical sets from the HomoloGene ® database, a resource in PubMed ® . Empirical evaluation confirms the method is useful for small homogenous datasets in producing meaningful clusters with descriptive titles.

Availability and implementation: A web-based demonstration of the algorithm applied to a collection of sets from the HomoloGene database is available at http://www.ncbi.nlm.nih.gov/CBBresearch/Wilbur/IRET/CLUSTERING_HOMOLOGENE/index.html .

Contact:  lana.yeganova@nih.gov

Supplementary Information:  Supplementary data are available at Bioinformatics online.
The telomeric protein Pot1 from Schizosaccharomyces pombe binds ssDNA in two modes with differing 3′ end availability
Authors: Dickey Thayne H. , Wuttke Deborah S.
Published: July 2014

Telomere protection and length regulation are important processes for aging, cancer and several other diseases. At the heart of these processes lies the single-stranded DNA (ssDNA)-binding protein Pot1, a component of the telomere maintenance complex shelterin, which is present in species ranging from fission yeast to humans. Pot1 contains a dual OB-fold DNA-binding domain (DBD) that fully confers its high affinity for telomeric ssDNA. Studies of S. pombe Pot1-DBD and its individual OB-fold domains revealed a complex non-additive behavior of the two OB-folds in the context of the complete Pot1 protein. This behavior includes the use of multiple distinct binding modes and an ability to form higher order complexes. Here we use NMR and biochemical techniques to investigate the structural features of the complete Pot1-DBD. These experiments reveal one binding mode characterized by only subtle alternations to the individual OB-fold subdomain structures, resulting in an inaccessible 3′ end of the ssDNA. The second binding mode, which has equivalent affinity, interacts differently with the 3′ end, rendering it available for interaction with other proteins. These findings suggest a structural switch that contributes to telomere end-protection and length regulation.
Cortical Bone Trajectory for Thoracic Pedicle Screws
Authors: Matsukawa Keitaro , Yato Yoshiyuki , Hynes Richard A. , Imabayashi Hideaki , Hosogane Naobumi , Asazuma Takashi , Matsui Toshiyasu , Kobayashi Yasushi , Nemoto Koichi
Published: July 2014

Study Design:

A morphometric measurement of new thoracic pedicle screw trajectory using computed tomography and a biomechanical study on cadaveric thoracic vertebrae using insertional torque.

Objective:

To introduce a new thoracic pedicle screw trajectory which maximizes engagement with denser bone.

Summary of Background Data:

Cortical bone trajectory (CBT) which maximizes the thread contact with cortical bone provides enhanced screw purchase. Despite the increased use of CBT screws in the lumbar spine, no study has yet reported the insertional technique for thoracic CBT.

Methods:

First, the computed tomography scans of 50 adults were studied for morphometric measurement of lower thoracic CBT. The starting point was determined to be the intersection of the lateral two thirds of the superior articular process and the inferior border of the transverse process. The trajectory was straight forward in the axial plane angulated cranially targeting the posterior third of the superior endplate. The maximum diameter, length, and the cephalad angle were investigated. Next, the insertional torque of pedicle screws using this new technique was measured and compared with that of the traditional technique on 24 cadaveric thoracic vertebrae.

Results:

All morphometric parameters of thoracic CBT increased from T9 to T12 (the mean diameter: from 5.8 mm at T9 to 8.5 mm at T12; the length: from 29.7 mm at T9 to 32.0 mm at T12; and the cephalad angle: from 21.4 degrees at T9 to 27.6 degrees at T12). The mean maximum insertional torque of CBT screws and traditional screws were 1.02±0.25 and 0.66±0.15 Nm, respectively. The new technique demonstrated average 53.8% higher torque than the traditional technique (P<0.01).

Conclusions:

The detailed morphometric measurement and favorable screw fixation stability of thoracic CBT are reported. The insertional torque using thoracic CBT technique was 53.8% higher than that of the traditional technique.
Atolchelys lepida, a new side-necked turtle from the Early Cretaceous of Brazil and the age of crown Pleurodira
Authors: Romano Pedro S. R. , Gallo Valéria , Ramos Renato R. C. , Antonioli Luzia
Published: July 2014

We report a new pleurodiran turtle from the Barremian Morro do Chaves Formation, Sergipe-Alagoas Basin, Brazil. We tested the phylogenetic position ofAtolchelys lepidagen. et sp. nov. by including it in a comprehensive cladistic analysis of pleurodires. The new species is a basal member of Bothremydidae and simultaneously the oldest unambiguous crown Pleurodira. The biogeographic and chronostratigraphic significance of the finding has implications for the calibration of molecular clocks studies by pushing back the minimum age of crown Pleurodira by more than 12 Ma (ca125 Ma). The reanalysis of Pelomedusoides relationships provides evidence that the early evolution and relationships among the main lineages of side-necked turtles can be explained, at least partially, by a sequence of vicariance events.
Modelling plant species distribution in alpine grasslands using airborne imaging spectroscopy
Authors: Pottier Julien , Malenovský Zbyněk , Psomas Achilleas , Homolová Lucie , Schaepman Michael E. , Choler Philippe , Thuiller Wilfried , Guisan Antoine , Zimmermann Niklaus E.
Published: July 2014

Remote sensing using airborne imaging spectroscopy (AIS) is known to retrieve fundamental optical properties of ecosystems. However, the value of these properties for predicting plant species distribution remains unclear. Here, we assess whether such data can add value to topographic variables for predicting plant distributions in French and Swiss alpine grasslands. We fitted statistical models with high spectral and spatial resolution reflectance data and tested four optical indices sensitive to leaf chlorophyll content, leaf water content and leaf area index. We found moderate added-value of AIS data for predicting alpine plant species distribution. Contrary to expectations, differences between species distribution models (SDMs) were not linked to their local abundance or phylogenetic/functional similarity. Moreover, spectral signatures of species were found to be partly site-specific. We discuss current limits of AIS-based SDMs, highlighting issues of scale and informational content of AIS data.
An absolute interval scale of order for point patterns
Authors: Protonotarios Emmanouil D. , Baum Buzz , Johnston Alan , Hunter Ginger L. , Griffin Lewis D.
Published: July 2014

Human observers readily make judgements about the degree of order in planar arrangements of points (point patterns). Here, based on pairwise ranking of 20 point patterns by degree of order, we have been able to show that judgements of order are highly consistent across individuals and the dimension of order has an interval scale structure spanning roughly 10 just-notable-differences (jnd) between disorder and order. We describe a geometric algorithm that estimates order to an accuracy of half a jnd by quantifying the variability of the size and shape of spaces between points. The algorithm is 70% more accurate than the best available measures. By anchoring the output of the algorithm so that Poisson point processes score on average 0, perfect lattices score 10 and unit steps correspond closely to jnds, we construct an absolute interval scale of order. We demonstrate its utility in biology by using this scale to quantify order during the development of the pattern of bristles on the dorsal thorax of the fruit fly.