The Alzheimer’s disease γ-secretase generates higher 42:40 ratios for β-amyloid than for p3 peptides

Alzheimer’s disease is characterized by intracerebral deposition of β-amyloid (Aβ). While Aβ40 is the most abundant form, neurotoxicity is mainly mediated by Aβ42. Sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases gives rise to full-length Aβ (Aβ1-x) and N-terminally truncated Aβ′ (Aβ11-x) whereas cleavage by α- and γ-secretases leads to the shorter p3 peptides (Aβ17-x). We uncovered significantly higher ratios of 42- versus 40-ending variants for Aβ and Aβ′ than for p3 secreted by mouse neurons and human induced pluripotent stem cell (iPSC)-derived neurons or produced in a cell-free γ-secretase assay with recombinant APP-CTFs. The 42:40 ratio was highest for Aβ′, followed by Aβ and then p3. Mass spectrometry analysis of APP intracellular domains revealed differential processing of APP-C83, APP-C89, and APP-C99 by γ-secretase already at the ε-cleavage stage. This mechanistic insight could aid in developing substrate-targeted modulators of APP-C99 processing to specifically lower the Aβ42:Aβ40 ratio without compromising γ-secretase function

M-branes and N=2 Strings

The string field theory of N=(2,1) heterotic strings describes a set of self-dual Yang-Mills fields coupled to self-dual gravity in 2+2 dimensions. We show that the exact classical action for this field theory is a certain complexification of the Green-Schwarz/Dirac-Born-Infeld string action, closely related to the four dimensional Wess-Zumino action describing self-dual gauge fields. This action describes the world-volume of a 2+2d ``M-brane'', which gives rise upon different null reductions to critical strings and membranes. We discuss a number of further properties of N=2 heterotic strings, such as the geometry of null reduction, general features of a covariant formulation, and possible relations to BPS and GKM algebras.Comment: 49 pages, harvmac; 1 figure (uses epsf.tex). References adde

Port-access coronary artery bypass grafting: A proposed surgical method

AbstractMinimally invasive surgical methods have been developed to provide patients the benefits of open operations with decreased pain and suffering. We have developed a system that allows the performance of cardiopulmonary bypass and myocardial protection with cardioplegic arrest without sternotomy or thoracotomy. In a canine model, we successfully used this system to anastomose the internal thoracic artery to the left anterior descending coronary artery in nine of 10 animals. The left internal thoracic artery was dissected from the chest wall, and the pericardium was opened with the use of thoracoscopic techniques and single lung ventilation. The heart was arrested with a cold blood cardioplegic solution delivered through the central lumen of a balloon occlusion catheter (Endoaortic Clamp; Heartport, Inc., Redwood City, Calif.) in the ascending aorta, and cardiopulmonary bypass was maintained with femorofemoral bypass. An operating microscope modified to allow introduction of the 3.5× magnification objective into the chest was positioned through a 10 mm port over the site of the anastomosis. The anastomosis was performed with modified surgical instruments introduced through additional 5 mm ports. In the cadaver model (n = 7) the internal thoracic artery was harvested and the pericardium opened by means of similar techniques. A precise arteriotomy was made with microvascular thoracoscopic instruments under the modified microscope on four cadavers. In three other cadavers we assessed the exposure provided by a small anterior incision (4 to 6 cm) over the fourth intercostal space. This anterior port can assist in dissection of the distal internal thoracic artery and provides direct access to the left anterior descending, circumflex, and posterior descending arteries. We have demonstrated the potential feasibility of grafting the internal thoracic artery to coronary arteries with the heart arrested and protected, without a major thoracotomy or sternotomy. (J THORAC CARDIOVASC SURG 1996;111:567-73

The Structure of Episodic Memory: Ganeri's ‘Mental Time Travel and Attention’

We offer a framework for assessing what the structure of episodic memory might be, if one accepts the Buddhist denial of persisting selves. This paper is a response to Jonardon Ganeri's paper "Mental time travel and attention", which explores Buddhaghosa's ideas about memory. (It will eventually be published with a reply by Ganeri)

No straight lines – young women’s perceptions of their mental health and wellbeing during and after pregnancy: a systematic review and meta-ethnography

Background: Young mothers face mental health challenges during and after pregnancy including increased rates of depression compared to older mothers. While the prevention of teenage pregnancy in countries such as the United States and the United Kingdom has been a focus for policy and research in recent decades, the need to understand young women’s own experiences has been highlighted. The aim of this meta-ethnography was to examine young women’s perceptions of their mental health and wellbeing during and after pregnancy to provide new understandings of those experiences. Methods: A systematic review and meta-ethnographic synthesis of qualitative research was conducted. Seven databases were systematically searched and forward and backward searching conducted. Papers were included if they were from Organisation for Economic Co-operation and Development countries and explored mental health and wellbeing experiences of young mothers (age under 20 in pregnancy; under 25 at time of research) as a primary research question – or where evidence about mental health and wellbeing from participants was foregrounded. Nineteen papers were identified and the Critical Appraisal Skills Programme checklist for qualitative research used to appraise the evidence. Following the seven-step process of meta-ethnography, key constructs were examined within each study and then translated into one another. Results: Seven translated themes were identified forming a new line of argument wherein mental health and wellbeing was analysed as relating to individual bodily experiences; tied into past and present relationships; underpinned by economic insecurity and entangled with feelings of societal surveillance. There were ‘no straight lines’ in young women’s experiences, which were more complex than dominant narratives around overcoming adversity suggest. Conclusions: The synthesis concludes that health and social care professionals need to reflect on the operation of power and stigma in young women’s lives and its impact on wellbeing. It adds to understanding of young women’s mental health and wellbeing during and after pregnancy as located in physical and structural factors rather than individual capacities alone

Radiation dose reduction at a price: the effectiveness of a male gonadal shield during helical CT scans

BACKGROUND: It is estimated that 60 million computed tomography (CT) scans were performed during 2006, with approximately 11% of those performed on children age 0–15 years. Various types of gonadal shielding have been evaluated for reducing exposure to the gonads. The purpose of this study was to quantify the radiation dose reduction to the gonads and its effect on image quality when a wrap-around male pediatric gonad shield was used during CT scanning. This information is obtained to assist the attending radiologist in the decision to utilize such male gonadal shields in pediatric imaging practice. METHODS: The dose reduction to the gonads was measured for both direct radiation and for indirect scattered radiation from the abdomen. A 6 cm(3 )ion chamber (Model 10X5-6, Radcal Corporation, Monrovia, CA) was placed on a Humanoid real bone pelvic phantom at a position of the male gonads. When exposure measurements with shielding were made, a 1 mm lead wrap-around gonadal shield was placed around the ion chamber sensitive volume. RESULTS: The use of the shields reduced scatter dose to the gonads by a factor of about 2 with no appreciable loss of image quality. The shields reduced the direct beam dose by a factor of about 35 at the expense of extremely poor CT image quality due to severe streak artifacts. CONCLUSION: Images in the direct exposure case are not useful due to these severe artifacts and the difficulties in positioning these shields on patients in the scatter exposure case may not be warranted by the small absolute reduction in scatter dose unless it is expected that the patient will be subjected to numerous future CT scans

Towards a Resolution of the Cosmological Singularity in Non-local Higher Derivative Theories of Gravity

One of the greatest problems of standard cosmology is the Big Bang singularity. Previously it has been shown that non-local ghostfree higher-derivative modifications of Einstein gravity in the ultra-violet regime can admit non-singular bouncing solutions. In this paper we study in more details the dynamical properties of the equations of motion for these theories of gravity in presence of positive and negative cosmological constants and radiation. We find stable inflationary attractor solutions in the presence of a positive cosmological constant which renders inflation {\it geodesically complete}, while in the presence of a negative cosmological constant a cyclic universe emerges. We also provide an algorithm for tracking the super-Hubble perturbations during the bounce and show that the bouncing solutions are free from any perturbative instability.Comment: 38 pages, 6 figures. V2: Added: a word to the title, clarifications, an appendix, many references. To appear in JCA

From green technology development to green innovation: inducing regulatory adoption of pathogen detection technology for sustainable forestry

Technological entrepreneurship has been widely acknowledged as a key driver of modern industrial economies, and more recently, a panacea for environmental and social problems. However, our current understanding of how green-technology ventures emerge and diffuse more sustainable innovations remains limited. We advance theory on green entrepreneurship by drawing on institutional work to refine and extend our understanding of how entrepreneurs may influence government policies and practices in their attempts to diffuse green technology. We develop a theoretical framework that combines institutional work with a search tool, the technological, commercial, organizational, and societal (TCOS) framework of innovative uncertainties, which identifies key opportunities, hurdles, and potential unintended consequences at early stages of technology development. We present a detailed case study of a potential university-based green-tech venture developing pathogen detection technology for forestry protection. Foreign pathogens spread by international trade can have major detrimental impacts on forests and the industries that rely on them. Our analysis found that green technology demonstrating technological feasibility is necessary but not sufficient; green-tech ventures must also engage in institutional work, in this case, articulating the technology’s benefits to regulators to establish legitimacy and avoid misuse that can hinder its adoption. We thus add to previous studies by emphasizing that institutional work could be a main activity for a green-tech venture, a core entrepreneurial strategy rather than an afterthought

Pre-HEAT: submillimeter site testing and astronomical spectra from Dome A, Antarctica

Pre-HEAT is a 20 cm aperture submillimeter-wave telescope with a 660 GHz (450 micron) Schottky diode heterodyne receiver and digital FFT spectrometer for the Plateau Observatory (PLATO) developed by the University of New South Wales. In January 2008 it was deployed to Dome A, the summit of the Antarctic plateau, as part of a scientific traverse led by the Polar Research Institute of China and the Chinese Academy of Sciences. Dome A may be one of the best sites in the world for ground based Terahertz astronomy, based on the exceptionally cold, dry and stable conditions which prevail there. Pre-HEAT is measuring the 450 micron sky opacity at Dome A and mapping the Galactic Plane in the ^(13)CO J=6-5 line, constituting the first submillimeter measurements from Dome A. It is field-testing many of the key technologies for its namesake -- a successor mission called HEAT: the High Elevation Antarctic Terahertz telescope. Exciting prospects for submillimeter astronomy from Dome A and the status of Pre-HEAT will be presented