1,397 research outputs found
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 g C m−2 yr−1,
comparable to studies of intact peatlands, to a substantial C source of +205±80 g C m−2 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 g C-CH4 m−2 yr−1 to 14.2±4.8 g C-CH4 m−2 yr−1. Average annual aquatic C
losses were 14.4 g C m−2 yr−1
with DOC, DIC, and CO2 evasion of 10.4 g C m−2 yr−1,
1.3 g C m−2 yr−1, and 2.7 g C m−2 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
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