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)

We agree with Archer that human sex differences in aggression are well explained by sexual selection, but note that explanations of human behaviors are not logically mutually exclusive from explanations and therefore should not be framed as such. We discuss why this type of framing hinders the development of both social learning and evolutionary theories of human behavior.

We present a one per cent measurement of the cosmic distance scale from the detections of the baryon acoustic oscillations in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey, which is part of the Sloan Digital Sky Survey III. Our results come from the Data Release 11 sample, containing nearly one million galaxies and covering approximately 8500 square degrees and the redshift range 0.2 < z < 0.7. We also compare these results with those from the publicly released (...) DR9 and DR10 samples. Assuming a concordance Λ cold dark matter cosmological model, the DR11 sample covers a volume of 13 Gpc3 and is the largest region of the Universe ever surveyed at this density. We measure the correlation function and power spectrum, including density-field reconstruction of the BAO feature. The acoustic features are detected at a significance of over 7σ in both the correlation function and power spectrum. Fitting for the position of the acoustic features measures the distance relative to the sound horizon at the drag epoch, rd, which has a value of rd,fid = 149.28 Mpc in our fiducial cosmology. We find DV = at z = 0.32 and DV = at z = 0.57. At 1.0 per cent, this latter measure is the most precise distance constraint ever obtained from a galaxy survey. Separating the clustering along and transverse to the line of sight yields measurements at z = 0.57 of DA = and H =. Our measurements of the distance scale are in good agreement with previous BAO measurements and with the predictions from cosmic microwave background data for a spatially flat CDM model with a cosmological constant. © 2014 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society. (shrink)

© 2017. The American Astronomical Society. All rights reserved.We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J and H bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au orbit with a 68% confidence interval between 14 and 28 au, an eccentricity (...) of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object. (shrink)

Study of rationalism in Urdu literature.

On Sikh ethics; includes brief biographies of Sikh religious leaders.

Islamic ethics in the light of Qurʼanic teaching and Hadith; Customs and practices.

Context: Although second-order cybernetics was proposed as a new way of cybernetic investigations around 1970, its general status and its modus operandi are still far from obvious. Problem: We want to provide a new perspective on the scope and the currently available potential of second-order cybernetics within today’s science landscapes. Method: We invited a group of scholars who have produced foundational work on second-order cybernetics in recent years, and organized an open call for new approaches to second-order cybernetics. The accepted (...) contributions are discussed and mapped. We also investigate the relations between second-order cybernetics and second-order science. Results: We present a coherent outlook on the scope of second-order cybernetics today, identify a general methodology of science and show that second-order cybernetics can be used in a large number of disciplines that go well beyond purely scientific domains. These results are based on a new epistemic mode “from within,” which can be traced back directly to von Foerster. We also arrived at the conclusion that from its early years onwards second-order cybernetics was developed in two different ways, so that second-order cybernetics and second-order science operate in different domains. Implications: Both the coherent perspective of the scope of second-order cybernetics with a new five-part agenda and the outline for a general methodology of science based on a new epistemic mode that was created within and for second-order cybernetics demonstrate the growing importance of reflexivity in science, which, so far, has not been widely recognized. (shrink)

Context: The journal Constructivist Foundations celebrates ten years of publishing articles on constructivist approaches, in particular radical constructivism. Problem: In order to preserve the sustainability of radical constructivism and regain its appeal to new generations of researchers, we set up a new course of action for and with the radical constructivist community to study its innovative potential. This new avenue is “second-order science.” Method: We specify two motivations of second-order science, i.e., the inclusion of the observer, and self-reflexivity that allows (...) second-order science to operate on the products of normal or first-order science. Also, we present a short overview of the contributions that we have collected for this inaugural issue on second-order science. Results: These six initial contributions demonstrate the potential of the new set of approaches to second-order science across several disciplines. Implications: Second-order science is believed to be a cogent concept in the evolution of science, leading to a new wave of innovations, novel experiments and a much closer relationship with current research in the cognitive neurosciences in particular, and with evolutionary and complexity theories in general. (shrink)

Purpose: Josef Mitterer's essays are considered to be important philosophical advancements of radical constructivism. The main purposes of this paper are, on the one hand, to structure the RC landscape and, on the other hand, to investigate the relations of Mitterer's work to radical constructivism in particular and to philosophy in general. Findings: In this short essay focusing on Mitterer's Das Jenseits der Philosophie, I would like to stress two major points. First, Mitterer's book should be considered as one of (...) several contemporary variants of a radical critique of the semantic turn in the philosophy of science that has taken place since the mid-thirties with the works of Rudolf Carnap, Carl G. Hempel, Hilary Putnam, Alfred Tarski and others. Second, it is by no means clear how to determine the relevance of the new semantic critique for the present and future cognitive status of radical constructivism. The degree of relevance depends crucially on the use of the term "radical constructivism." If radical constructivism, as I will argue, is seen as an umbrella term for a group of empirical research programs, then, by sheer necessity, the relevance can be marginal only. If, however, radical constructivism is viewed as a special form of philosophy of language and/or as a new epistemology, then the importance of Josef Mitterer's approach must be judged within the context of available functional alternatives. Implications: An immediate consequence of this article lies in a renewed emphasis on advancing an empirical research agenda for radical constructivism and in an effective downsizing of radical constructivism as a philosophical perspective. (shrink)

The aim of this dissertation is to present a systematic account of F. H. Bradley's philosophy in so far as it is relevant to an understanding of his conception of the nature and criterion of truth. I argue that, for Bradley, the nature of truth is the identity of thought with reality given in immediate experience. There is no absolute separation between thought and its object. Bradley therefore rejects both the correspondence theory and epistemological realism. Thought is not just a (...) mirror which reflects an independently existing reality. ;Concerning the criterion of truth, I argue that his criterion for our ordinary and scientific beliefs is practice, and the criterion for philosophical positions is a kind of coherence based on the doctrine of relative truth. For Bradley, some positions are truer than others, and the best philosophy is a comprehensive system which contains the truth of all different positions. ;Bradley does not accept the coherence theory of justification as it is understood today, since it is based on the standard account of negation and the doctrine of absolute truth. Bradley has a different approach to negation and inconsistency, according to which there are no absolutely inconsistent beliefs. Further, he insists that truth is not absolute but "relative," a matter of degree. All philosophical positions contain some truth, and none is completely false. The truth in philosophy is a position which accounts for the whole of reality and includes all apparently inconsistent positions within it. ;I explain Bradley's place in the history of philosophy and show his connections with the British empiricist tradition. I believe one of Bradley's central concerns is to explain the nature and criterion of truth in philosophy within the constraints of empiricism. I also contrast Bradley's positions on important issues with those of philosophers in the Anglo-American analytic tradition, such as Russell, Moore, Ayer, Tarski, Quine, Churchland, Lehrer and Campbell. I argue that most recent commentators on Bradley overlook the importance of understanding his philosophy as a system constructed according to the doctrine of relative truth. (shrink)

The concept of experience has been central to European philosophy since Descartes. He was the first to use experience to distinguish between two kinds of substance, mental and material, on the basis of the fact that one kind of substance is extended but does not think, while the other kind thinks, doubts, wills, imagines and feels, but is not extended. Other philosophers, such as Hobbes, Locke and Hume, made the concept of experience the basis of their analysis of knowledge. These (...) ideas have become part of common sense, and provide the background for a range of philosophical problems from Descartes’ time to the present. While the concept of experience is important for philosophy, philosophers do not all have the same understanding of the nature of experience. (shrink)

Context: The main problem is the rather marginal status of radical constructivism within its core domains of brain research, cognition and learning. Problem: The basic goal is to provide a short history of radical constructivism and its institutionalization processes. Additionally, the article specifies critical conditions that should be met in order for radical constructivism to become a mainstream endeavor. Method: The main methods used are those of comparative historical research. Results: The main results lie in the specification of missing elements (...) that have blocked radical constructivism becoming a mainstream endeavor. Implications: The paper might serve as a common reference for necessary steps to be taken over the following years in order to move radical constructivism out of its current weak position. (shrink)

Purpose: The article pursues three aims. First, it intends to differentiate between two different approaches for knowledge studies, namely an empirical and a normative mode. In a second move, two different epistemologies in the work of Ernst von Glasersfeld will be introduced under the labels of “Epistemology I” and “Epistemology II.” Epistemology I relates to empirical research, Epistemology II is normative in nature. Third, the article makes the point that while Ernst von Glasersfeld’s Epistemology II has already been presented in (...) a finite and mature form, his empirical analysis of cognitive processes still provides a rich pool of tools and designs that should be further developed and advanced in the years and decades ahead. Method: The article is analytical in nature, identifying the different building blocks and relational networks of von Glasersfeld’s two epistemologies. By this, the article intends to contribute to a further advancement of von Glasersfeld’s Epistemology I. Results: The main finding lies in recognizing the radical and innovative elements of von Glasersfeld’s Epistemology I and on the still-challenging research designs of Epistemology I. (shrink)

Context: Many recent research areas such as human cognition and quantum physics call the observer-independence of traditional science into question. Also, there is a growing need for self-reflexivity in science, i.e., a science that reflects on its own outcomes and products. Problem: We introduce the concept of second-order science that is based on the operation of re-entry. Our goal is to provide an overview of this largely unexplored science domain and of potential approaches in second-order fields. Method: We provide the (...) necessary conceptual groundwork for explorations in second-order science, in which we discuss the differences between first- and second-order science and where we present a roadmap for second-order science. The article operates mainly with conceptual differentiations such as the separation between three seemingly identical concepts such as Science II, Science 2.0 and second-order science. Results: Compared with first-order science, the potential of second-order science lies in 1. higher levels of novelty and innovations, 2. higher levels of robustness and 3. wider integration as well as higher generality. As first-order science advances, second-order science, with re-entry as its basic operation, provides three vital functions for first-order science, namely a rich source of novelty and innovation, the necessary quality control and greater integration and generality. Implications: Second-order science should be viewed as a major expansion of traditional scientific fields and as a scientific breakthrough towards a new wave of innovative research. Constructivist content: Second-order science has strong ties with radical constructivism, which can be qualified as the most important root/origin of second-order science. Moreover, it will be argued that a new form of cybernetics is needed to cope with the new problems and challenges of second-order science. (shrink)

In the last few years there has been a revival of interest in F.H. Bradley and particularly the account of judgment contained in The Principles of Logic. Many of those who discuss Bradley’s theory of judgment mistakenly assume that it can best be seen as a linguistic account. They insist that what Bradley says can be understood as an account of the meaning and reference of words or sentences. In this paper I will argue that Bradley’s theory of judgment is (...) essentially a psychological theory. Judgment is the union of part of the content of an image or other mental particular with our immediate experience. There is no evidence for the linguisitc interpretation and its defenders cannot make sense of Bradley’s discussion of a number of technical points, particularly his criticism of the view that judgment is the synthesis of ideas, and his comments on the idea of “this.” I will also argue that Bradley’s account of judgment cannot be separated from his later metaphysics and is essentially Hegelian in character. To explain Bradley’s theory I will begin where he does, with an examination of the nature of ideas. (shrink)

Translation and interpretation of selected Hadith on Islamic ethics and coduct.

Open peer commentary on the article “Luhmann and the Constructivist Heritage: A Critical Reflection” by Armin Scholl. Upshot: The comment starts with Buchinger’s assessment that Luhmann’s contribution to constructivism is original and inspiring, but raises more questions than answers. In three variations, the comment tries to show that Luhmann can indeed be viewed as a big question-generator and that his heritage for radical constructivism may lie in the original and inspiring effects these new and additional questions can produce.

Purpose: Several accounts like Ernst von Glasersfeld's Who Conceives of Society? (2008) locate empirical research in the social sciences and radical constructivism in almost parallel universes. The main purpose of this paper is to argue for more inter-active relations and to stress the importance of establishing weak, medium and strong ties between radical constructivism and empirical social research in general. Findings: The article shows that that weak, medium and strong ties between radical constructivism and empirical research in the social sciences (...) can be established. Moreover, these weak, medium and strong ties play a crucial role for increasing and maintaining the relevance of radical constructivism within the social sciences and for contributing to the viability of radical constructivism in the long run. Implications: The most important consequence for radical constructivism lies in a new research agenda. In the course of this article weak, medium and strong ties to empirical research have been specified specifically and exclusively for the social sciences. But these specific links cannot be simply generalized or transferred to other disciplinary fields outside the social sciences. Since interactive links between radical constructivism and empirical research are currently missing in practically all disciplines, these weak, medium and strong links, as a new RC-agenda, have to be developed separately for each major scientific research arena. (shrink)

Open peer commentary on the target article “From Objects to Processes: A Proposal to Rewrite Radical Constructivism” by Siegfried J. Schmidt. Upshot: The subtitle of “An Austrian Contribution” emphasizes a basic distinction between German and Austrian traditions in the philosophy of fields of science. In S. J. Schmidt’s genuinely German way of writing, one can observe a high emphasis on terminology and a specific arena of heavy philosophical problems that have to be solved in a strictly philosophical manner, whereas the (...) Austrian tradition places its importance on scientific progress, especially in the natural sciences, and on the clarifying, mediating, and self-reflecting role of philosophy within the overall context of scientific evolution. (shrink)

Open peer commentary on the target article “Who Conceives of Society?” by Ernst von Glasersfeld. Excerpt: I will make the point that radical constructivism von Glasersfeld style unnecessarily plays only a passive or an inactive role. Quite obviously, I want to demonstrate that there is life for radical constructivism outside its seemingly irrelevant function in empirical social research and that it is possible to develop radical constructivism in designs with tangible consequences and effects for the cognitive routines in the social (...) sciences. In short, it is conceivable, despite “Who Conceives of Society?”, that radical constructivism matters. (shrink)

DaB fUr die Entwicklung der Phanomenologie Husserls nicht zuletzt auch,wissenschaftstheoretische' Motive ausschlaggebend waren, ist hinreichend bekannt. Umso mehr verwundert es, daB die Husserl-Rezeption sich diese Motive nur selten zueigen gemacht hat. Zwar sind in einer Reihe von Einzel­ wissenschaften, wie in der Literaturwissenschaft, der Sozialwissenschaft und besonders auch der Psychologie, phanomenologische Motive wirksam gewor­ den. Versuche einer ausdriicklichen wissenschaftskritischen Anwendung der Husserlschen Philosophie auf einzelwissenschaftliehe Theorien jedoch, wie sie z.B. Alfred Schiitz in seinem friihen Werk zur phanomenologischen Grundlegung der "verstehenden (...) Soziologie"l ansatzweise unternommen hat, sind rar. Freilich ging auch Husserl hier nieht eben mit gutem Beispiel voran. Auch er selbst hat seine wissenschaftstheoretische Programmatik nirgends einer ernsthaften Bewahrungsprobe unterzogen. Die vorliegende Untersuchung will diese Frage einer wissenschaftstheore­ tischen Anwendbarkeit der transzendentalen Phiinomenologie paradigmatisch im Hinblick auf die Problemstellungen der Geschiehtswissenschaft iiberprii­ fen. Was also kann die Phanomenologie fUr die Historik leisten? DaB sieh fiir eine solche Absieht gerade die geschichtstheoretischen Perspektiven in Hus­ serls Werk anbieten, hat vor allem zwei Griinde. (shrink)

Objective: This paper describes the variety of ways that information about ethics-related methods are included or not included in public health research articles. Methods: Information about the ethics-related content of all articles published in nine highly-respected public health journals in 2006 was extracted. Results: Of 989 primary analyses, 73% of the articles commented on ethics committee approval or exemption, 63% mentioned participant consent and 9% indicated whether or not inducement or compensation was given. 84% of articles mentioned a funding source, (...) but fewer than 4% identified any potential conflict of interest. Reporting rates for committee review and consent were higher for experimental than for observational studies and were comparatively higher in studies conducted among potentially vulnerable populations like children and residents of low income countries. Conclusions: More complete reporting would facilitate the design, evaluation and comparison of future research studies. (shrink)