Probe set algorithms: is there a rational best bet?

Affymetrix microarrays have become a standard experimental platform for studies of mRNA expression profiling. Their success is due, in part, to the multiple oligonucleotide features (probes) against each transcript (probe set). This multiple testing allows for more robust background assessments and gene expression measures, and has permitted the development of many computational methods to translate image data into a single normalized "signal" for mRNA transcript abundance. There are now many probe set algorithms that have been developed, with a gradual movement away from chip-by-chip methods (MAS5), to project-based model-fitting methods (dCHIP, RMA, others). Data interpretation is often profoundly changed by choice of algorithm, with disoriented biologists questioning what the "accurate" interpretation of their experiment is. Here, we summarize the debate concerning probe set algorithms. We provide examples of how changes in mismatch weight, normalizations, and construction of expression ratios each dramatically change data interpretation. All interpretations can be considered as computationally appropriate, but with varying biological credibility. We also illustrate the performance of two new hybrid algorithms (PLIER, GC-RMA) relative to more traditional algorithms (dCHIP, MAS5, Probe Profiler PCA, RMA) using an interactive power analysis tool. PLIER appears superior to other algorithms in avoiding false positives with poorly performing probe sets. Based on our interpretation of the literature, and examples presented here, we suggest that the variability in performance of probe set algorithms is more dependent upon assumptions regarding "background", than on calculations of "signal". We argue that "background" is an enormously complex variable that can only be vaguely quantified, and thus the "best" probe set algorithm will vary from project to project

The partitioning of poleward energy transport response between the atmosphere and Ekman flux to prescribed surface forcing in a simplified GCM

Recent studies have indicated that ocean circulation damps the atmospheric energy transport response to hemispherically differential energy perturbations, thereby muting the shifts of the Inter-Tropical Convergence Zone (ITCZ). Here, we focus on the potential role of Ekman heat transport in modulating this atmospheric response. An idealized representation of Ekman-driven heat transport (FE) is included in an aquaplanet slab ocean coupled to a gray radiation atmospheric model. We first alter the strength of FE in the control climate by tuning the gross stability of the Ekman layer SE. For a wide range of FE, the total poleward transport of energy remains nearly unchanged, but the ocean transports an increasing share for larger SE. The control climate is then perturbed by adding surface cooling in the Southern Hemisphere and warming in the Northern Hemisphere. The Ekman coupling damps the atmospheric energy transport response, as in previous coupled model experiments with full ocean dynamics. The ratio of the changes in Ekman to atmospheric energy transport is determined by the ratio of the gross stability in the Ekman layer to the atmosphere in the control climate, and is insensitive to the amplitude and location of forcing. We find that an unrealistically large SE is needed to reproduce the ratio of the changes in cross-equatorial oceanic to atmospheric energy transport in fully coupled models. The limited damping effect of Ekman transport highlights the need to examine the roles of deep circulation and subtropical gyres, as well as ocean heat uptake processes

Superconductivity at the Border of Electron Localization and Itinerancy

The superconducting state of iron pnictides and chalcogenides exists at the border of antiferromagnetic order. Consequently, these materials could provide clues about the relationship between magnetism and unconventional superconductivity. One explanation, motivated by the so-called bad-metal behaviour of these materials, proposes that magnetism and superconductivity develop out of quasi-localized magnetic moments which are generated by strong electron-electron correlations. Another suggests that these phenomena are the result of weakly interacting electron states that lie on nested Fermi surfaces. Here we address the issue by comparing the newly discovered alkaline iron selenide superconductors, which exhibit no Fermi-surface nesting, to their iron pnictide counterparts. We show that the strong-coupling approach leads to similar pairing amplitudes in these materials, despite their different Fermi surfaces. We also find that the pairing amplitudes are largest at the boundary between electronic localization and itinerancy, suggesting that new superconductors might be found in materials with similar characteristics.Comment: Version of the published manuscript prior to final journal-editting. Main text (23 pages, 4 figures) + Supplementary Information (14 pages, 7 figures, 3 tables). Calculation on the single-layer FeSe is added. Enhancement of the pairing amplitude in the vicinity of the Mott transition is highlighted. Published version is at http://www.nature.com/ncomms/2013/131115/ncomms3783/full/ncomms3783.htm

CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren’s syndrome patients and correlates with focus score and disease activity

Background: Primary Sjögren’s syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS. Methods: Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome a nd/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked immunosorbent assay. Results: Our study provides evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte salivary glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate and adaptive immune responses in pSS. Conclusions: These findings suggest that CD4+ T lymphocyte autophagy could play a key role in pSS pathogenesis. Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS

Bojungikgitang and banhabaekchulchonmatang in adult patients with tinnitus, a randomized, double-blind, three-arm, placebo-controlled trial - study protocol

<p>Abstract</p> <p>Background</p> <p>Tinnitus is the perception of hearing a sound for which there is no external acoustic source. It is often associated with sudden, temporary hearing loss and has a clear impact on a patient's quality of life. Despite numerous trials, there are no treatments that can be considered well established in terms of providing replicable long-term tinnitus reduction. Complementary and alternative medical approaches have been employed to relieve symptoms of tinnitus. Bojungikgitang and banhabaekchulchonmatang are among the most strongly preferred and widely used herbal medicines for tinnitus in Korea, as they cause very few serious adverse effects.</p> <p>We aim to establish basic clinical efficacy and safety data for bojungikgitang and banhabaekchulchonmatang, which are approved as herbal medications by the Korea Food and Drug Administration in adult patients with tinnitus.</p> <p>Methods/Design</p> <p>This study was a randomised, double-blind, placebo-controlled trial with three parallel arms (bojungikgitang, banhabaekchulchonmatang, and a placebo). Participants included in the study met the following criteria: typical conditions of intermittent or continuous tinnitus, for more than three months, with involuntary perceptions of the concept of a sound in the absence of an external source. Participants received bojungikgitang, banhabaekchulchonmatang, or a placebo-drug for eight weeks. The total duration of each arm was eleven weeks. Each participant was examined for signs and symptoms of tinnitus before and after taking medication. Post-treatment follow-up was performed two weeks after the final administration of medication.</p> <p>Discussion</p> <p>This trial provided evidence for the efficacy and safety of bojungikgitang and banhabaekchulchonmatang in adult patients with tinnitus. The primary outcome measure was the Tinnitus Handicap Inventory, an assessment used to identify difficulties that may be experienced due to tinnitus. The secondary measures were included an Acoustic Examination and the Visual Analogue Scale. We employed the Euro-Qol 5-Dimension and the Health Utilities Index Mark 3, a health-related quality of life questionnaire. Safety was assessed by complete blood cell count, erythrocyte sedimentation rate, blood chemistry, urine analysis, PA chest film, brain computed tomography, otologic examination, and vital signs.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN23691284</p

Dissociated Representations of Pleasant and Unpleasant Olfacto-Trigeminal Mixtures: An fMRI Study

How the pleasantness of chemosensory stimuli such as odorants or intranasal trigeminal compounds is processed in the human brain has been the focus of considerable recent interest. Yet, so far, only the unimodal form of this hedonic processing has been explored, and not its bimodal form during crossmodal integration of olfactory and trigeminal stimuli. The main purpose of the present study was to investigate this question. To this end, functional magnetic resonance imaging (fMRI) was used in an experiment comparing brain activation related to a pleasant and a relatively unpleasant olfacto-trigeminal mixture, and to their individual components (CO2 alone, Orange alone, Rose alone). Results revealed first common neural activity patterns in response to both mixtures in a number of regions: notably the superior temporal gyrus and the caudate nucleus. Common activations were also observed in the insula, although the pleasant mixture activated the right insula whereas the unpleasant mixture activated the left insula. However, specific activations were observed in anterior cingulate gyrus and the ventral tegmental area only during the perception of the pleasant mixture. These findings emphasized for the firs time the involvement of the latter structures in processing of pleasantness during crossmodal integration of chemosensory stimuli

Extratropical forcing and tropical rainfall distribution: energetics framework and ocean Ekman advection

Intense tropical rainfall occurs in a narrow belt near the equator, called the inter-tropical convergence zone (ITCZ). In the past decade, the atmospheric energy budget has been used to explain changes in the zonal-mean ITCZ position. The energetics framework provides a mechanism for extratropics-to-tropics teleconnections, which have been postulated from paleoclimate records. In atmosphere models coupled with a motionless slab ocean, the ITCZ shifts toward the warmed hemisphere in order for the Hadley circulation to transport energy toward the colder hemisphere. However, recent studies using fully coupled models show that tropical rainfall can be rather insensitive to extratropical forcing when ocean dynamics is included. Here, we explore the effect of meridional Ekman heat advection while neglecting the upwelling effect on the ITCZ response to prescribed extratropical thermal forcing. The tropical component of Ekman advection is a negative feedback that partially compensates the prescribed forcing, whereas the extratropical component is a positive feedback that amplifies the prescribed forcing. Overall, the tropical negative feedback dominates over the extratropical positive feedback. Thus, including Ekman advection reduces the need for atmospheric energy transport, dampening the ITCZ response. We propose to build a hierarchy of ocean models to systematically explore the full dynamical response of the coupled climate system

Synthesis of Tin Nitride SnxNyNanowires by Chemical Vapour Deposition

Tin nitride (SnxNy) nanowires have been grown for the first time by chemical vapour deposition on n-type Si(111) and in particular by nitridation of Sn containing NH4Cl at 450 °C under a steady flow of NH3. The SnxNynanowires have an average diameter of 200 nm and lengths ≥5 μm and were grown on Si(111) coated with a few nm’s of Au. Nitridation of Sn alone, under a flow of NH3is not effective and leads to the deposition of Sn droplets on the Au/Si(111) surface which impedes one-dimensional growth over a wide temperature range i.e. 300–800 °C. This was overcome by the addition of ammonium chloride (NH4Cl) which undergoes sublimation at 338 °C thereby releasing NH3and HCl which act as dispersants thereby enhancing the vapour pressure of Sn and the one-dimensional growth of SnxNynanowires. In addition to the action of dispersion, Sn reacts with HCl giving SnCl2which in turn reacts with NH3leading to the formation of SnxNyNWs. A first estimate of the band-gap of the SnxNynanowires grown on Si(111) was obtained from optical reflection measurements and found to be ≈2.6 eV. Finally, intricate assemblies of nanowires were also obtained at lower growth temperatures