Evolution of Grain-Boundary Microstructure and Texture in Interstitial-Free Steel Processed by Equal-Channel Angular Extrusion

The equal-channel angular extrusion (ECAE) of Ti-bearing interstitial-free (IF) steel was performed following two different routes, up to four passes, at a temperature of 300 degrees C. The ECAE led to a grain refinement to submicron size. After the second pass, the grain size attained saturation thereafter. The microstructural analysis indicated the presence of coincident-site lattice (CSL) boundaries in significant fraction, in addition to a high volume fraction of high-angle random boundaries and some low-angle boundaries after the deformation. Among the special boundaries, Sigma 3 and Sigma 13 were the most prominent ones and their fraction depended on the processing route followed. A deviation in the misorientation angle distribution from the Mackenzie distribution was noticed. The crystallographic texture after the first pass resembled that of simple shear, with the {112}, {110}, and {123} aligned to the macroscopic shear plane.

Oestrogen-induced synthesis of thiamin-binding protein in immature chicks. Kinetics of induction, hormonal specificity and modulation

A specific radioimmunoassay procedure was developed to monitor the plasma concentrations of thiamin-binding protein, a minor yolk constituent of the chicken egg. By using this sensitive assay, the kinetics of oestrogen-induced elaboration of this specific protein in immature chicks was investigated. After a single injection of the steroid hormone, with an initial lag period of 4–5h the thiamin-binding protein rapidly accumulated in the plasma, attaining peak concentrations around 75h and declining thereafter. A 4-fold amplification of the response was noticed during the secondary stimulation, and this increased to 9-fold during the tertiary stimulation with the steroid hormone. The magnitude of the response was dependent on the hormone dose, and the initial latent period and the duration of the ascending phase of induction were unchanged for the hormonal doses tested during both the primary and secondary stimulations. The circulatory half-life of the protein was 6h as calculated from the measurement of the rate of disappearance of the exogenously administered 125I-labelled protein. Simultaneous administration of progesterone, dihydrotestosterone or corticosterone did not alter the pattern of induction. On the other hand, hyperthyroidism markedly decreased the oestrogenic response, whereas propylthiouracil-induced hypothyroidism had the opposite effect. The anti-oestrogen E- and Z-clomiphene citrates, administered 30min before oestrogen, effectively blocked the hormonal induction. α-Amanitin and cycloheximide administered along with or shortly after the sex steroid severely curtailed the protein elaboration. A comparison of the kinetics of induction of thiamin- and riboflavin-binding proteins by oestrogen revealed that, beneath an apparent similarity, a clear-cut difference exists between the two vitamin-binding proteins, particularly with regard to hormonal dose-dependent sensitivity of induction and the half-life in circulation. The steroid-mediated elaboration of the two yolk proteins thus appears to be not strictly co-ordinated, despite several common regulatory features underlying their induction.

Hormonal modulation of riboflavin carrier protein secretion by immature rat Sertoli cells in culture

We report here that a protein species with biochemical and immunological similarity with chicken egg riboflavin carrier protein (RCP) is synthesized and secreted by immature rat Sertoli cells in culture. When quantitated by a specific heterologous radioimmunoassay, optimal concentrations of FSH (25 ng/ml) brought about 3-fold stimulation of RCP secretion. FSH, in the presence of testosterone (10−6 M) brought about 6-fold stimulation of secretion of RCP over the control cultures which were maintained in the absence of these two factors. The aromatase inhibitor (1,4,6-androstatrien-3,17-dione) curtailed 85% of the enhanced secretion of RCP, suggesting that the hormonal stimulation is mediated through in situ synthesized estrogen and this could be confirmed with exogenous estradiol-17 β which brought about 3 — fold enhancement of secretion of RCP at a concentration of 10−6 M. When tamoxifen (10 μM) was added along with FSH and testosterone, there was 75% decrease in the enhanced secretion of RCP. Addition of this anti-estrogen together with exogenous estradiol resulted in 55% decrease in elevated levels of RCP. Cholera toxin (1 μg/ml) and 8-bromo-cyclic AMP (0.5 mM) mimicked the action of FSH on the secretion of RCP thus suggesting that FSH stimulation of RCP production may be mediated through cyclic AMP. These findings suggest that estrogen mediates RCP induction in hormonally stimulated sertoli cells presumably to function as the carrier of riboflavin to the developing germ cells through blood-testis barrier in rodents.

Glutamatergic Modulation of Cue-Induced Drug-Seeking Behavior in the Rat

The characteristics of drug addiction include compulsive drug use despite negative consequences and re-occurring relapses, returns to drug use after a period of abstinence. Therefore, relapse prevention is one of the major challenges for the treatment of drug addiction. There are three main factors capable of inducing craving for drugs and triggering relapse long after cessation of drug use and dissipation of physical withdrawal signs: stress, re-exposure to the drug, and environmental stimuli (cues) that have been previously associated with drug use. The neurotransmitters dopamine and glutamate have been implicated in the modulation of drug-seeking behavior. The aim of this project was to examine the role of glutamatergic neurotransmission in relapse triggered by conditioned drug-associated stimuli. The focus was on clarifying whether relapse to drug seeking can be attenuated by blockade of glutamate receptors. In addition, as the nucleus accumbens has been proposed to participate in the modulation of drug-seeking behavior, the effects of glutamate receptor blockade in this brain structure on cue-induced relapse were investigated. The studies employed animals models in which rats were trained to press a lever in a test cage to obtain alcohol or intravenous cocaine. Drug availability was paired with distinct olfactory, auditory, or visual stimuli. This phase was followed by extinction training, during which lever presses did not result in the presentation of the drug or the drug-associated stimuli. Extinction training led to a gradual decrease in the number of lever presses during test sessions. Relapse was triggered by presenting the rats with the drug-associated stimuli in the absence of alcohol or cocaine. The drug-associated stimuli were alone capable of inducing resumption of lever pressing and maintaining this behavior during repeated testing. The number of lever presses during a session represented the intensity of drug-seeking and relapse behavior. The results suggest that glutamatergic neurotransmission is involved in the modulation of drug-seeking behavior. Both alcohol and cocaine relapse were attenuated by systemic pretreatment with glutamate receptor antagonists. However, differences were found in the ability of ionotropic AMPA/kainate and NMDA receptor antagonists to regulate drug-seeking behavior. The AMPA/kainate antagonists CNQX and NBQX, and L-701,324, an antagonist with affinity for the glycine site of the NMDA receptor, attenuated cue-induced drug seeking, whereas the competitive NMDA antagonist CGP39551 and the NMDA channel blocker MK-801 were without effect. MPEP, an antagonist at metabotropic mGlu5 glutamate receptors, also decreased drug seeking, but its administration was found to lead to conditioned suppression of behavior during subsequent treatment sessions, suggesting that MPEP may have undesirable side effects. The mGluR2/3 agonist LY379268 and the mGluR8 agonist (S)-3,4-DCPG decreased both cue-induced relapse to alcohol drinking and alcohol consumption. Control experiments showed however that administration of the agonists was accompanied by motor suppression limiting their usefulness. Administration of the AMPA/kainate antagonist CNQX, the NMDA antagonist D-AP5, and the mGluR5 antagonist MPEP into the nucleus accumbens resulted also in a decrease in drug-seeking behavior, suggesting that the nucleus accumbens is at least one of the anatomical sites regulating drug seeking and mediating the effects of glutamate receptor antagonists on this behavior.

Dynamic pressure modulation for solar desalination system

Obtaining drinking water from seawater is usually done through the process of desalination. The conventional desalination processes at present are centralized, require huge capital cost, and enormous amount of concentrated energy from fossil fuel. Issues like optimal chamber pressure, pressure control and energy savings for desalination are not adequately addressed. This paper proposes a novel pressure control method by means of dynamic pressure modulation within the evaporation chamber. A performance index is proposed that results in a dynamic optimal external pressure and maximum energy saving for a specific flow rate. Experimental results from the laboratory setup that validate the proposed concepts are presented in the paper. (C) 2009 Elsevier B.V. All rights reserved.

Third post-Newtonian angular momentum flux and the secular evolution of orbital elements for inspiralling compact binaries in quasi-elliptical orbits

The angular-momentum flux from an inspiralling binary system of compact objects moving in quasi-elliptical orbits is computed at the third post-Newtonian (3PN) order using the multipolar post-Minkowskian wave generation formalism. The 3PN angular-momentum flux involves the instantaneous, tail, and tail-of-tails contributions as for the 3PN energy flux, and in addition a contribution due to nonlinear memory. We average the angular-momentum flux over the binary's orbit using the 3PN quasi-Keplerian representation of elliptical orbits. The averaged angular-momentum flux provides the final input needed for gravitational-wave phasing of binaries moving in quasi-elliptical orbits. We obtain the evolution of orbital elements under 3PN gravitational radiation reaction in the quasi-elliptic case. For small eccentricities, we give simpler limiting expressions relevant for phasing up to order e(2). This work is important for the construction of templates for quasi-eccentric binaries, and for the comparison of post-Newtonian results with the numerical relativity simulations of the plunge and merger of eccentric binaries.

mRNA and microRNA analysis reveals modulation of biochemical pathways related to addiction in the ventral tegmental area of methamphetamine self-administering rats

Background Methamphetamine is a highly addictive central nervous system stimulant with increasing levels of abuse worldwide. Alterations to mRNA and miRNA expression within the mesolimbic system can affect addiction-like behaviors and thus play a role in the development of drug addiction. While many studies have investigated the effects of high-dose methamphetamine, and identified neurotoxic effects, few have looked at the role that persistent changes in gene regulation play following methamphetamine self-administration. Therefore, the aim of this study was to identify RNA changes in the ventral tegmental area following methamphetamine self-administration. We performed microarray analyses on RNA extracted from the ventral tegmental area of Sprague–Dawley rats following methamphetamine self-administration training (2 h/day) and 14 days of abstinence. Results We identified 78 miRNA and 150 mRNA transcripts that were differentially expressed (fdr adjusted p < 0.05, absolute log2 fold change >0.5); these included genes not previously associated with addiction (miR-125a-5p, miR-145 and Foxa1), loci encoding receptors related to drug addiction behaviors and genes with previously recognized roles in addiction such as miR-124, miR-181a, DAT and Ret. Conclusion This study provides insight into the effects of methamphetamine on RNA expression in a key brain region associated with addiction, highlighting the possibility that persistent changes in the expression of genes with both known and previously unknown roles in addiction occur.

Performance modulation of α-MnO2 nanowires by crystal facet engineering

Modulation of material physical and chemical properties through selective surface engineering is currently one of the most active research fields, aimed at optimizing functional performance for applications. The activity of exposed crystal planes determines the catalytic, sensory, photocatalytic, and electrochemical behavior of a material. In the research on nanomagnets, it opens up new perspectives in the fields of nanoelectronics, spintronics, and quantum computation. Herein, we demonstrate controllable magnetic modulation of α-MnO 2 nanowires, which displayed surface ferromagnetism or antiferromagnetism, depending on the exposed plane. First-principles density functional theory calculations confirm that both Mn- and O-terminated α-MnO2(1 1 0) surfaces exhibit ferromagnetic ordering. The investigation of surface-controlled magnetic particles will lead to significant progress in our fundamental understanding of functional aspects of magnetism on the nanoscale, facilitating rational design of nanomagnets. Moreover, we approved that the facet engineering pave the way on designing semiconductors possessing unique properties for novel energy applications, owing to that the bandgap and the electronic transport of the semiconductor can be tailored via exposed surface modulations.

Modulation of protease expression in prostate cancer cells after androgen deprivation

Understanding mechanisms associated with the emergence of castration resistant prostate cancer cells (CRPC) after androgen deprivation therapy (ADT) is essential to create new therapeutic agents to counteract this aggressive form of prostate cancer (PCa). Because proteases are involved in almost all cancer associated mechanisms such as cell proliferation, invasion and metastasis, we are interested in their modulation in PCa after ADT and their involvement in CRPC.

Modulation of growth by aromatase inhibitor treatment in boys: Efficacy and safety

Without estrogen action, the fusion of the growth plates is postponed and statural growth continues for an exceptionally long time. Aromatase inhibitors, blockers of estrogen biosynthesis, have therefore emerged as a new potential option for the treatment of children with short stature. We investigated the efficacy of the aromatase inhibitor letrozole in the treatment of boys with idiopathic short stature (ISS) using a randomised, placebo-controlled, double-blind research setting. A total of 30 boys completed the two-year treatment. By decreasing estrogen-mediated central negative feedback, letrozole increased gonadotrophin and testosterone secretion in pubertal boys, whereas the pubertal increase in IGF-I was inhibited. Treatment with letrozole effectively delayed bone maturation and increased predicted adult height by 5.9 cm (P0.001), while placebo had no effect on either parameter. The effect of letrozole treatment on near-final height was studied in another population, in boys with constitutional delay of puberty, who received letrozole (n=9) or placebo (n=8) for one year, in combination with low-dose testosterone for six months during adolescence. The mean near-final height of boys randomised to receive testosterone and letrozole was significantly greater than that of boys who received testosterone and placebo (175.8 vs. 169.1 cm, P=0.04). As regards safety, treatment effects on bone health, lipid metabolism, insulin sensitivity, and body composition were monitored in boys with ISS. During treatment, no differences in bone mass accrual were evident between the treatment groups, as evaluated by dual-energy x-ray absorptiometry measurements of the lumbar spine and femoral neck. Bone turnover and cortical bone growth, however, were affected by letrozole treatment. As indicated by differences in markers of bone resorption (U-INTP) and formation (S-PINP and S-ALP), the long-term rate of bone turnover was lower in letrozole-treated boys, despite their more rapid advancement in puberty. Letrozole stimulated cortical bone growth in those who progressed in puberty: the metacarpal index (MCI), a measure of cortical bone thickness, increased more in letrozole-treated pubertal boys than in placebo-treated pubertal boys (25% vs. 9%, P=0.007). The change in MCI correlated positively with the mean testosterone-to-estradiol ratio. In post-treatment radiographic evaluation of the spine, a high rate of vertebral deformities - mild anterior wedging and mild compression deformities - were found in both placebo and letrozole groups. In pubertal boys with ISS treated with letrozole, stimulated testosterone secretion was associated with a decrease in the percentage of fat mass and in HDL-cholesterol, while LDL-cholesterol and triglycerides remained unchanged. Insulin sensitivity, as evaluated by HOMA-IR, was not significantly affected by the treatment. In summary, treatment with the aromatase inhibitor letrozole effectively delayed bone maturation and increased predicted adult height in boys with ISS. Long-term follow-up data of boys with constitutional delay of puberty, treated with letrozole for one year during adolescence, suggest that the achieved gain in predicted adult height also results in increased adult height. However, until the safety of aromatase inhibitor treatment in children and adolescents is confirmed, such treatment should be considered experimental.

Novel flutamide regulated genes in the rat ventral prostate: differential modulation of their expression by castration and flutamide treatments

Aim: To identify flutamide regulated genes in the rat ventral prostate. Methods: Total RNA from ventral prostates control and flutamide treated rats were isolated. Differentially expressed transcripts were identified using display reverse transcriptase polymerase chain reaction. The effect of castration on the expression of regulated transcripts was studied. Results: We have identified beta 2-microglobulin, cytoplasmic FMR1 protein 2 and pumilio 1 as flutamide induced and spermine binding protein and ribophorin II as flutamide targets in the rat ventral prostate. Although flutamide treatment caused an induction of pumilio I mRNA, had no effect. Conclusion: Castration and flutamide treatments exert differential effects on gene expression. might also have direct AR independent effects, which might have implications in the emergence of androgen dent prostate cancer and the failure of flutamide therapy.

Vibrational phase relaxation of O–H stretch in bulk water: Role of large amplitude angular jumps and negative cross-correlations among the forces on the O–H bond

The ultrafast vibrational phase relaxation of O–H stretch in bulk water is investigated in molecular dynamics simulations. The dephasing time (T2) of the O–H stretch in bulk water calculated from the frequency fluctuation time correlation function (Cω(t)) is in the range of 70–80 femtosecond (fs), which is comparable to the characteristic timescale obtained from the vibrational echo peak shift measurements using infrared photon echo [W.P. de Boeij, M.S. Pshenichnikov, D.A. Wiersma, Ann. Rev. Phys. Chem. 49 (1998) 99]. The ultrafast decay of Cω(t) is found to be responsible for the ultrashort T2 in bulk water. Careful analysis reveals the following two interesting reasons for the ultrafast decay of Cω(t). (A) The large amplitude angular jumps of water molecules (within 30–40 fs time duration) provide a large scale contribution to the mean square vibrational frequency fluctuation and gives rise to the rapid spectral diffusion on 100 fs time scale. (B) The projected force, due to all the atoms of the solvent molecules on the oxygen (FO(t)) and hydrogen (FH(t)) atom of the O–H bond exhibit a large negative cross-correlation (NCC). We further find that this NCC is partly responsible for a weak, non-Arrhenius temperature dependence of the dephasing rate.

Gene modulation and immunoregulatory roles of Interferon gamma

Interferon-gamma (IFN gamma) is a central regulator of the immune response and signals via the Janus Activated Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) pathway. Phosphorylated STAT1 homodimers translocate to the nucleus, bind to Gamma Activating Sequence (GAS) and recruit additional factors to modulate gene expression. A bioinformatics analysis revealed that greater number of putative promoters of immune related genes and also those not directly involved in immunity contain GAS compared to response elements (RE) for Interferon Regulatory Factor (IRF)1, Nuclear factor kappa B (NF kappa B) and Activator Protein (AP)1. GAS is present in putative promoters of well known IFN gamma-induced genes, IRF1, GBP1, CXCL10, and other genes identified were TLR3, VCAM1, CASP4, etc. Analysis of three microarray studies revealed that the expression of asubset of only GAS containing immune genes were modulated by IFN gamma. As a significant correlation exists between GAS containing immune genes and IFN gamma-regulated gene expression, this strategy may identify novel IFN gamma-responsive immune genes. This analysis is integrated with the literature on the roles of IFN gamma in mediating a plethoraof functions: anti-microbial responses, antigen processing,inflammation, growth suppression, cell death, tumor immunity and autoimmunity. Overall, this review summarizes our present knowledge onIFN gamma mediated signaling and functions. (C) 2009 Elsevier Ltd. All rights reserved.

Multiwavelength studies of regolith effects in planetary remote sensing

A large proportion of our knowledge about the surfaces of atmosphereless solar-system bodies is obtained through remote-sensing measurements. The measurements can be carried out either as ground-based telescopic observations or space-based observations from orbiting spacecraft. In both cases, the measurement geometry normally varies during the observations due to the orbital motion of the target body, the spacecraft, etc.. As a result, the data are acquired over a variety of viewing and illumination angles. Surfaces of planetary bodies are usually covered with a layer of loose, broken-up rock material called the regolith whose physical properties affect the directional dependence of remote-sensed measurements. It is of utmost importance for correct interpretation of the remote-sensed data to understand the processes behind this alteration. In the thesis, the multi-angular effects that the physical properties of the regolith have on remote-sensing measurements are studied in two regimes of electromagnetic radiation, visible to near infrared and soft X-rays. These effects are here termed generally the regolith effects in remote sensing. Although the physical mechanisms that are important in these regions are largely different, notable similarities arise in the methodology that is used in the study of the regolith effects, including the characterization of the regolith both in experimental studies and in numerical simulations. Several novel experimental setups have been constructed for the thesis. Alongside the experimental work, theoretical modelling has been carried out, and results from both approaches are presented. Modelling of the directional behaviour of light scattered from a regolith is utilized to obtain shape and spin-state information of several asteroids from telescopic observations and to assess the surface roughness and single-scattering properties of lunar maria from spacecraft observations. One of the main conclusions is that the azimuthal direction is an important factor in detailed studies of planetary surfaces. In addition, even a single parameter, such as porosity, can alter the light scattering properties of a regolith significantly. Surface roughness of the regolith is found to alter the elemental fluorescence line ratios of a surface obtained through planetary soft X-ray spectrometry. The results presented in the thesis are among the first to report this phenomenon. Regolith effects need to be taken into account in the analysis of remote-sensed data, providing opportunities for retrieving physical parameters of the surface through inverse methods.

Space-Vector-Based Hybrid Pulsewidth Modulation Techniques for Reduced Harmonic Distortion and Switching Loss

Novel switching sequences can be employed in spacevector-based pulsewidth modulation (PWM) of voltage source inverters. Differentswitching sequences are evaluated and compared in terms of inverter switching loss. A hybrid PWM technique named minimum switching loss PWM is proposed, which reduces the inverter switching loss compared to conventional space vector PWM (CSVPWM) and discontinuous PWM techniques at a given average switching frequency. Further, four space-vector-based hybrid PWM techniques are proposed that reduce line current distortion as well as switching loss in motor drives, compared to CSVPWM. Theoretical and experimental results are presented.