Enhancer of zeste homolog 2 (EZH2) is a critical component of the polycomb-repressive complex 2 (PRC2), which is involved in gene silencing and histone H3 lysine 27 methylation. EZH2 has a master ...regulatory function in controlling such processes as stem cell differentiation, cell proliferation, early embryogenesis and X chromosome inactivation. Although benign epithelial cells express very low levels of EZH2, increased levels of EZH2 have been observed in aggressive solid tumors such as those of the prostate, breast and bladder. The mechanism by which EZH2 mediates tumor aggressiveness is unclear. Here, we demonstrate that EZH2 mediates transcriptional silencing of the tumor suppressor gene E-cadherin by trimethylation of H3 lysine 27. Histone deacetylase inhibitors can prevent EZH2-mediated repression of E-cadherin and attenuate cell invasion, suggesting a possible mechanism that may be useful for the development of therapeutic treatments. Taken together, these observations provide a novel mechanism of E-cadherin regulation and establish a functional link between dysregulation of EZH2 and repression of E-cadherin during cancer progression.
This review paper presents tribological and mechanical characteristics of hybrid polymer composite materials that exhibit low friction and low wear. Polymer fiber reinforced materials possess low ...weight and high specific quality along with high specific stiffness. This study targets a critical review of wear and frictional characteristics of hybrid polymer composite materials. Tribological properties have been evaluated by various researchers using a rotating pin‐on‐disc tribometer and reciprocating wear testing machine. Most likely filler materials are carbon, graphite, nano silica, bronze, glass fibers, MoS2, and polytetrafluoroethylene (PTFE) added in the polyether ether ketone (PEEK), polyamide 66, thermoses polymer, etc. It improves mechanical and tribological properties of hybrid composite materials. This review paper aims to highlights the comparative study of various fillers added in PEEK, Polyamide 66, and thermoses polymer hybrid materials. Recently hybrid composites are used in wide range of applications since it has light weight and high strength.
Polysulfone (Psf) hollow fiber membranes (HFMs) have been widely used in blood purification but their biocompatibility remains a concern. To enhance their biocompatibility, Psf/TPGS (d-α-tocopheryl ...polyethylene glycol 1000 succinate) composite HFMs and 2-methacryloyloxyethyl phosphorylcholine (MPC) coated Psf HFMs have been prepared. They have been evaluated for in vivo biocompatibility and graft acceptance and compared with sham and commercial membranes by intra-peritoneal implantation in rats at day 7 and 21. Normal body weights, tissue formation and angiogenesis indicate acceptance of implants by the animals. Hematological observations show presence of post-surgical stress which subsides over time. Serum biochemistry results reveal normal organ function and elevated liver ALP levels at day 21. Histological studies exhibit fibroblast recruitment cells, angiogenesis and collagen deposition at the implant surface indicating new tissue formation. Immuno-histochemistry studies show non-activation of MHC molecules signifying biocompatibilty. Additionally, Psf/TPGS exhibit most favorable tissue response as compared with other HFMs making them the material of choice for HFM preparation for hemodialysis applications.
Chickpea is an important cool season legume crop. The breeding efforts in chickpea are often hampered due to the narrow genetic base. Availability of diverse germplasm is an essential requirement for ...any crop improvement programme. This can facilitate development of desirable gene combinations and subsequently the improved cultivars. In any marker-assisted selection (MAS) programme, study of parental polymorphism using QTL linked markers is a pre-requisite for screening of desired genotypes. Any such study involving use of markers chosen randomly can only tell the diversity of the parents, but does not guarantee success of the MAS. The present study was undertaken to study the suitability of the SSR markers from the
QTL-hotspot
region linked with drought tolerance related traits in different genetic background. The study of polymorphism of the
QTL-hotspot
linked SSR markers NCPGR127, NCPGR21, TAA170, ICCM0249, STMS11, TR11 and GA24 between drought tolerant genotype ICC-4958 and remaining 32 chickpea genotypes revealed that most of the genotypes had monomorphic alleles as that of ICC-4958, while only a few genotypes showed polymorphic alleles. The markers that are found polymorphic between ICC-4958 and other chickpea genotypes can be used directly for foreground selection in MAS as they are mapped in the
QTL-hotspot
region. However, in cases where these are monomorphic, additional markers from
QTL-hotspot
region need to be screened. Besides validating the suitability of these markers, we also validated SSR markers that can be used for the background selection. Of the 21 SSR markers, 15 were found polymorphic between ICC-4958 and other genotypes suggesting their usefulness in the background selection.
Abstract Spasticity is often experienced by individuals with injury or illness of the central nervous system from etiologies such as stroke, spinal cord injury, brain injury, multiple sclerosis, or ...other neurologic conditions. Although spasticity may provide benefits in some patients, it more often leads to complications negatively impacting the patient. Nonpharmacologic treatment options often do not provide long-term reduction of spasticity, and systemic interventions, such as oral medications, can have intolerable side effects. The use of botulinum neurotoxin injections is one option for management of focal spasticity. Several localization techniques are available to physicians that allow for identification of the selected target muscles. These methods include anatomic localization in isolation or in conjunction with electromyography guidance, electrical stimulation guidance, or ultrasound guidance. This article will focus on further description of each of these techniques in relation to the treatment of adult spasticity and will discuss the advantages and disadvantages of each technique, as well as review the literature comparing the techniques.
Patient- and caregiver-reported data are lacking on the burden of spasticity, and the impact of botulinum neurotoxin type A (BoNT-A) treatment for this condition, on patients' daily lives. As ...recommended in recent guidance from the US Food and Drug Administration, online patient communities can represent a platform from which to gather specific information outside of a clinical trial setting on the burden of conditions experienced by patients and caregivers and their views on treatment options in order to inform evidence-based medicine and drug development.
The objective of our study is to characterize spasticity symptoms and their associated burdens on Western European and US patients and caregivers in the realms of work, daily activities, quality of life (QoL), as well as the positive and negative impacts of treatment with BoNT-A (cost, time, QoL) using Carenity, an international online community for people with chronic health conditions.
We performed a noninterventional, multinational survey. Eligible participants were 18 years old or older and had, or had cared for, someone with spasticity who had been treated with BoNT-A for at least 1 year. Patients and caregivers were asked to complete an internet-based survey via Carenity; caregivers reported their own answers and answered on behalf of their patients. Questions included the burden of spasticity on the ability to work, functioning, daily-living activities, and QoL, the impact of BoNT A therapy on patients' lives, and the potential benefits of fewer injections.
There were 615 respondents (427 patients and 188 caregivers). The mean age of patients and caregivers was 41.7 years and 38.6 years, respectively, and the most commonly reported cause of spasticity was multiple sclerosis. Caregivers were most often the parents (76/188, 40%) or another family member (51/188, 27%) of their patients. Spasticity had a clear impact on patients' and caregivers' lives, including the ability to work and injection costs. For patients, spasticity caused difficulties with activities of daily living and reduced QoL indices. The median number of BoNT-A injections was 4 times per year, and 92% (393/427) of patients reported that treatment improved their overall satisfaction with life. Regarding the BoNT-A injection burden, the greatest patient-reported challenges were the cost and availability of timely appointments. Overall, 86% (368/427) of patients believed that a reduced injection frequency would be beneficial. Caregivers answering for their patients gave largely similar responses to those reported by patients.
Spasticity has a negative impact on both patients' and caregivers' lives. All respondents reported that BoNT A treatment improved their lives, despite the associated challenges. Patients believed that reducing the frequency of BoNT-A injections could alleviate practical issues associated with treatment, implying that a longer-acting BoNT-A injection would be well received.
Levodopa is the most efficacious treatment for Parkinson's disease (PD). Long-term treatment with levodopa is limited due to dyskinesia. Dyskinesia in PD can be socially and functionally disabling. ...Extended-release amantadine (amantadine ER) is the first approved medication for the treatment of dyskinesia. When it is given at bedtime, it reaches plasma concentration approximately twice the level achieved by amantadine immediate release. Amantadine ER reduces the severity and duration of dyskinesia during the day, reduces OFF time and increases ON time without troublesome dyskinesia. The most common side effects are hallucination, dizziness, orthostatic hypotension and pedal edema. This review discusses the safety and efficacy of amantadine ER in dyskinesia in PD patients.
A ~60 km long Veldurti–Kalva–Gani (VKG) fault is one of the identified strike-slip faults extending from Eastern Dharwar Craton (EDC) to Cuddapah basin in South Indian Shield. The recorded recent ...seismic activity during year 2012–2016 show occurrences of three microseismic events (<
M
w
2.0) in the vicinity of this fault. Historically, no major seismic events are recorded near this fault except magnitude of 5.0–5.9 (1843) earthquake at about ~80 km west of this fault near Bellary. In the present study, analysis of available gravity, aeromagnetic and newly acquired ground gravity and magnetic data in the vicinity of the fault has been carried out to understand subsurface characteristics of this VKG fault and nearby structural features related to recent seismic activity. Analysis of aeromagnetic and gravity data shows shallow origin of the fault and earthquakes are associated with the zone of intersection like cross faults/lineaments which are parallel and perpendicular to the VKG fault. The calculated log normalized radially averaged power spectrum of the available gravity and aeromagnetic data shows four average depths
h
0
(12.7 km),
h
1
(6 km),
h
2
(2.0 km) and
h
3
(0.5 km). These estimated depths are possibly, bottom of the upper crust, thickness of the Cuddapah basin sediments, horizon of the basic sills, flows and the ferruginous quartzites and cumulative stratigraphic thickness of the Tadpatri shales and the Kurnools in the areas, respectively. The jointly inverted 2-D model from the ground gravity and aeromagnetic data along 2.7 km profile across VKG fault shows, faulting between Banganapalli Quartzite and Tadpatri Shales. The estimated average focal depth from the observed microseismic events is around 13 km. It is concluded from the present study that the observed microseismic events in the vicinity of VKG fault are associated with the intersection zones of cross faults/lineaments near the VKG fault and originated at an average depth of 13 km might be bottom of the upper crust. The estimated depths from the present analysis are well corroborated with previous geophysical studies.
Highlights
Mapping of Veldurti–Kalva–Gani fault through gravity, magnetic and aeromagnetic data which is associated with recent seismic activity.
Understanding of origin of the seismic activity through spectral analysis.
Estimation of depth to the basement, upper crust and thickness of Cuddapah basin sediments in the study region.
Estimation of focal depth from seismological data and corroboration with spectral analysis of gravity and aeromagnetic data.
Drought is an important global hazard, challenging the sustainable agriculture and food security of nations. Measuring agricultural drought vulnerability is a prerequisite for targeting interventions ...to improve and sustain the agricultural performance of both irrigated and rain-fed agriculture. In this study, crop-generic agricultural drought vulnerability status is empirically measured through a composite index approach. The study area is Haryana state, India, a prime agriculture state of the country, characterised with low rainfall, high irrigation support and stable cropping pattern. By analysing the multiyear rainfall and crop condition data of kharif crop season (June–October) derived from satellite data and soil water holding capacity and groundwater quality, nine contributing indicators were generated for 120 blocks (sub-district administrative units). Composite indices for exposure, sensitivity and adaptive capacity components were generated after assigning variance-based weightages to the respective input indicators. Agricultural Drought Vulnerability Index (ADVI) was developed through a linear combination of the three component indices. ADVI-based vulnerability categorisation revealed that 51 blocks are with vulnerable to very highly vulnerable status. These blocks are located in the southern and western parts of the state, where groundwater quality is saline and water holding capacity of soils is less. The ADVI map has effectively captured the spatial pattern of agricultural drought vulnerability in the state. Districts with large number of vulnerable blocks showed considerably larger variability of de-trended crop yields. Correlation analysis reveals that crop condition variability, groundwater quality and soil factors are closely associated with ADVI. The vulnerability index is useful to prioritise the blocks for implementation of long-term drought management plans. There is scope for improving the methodology by adding/fine-tuning the indicators and by optimising the weights.
Three distinct alkaline magmas, represented by shonkinite, lamprophyre and alkali basalt dykes, characterize a significant magmatic expression of rift-related mantle-derived igneous activity in the ...Mesoproterozoic Prakasam Alkaline Province, SE India. In the present study we have estimated emplacement
velocities (ascent rates)
for these three varied alkaline magmas and compared with other silicate magmas to explore composition control on the ascent rates. The alkaline dykes have variable widths and lengths with none of the dykes wider than 1 m. The shonkinites are fine- to medium-grained rocks with clinopyroxene, phologopite, amphibole, K-feldspar perthite and nepheline as essential minerals. They exhibit equigranular hypidiomorphic to foliated textures. Lamprophyres and alkali basalts characteristically show porphyritic textures. Olivine, clinopyroxene, amphibole and biotite are distinct phenocrysts in lamprophyres whereas olivine, clinopyroxene and plagioclase form the phenocrystic mineralogy in the alkali basalts. The calculated densities 2.54–2.71 g/cc for shonkinite; 2.61–2.78 g/cc for lamprophyre; 2.66–2.74 g/cc for alkali basalt and viscosities 3.11–3.39 Pa s for shonkinite; 3.01–3.28 Pa s for lamprophyre; 2.72–3.09 Pa s for alkali basalt are utilized to compute velocities (ascent rates) of the three alkaline magmas. Since the lamprophyres and alkali basalts are crystal-laden, we have also calculated effective viscosities to infer crystal control on the velocities. Twenty percent of crystals in the magma increase the viscosity by 2.7 times consequently decrease ascent rate by 2.7 times compared to the crystal-free magmas. The computed
ascent rates
range from 0.11–2.13 m/sec, 0.23–2.77 m/sec and 1.16–2.89 m/sec for shonkinite, lamprophyre and alkali basalt magmas respectively. Ascent rates increase with the width of the dykes and density difference, and decrease with magma viscosity and proportion of crystals. If a constant width of 1 m is assumed in the magma-filled dyke propagation model, then the sequence of emplacement velocities in the decreasing order is alkaline magmas (4.68–15.31 m/sec) > ultramafic-mafic magmas (3.81–4.30 m/sec) > intermediate-felsic magmas (1.76–2.56 m/sec). We propose that SiO
2
content in the terrestrial magmas can be modeled as a semi-quantitative “geospeedometer” of the magma ascent rates.
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