Long noncoding RNAs in liver cancer: what we know in 2014.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer with an estimated over half a million new cases diagnosed annually. Due to the difficulty in early diagnosis and lack of effective treatment options, HCC is currently ranked as the second highest neoplastic-related mortality in the world, with an extremely low 5-year survival rate of between 6 and 11%. Long noncoding RNAs (lncRNAs), are genes lacking protein coding ability, have recently emerged as pivotal participants in biological processes, often dysregulated in a range of cancers, including HCC. AREAS COVERED: In this review, we highlight the recent findings of lncRNAs in HCC pathogenesis, with particular attention on epigenetic events. In silico analysis was utilized to emphasize intrinsic linkages within the ncRNA families associated with hepatocarcinogenesis. EXPERT OPINION: While our understanding of lncRNAs in the onset and progression of HCC is still in its infancy, there is no doubt that understanding the activities of ncRNAs will certainly secure strong biomarkers and improve treatment options for HCC patients

First-principles investigation of 180-degree domain walls in BaTiO_3

We present a first-principles study of 180-degree ferroelectric domain walls in tetragonal barium titanate. The theory is based on an effective Hamiltonian that has previously been determined from first-principles ultrasoft-pseudopotential calculations. Statistical properties are investigated using Monte Carlo simulations. We compute the domain-wall energy, free energy, and thickness, analyze the behavior of the ferroelectric order parameter in the interior of the domain wall, and study its spatial fluctuations. An abrupt reversal of the polarization is found, unlike the gradual rotation typical of the ferromagnetic case.Comment: Revtex (preprint style, 13 pages) + 3 postscript figures. A version in two-column article style with embedded figures is available at http://electron.rutgers.edu/~dhv/preprints/index.html#pad_wal

Identification of Commercially Available Antibodies that Block Ligand Binding by BMPR2

Osteoporosis, a disease of low bone mineral density, affects 10 million Americans and triggers significant health problems and considerable socioeconomic burdens. Current treatments for osteoporosis have significant limitations, necessitating identifying new treatment strategies via building a better understanding of the endogenous mechanisms regulating bone mass. A recent study demonstrated that removal of the BMP type 2 receptor (BMPR2) in skeletal progenitor cells of Bmpr2-cKO mice during embryonic development leads to reduced age-related bone loss by sustained elevation in bone formation rate. This present study sought to advance the translational potential of the genetic model by identifying antibodies that neutralize the ligand-binding function of the BMPR2 extracellular domain (BMPR2-ECD). This study first established a modified, cell-free immunoprecipitation assay wherein the ligand BMP2 was pulled-down by BMPR2-ECD conjugated to Protein G beads; the unbound BMP2 (found in the supernatant) was subsequently quantified by ELISA. This yielded a standard assay wherein approximately 2 ug BMPR2-ECD leads to a 70% reduction in BMP2 signal. Next, the neutralizing ability of 3F6, a mouse monoclonal antibody raised against the ligand-binding region of BMPR2, was examined and was found to cause a dose-dependent inhibition of BMPR2-ECD ligand-binding. Given the ascites preparation of 3F6, specificity of this assay was confirmed by demonstrating that ligand-binding activity of BMPR2-ECD is unchanged in the presence of non-specific, negative-control ascites. Using these results as a guide, 1F12, another mouse monoclonal antibody raised against the ligand-binding region of BMPR2, was evaluated and was also found to neutralize the ligand-binding function of BMPR2-ECD. In contrast, no effect on ligand-binding function of BMPR2-ECD was observed with 9A10 even though this mouse monoclonal antibody is also raised against the ligand-binding region of BMPR2. These results provide proof-of-concept data for future studies evaluating inhibition of BMPR2 function in vivo as a means to reduce age-related bone loss

Corporate tax and location choice for multinational firms

This paper examines the effects of corporate tax on these location decisions of newly established multinational subsidiaries across 26 European countries over an eight year period. We contribute to the existing literature by examining the effects of a non-linear response of firm location decisions to changes in the tax rate. We also show that there are large variations in the sensitivity to tax rates across sectors and firm size groups. In particular, financial sector firms are more than twice as sensitive to changes in corporation tax rates relative to other sectors. Our baseline result is a finding that a one percent increase in the statutory or policy rate of corporation tax would lead to a reduction in the conditional location probability of 0.68 percent. Using the effective average tax rate (EATR), the marginal effect implies a reduction in the location probability of 1.15 percent following a 1 percent increase in the tax rate. Although overall tax has the expected negative effect on location probability, the marginal effect of an increase is lower at higher rates of tax

Identification of a bone morphogenetic protein type 2 receptor neutralizing antibody

The bone morphogenetic protein (BMP) signaling pathway comprises the largest subdivision of the transforming growth factor (TGFβ) superfamily. BMP signaling plays essential roles in both embryonic development and postnatal tissue homeostasis. Dysregulated BMP signaling underlies human pathologies ranging from pulmonary arterial hypertension to heterotopic ossification. Thus, understanding the basic mechanisms and regulation of BMP signaling may yield translational opportunities. Unfortunately, limited tools are available to evaluate this pathway, and genetic approaches are frequently confounded by developmental requirements or ability of pathway components to compensate for one another. Specific inhibitors for type 2 receptors are poorly represented. Thus, we sought to identify and validate an antibody that neutralizes the ligand-binding function of BMP receptor type 2 (BMPR2) extracellular domain (ECD)

Thermal Diffusion and Quench Propagation in YBCO Pancake Coils Wound with ZnO-and Mylar Insulations

The thermal diffusion properties of several different kinds of YBCO insulations and the quench properties of pancake coils made using these insulations were studied. Insulations investigated include Nomex, Kapton, and Mylar, as well as insulations based on ZnO, Zn2GeO4, and ZnO-Cu. Initially, short stacks of YBCO conductors with interlayer insulation, epoxy, and a central heater strip were made and later measured for thermal conductivity in liquid nitrogen. Subsequently, three different pancake coils were made. The first two were smaller, each using one meter total of YBCO tape present as four turns around a G-10 former. One of these smaller coils used Mylar insulation co-wound with the YBCO tape, the other used YBCO tape onto which ZnO based insulation had been deposited. One larger coil was made which used 12 total meters of ZnO-insulated tape and had 45 turns. The results for all short sample and coil thermal conductivities were ~1-3 Wm-1K-1. Finally, quench propagation velocity measurements were performed on the coils (77 K, self field) by applying a DC current and then using a heater pulse to initiate a quench. Normal zone propagation velocity (NZP) values were obtained for the coils both in the radial direction and in the azimuthal direction. Radial NZP values (0.05-0.7 mm/s) were two orders of magnitude lower than axial values (~14-17 mm/s). Nevertheless, the quenches were generally seen to propagate radially within the coils, in the sense that any given layer in the coil is driven normal by the layer underneath it.Comment: 58 pages, 5 tables, 16 fig

Trends in the Statistical Assessment of Reliability

Changes in technology have had and will continue to have a strong effect on changes in the area of statistical assessment of reliability data. These changes include higher levels of integration in electronics, improvements in measurement technology and the deployment of sensors and smart chips into more products, dramatically improved computing power and storage technology, and the development of new, powerful statistical methods for graphics, inference, and experimental design and reliability test planning. This paper traces some of the history of the development of statistical methods for reliability assessment and makes some predictions about the future

Carbon balance of a restored and cutover raised bog: implications for restoration and comparison to global trends

The net ecosystem exchange (NEE) and methane (CH4) flux were measured by chamber measurements for five distinct ecotypes (areas with unique eco-hydrological characteristics) at Abbeyleix Bog in the Irish midlands over a 2-year period. The ecotypes ranged from those with high-quality peat-forming vegetation to communities indicative of degraded, drained conditions. Three of these ecotypes were located in an area where peat was extracted by hand and then abandoned and left to revegetate naturally at least 50 years prior to the start of the study. Two of the ecotypes were located on an adjacent raised bog, which although never mined for peat, was impacted by shallow drainage and then restored (by drain blocking) 6 years prior to the start of the study. Other major aspects of the carbon (C) balance, including dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), and open-water CO2 evasion, were quantified for a catchment area at the study site over the same 2-year period. The ecotype average annual ecotype C balance ranged from a net C sink of -58±60&thinsp;g&thinsp;C&thinsp;m−2&thinsp;yr−1, comparable to studies of intact peatlands, to a substantial C source of +205±80&thinsp;g&thinsp;C m−2&thinsp;yr−1, with NEE being the most variable component of the C balance among the five ecotypes. Ecotype annual CH4 flux ranged from 2.7±1.4&thinsp;g&thinsp;C-CH4&thinsp;m−2&thinsp;yr−1 to 14.2±4.8&thinsp;g&thinsp;C-CH4&thinsp;m−2&thinsp;yr−1. Average annual aquatic C losses were 14.4&thinsp;g&thinsp;C&thinsp;m−2&thinsp;yr−1 with DOC, DIC, and CO2 evasion of 10.4&thinsp;g&thinsp;C&thinsp;m−2&thinsp;yr−1, 1.3&thinsp;g&thinsp;C&thinsp;m−2&thinsp;yr−1, and 2.7&thinsp;g&thinsp;C&thinsp;m−2&thinsp;yr−1, respectively. A statistically significant negative correlation was found between the mean annual water table (MAWT) and the plot-scale NEE but not the global warming potential (GWP). However, a significant negative correlation was observed between the plot-scale percentage of Sphagnum moss cover and the GWP, highlighting the importance of regenerating this keystone genus as a climate change mitigation strategy in peatland restoration. The data from this study were then compared to the rapidly growing number of peatland C balance studies across boreal and temperate regions. The trend in NEE and CH4 flux with respect to MAWT was compared for the five ecotypes in this study and literature data from degraded/restored/recovering peatlands, intact peatlands, and bare peat sites.</p

I smoke to cope with pain: patients\u27 perspectives on the link between cigarette smoking and pain

BACKGROUND: For people with chronic pain, cigarette smoking is associated with greater pain intensity and impairment. Researchers have hypothesized a reciprocal relationship in which pain and smoking exacerbate each other, resulting in greater pain and increased smoking. This study aimed to qualitatively examine patient perspectives on this association. METHODS: A retrospective thematic analysis of smoking cessation counseling notes for 136 veterans in the Pain and Smoking Study, a tailored smoking cessation trial, was conducted. A validated codebook was applied to each counseling note by four independent coders using Atlas.ti (Atlas.ti, Berlin, Germany). Coders participated in a consensus-forming exercise with salient themes validated among the wider research team. KEY RESULTS: Participants averaged 60 years of age (range 28-77 years) and were 9% female. The median number of cigarettes smoked per day was 15, with a mean pain intensity score in the last week (from 0-10) of 5.1. While not all patients acknowledged a connection between pain and smoking, we found that (1) pain motivates smoking and helps manage pain-related distress, as a coping strategy and through cognitive distraction, and (2) pain motivates smoking but smoking does not offer pain relief. Concerns about managing pain without smoking was identified as a notable barrier to cessation. CONCLUSION: Many patients with chronic pain who smoke readily identified pain as a motivator of their smoking behavior and are reluctant to quit for this reason. Integrated interventions for smokers with pain should address these perceptions and expectancies and promote uptake of more adaptive self-management strategies for pain