Mechanical processing and microstructural control in hot working of hot isostatically pressed P/M IN-100 superalloy

The hot deformation behavior of hot isostatically pressed (HIPd) P/M IN-100 superalloy has been studied in the temperature range 1000-1200 degrees C and strain rate range 0.0003-10 s(-1) using hot compression testing. A processing map has been developed on the basis of these data and using the principles of dynamic materials modelling. The map exhibited three domains: one at 1050 degrees C and 0.01 s(-1), with a peak efficiency of power dissipation of approximate to 32%, the second at 1150 degrees C and 10 s(-1), with a peak efficiency of approximate to 36% and the third at 1200 degrees C and 0.1 s(-1), with a similar efficiency. On the basis of optical and electron microscopic observations, the first domain was interpreted to represent dynamic recovery of the gamma phase, the second domain represents dynamic recrystallization (DRX) of gamma in the presence of softer gamma', while the third domain represents DRX of the gamma phase only. The gamma' phase is stable upto 1150 degrees C, gets deformed below this temperature and the chunky gamma' accumulates dislocations, which at larger strains cause cracking of this phase. At temperatures lower than 1080 degrees C and strain rates higher than 0.1 s(-1), the material exhibits flow instability, manifested in the form of adiabatic shear bands. The material may be subjected to mechanical processing without cracking or instabilities at 1200 degrees C and 0.1 s(-1), which are the conditions for DRX of the gamma phase.

Early life stress, nicotinic acetylcholine receptors and alcohol use disorders

Stress is a major driving force in alcohol use disorders (AUDs). It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual’s brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc) following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs) play in this process. Understanding the neural pathways and mechanism determining stress resilience or susceptibility will improve our ability to identify individuals susceptible to developing AUDs, formulate cognitive interventions to prevent AUDs in susceptible individuals and to elucidate and enhance potential therapeutic targets, such as the nAChRs, for those struggling to overcome an AUD.

Roles of forced nicotine exposure and Comt gene disruption in the development of addiction-related behavioural and neurochemical changes in mice

Activation of midbrain dopamine systems is thought to be critically involved in the addictive properties of abused substances. Drugs of abuse increase dopamine release in the nucleus accumbens and dorsal striatum, which are the target areas of mesolimbic and nigrostriatal dopamine pathways, respectively. Dopamine release in the nucleus accumbens is thought to mediate the attribution of incentive salience to rewards, and dorsal striatal dopamine release is involved in habit formation. In addition, changes in the function of prefrontal cortex (PFC), the target area of mesocortical dopamine pathway, may skew information processing and memory formation such that the addict pays an abnormal amount of attention to drug-related cues. In this study, we wanted to explore how long-term forced oral nicotine exposure or the lack of catechol-O-methyltransferase (COMT), one of the dopamine metabolizing enzymes, would affect the functioning of these pathways. We also wanted to find out how the forced nicotine exposure or the lack of COMT would affect the consumption of nicotine, alcohol, or cocaine. First, we studied the effect of forced chronic nicotine exposure on the sensitivity of dopamine D2-like autoreceptors in microdialysis and locomotor activity experiments. We found that the sensitivity of these receptors was unchanged after forced oral nicotine exposure, although an increase in the sensitivity was observed in mice treated with intermittent nicotine injections twice daily for 10 days. Thus, the effect of nicotine treatment on dopamine autoreceptor sensitivity depends on the route, frequency, and time course of drug administration. Second, we investigated whether the forced oral nicotine exposure would affect the reinforcing properties of nicotine injections. The chronic nicotine exposure did not significantly affect the development of conditioned place preference to nicotine. In the intravenous self-administration paradigm, however, the nicotine-exposed animals self-administered nicotine at a lower unit dose than the control animals, indicating that their sensitivity to the reinforcing effects of nicotine was enhanced. Next, we wanted to study whether the Comt gene knock-out animals would be a suitable model to study alcohol and cocaine consumption or addiction. Although previous work had shown male Comt knock-out mice to be less sensitive to the locomotor-activating effects of cocaine, the present study found that the lack of COMT did not affect the consumption of cocaine solutions or the development of cocaine-induced place preference. However, the present work did find that male Comt knock-out mice, but not female knock-out mice, consumed ethanol more avidly than their wild-type littermates. This finding suggests that COMT may be one of the factors, albeit not a primary one, contributing to the risk of alcoholism. Last, we explored the effect of COMT deficiency on dorsal striatal, accumbal, and prefrontal cortical dopamine metabolism under no-net-flux conditions and under levodopa load in freely-moving mice. The lack of COMT did not affect the extracellular dopamine concentrations under baseline conditions in any of the brain areas studied. In the prefrontal cortex, the dopamine levels remained high for a prolonged time after levodopa treatment in male, but not female, Comt knock-out mice. COMT deficiency induced accumulation of 3,4-dihydroxyphenylacetic acid, which increased further under levodopa load. Homovanillic acid was not detectable in Comt knock-out animals either under baseline conditions or after levodopa treatment. Taken together, the present results show that although forced chronic oral nicotine exposure affects the reinforcing properties of self-administered nicotine, it is not an addiction model itself. COMT seems to play a minor role in dopamine metabolism and in the development of addiction under baseline conditions, indicating that dopamine function in the brain is well-protected from perturbation. However, the role of COMT becomes more important when the dopaminergic system is challenged, such as by pharmacological manipulation.

The Effects of Nicotine on the Regulation of Neuronal Alpha7 Nicotinic Acetylcholine Receptors and Intracellular Signalling Pathways

Nicotine, the addictive compound of tobacco products, exerts its effects in the brain by binding to neuronal acetylcholine nicotinic receptors (nAChRs). The aim of the present study was to increase the knowledge of nicotine s complex effects, the focus being on homomeric alpha7-nAChRs that are widely expressed in the brain. Nicotinic regulation of differential signalling molecules including transcriptional regulators was also studied. We found that the number of alpha7-nAChRs is increased in specific brain regions in mice, in a time-dependent manner after chronic oral nicotine administration. Our results suggest that in addition to alpha4beta2-nAChRs, the other major nAChR subtype expressed in the brain, the number of alpha7-nAChRs is affected by chronic presence of nicotine. We suggest that when studying the long-term effects of nicotine, the duration on administration is of great importance. Next, we observed that nicotine exposure induces accumulation of cAMP in cell cultures expressing nAChRs. Furthermore, nicotine-induced alpha7-nAChR upregulation was potentiated by treatments enhancing cAMP-signalling, suggesting a role for cAMP in the upregulation process. Protein kinase C (PKC) was found essential for the basal regulation of alpha7-nAChR number. The nicotine-evoked alpha7-nAChR upregulation could be further increased by PKC overexpression. Thirdly, the effects of nicotine on dopamine and cAMP regulated phosphoprotein (DARPP-32) were characterised in rat brain. The results show that DARPP-32 is regulated by both acute and long-term nicotine treatment in the striatal subdivisions. The effect of acute nicotine is dose-dependent and the three striatal regions display differential sensitivities to nicotine. Chronic nicotine is also able to regulate DARPP-32 signalling with prominent effect seen in the nucleus accumbens (NAc), suggesting a role for DARPP-32 in the mediation of long-term effects of nicotine. Finally, the regulation of transcription factors Elk-1 and FosB/deltaFosB by nicotine was investigated. We found that Elk-1 is activated by acute nicotine selectively in the NAc core and hippocampal area CA1, whereas acute nicotine does not affect FosB/deltaFosB. Long-term intermittent or continuous nicotine increases the level of total Elk-1 in the same brain regions as acute nicotine. FosB/deltaFosB is also affected by chronic nicotine. Thus, similarly to other drugs of abuse, nicotine regulates transcriptional regulators Elk-1 and FosB/deltaFosB. These results bring further support for a common mechanism underlying the development of addiction. Nicotine s positive effects on learning and memory might involve the transcription factor Elk-1 based on the changes seen in the hippocampus, the key area in cognitive functions.

High-Pressure Low-Temperature Locknut Cell For Both Electron-Paramagnetic-Res And Nmr-Studies To 10 Kilobars And 77-K

A locked high-pressure cell with working pressure range up to 10 kbars suitable for low-temperature studies to 77 K has been described. It can be used for both EPR and NMR studies of single crystals (and other solid samples). The high-pressure seal and all other aspects of the cell remain the same for either application. Only a change of the bottom plug is required for a switch from a nuclear-magnetic-resonance (NMR) to an electron-paramagnetic-resonance (EPR) experiment. Details of the procedure for the calibration of pressure inside the cell at various temperatures are discussed. The performance of the cell in EPR (Cr3+ion) and NMR (27Al nucleus) studies is reported.

Mapinduzi Daima – Revolution Forever : Using the 1964 Revolution in Nationalistic Political Discourses in Zanzibar

This Master's thesis examines two opposite nationalistic discourses on the revolution of Zanzibar. Chama cha Mapinduzi (CCM), the party in power since the 1964 revolution defends its revolutionary and "African" heritage in the current multi-party system. New nationalists, including among others the main opposition party Civic United Front (CUF), question both the 1964 revolution and the post-revolution period and blame CCM for empty promises, corruption and ethnic discrimination. This study analyzes the role of a significant historical event in the creation of nationalistic ideology and national identity. The 1964 revolution forms the nucleus of various debates related to the history of Zanzibar: slavery, colonialism, racial discrimination and political violence. Representations of these Social constructivist principles form the basis of this study, and central concepts in the theoretical framework are nationalism, national identity, ethnicity and race. I use critical discourse analysis as my research method, lean on the work by Teun A. van Dijk and Norman Fairclough as the most significant researchers in this field. I examine particularly the ways in which linguistic methods, such as stereotypes and metaphors are used to form in- and out-groups ("us" vs. "others"). My material, both in Swahili and English, was collected mainly in Tanzania in the fall of 2007 and from online sources in the spring of 2009. It includes publications by the Zanzibari government between the years of 1964-2000 (12), official speeches for the Revolution Day or the Union Day (12), articles from Tanzanian newspapers from the 1990s until the year of 2009 (15), memoirs and political pamphlets (10), blog posts and opinion pieces from four different websites (8), and interviews or personal communication in Zanzibar, Dar es Salaam and Uppsala (8). Nationalistic rhetoric often creates enemy images by using binary good-bad oppositions. Both discourses in this study build identities on the basis of "otherness" and exclusion, with the intent of emphasizing the particularity of the own group and excluding "evilness" outside the own reference group. These opposite views on the 1964 revolution as the main axis of the history of Zanzibar build different portraits of the nation and Zanzibari-ness (Uzanzibari). CCM still relies on the pre-revolutionary enemy images of Arabs as selfish rulers and cruel slave traders. For CCM, Zanzibar is primarily an "African" nation and a part of Tanzania which is threatened by "Arabs", the outsiders. In contrast, the new nationalists stress the long history of Zanzibar as multi-racial, cosmopolitan and formerly independent country which has its own, separate culture and identity from mainland Tanzanians. Heshima, honour/respect, one of the basic values of Swahili culture, occupies a central role in both discourses: the main party emphasizes that the revolution returned "heshima" to the Zanzibari Africans after centuries of humiliation, whereas the new nationalists claim that ever since the revolution all "non-Africans" have been humiliated and lost their "heshima". According to the new nationalists, true Zanzibari values which include tolerance and harmony between different "races" were lost when the "foreign" revolutionaries arrived from the mainland. Consequently, they see the 1964 revolution as Tanganyikan colonialism which began with the help of Western countries, and maintain that this "colonialism" still continues in the violent multi-party elections.

Mössbauer studies of the corrosion products of iron formed in aqueous ammonium nitrate solution

The products of corrosion reaction of electrolytic iron in 45% ammonium nitrate solution formed under various conditions of time, temperature and pH have been analysed mainly by Mössbauer spectroscopy, in combination with X-ray diffraction, infrared absorption and electron microscopy techniques. γ-Fe00H is found to be the major product of hydrolytic precipitation at pH > 5.6 while only α-FeOOH is formed at pH < 3.0. In the pH range 3.0 < pH < 5.0, α-Fe00H and ferrihydrite are both formed. However, once the nuclei of α-Fe00H are formed under low pH conditions, their growth is favoured even in the otherwise unfavourable slightly acidic medium, resulting in a hydrous α-Fe00H which has two distinct hyperfine fields at the 57Fe nucleus. Magnetite is always formed in the vicinity of the metal and its rate of formation on the surface increases with temperature. α-Fe203 is the major product of hydrolytic precipitation at temperatures >80C. The possible mechanisms for the formation of each of the corrosion products are discussed.

Dark Spots, Bubbles, and Shells in the Lobes of Extragalactic Radio Sources

Based on maps of the extragalactic radio sources Cyg A, Her A, Cen A, 3C 277.3 and others, arguments are given that the twin-jets from the respective active galactic nucleus ram their channels repeatedly through thin, massive shells. The jets are thereby temporarily choked and blow radio bubbles. Warm shell matter in the cocoon shows up radio-dark through electron-scattering.

Evolution of crystallographic texture and microstructure in the orthorhombic phase of a two-phase alloy Ti-22Al-25Nb

Evolution of crystallographic texture in the orthorhombic phase of a two-phase alloy Ti–22Al–25Nb (at%), consisting of orthorhombic (O) and bcc (β/B2) phases, was studied. The material was subjected to deformation in two-phase field as well as in the single β phase field. The resulting evolution of microstructure and crystallographic texture were recorded using scanning electron microscopy and X-ray diffraction. The orthorhombic phase underwent change in morphology (from platelets to equiaxed) on rolling in the two-phase field with the texture getting sharper with the amount of deformation. Rolling above β transus temperature led to hot deformation of single β phase microstructure and its subsequent cooling produced transformed coarse platelets of orthorhombic phase with texture in orientation relation with the high temperature deformed β phase.

Inter-lamellar shear resistance confers compressive stiffness in the intervertebral disc: An image-based modelling study on the bovine caudal disc

The intervertebral disc withstands large compressive loads (up to nine times bodyweight in humans) while providing flexibility to the spinal column. At a microstructural level, the outer sheath of the disc (the annulus fibrosus) comprises 12–20 annular layers of alternately crisscrossed collagen fibres embedded in a soft ground matrix. The centre of the disc (the nucleus pulposus) consists of a hydrated gel rich in proteoglycans. The disc is the largest avascular structure in the body and is of much interest biomechanically due to the high societal burden of disc degeneration and back pain. Although the disc has been well characterized at the whole joint scale, it is not clear how the disc tissue microstructure confers its overall mechanical properties. In particular, there have been conflicting reports regarding the level of attachment between adjacent lamellae in the annulus, and the importance of these interfaces to the overall integrity of the disc is unknown. We used a polarized light micrograph of the bovine tail disc in transverse cross-section to develop an image-based finite element model incorporating sliding and separation between layers of the annulus, and subjected the model to axial compressive loading. Validation experiments were also performed on four bovine caudal discs. Interlamellar shear resistance had a strong effect on disc compressive stiffness, with a 40% drop in stiffness when the interface shear resistance was changed from fully bonded to freely sliding. By contrast, interlamellar cohesion had no appreciable effect on overall disc mechanics. We conclude that shear resistance between lamellae confers disc mechanical resistance to compression, and degradation of the interlamellar interface structure may be a precursor to macroscopic disc degeneration.

GABAAα1 and GABAAρ1 subunits are expressed in cultured human RPE cells and GABAA receptor agents modify the intracellular calcium concentration.

Purpose: Gamma-aminobutyric acid A (GABAA) receptors (GABAARs), which are ionotropic receptors involving chloride channels, have been identified in various neural (e.g., mouse retinal ganglion cells) and nonneural cells (e.g., mouse lens epithelial cells) regulating the intracellular calcium concentration ([Ca(2+)]i). GABAAR β-subunit protein has been isolated in the cultured human and rat RPE, and GABAAα1 and GABAAρ1 mRNAs and proteins are present in the chick RPE. The purpose of this study was to investigate the expression of GABAAα1 and GABAAρ1, two important subunits in forming functional GABAARs, in the cultured human RPE, and further to explore whether altering receptor activation modifies [Ca(2+)]i. Methods: Human RPE cells were separately cultured from five donor eye cups. Real-time PCR, western blots, and immunofluorescence were used to test for GABAAα1 and GABAAρ1 mRNAs and proteins. The effects of the GABAAR agonist muscimol, antagonist picrotoxin, or the specific GABAAρ antagonist 1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) on [Ca(2+)]i in cultured human RPE were demonstrated using Fluo3-AM. Results: Both GABAAα1 and GABAAρ1 mRNAs and proteins were identified in cultured human RPE cells; antibody staining was mainly localized to the cell membrane and was also present in the cytoplasm but not in the nucleus. Muscimol (100 μM) caused a transient increase of the [Ca(2+)]i in RPE cells regardless of whether Ca(2+) was added to the buffer. Muscimol-induced increases in the [Ca(2+)]i were inhibited by pretreatment with picrotoxin (300 μM) or TPMPA (500 μM). Conclusions: GABAAα1 and GABAAρ1 are expressed in cultured human RPE cells, and GABAA agents can modify [Ca(2+)]i.

Kinetics of interaction of Cotton Leaf Curl Kokhran Virus-Dabawali (CLCuKV-Dab) coat protein and its mutants with ssDNA

Gemini viral assembly and transport of viral DNA into nucleus for replication, ssentially involve DNA-coat protein interactions. The kinetics of interaction of Cotton LeafCtirl Kokhran Virus-Dabawali recombinant coat protein (rCP) with DNA was studied by electrophoretic mobility shift assay (EMSA) and Surface plasmon resonance (SPR). The rCP interacted with ssDNA with a K-A, of 2.6 +/- 0.29 x 10(8) M-1 in a sequence non-specific manner. The CP has a conserved C2H2 type zinc finger motif composed of residues C68, C72, H81 and H85. Mutation of these residues to alanine resulted in reduced binding to DNA probes. The H85A mutant rCP showed the least binding with approximately 756 fold loss in the association rate and a three order magnitude decrease in the binding affinity as compared to rCP. The CP-DNA interactions via the zinc finger motif could play a Crucial role ill Virus assembly and in nuclear transport. (C) 2009 Elsevier Inc.

Role of free volume in strain softening of as-cast and annealed bulk metallic glass

Plasticity in amorphous alloys is associated with strain softening, induced by the creation of additional free volume during deformation. In this paper, the role of free volume, which was a priori in the material, on work softening was investigated. For this, an as-cast Zr-based bulk metallic glass (BMG) was systematically annealed below its glass transition temperature, so as to reduce the free volume content. The bonded-interface indentation technique is used to generate extensively deformed and well defined plastic zones. Nanoindentation was utilized to estimate the hardness of the deformed as well as undeformed regions. The results show that the structural relaxation annealing enhances the hardness and that both the subsurface shear band number density and the plastic zone size decrease with annealing time. The serrations in the nanoindentation load-displacement curves become smoother with structural relaxation. Regardless of the annealing condition, the nanohardness of the deformed regions is similar to 12-15% lower, implying that the prior free volume only changes the yield stress (or hardness) but not the relative flow stress (or the extent of strain softening). Statistical distributions of the nanohardness obtained from deformed and undeformed regions have no overlap, suggesting that shear band number density has no influence on the plastic characteristics of the deformed region.

Synthesis and in vitro cytotoxic evaluation of novel diazaspiro bicyclo hydantoin derivatives in human leukemia cells: A SAR study

To study the structure activity relationship (SAR) on the cytotoxic activity and probe the structural requirement for the potent antitumor activity, a series of novel diazaspiro bicyclo hydantoin derivatives were designed and synthesized. Their structures were confirmed by H-1 NMR, LCMS and IR analyses. The antiproliferative effect of these compounds were determined against human leukemia, K562 (chronic myelogenous leukemia) and CEM (T-cell leukemia) cells using trypan blue and MTT assay, and the SAR associated with the position of N-terminal substituents in diazaspiro bicyclo hydantoin have also been discussed. It has been observed that these compounds displayed strong, moderate and weak cytotoxic activities. Interestingly, compounds having electron withdrawing groups at third and fourth position of the phenyl ring displayed selectively cytotoxic activities to both the cell lines tested with IC50 value lower than 50 mu M. In addition, the cytotoxic activities of the compounds 7(a-o) bearing the substituents at N-3 position of diazaspiro bicyclo hydantoin increases in the order alkene > ester > ether and plays an important role in determining their antitumor activities. The position and number of substituents in benzyl group attached to N-8 of diazaspiro bicyclo hydantoin nucleus interacted selectively with specific targets leading to the difference of biochemical and pharmacological effects.

Post capture necrosis of the feet caused by soft-catch traps – incidents, cause and prevention.

When recapturing satellite collared wild dogs that had been trapped one month previous in padded foothold traps, we noticed varying degrees of pitting on the pads of their trapped paw. Veterinary advice, based on images taken of the injuries, suggests that the necrosis was caused by vascular compromise. Five of six dingoes we recaptured had varying degrees of necrosis restricted only to the trapped foot and ranging from single 5 mm holes to 25% sections of the toe pads missing or deformed, including loss of nails. The traps used were rubber-padded, two–coiled, Victor Soft Catch #3 traps. The springs are not standard Victor springs but were Beefer springs; these modifications slightly increase trap speed and the jaw pressure on the trapped foot. Despite this modification the spring pressure is still relatively mild in comparison to conventional long spring or four-coiled wild dog traps. The five wild dogs developing necrosis were trapped in November 2006 at 5-6 months of age. Traps were checked each morning so the dogs were unlikely to have been restrained in the trap for more than 12 hours. All dogs exhibited a small degree of paw damage at capture which presented itself as a swollen paw and compression at the capture point. In contrast, eight wild dogs, 7-8 month-old, were captured two months later in February. Upon their release, on advice from a veterinarian, we massaged the trapped foot to get blood flow back in to the foot and applied a bruise treatment (Heparinoid 8.33 mg/ml) to assist restoring blood flow. These animals were subsequently recaptured several months later and showed no signs of necrosis. While post-capture foot injuries are unlikely to be an issue in conventional control programs where the animal is immediately destroyed, caution needs to be used when releasing accidentally captured domestic dogs or research animals captured in rubber-padded traps. We have demonstrated that 7-8 month old dogs can be trapped and released without any evidence of subsequent necrosis following minimal veterinary treatment. We suspect that the rubber padding on traps may increase the tourniquet effect by wrapping around the paw and recommend the evaluation of offset laminated steel jaw traps as an alternative. Offset laminated steel jaw traps have been shown to be relatively humane producing as few foot injuries as rubber-jawed traps.