CDCA3 regulates the cell cycle and modulates cisplatin sensitivity in non-small cell lung cancer

Cisplatin-based regimens are currently the most effective chemotherapy for non-small cell lung cancer (NSCLC). Cisplatin forms DNA crosslinks to stall DNA replication and induce apoptosis. However, intrinsic and acquired chemoresistance is a major therapeutic problem. We have identified ‘cell division cycle associated protein 3’ (CDCA3) as a novel protein that may prove useful in delaying or preventing cisplatin resistance in NSCLC. CDCA3 functions as part of an ubiquitin ligase complex to degrade the endogenous cell cycle inhibitors. While a role for CDCA3 in disease is emerging with elevated expression noted in oral squamous cell carcinoma, little else is known about CDCA3 or whether this protein may prove useful clinically.

Design of a high sensitivity FET integrated MEMS microphone

FET based MEMS microphones comprise of a flexible diaphragm that works as the moving gate of the transistor. The integrated electromechanical transducer can be made more sensitive to external sound pressure either by increasing the mechanical or the electrical sensitivities. We propose a method of increasing the overall sensitivity of the microphone by increasing its electrical sensitivity. The proposed microphone uses the transistor biased in the sub-threshold region where the drain current depends exponentially on the difference between the gate-to-source voltage and the threshold voltage. The device is made more sensitive without adding any complexity in the mechanical design of the diaphragm.

Effect of cold exposure on the metabolism of ubiquinone in the rat

1. Accumulation of ubiquinone in the livers of rats exposed to a cold environment was shown to be due to both decreased catabolism during the entire experimental period and increased synthesis during an intermediate stage (10–20 days). 2. The increased endogenous synthesis in the cold-exposed rats was eliminated when ubiquinone accumulated in the liver after exposure for 40 days (coinciding with cclimatization), or by absorption of the exogenous dietary supply, possibly by the mechanism of end-product regulation.

Structural and Biochemical Bases for the Redox Sensitivity of Mycobacterium tuberculosis RslA

An effective transcriptional response to redox stimuli is of particular importance for Mycobacterium tuberculosis, as it adapts to the environment of host alveoli and macrophages. The M. tuberculosis a factor sigma(L) regulates the expression of genes involved in cell-wall and polyketide syntheses. sigma(L) interacts with the cytosolic anti-sigma domain of a membrane-associated protein, RslA. Here we demonstrate that RslA binds Zn2+ and can sequester sigma(L) in a reducing environment. In response to an oxidative stimulus, proximal cysteines in the CXXC motif of RslA form a disulfide bond, releasing bound Zn2+. This results in a substantial rearrangement of the sigma(L)/RslA complex, leading to an 8-fold decrease in the affinity of RslA for sigma(L). The crystal structure of the -35-element recognition domain of sigma(L), sigma(L)(4), bound to RslA reveals that RslA inactivates sigma(L) by sterically occluding promoter DNA and RNpolymerase binding sites. The crystal structure further reveals that the cysteine residues that coordinate Zn2+ in RslA are solvent exposed in the complex, thus providing a structural basis for the redox sensitivity of RslA. The biophysical parameters of sigma(L)/RslA interactions provide a template for understanding how variations in the rate of Zn2+ release and associated conformational changes could regulate the activity of a Zn2+-associated anti-sigma factor. (C) 2010 Elsevier Ltd. All rights reserved.

Between West and East: A Social History of Business Journalism in Cold War Finland

The Cold War era was characterized by ideological struggles that had a major impact on economic decision-making, and also on management practice. To date, however, these ideological struggles have received little attention from management and organizational scholars. To partially fill this research gap, we focus on the role of the media in these ideological struggles. Our starting point is that the media both reflect more general societal debates but also act as an agency promoting specific kinds of ideas and ideologies. In this sense, the media exercise significant power in society; this influece, however, is often subtle and easily dismissed in historical analyses focusing on political and corporate decision-making. In this article, we focus on the role of business journalism in the ideological struggles of the Cold War era. Our case in point is Finland, which is arguably a particularly interesting example due to its geo-political position between East and West. Our approach is socio-historical: we focus on the emergence and development of business journalism in the context of the specific struggles in the Finnish political and economic fields. Our analysis shows how the business journalists struggled between nationalist, pro-Soviet and pro-West political forces, but gradually developed into an increasingly influential force promoting neo-liberal ideology.

Rotation sensitivity of Lau fringes: an analysis based on coherence theory

An analysis based on coherence theory is presented, which explains the experimentally observed rotation sensitivity of the contrast of Lau fringes obtained under spatially incoherent illumination.

SC-FDMA versus OFDMA: Sensitivity to Large Carrier Frequency and Timing Offsets on the Uplink

In this paper, we present a comparison between the sensitivity of SC-FDMA and OFDMA schemes to large carrier frequency offsets (CFO) and timing offsets (TO) of different users on the uplink. Our study shows the following observations: 1) In the ideal case of zero CFOs and TOs (i.e., perfect synchronization), the uncoded BER performance of SC-FDMA with frequency domain MMSE equalizer is better than that of OFDMA due to the inherent frequency diversity that is possible in SCFDMA. Also, because of inter-symbol interference in SC-FDMA, the performance of SC-FDMA with MMSE equalizer can be further improved by using low-complexity interference cancellation (IC) techniques. 2) In the presence of large CFOs and TOs, significant multiuser interference (MUI) gets introduced, and hence the performance of SC-FDMA with MMSE equalizer can get worse than that of OFDMA. However, the performance advantage of SC-FDMA with MMSE equalizer over OFDMA (due to the potential for frequency diversity benefit in SC-FDMA) can be restored by adopting multistage IC techniques, using the knowledge of CFOs and TOs of different users at the receiver

The ability of prolactin to change the sensitivity of the pituitary of the lactating rat to luteinising hormone releasing hormonein vitro

The ability of prolactin to influence the responsiveness of the lactating rat pituitary to luteinising hormone releasing hormone has been examinedin vitro. The pituitary responsivenessin vivo to luteinising hormone releasing hormone decreased as a function of increase in the lactational stimulus. Prolactin inhibited the spontaneousin vitro release of luteinising hormone and follicle stimulating hormone to a small extent, from the pituitary of lactating rats with the suckling stimulus. However, it significantly inhibited the release of these two hormones from luteinising hormone releasing hormone-stimulated pituitaries. The responsiveness of pituitaries of rats deprived of their litter 24 h earlier, to luteinising hormone releasing hormone was also inhibited by prolactin, although minimal. It was concluded that prolactin could be influencing the functioning of the pituitary of the lactating rat by (a) partially suppressing the spontaneous release of gonadotropin and (b) inhibiting the responsiveness of the pituitary to luteinising hormone releasing hormone.

Nationalism Circumscribed : Transnational Governance of Minority Rights in Post-Cold War Europe

For the past two centuries, nationalism has been among the most influential legitimizing principles of political organization. According to its simple definition, nationalism is a principle or a way of thinking and acting which holds that the world is divided into nations, and that national and political units should be congruent. Nationalism can thus be divided into two aspects: internal and external. Internally, the political units, i.e., states, should be made up of only one nation. Externally each nation-state should be sovereign. Transnational national governance of rights of national minorities violates both these principles. This study explores the formation, operation, and effectiveness of the European post-Cold War minorities system. The study identifies two basic approaches to minority rights: security and justice. These approaches have been used to legitimize international minority politics and they also inform the practice of transnational governance. The security approach is based on the recognition that the norm of national self-determination cannot be fulfilled in all relevant cases, and so minority rights are offered as a compensation to the dissatisfied national groups, reducing their aspiration to challenge the status quo. From the justice perspective, minority rights are justified as a compensatory strategy against discrimination caused by majority nation-building. The research concludes that the post-Cold War minorities system was justified on the basis of a particular version of the security approach, according to which only Eastern European minority situations are threatening because of the ethnic variant of nationalism that exists in that region. This security frame was essential in internationalising minority issues and justifying the swift development of norms and institutions to deal with these issues. However, from the justice perspective this approach is problematic, since it justified double standards in European minority politics. Even though majority nation-building is often detrimental to minorities also in Western Europe, Western countries can treat their minorities more or less however they choose. One of the main contributions of this thesis is the detailed investigation of the operation of the post-Cold War minorities system. For the first decade since its creation in the early 1990s, the system operated mainly through its security track, which is based on the field activities of the OSCE that are supported by the EU. The study shows how the effectiveness of this track was based on inter-organizational cooperation in which various transnational actors compensate for each other s weaknesses. After the enlargement of the EU and dissolution of the membership conditionality this track, which was limited to Eastern Europe from the start, has become increasingly ineffective. Since the EU enlargement, the focus minorities system has shifted more and more towards its legal track, which is based on the Framework Convention for the Protection of National Minorities (Council of Europe). The study presents in detail how a network of like-minded representatives of governments, international organizations, and independent experts was able strengthen the framework convention s (originally weak) monitoring system considerably. The development of the legal track allows for a more universal and consistent, justice-based approach to minority rights in contemporary Europe, but the nationalist principle of organization still severely hinders the materialization of this possibility.

Strain-rate sensitivity and microstructural evolution in a Mg-Al-Zn alloy

Strain rate sensitivity measurements are used to identify twinning and changes in deformation mechanisms in a Mg AZ31 alloy over a wide range of temperatures and grain sizes. At low temperatures, there is significant twinning at low strains with strain-rate insensitivity; at large strains, strain rate sensitivity is noted, corresponding to deformation by multiple slip. At high temperatures, there is very little twinning and this leads to a significant strain rate sensitivity from the early stages of deformation. (C) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Role of spatial coherence on the rotation sensitivity of Lau fringes: an experimental study

A simple technique involving the use of a rotating and a stationary diffuser has been developed to vary the spatial coherence of light from a He-Ne laser. Using this technique an experimental investigation of the dependence of rotation sensitivity of Lau fringes on the spatial coherence of the illuminating wavefield has been carried out. It is observed that (i) the rotation sensitivity of Lau fringes varies in a well-defined manner as a function of the spatial coherence of the light used; (ii) the extremely good rotation sensitivity of Lau fringes can be used to great advantage (compared to the conventional double slit method) in the measurement of the spatial coherence of a wavefield; (iii) Lau fringes are formed at various levels of spatial coherence and as such it appears that the Lau effect need not be associated with an incoherent optical field