Parametric investigation of W-EDM factors for machining AM60B conductive biomaterial.

Wire-electrical discharge machining (W-EDM) is a precise and efficient non-traditional technology employed to cut intricate shapes in conductive biomaterials. These biomaterials are challenging to machine using traditional methods. This present study delves into the impact of various process parameters, namely discharge duration (Ddur), spark gap time (Stime), discharge voltage (Dvolt), and wire advance rate rate (Wadv). This research evaluates the impact of several factors on response variables, namely the machining rate (MR) and surface irregularity (SR), during the machining process of the AM60B magnesium alloy. The confirmation of the material used in the machining process is achieved via the utilisation of a scanning electron microscopy (SEM) image in conjunction with an energy dispersive spectroscopic (EDS) image. The experiment is designed as L9 orthogonal array by using Taguchi's approach, taking into account 4 factors with 3 levels. The objective of this experiment is to ascertain the most favourable values for machining parameters while working with AM60B magnesium alloy using brass wire. Through analysis of variance (ANOVA), the study confirms that wire advance rate (43.10%) is the most influencing parameter for machining rate and surface irregularity followed by spark gap time (33.91%) and discharge duration (11.48%). Additionally, The TOPSIS-CRITIC and the desirability approach were used in order to determine the optimum parameter combinations that provide the most favourable combined output. Confirmatory testing is used to evaluate the efficiency of the stated ideal conditions. The maximum improvement in Desirability approach is obtained at 4.56% and 4.193% for MR and SR respectively. The maximum improvement in TOPSIS approach is obtained at 1.77% and 2.78% for MR and SR respectively.

Effect of silicon carbide on kerf convergence and irregularity of the surface during abrasive water jet machining of fiber-metal hybrid composites.

The traditional way to machine hybrid composites is hard because they tend to break, have a high retraction, have a high service temperature, and have an uneven surface irregularity. For high-strength fiber/metal composite constructions, alternative machining methods have drawn interest as a solution to these problems. Current research focuses on enhancing the Abrasive Water Jet Machining process by optimizing its variables using a composite material of epoxy reinforced with silicon carbide, stainless steel wire mesh, and Kevlar. The variables assessed are the Nozzle-to-substrate gap (S), the Abrasive discharge molding and different percentages of silicon carbide (SiC) filler (0%, 3%, and 6% by weight), three different types of hybrid laminates (H1, H2, and H3) were produced. The response surface method (RSM) was utilized in this learning, specifically on a central composite design, to calculate and optimize machining variables based on the Kerf convergence ratio (Kt) and Surface irregularity (Ra) as responses. According to the results, the traverse feed velocity, Abrasive discharge proportion, and Nozzle-to-substrate gap are the critical factors in determining Surface irregularity and Kerf convergence width (H1 laminate) for a fiber/metal laminate with 0%, 3% and 6% weight fraction. In the case of a 3% weight fraction H2 laminate, the traverse feed velocity was identified as the primary factor affecting the Kerf convergence ratio. In contrast, traverse feed velocity and Nozzle-to-substrate gap had the most significant influence on Surface irregularity. The findings also indicated that S, followed by Abrasive discharge proportion and traverse feed velocity, are the variables that have the most significant influence when cutting 6 wt% SiC filler particle fiber/metal laminate (H3 laminate). For Surface irregularity, the combination of traverse feed velocity and Nozzle-to-substrate gap had the most significant impact. To validate the optimization results, confirmatory tests was conducted, and the findings were very similar to the experimental values, indicating the accuracy and effectiveness of the optimization process. To better understand the manufacturing processes, a scanning electron microscope was used to examine the morphological features of the machined surfaces, such as delamination, fibre breakage, and fibre pull-out.

Paternal stress alters synaptic density and expression of GAP-43, GRIN1, M1 and SYP genes in the hippocampus and cortex of offspring of stress-induced male rats.

Adverse experiences during pregnancy have a negative impact on the neuronal structure and behavior of offspring, but the effects of a father's life events on the outcome of progeny are scarce. The present study is intended to investigate whether paternal stress affects the offspring brain structure, especially those regions concerned with learning and formation of memory, namely the hippocampus (HC) and prefrontal cortex (PFC), and also the expression of certain genes linked to learning and memory in the offspring. Induced stress to male rats by five stressors, one per day followed by allowing them to mate with the normal, unstressed female. Synaptophysin immunoreactivity was assessed in the tissue sections of the HC and PFC as well as expression of genes concerned with learning and memory was evaluated by RT-PCR in the progeny of stress-received males. The progeny of stressed rats had reduced antisynaptophysin immunoreactivity in the HC and PFC. The synaptic density in HC was less in the A-S (Offspring of male rats who received stress during adulthood) and PA-S (offspring of male rats who received stress during both adolescence and adulthood) than in P-S (offspring of male rats who received stress during adolescence) and C-C (offspring of control) groups. Similar results were observed even in the PFC. The results of post hoc tests proved that the HC and PFC of the progeny of stress-exposed rats exhibited considerably less synaptic density than control (P<0.05), and the levels of expression of GAP-43, GRIN1, M1, and SYP genes in HC and PFC were down-regulated. This study concludes that paternal adverse experiences can affect the offspring's synaptic plasticity and also the genes, which can regulate learning and formation of memory.

Influence of Alkaline-Earth-Metal Substitutions on the Bismuth Ruthenate Structure: Bi2-xA'xRu2O6O'1-y (A' = Mg, Ca, Sr).

Solid solutions with the formula of Bi2-xA'xRu2O7-y (A' = Mg, Ca, Sr; 0 ≤ x ≤ 0.2 for Mg, 0 ≤ x ≤ 1 for Ca, and 0 ≤ x ≤ 0.5 for Sr) have been synthesized and characterized. The crystal structures for these phases are found to be in the pyrochlore family, crystallizing in the cubic space group Fd3̅m with complex A/A' cation coordination environments. The Bi cation is found to be off-center from the ideal position because of a lone-pair distortion, while the positions of the substituted A' cations vary based on the size and ionicity. The neutron structure refinements reveal a similar propensity to off-center regarding Ca and Sr, while Mg features the largest static displacement of up to 0.48 Å. Interestingly, this is one of only two known pyrochlores with Mg2+ located in an 8-coordinated site. The average Ru oxidation state for each substitution is found to increase, and charge compensates for the lower divalent A' substitution. The solid solutions show temperature-independent resistance across the series with small changes in magnitude that scale with the amount of substitution, while displaying Pauli paramagnetic behavior throughout.

Os4+ Instability in the Pyrochlore Structure: Tl2-xBixOs2O7-y.

Osmium-containing oxides are rare due to the difficulty in stabilizing complex structures with a fixed stoichiometry and metastability of the phases. Bismuth-substituted thallium osmate pyrochlore samples, Tl2-xBixOs2O7-y, were synthesized using solid-state reactions where the solubility limit was found to be approximately x = 1.4. Members of this solid solution were characterized by their structural, electronic, magnetic, and thermal properties to understand the influence of Bi3+ substitution on the ground state. The Os-containing pyrochlores crystallize in the ideal cubic pyrochlore structure (Fd3m), and the lattice parameter a was found to slightly increase as a function of Bi content. A possible interplay between structure and cation valence states was explored using both neutron powder diffraction and X-ray absorption spectroscopy, suggesting that a combination of Os4+/Os5+ and Tl1+/Tl3+ mixed valency throughout the solid solution allows for the stabilization of the pyrochlore structure. The system is metallic for the entire solid solution and predominantly exhibits temperature-independent paramagnetism. Specific heat measurements show an enhanced Sommerfeld coefficient, a possible flat-band signature. This system gave insight into the bonding preferences of Os, indicating a dependence on high oxidation states and mixed valence for the stability of complex structures.

Estimating transfection efficiency in differentiated and undifferentiated neural cells.

OBJECTIVE: Delivery of constructs for silencing or over-expressing genes or their modified versions is a crucial step for studying neuronal cell biology. Therefore, efficient transfection is important for the success of these experimental techniques especially in post-mitotic cells like neurons. In this study, we have assessed the transfection rate, using a previously established protocol, in both primary cortical cultures and neuroblastoma cell lines. Transfection efficiencies in these preparations have not been systematically determined before. RESULTS: Transfection efficiencies obtained herein were (10-12%) for neuroblastoma, (5-12%) for primary astrocytes and (1.3-6%) for primary neurons. We also report on cell-type specific transfection efficiency of neurons and astrocytes within primary cortical cultures when applying cell-type selective transfection protocols. Previous estimations described in primary cortical or hippocampal cultures were either based on general observations or on data derived from unspecified number of biological and/or technical replicates. Also to the best of our knowledge, transfection efficiency of pure primary neuronal cultures or astrocytes cultured in the context of pure or mixed (neurons/astrocytes) population cultures have not been previously determined. The transfection strategy used herein represents a convenient, and a straightforward tool for targeted cell transfection that can be utilized in a variety of in vitro applications.

Hibonite Blue: A New Class of Intense Inorganic Blue Colorants.

Commercially available spinel cobalt blue (CoAl2O4) utilizes a significant amount of carcinogenic Co2+, which makes its synthesis more hazardous and environmentally harmful. Considerable effort has been put into developing more environmentally benign and robust blue pigments to replace cobalt blue. A new class of blue pigments with tunable hue were prepared. The solid solution series, CaAl12-2x Co x Ti x O19 (0 < x ≤ 1), crystallizes in a hexagonal mineral hibonite (CaM12O19) structure with five distinct crystallographic sites for M cations (M = Al, Co, and Ti). The origin of intense blue color is attributed to a synergistic effect of allowed d-d transitions involving the chromophore Co2+ in both tetrahedral and trigonal bipyramidal crystal fields. Compared with commercial cobalt blue, these tunable hibonite blues possess a reddish hue that intensifies the blue color as observed in Y(In,Mn)O3 (YInMn) blues, with a significant reduction of Co2+ concentration from 33% to as low as 4% by mass. A significant advantage of hibonite blues over cobalt blue is the substantial reduction in carcinogenic cobalt content while enhancing the color properties at a reduced cost for raw materials.

Ingestion of subthreshold doses of environmental toxins induces ascending Parkinsonism in the rat.

Increasing evidence suggests that environmental neurotoxicants or misfolded α-synuclein generated by such neurotoxicants are transported from the gastrointestinal tract to the central nervous system via the vagus nerve, triggering degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and causing Parkinson's disease (PD). We tested the hypothesis that gastric co-administration of subthreshold doses of lectins and paraquat can recreate the pathology and behavioral manifestations of PD in rats. A solution containing paraquat + lectin was administered daily for 7 days via gastric gavage, followed by testing for Parkinsonian behavior and gastric dysmotility. At the end of the experiment, brainstem and midbrain tissues were analyzed for the presence of misfolded α-synuclein and neuronal loss in the SNpc and in the dorsal motor nucleus of the vagus (DMV). Misfolded α-synuclein was found in DMV and SNpc neurons. A significant decrease in tyrosine hydroxylase positive dopaminergic neurons was noted in the SNpc, conversely there was no apparent loss of cholinergic neurons of the DMV. Nigrovagally-evoked gastric motility was impaired in treated rats prior to the onset of parkinsonism, the motor deficits of which were improved by l-dopa treatment. Vagotomy prevented the development of parkinsonian symptoms and constrained the appearance of misfolded α-synuclein to myenteric neurons. These data demonstrate that co-administration of subthreshold doses of paraquat and lectin induces progressive, l-dopa-responsive parkinsonism that is preceded by gastric dysmotility. This novel preclinical model of environmentally triggered PD provides functional support for Braak's staging hypothesis of idiopathic PD.

Local Moment Instability of Os in Honeycomb Li2.15Os0.85O3.

Compounds with honeycomb structures occupied by strong spin orbit coupled (SOC) moments are considered to be candidate Kitaev quantum spin liquids. Here we present the first example of Os on a honeycomb structure, Li2.15(3)Os0.85(3)O3 (C2/c, a = 5.09 Å, b = 8.81 Å, c = 9.83 Å, ß = 99.3°). Neutron diffraction shows large site disorder in the honeycomb layer and X-ray absorption spectroscopy indicates a valence state of Os (4.7 ± 0.2), consistent with the nominal concentration. We observe a transport band gap of Δ = 243 ± 23 meV, a large van Vleck susceptibility, and an effective moment of 0.85 µB, much lower than expected from 70% Os(+5). No evidence of long range order is found above 0.10 K but a spin glass-like peak in ac-susceptibility is observed at 0.5 K. The specific heat displays an impurity spin contribution in addition to a power law ∝T(0.63±0.06). Applied density functional theory (DFT) leads to a reduced moment, suggesting incipient itineracy of the valence electrons, and finding evidence that Li over stoichiometry leads to Os(4+)-Os(5+) mixed valence. This local picture is discussed in light of the site disorder and a possible underlying quantum spin liquid state.

HBeAg levels at week 24 predict response to 8 years of tenofovir in HBeAg-positive chronic hepatitis B patients.

BACKGROUND: Hepatitis B e antigen (HBeAg) seroconversion is a treatment endpoint for HBeAg-positive CHB, and a necessary precursor to HBsAg loss. Biomarkers that predict serological outcomes would be useful. AIM: To evaluate the utility of measuring HBeAg levels for predicting HBeAg seroconversion and HBsAg loss under long-term tenofovir (TDF) therapy. METHODS: A total of 266 patients were enrolled into a phase III study of TDF vs adefovir (ADV) for 48 weeks in HBeAg-positive patients, followed by open-label TDF up to 384 weeks. Serum HBeAg levels were measured for subjects with samples available at both baseline and week 24 of treatment (n = 200). Analysis compared subjects who achieved HBeAg seroconversion by week 384 vs no HBeAg seroconversion. RESULTS: HBeAg seroconversion rate was 52% by week 384. Time to HBeAg seroconversion was 80 weeks (IQR: 36-162). HBeAg decline at week 24 was associated with HBeAg seroconversion (1.63 vs 0.90 log10 PEIU/mL, P = .002). The optimal threshold for identifying HBeAg seroconversion was HBeAg decline ≥2.2 log10 PEIU/mL at week 24, with HBeAg seroconversion achieved by 76% of patients, compared to 44% if HBeAg decline <2.2 log10 (P < .0001). HBeAg decline ≥2.2 log10 PEIU/mL at week 24 was associated with HBsAg loss in genotype A or D patients (38% vs 15%, P = .03). Precore/basal core promotor variants were associated with lower baseline HBeAg levels, but not HBeAg seroconversion. CONCLUSION: Decline in HBeAg levels by week 24 was associated with HBeAg seroconversion and HBsAg loss in HBeAg-positive chronic hepatitis B patients treated with long-term TDF.

Bi2-xCaxIr2O6+y Pyrochlore Phases: Structure and Properties with Varied Ir Oxidation State from 3.9+ to 4.3.

Pyrochlore phases Bi2-xCaxIr2O6Oy' with x from 0.0 to 1.0 have been evaluated based on Rietveld analysis of neutron diffraction data, electrical resistivity and thermopower data from 3 to 756 K, and magnetic susceptibility data from 3 to 298 K. The average Ir oxidation state is less than 4+ at low x, above 4+ for high x, and is very close to 4+ at x = 0.5. All samples show metallic properties with an electrical resistivity of ∼10-3 Ω·cm at room temperature. For low x, the sign of the Seebeck coefficient is negative at low temperature but becomes positive at high temperature. For high x, the sign of the Seebeck coefficient is positive from 3 to 756 K. Magnetic measurements indicate no magnetic ordering down to 3 K for all values of x. All Bi is in its ideal position for all values of x, but much of the Ca is strongly displaced from the ideal A cation site. This displacement of Ca apparently only occurs when there is an adjacent vacancy at the O' site.

Rapid Proteomics to Prospect and Validate Novel Bacterial Metabolism Induced by Environmental Burden.

Understanding the pathophysiology of genes and enzymes involved in caffeine metabolism can have extracurricular benefits, such as providing distinct methylxanthines as intermediates for pharmaceutical synthesis, and also improve environmental waste remediation. The strains Pseudomonas putida CBB5 and CES may provide insights into these applications because they may both be induced to degrade caffeine, yet the latter thrives in concentrations >8.0gL-1; threefold higher than any other bacteria. We took a novel approach toward identifying the enzymatic pathways in both Pseudomonas sp. CES and a deletion mutation of strain CBB5, which largely circumvented the need for exhaustive isolation of enzymes and the stepwise reconstitution of their activities to determine caffeine response elements. Here, we describe two optimized, rapid alternative strategies based on multiplexed SIL assays and demonstrate their application by discovering caffeine-degrading enzymes in the CES strain based on quantitative comparison between enriched lysate fractions drawn from bacterial proteomes grown in the absence and presence of caffeine. Comparisons were made using stable isotope dimethyl labeling and expression differences were substantiated by reciprocal labeling experiments. The role of the identified proteins in caffeine degradation was independently verified by genetic sequencing. Multiple new components of N-demethylase system were discovered within a fraction of the lysate enriched specifically for this activity. We also describe how to expand the biological context (and reduce systemic bias) by adapting the protocol for total lysate analysis. We combined off-line prefractionation with the speed and resolution advantages of the Orbitrap LUMOS. The global protocol revealed 2406 proteins 1789 of which were quantified between treatments revealing, among other insights, a new antagonistic degradation pathway for vanillin that is completely suppressed by caffeine treatment.

Sofosbuvir plus ribavirin in treatment-naïve patients with chronic hepatitis C virus genotype 1 or 3 infection in India.

Until 2014, pegylated interferon plus ribavirin was the recommended standard of care for the treatment of chronic hepatitis C virus (HCV) infection in India. This open-label phase 3b study, conducted across 14 sites in India between 31 March 2014 and 30 November 2015, evaluated the efficacy and safety of sofosbuvir plus ribavirin therapy among treatment-naïve patients with chronic genotype 1 or 3 HCV infection. A total of 117 patients with genotype 1 or 3 HCV infection were randomized 1:1 to receive sofosbuvir 400 mg and weight-based ribavirin (1000 or 1200 mg) daily for 16 or 24 weeks. Among those with genotype 1 infection, the primary efficacy endpoint of sustained virologic response at 12 weeks post-treatment (SVR12) was reported in 90% (95% confidence intervals [CI], 73-98) and 96% (95% CI, 82-100) of patients following 16 and 24 weeks of treatment, respectively. For patients with genotype 3 infection, SVR12 rates were 100% (95% CI, 88-100) and 93% (95% CI, 78-99) after 16 and 24 weeks of therapy, respectively. Adverse events, most of which were mild or moderate in severity, occurred in 69% and 57% of patients receiving 16 and 24 weeks of treatment, respectively. The most common treatment-emergent adverse events were asthenia, headache and cough. Only one patient in the 24-week group discontinued treatment with sofosbuvir during this study. Overall, sofosbuvir plus ribavirin therapy achieved SVR12 rates ≥90% and was well tolerated among treatment-naïve patients with chronic genotype 1 or 3 HCV infection in India.

From Serendipity to Rational Design: Tuning the Blue Trigonal Bipyramidal Mn3+ Chromophore to Violet and Purple through Application of Chemical Pressure.

We recently reported that an allowed d-d transition of trigonal bipyramidal (TBP) Mn3+ is responsible for the bright blue color in the YIn1-xMnxO3 solid solution. The crystal field splitting between a'(dz2) and e'(dx2-y2, dxy) energy levels is very sensitive to the apical Mn-O distance. We therefore applied chemical pressure to compress the apical Mn-O distance in YIn1-xMnxO3, move the allowed d-d transition to higher energy, and thereby tune the color from blue to violet/purple. This was accomplished by substituting smaller cations such as Ti4+/Zn2+ and Al3+ onto the TBP In/Mn site, which yielded novel violet/purple phases. The general formula is YIn1-x-2y-zMnxTiyZnyAlzO3 (x = 0.005-0.2, y = 0.1-0.4, and z ≤ 0.1), where the color darkens with the increasing amount of Mn. Higher y or small additions of Al provide a more reddish hue to the resulting purple colors. Substituting other rare earth cations for Y has little impact on color. Crystal structure analysis by neutron powder diffraction confirms a shorter apical Mn-O distance compared with that in the blue YIn1-xMnxO3. Magnetic susceptibility measurements verify the 3+ oxidation state for Mn. Diffuse reflection spectra were obtained over the wavelength region 200-2500 nm. All samples show excellent near-infrared reflectance comparable to that of commercial TiO2, making them ideal for cool pigment applications such as energy efficient roofs of buildings and cars where reducing solar heat to save energy is desired. In a comparison with commercial purple pigments, such as Co3(PO4)2, our pigments are much more thermally stable and chemically inert, and are neither toxic nor carcinogenic.

Structure and Properties of Ir-Containing Oxides with Large Spin-Orbit Coupling: Ba2In(2-x)Ir(x)O(5+δ).

In this work, the solid solution series Ba2In(2-x)Ir(x)O5+δ (x = 0-1.4, 2) was synthesized, and its structural, magnetic, and charge-transport properties were measured. With increasing Ir content, three transitions in the room-temperature structure were observed: orthorhombic to tetragonal to cubic to a monoclinic distortion of a hexagonal BaTiO3 structure. Neutron diffraction shows Ba2In(1.6)Ir(0.4)O5.4 to be cubic and Ba2InIrO6 to be monoclinic, the latter contrary to previously published X-ray diffraction refinements. Magnetization measurements show Curie-Weiss behavior for x = 0.2-0.6, which arises from nearly 50:50 ratio of Ir(V) and Ir(VI). To our knowledge, this is the first time Ir(VI) has been stabilized with standard solid-state methods under ambient conditions. The electrical resistivity measurements show all the compounds studied are semiconducting and that resistivity decreases with increasing Ir content, suggesting the proximity to a metal-insulator transition. A sign reversal in the high-temperature Seebeck coefficient is observed indicating both electron and hole charge transport.

Influence of Structural Disorder on Hollandites A(x)Ru4O8 (A(+) = K, Rb, Rb(1-x)Na(x)).

Structural disorder can play an important role in the electrical properties of correlated materials. In this work we examine the average and local disorder in hollandites A(x)Ru4O8 (A(+) = K, Rb, Rb(1-x)Na(x)) through neutron total scattering techniques. Samples with A(+) = Rb, Rb(1-x)Na(x) exhibit the largest amount of local disorder as evidenced by higher atomic displacement parameters, and as a result, a weakened temperature dependence of the resistivity is observed upon cooling as compared to K(x)Ru4O8. All samples exhibit anisotropic resistivity that is dominated by metallic conductivity at lower temperatures, and this is corroborated by Pauli paramagnetic behavior throughout the measured temperature regime.

trans-4,4'-Dihydroxystilbene (DHS) protects PC12 cells from oxidative damage but induces reactive oxygen species-mediated apoptosis in SHSY-5Y cell line.

Polyphenols can exert both, antioxidant and pro-oxidant properties, depending on cell types as well as their concentrations. Hence, it was of interest to examine if the naturally occurring resveratrol analog, trans-4,4'-dihydroxystilbene (DHS) also exert both these activities in a biphasic or cell-specific manner. In this study, we established the cytoprotective action of DHS against hydrogen peroxide (H2O2)-induced apoptotic death of the PC12 cells. DHS reduced mitochondrial membrane permeabilization and deactivated reactive oxygen species (ROS)-mediated caspase-3 activation in the H2O2-treated PC12 cells. However, it induced apoptosis in the human neuroblastoma SHSY-5Y cell line by destabilizing mitochondrial membrane, augmenting ROS and activating caspapse-3. DHS showed better activity than resveratrol in both the chosen models.

Magnetic properties and electronic structure of manganese-based blue pigments: a high-frequency and -field EPR study.

A variety of new oxide-based materials based on hexagonal phase of YInO3 have been recently described. In some of these materials, the In(III) ions are substituted by Mn(III), which finds itself in a trigonal-bipyramidal (TBP) coordination environment. While YInO3 is colorless and YMnO3 is black, mixed systems YIn1-xMnxO3 (0.02 < x < 0.25) display intense blue color and have been proposed as novel blue pigments. Since the Mn(III) ion is paramagnetic, its presence imparts distinct magnetic properties to the whole class of materials. These properties were investigated by electron paramagnetic resonance (EPR) in its high-frequency and -field version (HFEPR), a technique ideally suited for transition metal ions such as Mn(III) that, in contrast to, for example, Mn(II), are difficult to study by EPR at (conventional) low frequency and field. YIn1-xMnxO3 with 0.02 < x < 0.2 exhibited high-quality HFEPR spectra up to room temperature that could be interpreted as arising from isolated S = 2 paramagnets. A simple ligand-field model, based on the structure and optical spectra, explains the spin Hamiltonian parameters provided by HFEPR, which were D = +3.0 cm(-1), E = 0; g⊥ = 1.99, g∥ = 2.0. This study demonstrates the general applicability of a combined spectroscopic and classical theoretical approach to understanding the electronic structure of novel materials containing paramagnetic dopants. Moreover, HFEPR complements optical and other experimental methods as being a sensitive probe of dopant level.

Growth differentiation factor-15 encodes a novel microRNA 3189 that functions as a potent regulator of cell death.

According to the latest version of miRBase, approximately 30% of microRNAs (miRNAs) are unique to primates, but the physiological function of the vast majority remains unknown. In this study, we identified miR-3189 as a novel, p53-regulated, primate-specific miRNA embedded in the intron of the p53-target gene GDF15. Antagonizing miR-3189 increased proliferation and sensitized cells to DNA damage-induced apoptosis, suggesting a tumor suppressor function for endogenous miR-3189. Identification of genome-wide miR-3189 targets revealed that miR-3189 directly inhibits the expression of a large number of genes involved in cell cycle control and cell survival. In addition, miR-3189 downregulated the expression of multiple p53 inhibitors resulting in elevated p53 levels and upregulation of several p53 targets including p21 (CDKN1A), GADD45A and the miR-3189 host gene GDF15, suggesting miR-3189 auto-regulation. Surprisingly, miR-3189 overexpression in p53-/- cells upregulated a subset of p53-targets including GDF15, GADD45A, and NOXA, but not CDKN1A. Consistent with these results, overexpression of miR-3189 potently induced apoptosis and inhibited tumorigenicity in vivo in a p53-independent manner. Collectively, our study identified miR-3189 as a novel, primate-specific miRNA whose effects are mediated by both p53-dependent and p53-independent mechanisms. miR-3189 may, therefore, represent a novel tool that can be utilized therapeutically to induce a potent proapoptotic effect even in p53-deficient tumors.