ZusammenfassungPrinzipien und Dialektik. Zwei Arten Dialektik: Die Rückkehr zum «Anhypoteton» und das dialektisierende Denken. Beide Tendenzen sind gleichsam charakterisiert durch die Hervorhebung der Aktivität des Denkens. Das formale Denken aber sucht den Ursprung dieser Aktivität, während das dialektisierende Denken deren Anwendung feststellen will. Auf dem Suchen nach einem ersten Ursprung ist das formale Denken in Gefahr bloss formale Bedingungen zu erreichen. Das dialektisierende Denken will aber nur die Orientierung in dem gegebenen gegenwärtigen Suchen feststellen; dabei scheint es die Idee einer (...) ewigen Ordnung der Dinge preiszugcben, bleibt jedoch der menschlichen Situation treu. Beide Richtungen haben Sinn für entgegengesetzte Ziele. Möglichkeit einer anthropologischen Problematik. (shrink)

This article discusses the early history of academic statistics in the Netherlands in relation to the reform challenges of the Dutch state. Statistics, before it developed into a predominantly quantitative social science, was adopted around 1800 by Adriaan Kluit as a method for shaping and articulating his political vision. Kluit's politics, the article suggests, echoed the specific outlook on the ‘intrinsic power’ of the Dutch Republic as a trading state that was developed during William IV's stadholderate in the mid eighteenth (...) century. Through the ideas of later writers and statesmen who had trained as statisticians this same approach to envisaging the Dutch future in international trade and politics was carried over into nineteenth-century Dutch political economy and constitutional reform. (shrink)

D‐amino acids are being recognized as functionally important molecules in mammals. We recently identified endogenous D‐cysteine in mammalian brain. D‐cysteine is present in neonatal brain in substantial amounts (mM) and decreases with postnatal development. D‐cysteine binds to MARCKS and a host of proteins implicated in cell division and neurodevelopmental disorders. D‐cysteine decreases phosphorylation of MARCKS in neural progenitor cells (NPCs) affecting its translocation. D‐cysteine controls NPC proliferation by inhibiting AKT signaling. Exogenous D‐cysteine inhibits AKT phosphorylation at Thr 308 and Ser (...) 473 in NPCs. D‐cysteine treatment of NPCs led to 50% reduction in phosphorylation of Foxo1 at Ser 256 and Foxo3a at Ser 253. We hypothesize that in the developing brain endogenous D‐cysteine is as a physiologic regulator of NPC proliferation by inhibiting AKT signaling mediated by Foxo1 and Foxo3a. Endogenous D‐cysteine may regulate mammalian neurodevelopment with roles in schizophrenia and Alzheimer's disease (AD). (shrink)

Precision targeting of specific white matter bundles that traverse the subcallosal cingulate has been linked to efficacy of deep brain stimulation for treatment resistant depression. Methods to confirm optimal target engagement in this heterogenous region are now critical to establish an objective treatment protocol. As yet unexamined are the time-frequency features of the SCC evoked potential, including spectral power and phase-clustering. We examined these spectral features—evoked power and phase clustering—in a sample of TRD patients with implanted SCC stimulators. Electroencephalogram was (...) recorded during wakeful rest. Location of electrical stimulation in the SCC target region was the experimental manipulation. EEG was analyzed at the surface level with an average reference for a cluster of frontal sensors and at a time window identified by prior study. Morlet wavelets generated indices of evoked power and inter-trial phase clustering. Enhanced phase clustering at theta frequency was observed in every subject and was significantly correlated with SCC-EP magnitude, but only during left SCC stimulation. Stimulation to dorsal SCC evinced stronger phase clustering than ventral SCC. There was a weak correlation between phase clustering and white matter density. An increase in evoked delta power was also coincident with SCC-EP, but was less consistent across participants. DBS evoked time-frequency features index mm-scale changes to the location of stimulation in the SCC target region and correlate with structural characteristics implicated in treatment optimization. Results also imply a shared generative mechanism between evoked potentials evinced by electrical stimulation and evoked potentials evinced by auditory/visual stimuli and behavioral tasks. Understanding how current injection impacts downstream cortical activity is essential to building new technologies that adapt treatment parameters to individual differences in neurophysiology. (shrink)

Patients fit with cochlear implants commonly indicate at the time of device fitting and for some time after, that the speech signal sounds abnormal. A high pitch or timbre is one component of the abnormal percept. In this project, our aim was to determine whether a number of years of CI use reduced perceived upshifts in frequency spectrum and/or voice fundamental frequency. The participants were five individuals who were deaf in one ear and who had normal hearing in the other (...) ear. The deafened ears had been implanted with a 18.5 mm electrode array which resulted in signal input frequencies being directed to locations in the spiral ganglion that were between one and two octaves higher than the input frequencies. The patients judged the similarity of a clean signal presented to their implanted ear and candidate, implant-like, signals presented to their normal-hearing ear. Matches to implant sound quality were obtained, on average, at 8 months after device activation and at 35 months after activation. At Time 1, the matches to CI sound quality were characterized, most generally, by upshifts in the frequency spectrum and in voice pitch. At Time 2, for four of the five patients, frequency spectrum values remained elevated. For all five patients F0 values remained elevated. Overall, the data offer little support for the proposition that, for patients fit with shorter electrode arrays, cortical plasticity nudges the cortical representation of the CI voice toward more normal, or less upshifted, frequency values between 8 and 35 months after device activation. Cortical plasticity may be limited when there are large differences between frequencies in the input signal and the locations in the SG stimulated by those frequencies. (shrink)

Calpain (Cp) is a calcium (Ca2+)‐dependent cysteine protease. Activation of the major isoforms of Cp, CpI and CpII, are required for a number of important cellular processes including adherence, shape change and migration. The current concept that cytoplasmic Cp locates and associates with its regulatory subunit (Rs) and substrates as well as translocates throughout the cell via random diffusion is not compatible with the spatial and temporal constraints of cellular metabolism. The novel finding that Cp and Rs function relies upon (...) tenacious hydrophobic interactions with organelle membranes offers a unifying explanation for the paradoxical and puzzling features of Cp activation and regulation such as how nM concentrations of intracellular Ca2+ can activate Cp molecules requiring μM to mM concentrations of Ca2+ for in vitro activation, and how this protease can spatially and temporally locate specific substrates and translocate throughout the cell. We hypothesize that Cp and its regulatory moieties associate with organelles to facilitate the activation of this protease resulting in the cleavage of substrates and aid in its translocation throughout the cell. BioEssays 28: 850–859, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

In this philosophically sophisticated and historically significant work, John H. Zammito reconstructs Kant's composition of The Critique of Judgment and reveals that it underwent three major transformations before publication. He shows that Kant not only made his "cognitive" turn, expanding the project from a "Critique of Taste" to a Critique of Judgment but he also made an "ethical" turn. This "ethical" turn was provoked by controversies in German philosophical and religious culture, in particular the writings of Johann Herder and the (...) Sturm und Drang movement in art and science, as well as the related pantheism controversy. Such topicality made the Third Critique pivotal in creating a "Kantian" movement in the 1790s, leading directly to German Idealism and Romanticism. The austerity and grandeur of Kant's philosophical writings sometimes make it hard to recognize them as the products of a historical individual situated in the particular constellation of his time and society. Here Kant emerges as a concrete historical figure struggling to preserve the achievements of cosmopolitan Aufkl-rung against challenges in natural science, religion, and politics in the late 1780s. More specifically Zammito suggests that Kant's Third Critique was animated throughout by a fierce personal rivalry with Herder and by a strong commitment to traditional Christian ideas of God and human moral freedom. "A work of extraordinary erudition. Zammito's study is both comprehensive and novel, connecting Kant's work with the aesthetic and religious controversies of the late eighteenth century. He seems to have read everything. I know of no comparable historical study of Kant's Third Critique."-Arnulf Zweig, translator and editor of Kant's ;IPhilosophical Correspondence, 1759-1799;X "An intricate, subtle, and exciting explanation of how Kant's thinking developed and adjusted to new challenges over the decade from the first edition of the Critique of Pure Reason to the appearance of the Critique of Judgment. "--John W. Burbidge, Review of Metaphysics "There has been for a long time a serious gap in English commentary on Kant's Critique of Judgment Zammito's book finally fills it. All students and scholars of Kant will want to consult it."--Frederick Beiser, Times Literary Supplement. (shrink)

Introduction: Platonic dramatology -- The political and philosophical problems. Using pre-Socratic philosophy to support political reform: the Athenian stranger ; Plato's Parmenides: Parmenides' critique of Socrates and Plato's critique of Parmenides ; Becoming Socrates ; Socrates interrogates his contemporaries about the noble and good -- Paradigms of philosophy. Socrates' positive teaching ; Timaeus-Critias: completing or challenging Socratic political philosophy? ; Socratic practice -- The trial and death of Socrates. The limits of human intelligence ; The Eleatic challenge ; The trial (...) and death of Socrates -- Conclusion: Why Plato made Socrates his hero. (shrink)

In 'Een handvol filosofen' staan de filosofen centraal die sinds de oprichting van de Vrije Universiteit in 1880 aan deze instelling verbonden zijn geweest. Het gaat hierbij niet alleen om de inhoud van hun werk, maar ook om de personen zelf. Er waren filosofiedocenten die zich met de universiteit identificeerden en zich volledig konden ontplooien. Er waren er echter ook voor wie dit niet gold, die geïsoleerd of in gewetensnood raakten. Veel filosofiestudenten waren actief betrokken bij wat er in hun (...) faculteit gebeurde. Zij namen initiatieven, protesteerden soms tegen de gang van zaken en kozen partij in conflictsituaties. Sinds het eind van de jaren zestig van de twintigste eeuw verloor de Vrije Universiteit geleidelijk haar christelijk karakter. Tegenwoordig werken alle stafleden vanuit hun eigen motivatie mee aan een hoofdzakelijk seculier geworden universiteit, die ruimte biedt voor religieuze en levensbeschouwelijke diversiteit. (shrink)