Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

Buddhisms and Deconstructions considers the connection between Buddhism and Derridean deconstruction, focusing on the work of Robert Magliola. Fourteen distinguished contributors discuss deconstruction and various Buddhisms—Indian, Tibetan, and Chinese —followed by an afterword in which Magliola responds directly to his critics.

L(ow) tone in Mandarin Chinese causes both downstep and post-low-bouncing. Downstep refers to the lowering of a H(igh) tone after a L tone, which is usually measured by comparing the H tones in a “H…HLH…H” sentence with a “H…HHH…H” sentence (cross-comparison), investigating whether downstep sets a new pitch register for the scaling of subsequent tones. Post-low-bouncing refers to the raising of a H tone after a focused L tone. The current study investigates how downstep and post-low-bouncing interact with focus and (...) phrasing in Mandarin Chinese. In the experiment, we systematically manipulated (a) the tonal environment by embedding two syllables with either LH or HH tone (syllable X and Y) sentence-medially in the same carrier sentences containing only H tones; (b) boundary strength between X and Y by introducing either a syllable boundary or a phonological phrase boundary; and (c) information structure by either placing a contrastive focus in the HL/HH word (XF), syllable Y (YF), or the sentence-final word (ZF). A wide-focus condition served as the baseline. With systematic control of focus and boundary strength around the L tone, the current study shows that the downstep effect in Mandarin is quite robust, lasting for 3–5 H tones after the L tone, but eventually levelling back again to the register reference line of a H tone. The way how focus and phrasing interact with the downstep effect is unexpected. Firstly, sentence-final focus has no anticipatory effect on shortening the downstep effect; instead, it makes the downstep effect lasts longer as compared to the wide focus condition. Secondly, the downstep effect still shows when the H tone after the L tone is on-focus (YF), in a weaker manner than the wide focus condition, and is overridden by the post-focus-compression. Thirdly, the downstep effect gets greater when the boundary after the L tone is stronger, because the L tone is longer and more likely to be creaky. We further analyzed downstep by measuring the F0 drop between the two H tones surrounding the L tone (sequential-comparison). Comparing it with F0 drop in all-H sentences (i.e., declination), it showed that the downstep effect was much greater and more robust than declination. However, creaky voice in the L tone was not the direct cause of downstep. At last, when the L tone was under focus (XF), it caused a post-low-bouncing effect, which is weakened by a phonological phrase boundary. Altogether, the results showed that although intonation is largely controlled by informative functions, the physical-articulatory controls are relatively persistent, varying within the pitch range of 2.5 semitones. Downstep and post-low-bouncing in Mandarin Chinese thus seem to be mainly due to physical-articulatory movement on varying pitch, with the gradual tonal F0 change meeting the requirement of smooth transition across syllables, and avoiding confusion in informative F0 control. (shrink)

This paper discusses the stability and Hopf bifurcation analysis of the diffusive Kaldor–Kalecki model with a delay included in both gross product and capital stock functions. The reaction-diffusion domain is considered, and the Galerkin analytical method is used to derive the system of ordinary differential equations. The methodology used to determine the Hopf bifurcation points is discussed in detail. Furthermore, full diagrams of the Hopf bifurcation regions considered in the stability analysis are shown, and some numerical simulations of the limit (...) cycle are used to confirm the theoretical outcomes. The delay investment parameter and diffusion coefficient can have great impacts on the Hopf bifurcations and stability of the business cycle model. The investment parameters for the gross product and capital stock as well as the adjustment coefficient of the production market are also studied. These parameters can cause instability in, and the stabilization of, the business cycle model. In addition, we point out that, as the delay investment parameter increases, the Hopf bifurcation points for the diffusion coefficient values decrease considerably. When the delay investment parameter has a very small value, the solution of the business cycle model tends to become steady. (shrink)

Cheating is a serious issue among business students worldwide. However, research investigating the social factors that may help prevent cheating in Chinese higher education is rare. The present study examined two key social relationship factors of perceived teacher-student relationships and peer relationships by the students. It attempted to build a model which addressed the effects of two variables on Chinese business students’ cheating behaviour: the teacher’s approachability and the relationship goal of the students. Two important social influence factors were also (...) tested as mediators: neutralizing attitudes and perceived cheating norms of the students. A student survey was conducted with 1329 questionnaires collected. The results showed the negative effects of both social relationship variables on cheating, and that their effects were fully mediated by neutralizing attitudes. Moreover, perceived cheating norms fully mediated the effect of the teacher’s approachability, but not so for the relationship goal of the students. This study provided novel insights and recommendations for promoting academic integrity in Chinese business schools and universities. (shrink)

This study investigates the impact of labor unionization on stock price crash risk. We find that labor unionization is negatively associated with stock price crash risk. Such negative relation is more pronounced when firms can intimate more credible evidence on unfavorable prospects and when firms face more powerful labor unions. Our findings are consistent with the notion that firms take strategic actions to reduce the bargaining advantages enjoyed by labor unions and that labor unions force firms to take less risky (...) investments and discontinue underperformed projects more timely, which leads to lower stock price crash risk. (shrink)

Little attention has been given in medical ethics literature to issues relating to the truthfulness of patients. Beginning with an actual medical case, this paper first explores truth-telling by doctors and patients as related to two prominent models of the physician-patient relationship. Utilizing this discussion and the literature on the truthfulness and accuracy of the information patients convey to doctors, these models are then critically assessed. It is argued that the patient agency (patient autonomy or contractual) model is inherently and (...) seriously flawed in numerous circumstances, even those involving informed and competent adult patients. (shrink)

The 25th of January, 2011 witnessed a wave of political unrest all over Egypt, with repercussions that have re-shaped the future of contemporary Egypt. For the first time in the modern history of Egypt since the 1952 Nasserite revolution, grass-root protestors went to streets chanting slogans against the military regime headed by the (since then ex-) President of Egypt, Hosni Mubarak. This placed the then regime, as well as its mainstay, the National Democratic Party (NDP), in a political crisis on (...) both local and international scales. It is this critical moment that led Mubarak to give his unprecedented speech on February 1st, 2011. The speech has brought about epoch-making political changes in the history of contemporary Egypt. Under public pressure, two seminal declarations were made in this speech: (1) Mubarak’s intention not to nominate himself for a new presidential term; (2) a call on the Houses of Parliament to amend articles 76 and 77 of the constitution concerning the conditions on running for presidency and the period for the presidential term in Egypt. The present paper seeks to answer the following overarching question: what are the discursive strategies used for saving the political face of Mubarak in his speech on February 1st, 2011? I follow a text-analytic framework based on the socio-semantic theory of social actors and the pragmatic models of speech acts and face-threatening acts. The analysis reveals Mubarak’s attempt to save his positive political face as a legitimate President who regarded himself as the official ruler invested with absolute power over Egypt. (shrink)