Hedgehog proteins are of pivotal importance for development and maintenance of tissue patterns in adult organisms. Despite the role of Hedgehogs in differentiation and tumorigenesis, signal transduction of Hedgehog remains a relatively uncharted area of signalling biochemistry. For proper Hedgehog distribution into tissues, two highly unusual covalent modifications are necessary, palmitoylation of a secreted protein and the attachment of a cholesterol group, making Hedgehog the only established sterolated protein in nature. Hedgehog exerts its function via two membrane‐bound receptors, Patched and (...) Smoothened; presumably, Patched transports a cholesterol derivate out of cells which inhibits Smoothened. Binding of Hedgehog to Patched impedes this proposed pump function and thus Inhibition of Smoothened, which leads to expression of genetic Hedgehog targets via relief of transcriptional repression. These atypical features make Hedgehog physiology unique in biology and may explain why this field has attracted such significant attention. BioEssays 26:387–394, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Titles and abstracts for the Pitt-London Workshop in the Philosophy of Biology and Neuroscience: September 2001.

This paper examines the implications of the General Agreement on Trade in Services (GATS), the World Trade Organization’s agreement governing trade in health-related services, for health policy and healthcare reform in the United States. The paper describes the nature and scope of US obligations under the GATS, the ways in which the trade agreement intersects with domestic health policy, and the institutional factors that mediate trade-offs between health and trade policy. The analysis suggests that the GATS provisions on market access, (...) national treatment and domestic regulation, which are designed to eliminate ‘regulatory barriers’ to global trade in health services, limit the range of options that state and federal regulators and legislative bodies can employ to regulate the health sector and implement healthcare reforms. As such, the paper identifies the broader social and ethical implications of free trade policy. (shrink)

Structural equation model trees are data-driven tools for finding variables that predict group differences in SEM parameters. SEM trees build upon the decision tree paradigm by growing tree structures that divide a data set recursively into homogeneous subsets. In past research, SEM trees have been estimated predominantly with the R package semtree. The original algorithm in the semtree package selects split variables among covariates by calculating a likelihood ratio for each possible split of each covariate. Obtaining these likelihood ratios is (...) computationally demanding. As a remedy, we propose to guide the construction of SEM trees by a family of score-based tests that have recently been popularized in psychometrics. These score-based tests monitor fluctuations in case-wise derivatives of the likelihood function to detect parameter differences between groups. Compared to the likelihood-ratio approach, score-based tests are computationally efficient because they do not require refitting the model for every possible split. In this paper, we introduce score-guided SEM trees, implement them in semtree, and evaluate their performance by means of a Monte Carlo simulation. (shrink)

The rise of the platform economy in the past two decades (and neoliberal capitalist expansion and crises more in general), have on the whole negatively affected working conditions, leading to growing concerns about the “human side” of organizations. To address these concerns, the purpose of this paper is to apply Axel Honneth’s recognition theory and method of normative reconstruction to working conditions in the platform economy. The paper concludes that the ways in which platform organizations function constitutes a normative paradox, (...) promising flexibility and autonomy while at the same time creating working conditions that undercut these promises. The paper ends with a critical discussion of Honneth’s approach, possible supplementing ideas and further lines of future research. (shrink)

The ease with which genotyping technologies generate tremendous amounts of data on research participants has been well chronicled, a feat that continues to become both faster and cheaper to perform. In parallel to these advances come additional ethical considerations and debates, one of which centers on providing individual research results and incidental findings back to research participants taking part in genetic research efforts. In 2006 the Industry Pharmacogenomics Working Group offered some ‘Points-to-Consider’ on this topic within the context of the (...) drug development process from those who are affiliated to pharmaceutical companies. Today many of these points remain applicable to the discussion but will be expanded upon in this updated viewpoint from the I-PWG. The exploratory nature of pharmacogenomic work in the pharmaceutical industry is discussed to provide context for why these results typically are not best suited for return. Operational challenges unique to this industry which cause barriers to returning this information are also explained. (shrink)

A Correction to this paper has been published: 10.1007/s40926-021-00173-1.

For the safe and economical construction of embankment dams, the mechanical behaviour of the rockfill materials used in the dam’s shell must be analyzed. The characterization of rockfill materials with specified shear strength is difficult and expensive due to the presence of particles greater than 500 mm in diameter. This work investigates the feasibility of using an extreme gradient boosting computing paradigm to estimate the shear strength of rockfill materials. To train and validate the proposed XGBoost model, a total of (...) 165 databases obtained from the literature are chosen. The XGBoost model was compared against support vector machine, adaptive boosting, random forest, and K-nearest neighbor models described in the literature. XGBoost beats SVM, RF, AdaBoost, and KNN models in terms of performance evaluation metrics such as coefficient of determination, Nash–Sutcliffe coefficient, and error in the root mean square ratio to the standard deviation of the measured data. The results demonstrated that the XGBoost model has the highest prediction performance with, followed by the SVM model with, RF, the AdaBoost model with and the KNN model with. A sensitivity analysis has been conducted to ascertain the impact of each investigated input parameter. This study demonstrates that the established XGBoost model for estimating the shear strength of rockfill materials is reliable. (shrink)

This book is the scholarly & fully annotated edition of the award-winning _The Illustrated To Think Like God.__ _To Think Like God_ focuses on the emergence of philosophy as a speculative science, tracing its origins to the Greek colonies of Southern Italy, from the late 6th century to mid-5th century B.C. Special attention is paid to the sage Pythagoras and his movement, the poet Xenophanes of Colophon, and the lawmaker Parmenides of Elea. In their own ways, each thinker held that (...) true insight, whether as wisdom or certainty, belonged not to mortal human beings but to the gods. The Pythagoreans sought to approach this otherwordly knowledge by studying numerical relationships, believing them to govern the universe, and that those who know the number of a thing know its true nature. Yet their quest was a hopeless one, bogged down by cultism, numerology, political conspiracies, bloody uprisings, and exile. Above all, number did not turn out as the most reliable of mediums; it was certainly not a key to the realm of the divine. Thus, their contributions to philosophy's inception, while much better-publicized, was not the most significant. That particular role was reserved for an unusual challenge and the elaborate reaction it provoked. The challenge came from Xenophanes, who had argued that reliable truth was beyond mortal reach, because even if by accident a human being should state what is exactly the case, he had no way of knowing that he did, all things being susceptible to opinion. This dilemma is sure to have bothered a legislative mind like that of Parmenides, and we find him introducing techniques for testing the veracity of statements. These methods were meant to be carried out by reasoning and argument alone, without relying in physical evidence or mortal sense-perception, which was deemed untrustworthy. Reason was that one faculty shared by gods and humans alike. In time, Parmenides' ingenious arguments have earned him the titled of the first logician and metaphysician whose influence on subsequent thinkers was immeasurable. Parmenides taught us that philosophy was not about claims but about proof, which also makes him the father of theoretical science -- which, curiously, began as a quest into the mind of God. "Arnold Hermann makes a genuine contribution to Presocratics studies. This book, which is both an introduction to Pythagoras and Parmenides and a scholarly study, will interest novices and experts alike. Hermann's multi-leveled approach and his careful analyses of alternate views make his work a useful teaching tool, while his systematic inquiry into Pythagoreanism, the poem of Parmenides, and the development of early Greek thought will well repay the attention of scholars. — Patricia Curd_,_ _Purdue University_ "_To Think Like God_ is a highly ambitious book... Hermann's approach deserves to be taken seriously as an alternative to standard interpretations." — Richard D. McKirahan, Jr.,___ __Edwin Clarence Norton Professor of Classics and Professor of Philosophy, Pomona College_ "Arnold Hermann brings fresh life into the specialists' debates... a blow of wind that dissipates much fog." — Walter Burkert_, Professor Emeritus of Classical Philology, University of Zurich_ ARNOLD HERMANN_ is pursuing independent research on the origins of philosophy and methods of thinking. He specialices on subjects connected with Parmenides and Plato's _Parmenides._. (shrink)

Przekład i opracowanie naukowe - Rafał Michalski, Jarosław Rolewski, redakcja naukowa przekładu - Stanisław Czerniak, rozdział 7, 8 i 10 przełożyła - Elżbieta Paczkowska-Łagowska Arnold Gehlen (1904–1976), wybitny niemiecki filozof i socjolog, współtwórca antropologii filozoficznej. Autor licznych prac podejmujących zagadnienia antropologiczne w kontekście współczesnych przemian społeczno-kulturowych. W swojej twórczości rozwijał oryginalną filozofię techniki, psychologię społeczną, teorię instytucji oraz antropologiczną estetykę. Prezentowane polskiemu czytelnikowi ostatnie dzieło filozofa Moralność i hipertrofia moralności zawiera koncepcję pluralizmu etycznego oraz antropologiczną teorię genezy norm moralnych. (...) Gehlen opiera swoje wywody na rozbudowanych socjologiczno-historycznych analizach, które uwzględniają kulturową zmienność wyróżnionych przez niego etosów, a jednocześnie wskazuje na inwariantny charakter popędowych źródeł moralności. W swojej rozprawie antropolog przeprowadza również krytyczną diagnozę stanu współczesnej kultury i życia politycznego. W zglobalizowanej, przemysłowej kulturze opanowanej przez „superstruktury” (zintegrowane systemy techniki, gospodarki i nauki) dominuje według niego zuniwersalizowany etos eudajmonistycznego humanitaryzmu, marginalizujący pozostałe imperatywy, a zwłaszcza nakaz ochrony państwa. W rezultacie tego rodzaju hipertrofii moralności zanika biologicznie ugruntowana metaetyczna równowaga równorzędnych systemów wartości, narażając na szwank, o czym świadczą skutki uboczne nadmiernej subiektywizacji, antropologiczne zdrowie ludzkiego gatunku. Po opublikowaniu Moralności i hipertrofii moralności Gehlen zaczął uchodzić za nieprzejednanego krytyka lewicowych intelektualistów i wywarł znaczący wpływ na niemiecki neokonserwatyzm. (shrink)

Sir Karl Popper is well known for explicating science in falsificationist terms, for which his degree of corroboration formalism, C(h,e,b), has become little more than a symbol. For example, de Queiroz and Poe in this issue argue that C(h,e,b) reduces to a single relative (conditional) probability, p(e,hb), the likelihood of evidence e, given both hypothesis h and background knowledge b, and in reaching that conclusion, without stating or expressing it, they render Popper a verificationist. The contradiction they impose is easily (...) explained--de Queiroz and Poe fail to take account of the fact that Popper derived C(h,e,b) from absolute (logical) probability and severity of test, S(e,h,b), where critical evidence, p(e,b), is fundamental. Thus, de Queiroz and Poe's conjecture that p(e,hb) = C(h,e,b) is refuted. Falsificationism, not verificationism, remains a fair description of the parsimony method of inference used in phylogenetic systematics, not withstanding de Queiroz and Poe's mistaken understanding that "statistical" probability justifies that method. Although de Queiroz and Poe assert that maximum likelihood has the power "to explain data", they do not successfully demonstrate how causal explanation is achieved or what it is that is being explained. This is not surprising, bearing in mind that what is assumed about character evolution in the accompanying likelihood model M cannot then be explained by the results of a maximum likelihood analysis. (shrink)

The main purpose of this paper is to define and study a particular variety of Montague-Scott neighborhood semantics for modal propositional logic. We call this variety the first-order neighborhood semantics because it consists of the neighborhood frames whose neighborhood operations are, in a certain sense, first-order definable. The paper consists of two parts. In Part I we begin by presenting a family of modal systems. We recall the Montague-Scott semantics and apply it to some of our systems that have hitherto (...) be uncharacterized. Then, we define the notion of a first-order indefinite semantics, along with the more specific notion of a first-order uniform semantics, the latter containing as special cases the possible world semantics of Kripke. In Part II we prove consistency and completeness for a broad range of the systems considered, with respect to the first-order indefinite semantics, and for a selected list of systems, with respect to the first-order uniform semantics. The completeness proofs are algebraic in character and make essential use of the finite model property. A by-product of our investigations is a result relating provability in S-systems and provability in T-systems, which generalizes a known theorem relating provability in the systems S 2° and C 2. (shrink)

Rockburst phenomenon is the primary cause of many fatalities and accidents during deep underground projects constructions. As a result, its prediction at the early design stages plays a significant role in improving safety. The article describes a newly developed model to predict rockburst intensity grade using Adaptive Boosting classifier. A database including 165 rockburst case histories was collected from across the world to achieve a comprehensive representation, in which four key influencing factors such as maximum tangential stress of the excavation (...) boundary, uniaxial compressive strength of rock, tensile rock strength, and elastic energy index were selected as the input variables, and the rockburst intensity grade was selected as the output. The output of the AdaBoost model is evaluated using statistical parameters including accuracy and Cohen's kappa index. The applications for the aforementioned approach for predicting the rockburst intensity grade are compared and discussed. Finally, two real-world applications are used to verify the proposed AdaBoost model. It is found that the prediction results are consistent with the actual conditions of the subsequent construction. (shrink)

Fascinating illustrations contribute to this illuminating and award-winning account of how and why philosophy emerged and make it a must-read for any inquisitive thinker unsatisfied with prevailing assumptions on this timely and highly relevant subject._ By taking the reader back to the Greek colonies of Southern Italy more than 500 years B.C., the author, with unparalleled insight, tells the story of the Pythagorean quest for otherwordly konwledge -- a tale of cultism, political conspiracies, and bloody uprisings that eventually culminate in (...) tragic failure. The emerging hero is Parmenides, who introduces for the first time a technique for testing the truth of a statement that was not based on physical evidence or mortal sense-perception, but instead relied exclusively on the faculty we humans share with the gods: the ability to reason. "Figures from Anaximander to Zeno, the ruins where they lived and thought, and the paradoxes and thought-experiments they proposed are depicted among the [many] well-chosen color illustrations. The results read like an introductory textbook, but one that has been lovingly written, lavishly laid-out and crisply printed-- making it engaging enough to draw in readers to whom it has not been assigned." - _ Publishers Weekly___ "_To Think Like God_ is a highly ambitious book... Hermann's approach deserves to be taken seriously as an alternative to standard interpretations." - _ Richard D. McKirahan, Jr., Edwin Clarence Norton Professor of Classics and Professor of Philosophy, Pomona College___ "Arnold Hermann brings fresh life into the specialists' debates... a blow of wind that dissipates much fog." - _ Walter Burkert, Professor Emeritus of Classical Philology, University of Zurich___ ARNOLD HERMANN_ is pursuing independent research on the origins of philosophy and methods of thinking. He specialices on subjects connected with Parmenides and Plato's _Parmenides._. (shrink)

The arguments contained in books criticizing American social scientists by C. Wright Mills ( The Sociological Imagination) and Bernard Crick (The Science of American Politics) are discussed, compared and criticized. It is argued that Mills' criteria of evaluation and constructive alternatives to the tendencies he criticizes are immeasurably sounder than those found in Crick's book. An effort to supplement Mills' argument by providing a more explicit statement of its moral underpinnings is made. Finally, it is argued that though both critiques (...) have serious empirical flaws, the authors have undeniably demonstrated that important tendencies for irresponsible thought and action do exist within the American social sciences. (shrink)

Most shoppers like bargains. Do bargains come at the expense of workers in sweatshops around the world? The authors argue that many large multinational corporations are running the moral equivalents of sweatshops and are not properly respecting the rights of persons. They list a set of minimum standards of safety and decency that they claim all corporations should meet (and that many are not). Finally, they defend their call for improved working conditions by replying to objections that meeting improved conditions (...) will cause greater harm than good, even to the workers themselves. They consider many specifi c corporations and name names and point the finger at various forms of disrespect for persons, along the way. (shrink)

Husserl beruft sich immer wieder programmatisch auf Platon als den Gründervater der europäischen Philosophie, arbeitet jedoch die Bezüge der Phänomenologie zum Platonismus nie auf - obwohl er die "historische Rückbesinnung" auf die Urstiftung seines Denkens als wesentlichen Bestandteil der "Selbstbesinnung auf ein Selbstverständnis dessen hin, worauf man eigentlich hinaus will, als der man ist, als historisches Wesen" charakterisiert. Die vorliegende Arbeit will diese Reflexion leisten. Ihr Gegenstand ist mithin die Transformation Platonischer Gedanken in Husserls Phänomenologie. Dabei werden sechs Problemgebiete thematisiert: (...) A) Philosophie als Wissenschaft, B) Philosophie als Ethik, C) Philosophie als Polemik, D) Philosophie und das Ende der Lebenswelt, E) Philosophie und das Eigenrecht des Eidetischen, F) Philosophie und das Absolute. Den Abschnitten folgen jeweils kritische Erwägungen zu den Spannungen, die vor dem Platonischen Hintergrund innerhalb der Phänomenologie sichtbar werden. Die Arbeit zeigt, dass die Phänomenologie tatsächlich als eine eigenwillige Endstiftung des Platonismus betrachtet werden kann, wodurch sich eine neue Perspektive auf ihre programmatische und systematische Grundkonfiguration ergibt. (shrink)

In this paper we prove three theorems about the theory of Borel sets in models of ZF without any form of the axiom of choice. We prove that if \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${B\subseteq 2^\omega}$$\end{document} is a Gδσ-set then either B is countable or B contains a perfect subset. Second, we prove that if 2ω is the countable union of countable sets, then there exists an Fσδ set \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} (...) \setlength{\oddsidemargin}{-69pt} \begin{document}$${C\subseteq 2^\omega}$$\end{document} such that C is uncountable but contains no perfect subset. Finally, we construct a model of ZF in which we have an infinite Dedekind finite \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${D\subseteq 2^\omega}$$\end{document} which is Fσδ. (shrink)

We consider equational theories for functions defined via recursion involving equations between closed terms with natural rules based on recursive definitions of the function symbols. We show that consistency of such equational theories can be proved in the weak fragment of arithmetic S 1 2 . In particular this solves an open problem formulated by TAKEUTI (c.f. [5, p.5 problem 9.]).

We define and study a new restricted consistency notion RCon ∗ for bounded arithmetic theories T 2 j . It is the strongest ∀ Π 1 b -statement over S 2 1 provable in T 2 j , similar to Con in Krajíček and Pudlák, 29) or RCon in Krajı́ček and Takeuti 107). The advantage of our notion over the others is that RCon ∗ can directly be used to construct models of T 2 j . We apply this by (...) proving preservation theorems for theories of bounded arithmetic of the following well-known kind: The ∀ Π 1 b -separation of bounded arithmetic theories S 2 i from T 2 j is equivalent to the existence of a model of S 2 i which does not have a Δ 0 b -elementary extension to a model of T 2 j . More specific, let M ⊨ Ω 1 nst denote that there is a nonstandard element c in M such that the function n ↦ 2 log c is total in M . Let BLΣ 1 b be the bounded collection schema for Σ 1 b -formulas. We obtain the following preservation results: the ∀ Π 1 b -separation of S 2 i from T 2 j is equivalent to the existence of 1. a model of S 2 i +Ω 1 nst which is 1 b -closed w.r.t. T 2 j , 2. a countable model of S 2 i + BLΣ 1 b without weak end extensions to models of T 2 j. (shrink)

Biologists, historians, lawyers, art historians, and literary critics all voice arguments in the critical dialogue about what constitutes evidence in research and scholarship. They examine not only the constitution and "blurring" of disciplinary boundaries, but also the configuration of the fact-evidence distinctions made in different disciplines and historical moments the relative function of such concepts as "self-evidence," "experience," "test," "testimony," and "textuality" in varied academic discourses and the way "rules of evidence" are themselves products of historical developments. The essays and (...) rejoinders are by Terry Castle, Lorraine Daston, Carlo Ginzburg, Ian Hacking, Mark Kelman, R. C. Lewontin, Pierre Vidal-Naquet, Mary Poovey, Donald Preziosi, Simon Schaffer, Joan W. Scott, Eve Kosofsky Sedgwick, and Barbara Herrnstein Smith. The critical responses are by Lauren Berlant, James Chandler, Jean Comaroff, Arnold I. Davidson, Harry D. harootunian, Elizabeth Helsinger, Thomas C. Holt, Francoise Meltzer, Robert J. Richards, Lawrence Rothfield, Joel Snyder, Cass R. Sunstein, and William Wimsatt. (shrink)